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Journal of Neurophysiology Apr 2023Muscle stiffness is altered following postmastectomy breast reconstruction and breast cancer treatment. The exact mechanisms underlying these alterations are unknown;...
Muscle stiffness is altered following postmastectomy breast reconstruction and breast cancer treatment. The exact mechanisms underlying these alterations are unknown; however, muscle stretch reflexes may play a role. This work examined short- (SLR) and long-latency (LLR) shoulder muscle stretch reflexes in breast cancer survivors. Forty-nine patients who had undergone postmastectomy breast reconstruction, 17 who had undergone chemoradiation, and 18 healthy, age-matched controls were enrolled. Muscle activity was recorded from the clavicular and sternocostal regions of the pectoralis major and anterior, middle, and posterior deltoids during vertical ab/adduction or horizontal flex/extension perturbations while participants maintained minimal torques. SLR and LLR were quantified for each muscle. Our major finding was that following postmastectomy breast reconstruction, SLR and LLR are impaired in the clavicular region of the pectoralis major. Individuals who had chemoradiation had impaired stretch reflexes in the clavicular and sternocostal region of the pectoralis major, anterior, middle, and posterior deltoid. These findings indicate that breast cancer treatments alter the regulation of shoulder muscle stretch reflexes and may be associated with surgical or nonsurgical damage to the pectoral fascia, muscle spindles, and/or sensory Ia afferents. Shoulder muscle stretch reflexes may be impacted following postmastectomy breast reconstruction and chemoradiation. Here, we examined short- and long-latency shoulder muscle stretch reflexes in two experiments following common breast reconstruction procedures and chemoradiation. We show impairments in pectoralis major stretch reflexes following postmastectomy breast reconstruction and pectoralis major and deltoid muscle stretch reflexes following chemoradiation. These findings indicate that breast cancer treatments alter the regulation of shoulder muscle stretch reflexes.
Topics: Humans; Female; Shoulder; Breast Neoplasms; Mastectomy; Muscle, Skeletal; Reflex, Stretch; Mammaplasty
PubMed: 36947887
DOI: 10.1152/jn.00081.2022 -
Head and Neck Pathology Mar 2023Spindled lesions are a challenging area in head and neck pathology. This is particularly true in the sinonasal tract, where several uncommon entities with both unique... (Review)
Review
BACKGROUND
Spindled lesions are a challenging area in head and neck pathology. This is particularly true in the sinonasal tract, where several uncommon entities with both unique and overlapping morphologic, immunophenotypic, and/or molecular features can occur.
METHODS
Review.
RESULTS
The clinicopathologic characteristics of biphenotypic sinonasal sarcoma and nine important differential diagnostic considerations with one or more overlapping feature are summarized to establish a practical framework for approaching spindled lesions of the sinonasal tract.
CONCLUSION
Morphologic evaluation is central to the work up of sinonasal spindle cell lesions-in particular, cellular morphology, tumor architecture and growth pattern, and the presence of admixed epithelial elements - however, focused immunohistochemical analysis of neural, myogenic, rhabdomyoblastic, epithelial, and/or melanocytic marker expression and/or ancillary tests for tumor-specific molecular alterations may be necessary for definitive diagnosis.
Topics: Humans; Sarcoma; Head; Neck; Paranasal Sinus Neoplasms; Soft Tissue Neoplasms; Biomarkers, Tumor; Diagnosis, Differential
PubMed: 36928738
DOI: 10.1007/s12105-023-01535-z -
Molecular and Clinical Oncology Apr 2020Adrenal leiomyosarcomas are rare mesenchymal tumors of the suprarenal region that are usually diagnosed after they have reached a large size. We report the case of a...
Adrenal leiomyosarcomas are rare mesenchymal tumors of the suprarenal region that are usually diagnosed after they have reached a large size. We report the case of a 62-year-old male with an incidentally found left adrenal mass. Magnetic resonance imaging of the retroperitoneal space showed a heterogeneously enhanced mass, measuring 10x8.2 cm, with characteristics suspicious of malignancy. The patient underwent left radical adrenalectomy after the hormonal evaluation of the tumor due to the high probability of adrenocortical carcinoma. However, microscopic examination of the tumor showed a spindle cell sarcoma. Immunohistochemically the neoplastic cells were found positive for desmin and smooth muscle actin and the diagnosis of a well differentiated adrenal leiomyosarcoma was established. During follow-up the patient presented an aggressive course as he developed bone, liver and pulmonary metastases early postoperatively, which were treated with radiation therapy and chemotherapy. The patient has progressive metastatic disease while on chemotherapy 31 months after surgery.
PubMed: 32190312
DOI: 10.3892/mco.2020.1987 -
Cells Nov 2021Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in...
Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. So far, selective integration of Schwann cells in these models has been hampered, due to technical limitations. Here we present robust protocols for derivation of Schwann cells from human induced pluripotent stem cells (hiPSC) and their coculture with hiPSC-derived motoneurons and C2C12 muscle cells. Upon differentiation with tuned BMP signaling, Schwann cells expressed marker proteins, S100b, Gap43, vimentin, and myelin protein zero. Furthermore, they displayed typical spindle-shaped morphologies with long processes, which often aligned with motoneuron axons. Inclusion of Schwann cells in coculture experiments with hiPSC-derived motoneurons and C2C12 myoblasts enhanced myotube growth and affected size and number of acetylcholine receptor plaques on myotubes. Altogether, these data argue for the availability of a consistent differentiation protocol for Schwann cells and their amenability for functional integration into neuromuscular in vitro models, fostering future studies of neuromuscular mechanisms and disease.
Topics: Animals; Biomarkers; Bone Morphogenetic Proteins; Cell Differentiation; Cell Line; Cell Shape; Coculture Techniques; Humans; Induced Pluripotent Stem Cells; Mice; Muscle Development; Muscle Fibers, Skeletal; Neuromuscular Junction; Receptors, Cholinergic; Schwann Cells; Signal Transduction
PubMed: 34943800
DOI: 10.3390/cells10123292 -
Frontiers in Neuroanatomy 2022Muscle spindles, an important proprioceptor scattered in the skeletal muscle, participate in maintaining muscle tension and the fine regulation of random movement....
Muscle spindles, an important proprioceptor scattered in the skeletal muscle, participate in maintaining muscle tension and the fine regulation of random movement. Although muscle spindles exist in all skeletal muscles, explanations about the distribution and morphology of muscle spindles remain lacking for the indetermination of spindle location across muscles. In this study, traditional time-consuming histochemical technology was utilized to determine the muscle spindle anatomical and morphological characteristics in the lower extremity skeletal muscle in C57BL/6 mice. The relative distance from spindles to nerve-entry points varied from muscles in the ventral-dorsal direction, in which spindles in the lateral of gastrocnemius were not considered to be close to its nerve-entry point. In the longitudinal pattern, the domain with the highest abundance of spindles corresponded to the nerve-entry point, excluding the tibialis anterior. Spindles are mainly concentrated at the middle and rostral domain in all muscles. The results suggest a heterogeneity of the distribution of spindles in different muscles, but the distribution trend generally follows the location pattern of the nerve-entry point. Histochemical staining revealed that the spindle did not have a symmetrical structure along the equator, and this result does not agree with previous findings. Exploring the distribution and structural characteristics of muscle spindles in skeletal muscle can provide some anatomical basis for the study of muscle spindles at the molecular level and treatment of exercise-related diseases and provide a comprehensive understanding of muscle spindle morphology.
PubMed: 35370570
DOI: 10.3389/fnana.2022.838951 -
Revista Espanola de Enfermedades... Jan 2023We present a 41-year-old female who was admitted to our hospital with a history of 2-month epigastric pain and vomiting. Physical examination was normal. Upper...
We present a 41-year-old female who was admitted to our hospital with a history of 2-month epigastric pain and vomiting. Physical examination was normal. Upper gastrointestinal endoscopy showed a sessile submucosal tumor with central ulceration in the gastric body-antrum. Biopsies revealed a gastric mucosa without changes. Nevertheless, endoscopic ultrasound-guided biopsies showed interlacing bundles of spindle cells. The immunohistochemical study was negative for CD117 and smooth muscle actin and positive for S100 protein. A CT scan identified a heterogeneous mass in the stomach wall.
Topics: Female; Humans; Adult; Stomach Neoplasms; Gastrointestinal Stromal Tumors; Tomography, X-Ray Computed; Biopsy
PubMed: 35704374
DOI: 10.17235/reed.2022.8974/2022 -
Current Opinion in Physiology Feb 2021The muscle spindle is an important sense organ for motor control and proprioception. Specialized intrafusal fibers are innervated by both stretch sensitive afferents and...
The muscle spindle is an important sense organ for motor control and proprioception. Specialized intrafusal fibers are innervated by both stretch sensitive afferents and γ motor neurons that control the length of the spindle and tune the sensitivity of the muscle spindle afferents to both dynamic movement and static length. γ motor neurons share many similarities with other skeletal motor neurons, making it challenging to identify and specifically record or stimulate them. This short review will discuss recent advances in genetic and molecular biology techniques, electrophysiological recording, optical imaging, computer modelling, and stem cell culture techniques that have the potential to help answer important questions about fusimotor function in motor control and disease.
PubMed: 36561377
DOI: 10.1016/j.cophys.2020.10.002 -
Scientific Reports Oct 2023During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously...
During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We observed a nuclear expression of apelin in SMCs within experimentally-induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localization of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded the direct interaction and nuclear expression of both apelin and S100A4. In conclusion, apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4.
Topics: Animals; Rats; Apelin; Atherosclerosis; Cell Movement; Cells, Cultured; Myocytes, Smooth Muscle; Phenotype; Swine
PubMed: 37907514
DOI: 10.1038/s41598-023-45470-z -
Experimental Physiology Jan 2024This paper is in two parts: 'There', which is a review of some of the major advances in the study of spindle structure and function during the past 50 years, serving as... (Review)
Review
This paper is in two parts: 'There', which is a review of some of the major advances in the study of spindle structure and function during the past 50 years, serving as an introduction to the symposium entitled 'Mechanotransduction, Muscle Spindles and Proprioception' held in Munich in July 2022; and 'And Back Again', presenting new quantitative morphological results on the equatorial nuclei of intrafusal muscle fibres and of the primary sensory ending in relationship to passive stretch of the spindle.
Topics: Mechanotransduction, Cellular; Muscle Fibers, Skeletal; Muscle Spindles
PubMed: 36628601
DOI: 10.1113/EP090760 -
American Journal of Physiology. Heart... Oct 2019Atherosclerosis is the most common underlying cause of cardiovascular morbidity and mortality worldwide. c-Kit (CD117) is a member of the receptor tyrosine kinase...
Atherosclerosis is the most common underlying cause of cardiovascular morbidity and mortality worldwide. c-Kit (CD117) is a member of the receptor tyrosine kinase family, which regulates differentiation, proliferation, and survival of multiple cell types. Recent studies have shown that c-Kit and its ligand stem cell factor (SCF) are present in arterial endothelial cells and smooth muscle cells (SMCs). The role of c-Kit in cardiovascular disease remains unclear. The aim of the current study is to determine the role of c-Kit in atherogenesis. For this purpose, atherosclerotic plaques were quantified in c-Kit-deficient mice (Kit) after they were fed a high-fat diet (HFD) for 16 wk. Kit mice demonstrated substantially greater atherosclerosis compared with control (Kit) littermates ( < 0.01). Transplantation of c-Kit-positive bone marrow cells into Kit mice failed to rescue the atherogenic phenotype, an indication that increased atherosclerosis was associated with reduced arterial c-Kit. To investigate the mechanism, SMC organization and morphology were analyzed in the aorta by histopathology and electron microscopy. SMCs were more abundant, disorganized, and vacuolated in aortas of c-Kit mutant mice compared with controls ( < 0.05). Markers of the "contractile" SMC phenotype (calponin, SM22α) were downregulated with pharmacological and genetic c-Kit inhibition ( < 0.05). The absence of c-Kit increased lipid accumulation and significantly reduced the expression of the ATP-binding cassette transporter G1 (ABCG1) necessary for lipid efflux in SMCs. Reconstitution of c-Kit in cultured Kit SMCs resulted in increased spindle-shaped morphology, reduced proliferation, and elevated levels of contractile markers, all indicators of their restored contractile phenotype ( < 0.05). This study describes the novel vasculoprotective role of c-Kit against atherosclerosis and its function in the preservation of the SMC contractile phenotype.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 1; Animals; Aorta; Aortic Diseases; Atherosclerosis; Calcium-Binding Proteins; Cells, Cultured; Disease Models, Animal; Foam Cells; Humans; Hyperlipidemias; Mice, Knockout, ApoE; Microfilament Proteins; Muscle Proteins; Muscle, Smooth, Vascular; Mutation; Myocytes, Smooth Muscle; Phenotype; Plaque, Atherosclerotic; Promoter Regions, Genetic; Proto-Oncogene Proteins c-kit; Signal Transduction; Calponins
PubMed: 31441677
DOI: 10.1152/ajpheart.00062.2019