BMP-1 Mediated Proteolytic Processing of Alternatively Spliced Isoforms of Collagen Type XI

Collagen type XI is a component of the extracellular fibrillar network of embryonic cartilage. Collagen type XI belongs to the family of fibrillar collagens, which includes types I, II, III, V, and XI (Yoshioka, H., Ramirez, F., 1990). Collagen type XI plays a role in the assembly of embryonic cartilage collagen fibrils, as the diameter of cartilage collagen fibrils is dependent on the relative ratio of collagen types II and XI (Eikenberry, E. F., Mendler, M., Burgin, R., Winterhalter, K. H., Bruckner, P., 1982). Collagen type XI is involved in the establishment and maintenance of healthy cartilage, is essential for the correct structure of the cartilage extracellular matrix to form, and for skeletal morphogenesis and growth. The work presented in this thesis significantly advances the current understanding of the biology of collagen type XI, a key component of cartilage, and provides new information about the function of the isoforms

Delayed Diagnosis of Spinal Tuberculosis in a 44-year-old Male with Acute on Chronic Low Back Pain

Spinal tuberculosis (STB), also known as tuberculous spondylitis, tuberculous vertebral osteomyelitis, or Pott’s disease is a rare subset of extrapulmonary tuberculosis. Although rare in developed countries, STB is an important diagnosis for the emergency physician to consider. We report a case of a 44-year-old African-American male with STB presenting as an acute exacerbation of chronic low back pain complicated by urinary retention and difficulty ambulating. Our patient had no known predisposing risk factors for tuberculosis. This patient’s STB was mistakenly diagnosed as nontuberculous vertebral osteomyelitis. This is not uncommon, as it is often difficult to distinguish the two clinically. This patient experienced advanced neurologic features at the time of initial presentation, which improved with surgical decompression. Ultimately, he re-presented to the emergency department 10 days after hospital discharge with recurrence of symptoms due to inaccurate antimicrobial selection. The diagnosis may hinge on the astute physician recognizing the characteristic, albeit subtle, imaging findings of STB

Delayed Diagnosis of Spinal Tuberculosis in a 44-year-old Male with Acute on Chronic Low Back Pain

Spinal tuberculosis (STB), also known as tuberculous spondylitis, tuberculous vertebral osteomyelitis, or Pott’s disease is a rare subset of extrapulmonary tuberculosis. Although rare in developed countries, STB is an important diagnosis for the emergency physician to consider. We report a case of a 44-year-old African-American male with STB presenting as an acute exacerbation of chronic low back pain complicated by urinary retention and difficulty ambulating. Our patient had no known predisposing risk factors for tuberculosis. This patient’s STB was mistakenly diagnosed as nontuberculous vertebral osteomyelitis. This is not uncommon, as it is often difficult to distinguish the two clinically. This patient experienced advanced neurologic features at the time of initial presentation, which improved with surgical decompression. Ultimately, he re-presented to the emergency department 10 days after hospital discharge with recurrence of symptoms due to inaccurate antimicrobial selection. The diagnosis may hinge on the astute physician recognizing the characteristic, albeit subtle, imaging findings of STB

BMP-1-mediated proteolytic processing of alternatively spliced isoforms of collagen type XI.

Collagen type XI is a minor constituent of heterotypic collagen fibrils of developing cartilage and plays a regulatory role in fibril diameter. Collagen type XI is a heterotrimer composed of the alpha1, alpha2 and alpha3 chains. The mRNA encoding exons 6a, 6b and 8 of the alpha1 chain are expressed alternatively to generate six possible isoforms. The 6b-containing isoform has the most restricted distribution of all isoforms. It is first localized in the developing long bone, where mineralized tissue initially forms, and is later restricted to regions of cartilage that will be subsequently converted into bone. Bone morphogenetic protein 1 (BMP-1) and related proteins cleave procollagens I-III, V and VII, yielding triple-helical molecules that associate into collagen fibrils. The present study demonstrates that the alpha1 chain of collagen type XI can serve as a substrate for BMP-1. In addition, the efficiency with which BMP-1 processes different isoforms of the alpha1 chain varies. The amino acid sequence adjacent to the processing site influences the rate and extent of processing, as do sequences further away. Smaller fragments identified from cartilage extracts indicated that processing by BMP-1, in combination with other processing enzymes, generates small fragments of p6b-containing isoforms

The Role of Primary Surgery in De Novo Metastatic Breast Carcinoma

Approximately 6-10% of all breast carcinoma is metastatic at diagnosis, termed de novo metastatic breast carcinoma (dnMBC). Systemic therapy remains the first line of treatment in dnMBC, but there is growing evidence that adjuvant locoregional treatment (LRT) of the primary tumor increases progression-free and overall survival (OS). Although selection bias may exist, real-world data from nearly half a million patients show that patients are undergoing primary tumor removal because of the survival benefit. The main question for the advocates for LRT in this patient population is not whether primary surgery is beneficial in dnMBC patients, but rather who is a good candidate for it. Oligometastatic disease (OMD) is a distinct subset of dnMBC that affects a limited number of organs. A better OS can be achieved with LRT in breast cancer patients, especially in those with OMD, bone only, or favorable subtypes. Though there is currently no consensus among breast care specialists on how to treat dnMBC patients, primary surgery for dnMBC should be taken into consideration for a subset of patients following an extensive multidisciplinary discussion. © Copyright 2023 by the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.38. Soran A, Soyder A, Ozbas S, Ozmen V, Karanlik H, Igci A, et al. Breast Health Working Group International (supported by the Turkish Federation of Breast Disease Societies). The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q. Support Care Cancer 2021; 29: 3823-3830. (PMID: 33242163) [Crossref

Pyometra, an Unusual Case of Acute Abdomen

A 49-year-old female six days post-endometrial biopsy presented to the emergency department with constant severe suprapubic abdominal pain, fevers and myalgia. A contrasted computed tomography noted an intrauterine fluid collection and a final diagnosis of pyometra was made in the operating room following total hysterectomy. Pyometra is an exceptionally rare clinical condition with significant mortality

Pyometra, an Unusual Case of Acute Abdomen

A 49-year-old female six days post-endometrial biopsy presented to the emergency department with constant severe suprapubic abdominal pain, fevers and myalgia. A contrasted computed tomography noted an intrauterine fluid collection and a final diagnosis of pyometra was made in the operating room following total hysterectomy. Pyometra is an exceptionally rare clinical condition with significant mortality

Suppression of MeCP2β Expression Inhibits Neurite Extension in PC12 Cells

Regulation of gene expression is critical to the proper development of neuronal cells. The methyl-CpG binding protein 2 (MeCP2) operates as a transcriptional repressor by facilitating histone deacetylation and DNA methylation-dependent transcriptional silencing. This study examined the importance of MeCP2 in the regulation of neurite formation in PC12 cells. Expression of MeCP2 increased in a time-dependent manner after induction of neuronal differentiation. Expression was assessed at both the transcriptional and translation levels, and reached a maximum at 24 h post-induction. In addition, a marked inhibition of neurite extension and proper localization of a marker for synapse formation, synapsin I, were observed when MeCP2 expression was decreased by the addition of an antisense morpholino oligomer directed to the translational initiation site for MeCP2β. The removal of the antisense oligomer allowed neurite extension to progress. However, the addition of antisense oligomer to previously differentiated PC12 cells did not affect established neurite processes. Taken collectively, our results indicate a role for MeCP2β early in the events of neurite formation and that the relative levels of MeCP2α and MeCP2β may be different in early differentiating neurons than is found in the adult brain. In addition, unique functions may exist for the two isoforms of MeCP2. Our results indicate that the inhibition of neurite elaboration caused by a reduction in MeCP2 may be reversible