Associations between ACTN3 and OPPERA pain-related genes in malocclusion

We have investigated an orthognathic surgery population to determine how variation in masticatory muscle gene expression and genotype plays a key role in development of both jaw-deformation malocclusion and temporomandibular joint disorders (TMD). A gene of particular interest is ACTN3 since the common R577X polymorphism results in α-actinin-3 protein loss, reduced myofiber Z-disc structural integrity in skeletal muscle and decreased osteoblast/osteoclast activity in bone formation. Secondly, since the prevalence of TMD in this population is quite high (30%) we sought to determine if genes related to pain processes─previously identified in the Orofacial Pain: Prospective Evaluation and Risk Assessment Study (OPPERA) were differentially expressed

Structural and molecular study of the supraspinatus muscle of modern humans (Homo sapiens ) and common chimpanzees (Pan troglodytes )

Objectives To analyze the muscle architecture and the expression pattern of the myosin heavy chain (MyHC) isoforms in the supraspinatus of Pan troglodytes and Homo sapiens in order to identify differences related to their different types of locomotion. Materials and methods We have analyzed nine supraspinatus muscles of Pan troglodytes and ten of Homo sapiens. For each sample, we have recorded the muscle fascicle length (MFL), the pennation angle, and the physiological cross?sectional area (PCSA). In the same samples, by real?time quantitative polymerase chain reaction, we have assessed the percentages of expression of the MyHC?I, MyHC?IIa, and MyHC?IIx isoforms. Results The mean MFL of the supraspinatus was longer (p?=?0.001) and the PCSA was lower (p?<?0.001) in Homo sapiens than in Pan troglodytes. Although the percentage of expression of MyHC?IIa was lower in Homo sapiens than in Pan troglodytes (p?=?0.035), the combination of MyHC?IIa and MyHC?IIx was expressed at a similar percentage in the two species. Discussion The longer MFL in the human supraspinatus is associated with a faster contractile velocity, which reflects the primary function of the upper limbs in Homo sapiens—the precise manipulation of objects—an adaptation to bipedal locomotion. In contrast, the larger PCSA in Pan troglodytes is related to the important role of the supraspinatus in stabilizing the glenohumeral joint during the support phase of knuckle?walking. These functional differences of the supraspinatus in the two species are not reflected in differences in the expression of the MyHC isoforms

Facial-muscle weakness, speech disorders and dysphagia are common in patients with classic infantile Pompe disease treated with enzyme therapy

Classic infantile Pompe disease is an inherited generalized glycogen storage disorder caused by deficiency of lysosomal acid α-glucosidase. If left untreated, patients die before one year of age. Although enzyme-replacement therapy (ERT) has significantly prolonged lifespan, it has also revealed new aspects of the disease. For up to 11 years, we investigated the frequency and consequences of facial-muscle weakness, speech disorders and dysphagia in long-term survivors. Sequential photographs were used to determine the timing and severity of facial-muscle weakness. Using standardized articulation tests and fibreoptic endoscopic evaluation of swallowing, we investigated speech and swallowing function in a subset of patients. This study included 11 patients with classic infantile Pompe disease. Median age at the start of ERT was 2.4 months (range 0.1-8.3 months), and median age at the end of the study was 4.3 years (range 7.7 months −12.2 years). All patients developed facial-muscle weakness before the age of 15 months. Speech was studied in four patients. Articulation was disordered, with hypernasal resonance and reduced speech intelligibility in all four. Swallowing function was studied in six patients, the most important findings being ineffective swallowing with residues of food (5/6), penetration or aspiration (3/6), and reduced pharyngeal and/or laryngeal sensibility (2/6). We conclude that facial-muscle weakness, speech disorders and dysphagia are common in long-term survivors receiving ERT for classic infantile Pompe disease. To improve speech and reduce the risk for aspiration, early treatment by a speech therapist and regular swallowing assessments are recommended

Clinical classification of cancer cachexia:phenotypic correlates in human skeletal muscle

Aim – To relate muscle phenotype to a range of current diagnostic criteria for cancer cachexia Methods – 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and / or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10% WL, LM, and LM + >2%WL. Patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, and Western blots for markers of autophagy, SMAD signalling, and inflammation. Results – Compared with non-cachectic cancer patients, if patients were classified by LM or LM + >2%WL, mean muscle fibre diameter was significantly reduced (p = 0.02 and p = 0.001) repectively. No difference in fibre diameter was observed if patients were classified with WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased if patients were classified by either >5% WL or LM + >2%WL. Compared with non-cachectic patients, when patients were classified according to >5% WL, SMAD3 protein levels were increased (p=0.022) and with >10% WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were also increased. There were no differences in pNFkB or pSTAT3 levels across any of the groups. Conclusions – Whereas fibre type is not targeted selectively, muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the criteria for cachexia include both a measure of low muscularity and weight loss

Fiber types in cat jaw closing muscles.

The existence of a distinct fiber type in the jaw closing muscles of carnivores and primates has yet to be substantiated by the isolation of a unique myosin heavy chain (MHC). The specific aims of this study were (1) to isolate and characterize the type IIM MHC by gel electrophoresis and production of polyclonal antisera and (2) to characterize the type IIM fiber by histochemical and immunohisotochemical staining. The glycerol SDS-PAGE technique was modified to enhance separation of MHCs, resulting in distinct separation of type I, atrial, ventricular, neonatal, fast skeletal and masticatory (type IIM) isoforms from limb, masticatory and cardiac muscle. The type IIM and I isoforms were used to produce western blot specific polyclonal antiserum. Immunohistochemical and histochemical staining was performed on representative areas of the soleus, extensor digitorum longus, sartorius major, temporalis, masseter, atrium and ventricle. Type I, IIA, IIB and IIC fibers of the limb muscles stained for myofibrillar ATPase activity in the standard fashion following pH preincubations. Type IIM fibers of the jaw closing muscles were reactive for ATPase activity after both acid and alkali preincubations and stained positively for the type IIM antiserum. The type I fibers of these muscles were relatively unreactive for ATPase at all pH preincubations, but positive for the type I antiserum. The fibers of the ventricle stained positively for the type I antiserum, but had an ATPase reactivity different from type I fibers of both limb and jaw closing muscles. SDS-PAGE of whole muscle extracts identified typical fast and slow myosin light chains (MLC) in limb skeletal muscles. But both type I and type IIM fibers of the jaw closing muscles contained the same distinct masticatory MLCs. It was concluded that the type IIM fiber does exist as a distinct fiber type which contains only the type IIM myosin heavy chain. Further, since the type I fibers of masticatory, skeletal and cardiac muscle have the same MHC, but differential reactivity for myofibrillar ATPase, other factors such as the MLCs may modify enzymatic properties.Ph.D.Oral BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/103143/1/9303818.pdfDescription of 9303818.pdf : Restricted to UM users only