The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
Atrophy ; Autophagy ; Calcium ; metabolism ; Caspases ; metabolism ; Connective Tissue ; metabolism ; pathology ; Contracture ; etiology ; metabolism ; pathology ; therapy ; Fibrosis ; Humans ; Immobilization ; adverse effects ; Joints ; Lysosomes ; metabolism ; Matrix Metalloproteinases ; metabolism ; Muscle, Skeletal ; metabolism ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Proteolysis ; Signal Transduction ; physiology ; Transforming Growth Factor beta1 ; metabolism ; Ubiquitin ; metabolism

SHORT syndrome is an extremely rare congenital condition due to a chromosomal mutation of the PIK3R1 gene found at 5q13.1. SHORT is a mnemonic representing six manifestations of the syndrome: (S) short stature, (H) hyperextensibility of joints and/or inguinal hernia, (O) ocular depression, (R) Rieger anomaly, and (T) teething delay. Other key aspects of this syndrome not found in the mnemonic include lipodystrophy, triangular face with dimpled chin (progeroid facies, commonly referred to as facial gestalt), hearing loss, vision loss, insulin resistance, and intrauterine growth restriction (IUGR). 3q duplication syndrome is rare syndrome that occurs due to a gain of function mutation found at 3q25.31-33 that presents with a wide array of manifestations including internal organ defects, genitourinary malformations, hand and foot deformities, and mental disability. We present a case of a 2 year and 3 month old male with SHORT syndrome and concurrent 3q duplication syndrome. The patient presented at birth with many of the common manifestations of SHORT syndrome such as bossing of frontal bone of skull, triangular shaped face, lipodystrophy, micrognathia, sunken eyes, and thin, wrinkled skin (progeroid appearance). Additionally, he presented with findings associated with 3q duplication syndrome such as cleft palate and cryptorchidism. Although there is no specific treatment for these conditions, pediatricians should focus on referring patients to various specialists in order to treat each individual manifestation.
Chin ; Cleft Palate ; Cryptorchidism ; Depression ; Facies ; Fetal Growth Retardation ; Foot Deformities ; Frontal Bone ; Hand ; Hearing Loss ; Hernia, Inguinal ; Humans ; Insulin Resistance ; Joints ; Lipodystrophy ; Male ; Micrognathism ; Parturition ; Skin ; Skull ; Specialization ; Tooth ; Tooth Eruption

BACKGROUND: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. METHODS: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. RESULTS: Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. CONCLUSIONS: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1–2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.
Breast Neoplasms ; Breast ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Joints ; Korea ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Neoplasm Staging ; Phenobarbital ; Prognosis ; Receptor, Epidermal Growth Factor ; Seoul

Transforming growth factor-β (TGF-β) is a cytokine that plays an important role in both normal joints and joints affected by osteoarthritis (OA), the most common joint disease. However, the role of this pleiotropic cytokine in a normal healthy joint is very different from its role in an OA joint. In a normal synovial joint, active TGF-β is only present after joint loading and only for a short period. In contrast, permanent and high levels of active TGF-β are detected in OA joints. Due to this difference in levels and exposure period of joint cells to active TGF-β, the function of TGF-β is strikingly different in normal and OA joints. The consequences of this difference in TGF-β levels on joint homeostasis and pathological changes in OA joints are discussed in this review.
Cytokines ; Homeostasis ; Joint Diseases ; Joints* ; Osteoarthritis ; Transforming Growth Factor beta

PURPOSE: The eighth American Joint Committee on Cancer staging system for breast cancer was recently published to more accurately predict the prognosis by adding biomarkers such as estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. However, this system is very complicated and difficult to use by clinicians. The authors developed a program to aid in setting up the staging system and confirmed its usefulness by applying it to theoretical combinations and actual clinical data. METHODS: The program was developed using the Microsoft Excel Macro. It was used for the anatomic, clinical and pathological prognostic staging of 588 theoretical combinations. The stages were also calculated the stages using 840 patients with breast cancer without carcinoma in situ or distant metastasis who did not undergo preoperative chemotherapy. RESULTS: The anatomic, clinical and pathological prognostic stages were identical in 240 out of 588 theoretical combinations. In the actual patients' data, stages IB and IIIB were more frequent in clinical and pathological prognostic stages than in the anatomic stage. The anatomic stage was similar to the clinical prognostic stage in 58.2% and to the pathological prognostic stage in 61.9% of patients. Oncotype DX changed the pathological prognostic stage in 2.1% of patients. CONCLUSION: We developed a program for the new American Joint Committee on Cancer staging system that will be useful for clinical prognostic prediction and large survival data analysis.
Biomarkers ; Breast Neoplasms* ; Breast* ; Carcinoma in Situ ; Drug Therapy ; Humans ; Joints* ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Estrogen ; Receptors, Progesterone ; Statistics as Topic

Cytomegalovirus (CMV) infection is one of the most common congenital infections. The first case of discordant congenital CMV infection in twins occurred in Korea. A 31-year-old woman became pregnant with twins (dichorionic-diamniotic). An elective caesarean section was performed at 37 weeks. The first baby was male, weighing 2,410 g with an Apgar score of 8/9. The second baby was female, weighing 1,380 g with an Apgar score of 5/8. She had experienced intrauterine growth retardation, and presented with microcephaly, micrognathia, and joint stiffness. During the work-up for discordant twins, the second baby's serum test was positive for CMV immunoglobulin M. Her urine, blood, and cerebrospinal fluid (CSF) were CMV polymerase chain reaction positive. The first baby's CMV tests were negative. Ophthalmologic exam and audiometry performed on the second baby showed CMV retinitis and bilateral sensorineural hearing loss. She was treated with intravenous ganciclovir. Currently, she is bed-ridden and has significant developmental delay. Although the causes of discordant congenital CMV infection in twins are unclear, this case shows that discordant congenital CMV infection should be considered in twins with significant differences in intrauterine growth or clinical symptoms after birth.
Adult ; Apgar Score ; Audiometry ; Cerebrospinal Fluid ; Cesarean Section ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Female ; Fetal Growth Retardation ; Ganciclovir ; Hearing Loss, Sensorineural ; Humans ; Immunoglobulin M ; Joints ; Korea ; Male ; Microcephaly ; Micrognathism ; Parturition ; Polymerase Chain Reaction ; Pregnancy ; Retinitis ; Twins*

This study evaluates the suitability of cadavers embalmed by the ethanol-glycerin fixative for the dissection course of medical students and the hands-on dissection workshop of clinicians. Five cadavers were embalmed by two different methods: two formalin-phenol fixation (FPF) and three ethanol-glycerin fixation (EGF) cadavers. The measurement of physical and chemical characteristics including ranges of motion (ROM), bacterial and fungal culture tests, and ultrasonography were performed for each cadaver. The EGF cadavers were evaluated to be significantly more suitable than FPF cadavers for the physical and chemical characteristics including color, texture, elasticity, wetness (softness), skin incision, vessel ligation and suture, decollement, odor, and irritant. In shoulder, elbow, and wrist joints, ROMs of the EGF cadavers were statistically more than those of the FPF except for elbow extension. On bacterial and fungal culture tests at 8 weeks after carrying out of refrigerator, one bacteria were detected in one EGF cadaver; however, some bacteria and fungi could be detected in all FPF cadavers. The ultrasound images of abdominal organ and thigh musculature could be more clearly detected in the EGF cadavers than those of FPF cadavers. These results indicate that the EGF method had a sufficient antibiotic effect and produced cadavers with flexible joints and a high tissue quality suitable for various cadaveric dissection courses.
Bacteria ; Cadaver* ; Education ; Elasticity ; Elbow ; Embalming* ; Epidermal Growth Factor ; Fungi ; Humans* ; Joints ; Ligation ; Methods ; Odors ; Shoulder ; Skin ; Students, Medical ; Sutures ; Thigh ; Ultrasonography ; Wrist Joint

OBJECTIVE: betaig-h3 is a 68kDa extracellular matrix protein which is overexpressed in synovial tissues of rheumatoid arthritis (RA). Previous results proved that betaig-h3 fragments are relevant to adhesion and migration of synovial fibroblast and angiogenesis through interaction with alphavbeta 3 integrin. We designed a recombinant betaig-h3 protein consisting of a fas-1 domain and RGD motif and evaluated the therapeutic efficacy in RA. METHODS: Inhibitory effect of adhesion and migration of NIH3T3 cell line was evaluated in 96 well microtiter and transwell plates coated with betaig-h3. Clinical arthritis index was evaluated after treating CIA mice with MFK12. Immunohistochemical staining in synovial tissues were performed. Expression of transcripts and proteins of inflammatory mediators were analyzed by semi-quantitative RT-PCR and immunoblotting. RESULTS: Recombinant protein consisted of 4th fas-1 domain truncated for H1 and H2 sequences and RGD peptide (MFK12), had M.W. of 10.4kDa. betaig-h3 mediated adhesion and migration of NIH3T3 cell line were significantly inhibited in a dose-dependent manner. Arthritis severity and incidence were efficiently reduced when CIA mice were treated with MFK12 at 30 mg/kg/day compared with the control. Immunohistochemical staining of joint tissues in MFK12 treated mice exhibited reduced angiogenesis. In treated mice, expression of transcripts regarding inflammatory mediators was markedly suppressed and immunoblotting of ICAM-1 and RANKL from whole extract of hind paws also showed a significant reduction. CONCLUSION: This study shows that MFK12 is effective in treating RA, although further study is warranted to improve the therapeutic efficacy.
Animals ; Arthritis ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Cell Line ; Extracellular Matrix ; Extracellular Matrix Proteins ; Fibroblasts ; Immunoblotting ; Incidence ; Inflammation ; Intercellular Adhesion Molecule-1 ; Joints ; Mice ; Oligopeptides ; Proteins ; Transforming Growth Factor beta

Acromegaly is generally caused by a benign growth hormone (GH)-secreting pituitary adenoma. It is characterized by a wide range of complications; cardiovascular, respiratory, bone and joint, and metabolic complications. Among them, impaired glucose tolerance and diabetes mellitus, due to GH-induced insulin resistance, has been reported in approximately 16-46% and 19-56%. They are usually improved following the treatment of acromegaly, surgical or medical therapy. We report a first case of 36-year-old man who was paradoxically diagnosed with GAD antibody positive latent autoimmune diabetes in adults (LADA) after the surgical cure of acromegaly.
Acromegaly ; Adult ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Glucose ; Growth Hormone ; Humans ; Insulin Resistance ; Joints ; Pituitary Neoplasms

OBJECTIVE: To further improve the accuracy of bone age identification using the time of secondary ossification center appearance and epiphyseal fusion of 7 joints to estimate the age of living individuals. METHODS: DR films were taken from 7 parts including sternal end of clavical and the left side of shoulder, elbow, carpal, hip, knee and ankle joints of 1 709 individuals who came from eastern China, central China and southern China, whose ages were between 11.0 and 20.0 years. From those 7 joints 24 osteal loci were selected as bone age indexes, which could better reflect age growth of teenagers. The characteristics of secondary ossification center appearance and epiphyseal fusion were observed, and the mean and age range of secondary ossification center appearance and epiphyseal fusion were calculated. RESULTS: The fusion time of the 24 epiphyses were advanced at different degrees, the most obvious epiphyses the sternal end of clavicle, scapular acromial end, distal end of the radius, distal end of the ulna, iliac crest, ischial tuberosity, the upper and lower end of tibia and fibula. The appearance time of sternal end of clavicle, scapular acromial end, iliac crest and ischial tuberosity epiphyses were all found to be after the age of 12, and the female's age, approximately 1 year ahead of schedule in comparison with the male's. CONCLUSION The relevant forensic information and data for bone age identification should be updated every 10-15 years so as to provide accurate and objective evidence for court testimony, conviction and sentencing.
Adolescent ; Age Determination by Skeleton/methods* ; Asian People/ethnology* ; Bone Development/physiology* ; Bone and Bones/diagnostic imaging* ; Child ; China/ethnology* ; Clavicle/growth & development* ; Epiphyses/growth & development* ; Female ; Forensic Anthropology/methods* ; Humans ; Joints/growth & development* ; Male ; Sex Characteristics ; Tomography, X-Ray Computed ; Young Adult