beta-Chimaerin, a 30-kDa GTPase-activating protein (GAP) for the p21 Ras-related Rac, is expressed specifically in late stage spermatocytes (Leung, T., How, B.-E., Manser, E., and Lim, L. (1993) J. Biol. Chem. 268, 3813-3816). Using antibodies raised against beta-chimaerin, we detected a major 46-kDa RacGAP in the rat cerebellum. With beta-chimaerin cDNA as a probe and using polymerase chain reaction, cDNAs from both human and rat cerebellum were isolated. The human and rat cDNAs encoded sequences containing cysteine-rich and GAP domains identical to those of testis beta-chimaerin. The cDNAs also encoded an additional N-terminal SH2 (Src homology 2) domain, probably derived from the beta-chimaerin gene by alternate splicing. This SH2 domain of the predicted 54-kDa protein was strikingly similar to that of alpha 2-chimaerin, including replacement by glutamic acid of the invariant tryptophan present at the start of other SH2 domains. The SH2 domains of alpha- and beta-chimaerin thus represent a subset of SH2 domains. The cerebellar beta-chimaerin (beta 2-) is expressed mainly in granule cells and exhibits postnatal developmental increases. beta 2-Chimaerin was enriched in particulate/synaptosomal fractions. In the mouse weaver mutant lacking mature granule cells, there is a corresponding decrease in beta 2-chimaerin, which could well serve as a marker of granule cell differentiation.
As the global population ages gracefully, the prevalence of chronic pain arising from degenerative disease, chronic medical conditions, and malignancy will continue to rise. It is estimated that 17% of the world population will be above the age of 60 years by 2030. By 2050, 2.1 billion of the global population will be 60 years and above, and 426 million will be 80 years and above.1 Our already strained healthcare systems would soon face an insurmountable demand for services. A good example would be the increasing demand for epidural injections. The first epidural anaesthetic injection for the management of sciatica was first described in the 1930s. Within a few short decades, it firmly gained its grounding as a cornerstone treatment for lumbago and neuropathic pain by the 1970s.2 In the United States (US), the general use of epidural injections for chronic pain has increased by 224% between 2000 and 2011. Per 100,000 Medicare recipients (US), the percentage increases were stark (123% interlaminar, 142% transforaminal) cervical/thoracic epidural injections (25% interlaminar, 665% transforaminal) lumbosacral epidural injections.3 While majority of the epidural injections are performed by Anaesthetists, there has been a paradigm shift and increased demand for image-guided epidural injections performed by Radiologists. Chronic pain management is often complex and requires inputs from multiple medical specialties and allied health disciplines. In Australia, the Faculty of Pain Medicine (FPM) is responsible for education, standards, and training health professionals in pain management. While being part of the Australian and New Zealand College of Anaesthetists (ANZCA), FPM encompasses members from the Royal Australasian College of Surgeons (RACS), Royal Australasian College of Physicians (RACP), Royal Australian and New Zealand College of Psychiatrists (RANZCP) and Australasian Faculty of Rehabilitation Medicine (AFRM).4 Despite having a vital role in pain management, the Royal Australian and New Zealand College of Radiologists (RANZCR) was overlooked and omitted from being part of the FPM. Clinical Radiology (CR), which encompasses the faculties of Interventional Radiology (IR) and Diagnostic Radiology (DR),5 has a quintessential and pivotal role in pain management. Equipped with a keen eye and a wide range of interventional techniques, Radiologists routinely diagnose, target, and treat a myriad of conditions. Being a technologically advanced medical specialty and with the advent of Artificial Intelligence (AI), the reach of CR will only increase with time. The IR therapeutic armamentarium consists of a wide range of percutaneous and extracorporeal image-guided techniques that are used in pain management. In addition to epidural, nerve root and joint injections, additional procedures like image-guided percutaneous neurolysis, nerve ablation, MR-guided focused high-intensity ultrasound and percutaneous fixation techniques have also been used in the treatment of a wide range of conditions including discogenic pain and facet joint syndromes.6 With these same techniques, Radiologists also play an important role in the management of debilitating and intractable oncologic pain. Different causes of pain and pain syndromes can be present in various stages of malignancy and have been found to be inadequately treated in 55–83% of patients.7 Image-guided percutaneous procedures are practical, reproducible, safe, and efficient palliative treatment alternatives for the management of refractory oncologic pain.7 The procedures, bolstered by good success rates (70–80%) and low complication rates (0.5%), can also help retain function, reduce incapacitation from strong analgesic medications, and improve the patient's quality of life.7 Without the need to use strong opioid analgesics, IR procedures are also an important and attractive therapeutic alternative in the current Opioid Epidemic.8 Since the first Opioid wave in the 1990s (ironically caused by prescription opioids), the number of drug overdose deaths has continued to increase through the years. In the US, the number of deaths attributed to drug overdose has recently increased by 16% within a year (2020–2021) and 645,000 individuals have died from an overdose involving an opioid (1999–2021).9 Australia has not been spared from this epidemic. Globally, Australia currently ranks number 8 for the daily doses of prescription opioids per million. In 2014, up to 3 million Australians were prescribed at least one opioid under the Repatriation PBS (RPBS) or Pharmaceutical Benefits Scheme (PBS).10 More recently, pharmaceutical opioid-related deaths have exceeded heroin-related deaths by 2–2.5 times in Australia.10 With the current trend of the medical field moving towards minimally invasive image-guided techniques, there would be an increased role and demand for Radiologists performing procedures.11 In the United Kingdom (UK), there was a 21% increase in IR procedures between 2010 and 2012.12 To sustain a safe IR service in the UK, the Royal College of Radiologists (RCR) recommended having 25 IR trainees a year to provide safe IR service across England.12 The UK Centre of Workforce Intelligence has also suggested that the UK would need a minimum of 200 additional IR consultants to provide adequate after-hours treatment in the UK.12 Minimally invasive interventional procedures have also been shown to shorten in-hospital admissions and improve patient flow.13 Imaging-guided procedures performed by Radiologists are also completed faster and more precisely with CT guidance. Most IR procedures could be performed in the outpatient setting and do not require expensive operating theatre time or general anaesthesia/sedation. This would ultimately reduce the pressure on the healthcare system and help with efficient resource allocation. However, it seems that the work and importance of CR and IR are somewhat under-represented. A recent 2019 systematic review found that this could be due to the lack of CR exposure during medical school. The review also found that early exposure to the CR could increase interest, improve awareness, and motivate medical students to pursue CR as a future career.14 The public is also relatively unaware about the role of CR in medicine. In an awareness study, only 6% of patients heard about IR before their referral, this is even though 21% of the patients had undergone a previous interventional procedure prior to the survey. Up to 98% of the surveyed patients believed that the public is not aware of the role of CR. With an overall post-procedural satisfaction score of 8.8/10 and with 97% of the patients preferring to choose an IR procedure over surgical intervention, this review speaks volumes of the procedural competency and effectiveness of IR.15 Locally and internationally, there is a trend of Radiologists establishing a physical presence and returning to the clinical setting.16 In Australia, many IRs have completed this transition and are full clinicians with admitting rights, clinic, and ward round duties. This transition into the clinical realm was made possible through the ceaseless work of the IR Committee in RANZCR, the strong advocacy from professional societies like the Interventional Radiology Society for Australasia (IRSA) and Australian and New Zealand Society of Neuroradiology (ANZSNR), and a generation of tireless IRs working to regain their status as clinicians. It would not be long before CR would have a bigger presence in the medical school curriculum and the public eye. With the increasingly indispensable role of CR in pain management, the FPM and ANZCA should formally recognise RANZCR as an important and quintessential ally in pain medicine. It would be imperative for ANZCA to formally invite RANZCR and Radiologists to be part of the FPM. The author declares no conflict of interest to disclose. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Abstract: Neuron‐specific enolase and creatine phosphokinase were found, by 2‐dimensional gel analysis, in rat brain synaptic plasma membranes (SPM). The identity of these enzymes was confirmed by comigration with purified rat brain NSE and CPK and by peptide analysis. The specific enzymatic activities of enolase and creatine phosphokinase, as well as of pyruvate kinase, also present on the membranes, were comparable to those in the homogenates when these three enzymes were fully activated. In the SPM all three enzymes, particularly enolase, were partially cryptic in that enzymatic activities were very low unless the membranes were treated with Triton X‐100. They were resistant to both low‐salt and high‐salt extraction and to trypsin, except when Triton X‐100 was present. These results suggest that the enzymes are tightly bound protein components of the membrane and that they may constitute an assembly capable of generating ATP.
Magnetic resonance imaging (MRI) is an indispensable medical imaging examination technique in musculoskeletal medicine. Modern MRI techniques achieve superior high-quality multiplanar imaging of soft tissue and skeletal pathologies without the harmful effects of ionizing radiation. Some current limitations of MRI include long acquisition times, artifacts, and noise. In addition, it is often challenging to distinguish abutting or closely applied soft tissue structures with similar signal characteristics. In the past decade, Artificial Intelligence (AI) has been widely employed in musculoskeletal MRI to help reduce the image acquisition time and improve image quality. Apart from being able to reduce medical costs, AI can assist clinicians in diagnosing diseases more accurately. This will effectively help formulate appropriate treatment plans and ultimately improve patient care. This review article intends to summarize AI's current research and application in musculoskeletal MRI, particularly the advancement of DL in identifying the structure and lesions of upper extremity joints in MRI images.
A major proportion of the hypothalamic nuclear oestrogen receptors were available for complexing with radioactive oestradiol in vitro at 4 degrees C and were apparently unoccupied . At 6 h after oestradiol administration the content of unoccupied nuclear receptors had increased 2.5-fold and represented 71% of the total nuclear receptor content. These results suggest that unoccupied receptors may be active elements in the ‘long-term’ receptor population of the hypothalamus. Androgenized females had lower contents of these receptors.
The binding of rat uterine cytosol oestrogen receptor in vitro to oligo(dT)-cellulose is mediated by an activating factor in the cytosol [Thrower, Hall, Lim & Davison (1976) Biochem. J. 160, 271-280]. A potent inhibitor of this binding is present in hypothalamic cytosol. This inhibitor may have a role in vivo in regulating receptor translocation in the hypothalamus.
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