Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease

Abstract:  In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 ( CELIAC3 ) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles −1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly −1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.     

Effects of pelvic and lower extremity stabilization on isometric trunk extension and flexion muscle strength*

The purpose of this study was to evaluate the effect of varying the type of pelvic and lower extremity stabilization on isometric trunk extension and flexion muscle strength measurements. Two pelvic stabilization systems, one consisting of fixation of the anterior superior iliac spines and sacrum (pelvic fixation) and the second, a strap across the anterior superior iliac spines and a posterior pad at the sacrum (pelvic strap) were compared. The lower extremities were or were not strapped at the thigh, calf, and feet. Torque values for the pelvic fixation system were not different from the pelvic strap system with lower extremity stabilization. Torque values were less with no lower extremity stabilization with both pelvic stabilization systems for flexion but not for extension muscle contractions. The use of an extensive pelvic stabilization system did not produce greater isometric force output than the use of a simple pelvic strap. The use of lower extremity stabilization did produce greater isometric flexion force output than the use of no lower extremity stabilization. J Ortho Sports Phys Ther 1987;9(3):111-117.     

Muscle strength at the trunk*

The purpose of this study was to determine the strength of trunk flexors and extensors in normal male subjects during isometric, concentric, and eccentric contractions. Subjects were tested in the sidelying position to minimize the effects of gravity. The pelvis and lower extremities were measured on a custom built force table (lowa Force Table). Muscle strength was expressed as a moment of force (external force times the moment arm) in Newton-meter (Nm) units. Greater Nm were registered in the muscle-lengthened position than in the muscle-shortened position for all isometric contractions. The Nm registered for eccentric contractions always exceeded the Nm registered for concentric contractions of the same muscle group. The Nm registered during contractions of trunk extensors always exceeded the values obtained during corresponding modes of contractions (isometric, eccentric, and concentric) of trunk flexors.J Orthop Sports Phys Ther 1980;1(3):165-170.     

Changes in antiplasmin and plasmin activities during extreme hemodilution and open heart surgery in dogs.

The effects of extreme hemodilution and open heart surgery on antiplasmin and plasmin activities were investigated in dogs. Assays for plasmin and antiplasmin activities were performed with a chromogenic peptide substrate for plasmin. After hemodilution and during cardiopulmonary bypass (CPB), plasmin activity on the substrate was observed and levels of both "fast-reacting" and "total" antiplasmins fell. The plasmin activity was shown to be due to the formation of alpha2-macroglobulin-plasmin complex which exhibited amidolytic activity on the chromogenic substrate. The falls in antiplasmin activity together with the appearance of the alpha2-macroglobulin-plasmin complex revealed that activation of the fibrinolytic system had occurred. After the operation and following reinfusion of autologous blood, decreased plasmin and increased antiplasmin activities were observed. On the first and sixth days following the operation plasmin activities were still slightly higher than pre-operation values, whilst antiplasmin activities were normal.     

Variations in strategy for the treatment of urethral obstruction after a pubovaginal sling procedure

PURPOSE: We evaluated the success of several techniques for treating urethral obstruction and erosion after a pubovaginal sling procedure. MATERIALS AND METHODS: Between April 1998 and June 1999, 32 women 33 to 79 years old (average age 62) who underwent a pubovaginal sling procedure with various materials were referred for the assessment of urethral obstruction. Patients were evaluated with a urogynecologic history, physical examination, voiding diary, cystoscopy and video urodynamics. Surgical procedures to resolve urethral obstruction were performed transvaginally and the specific techniques used were based on the type of sling material, urethral erosion and concomitant stress incontinence or other urethral pathology. Outcome measures were assessed by disease specific quality of life questionnaires, voiding diary and urogynecologic questionnaire. RESULTS: Preoperatively 30 of the 32 women (93.7%) noticed urge incontinence, 20 (62.5%) performed intermittent self-catheterization, 6 (18.7%) had an indwelling catheter and 3 (9%) complained of concomitant stress urinary incontinence. After the sling takedown 29 patients (93.5%) achieved efficient voiding within week 1 postoperatively. Urge incontinence symptoms resolved in 20 cases (67%) but stress incontinence developed in 3 (9%). Of the 32 women 27 (84%) indicated that continence was much better than before the initial sling procedure. CONCLUSIONS: Managing urethral obstruction after a pubovaginal sling procedure is challenging. Using various techniques based on sling material, urethral erosion and bladder neck integrity a successful outcome is possible in the majority of cases.     

Complications,risk factors,and patients-reported outcomes after skin-sparing mastectomy followed by breast reconstruction in women with BRCA mutations

Background: Women with a BRCA mutation have the option of undergoing prophylactic mastectomy and immediate breast reconstruction; however, the potential negative effects of reconstruction on women’s physical and psychological well-being are unclear. This study aimed to investigate complications, patient-reported pain, health-related quality-of-life (HRQoL) and satisfaction following reconstructive surgery at Oslo University Hospital between 2006 and 2013.

Methods: Data were collected retrospectively from the records of 238 patients. A cross-sectional survey was conducted to collect patient-reported HRQoL and satisfaction with outcome using the Short Form-12 questionnaires and Breast-Q. The self-administered Leeds assessment of neuropathic symptoms and signs was used to assess neuropathic pain.

Results: The majority of participants (89.5%) underwent implant-based breast reconstruction (IBBR); the remainder underwent autologous-tissue breast reconstruction (ATBR). Overall, 28.6% had complications within 30?days of surgery and 14.6% required resurgery because of complications. Women who underwent IBBR had a later onset of complications than those undergoing ATBR. Participants in the survey (n?=?175 of 219, response rate 79.9%) reported similar HRQoL to an age-matched general female population. Few (2.9%) reported neuropathic pain. Patients who underwent IBBR were significantly less satisfied with the reconstructed breast (p?=?.001) and overall outcome (p?=?.02) than those who underwent ATBR, but there were no significant differences in HRQoL scores between the two groups.

Conclusions: Overall, 28.6% of the women had complications within 30?days and 14.6% needed resurgery. Few had neuropathic pain. Women who underwent ATBR were more satisfied with the overall outcome than those who underwent IBBR.     

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.     

A comparison between two powder compaction parameters of plasticity: The effective medium A parameter and the Heckel 1/K parameter

The purpose of the research was to introduce a procedure to derive a powder compression parameter (EM A) representing particle yield stress using an effective medium equation and to compare the EM A parameter with the Heckel compression parameter (1/K).