Osteogenesis imperfecta (OI) is a rare, inherited connective tissue disorder that results in bone fragility and spontaneous fractures. A dominantly inherited form of OI is commonly associated with mutations in genes coding for type I collagen. However, recessive forms of OI can occur due to mutations of collagen modifying genes such as cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (LEPRE1, P3H1). CRTAP and P3H1 are part of a regulatory compound (which also includes Cyclophilin B) of type I collagen. The goal for this project was to generate a purified compound of CRTAP and P3H1 to acquire a crystal structure. Because CRTAP and P3H1 are mutually-dependent, each gene was cloned into one vector at different multiple cloning sites to co-express the proteins in bacteria. …show more content…
After successful cloning of CRTAP and P3H1 (verified by Sanger sequencing), the plasmid was transformed into competent E.
coli for testing of protein expression. Initial tests confirmed the expression of both proteins, with P3H1 being expressed in lower amounts compared to CRTAP. I will continue with Dr. Morello to conduct expression tests in different E. coli types until I obtain optimal expression of both proteins. Because patients with recessive forms of osteogenesis imperfecta typically have an incomplete CRTAP/P3H1 complex, an artificial drug is a possibility in the future for said patients to reestablish the function of the complex. Once the structure of the CRTAP/P3H1 complex is understood, similar components can be derived to reestablish the function of an incomplete CRTAP/P3H1 complex. A bacterial strain that can optimally express both CRTAP and P3H1 simultaneously is the current major stepping stone. Upon completion of a high expression of both CRTAP and P3H1, larger quantities of the CRTAP/P3H1 complex will need to be purified and analyzed for a crystal structure by a crystallographer, whom has already been contacted and informed of the project and
goal. The obtained crystal structure will be used to observe how the proteins CRTAP and P3H1, derived from the modification of bacteria, come into solution and interact with one another. The solution to this research would be the beginning of answering a major question I believe will have immense benefits if answered: how to introduce missing chemical components into patients. This is important for the fact that many disorders occur due to a missing piece in an individual's chemical composition. If answered, there would be a solution for many of the disorders that exist today. Regarding my project, osteogenesis imperfecta patients have an incomplete CRTAP/P3H1 complex; however, if we can find the structure of the complex, we will be able to derive a drug with components similar in shape that reestablish the function of the complex. If this method becomes more common, we will be closer to finding a solution to the problem of chemical imbalances.
In Bone Gap, by Laura Ruby, perception is everything. The people living in the town love to gossip about everything they see, whether it be accurate or not. For this reason, point of view adds a lot to the novel as the story is told from the views of many different people. The literary device of point of view is very important because the story can greatly change depending on the narrator’s own perception of what is occurring.
In order to study the gene mutation that is supposed to cause Paget’s Bone Disease researchers had to have viable candidates to host the gene mutation. They found the best candidate to host the gene mutation in mice so they implanted the gene mutation in embryos of mice offspring. The researchers hypothesized that p62P394L is sufficient to induce PDB, especially since the p62 gene is responsible for encoding 62 kDa protein which functions in signaling osteoclast precursors. Results were found by fixing the first through fifth lumbar vertebra of four, eight, and twelve month old homozygote, heterozygote and WT littermates in 10% buffered formalin for 24- 48 hours. The first through fourth vertebra were then completely decalcified while the fifth was not. Longitudinal sections of both decalcified and undecalcified vertebra were cut, mounted on glass slides and stained to analyze. The mice with p62P394L had histologically normal bones, indicating that p62 mutation is not enough to induce Paget’s disease of the bone in vivo, there are additional factors necessary. Knowing osteitis deformas is due to hyper responsive multinucleated osteoclasts, it seemed a sensible suggestion. However, there are many other variables that should be factored when considering possible causes for osteoclast hyperformation. If p62P349L is present, doesn’t necessarily mean a person will get PDB, though an environmental factor such as measles could easily open up transduction pathways that could eventually lead to pagetic bone lesions. We find this study to be a stepping stone for future researchers to use in order to actually identify what causes Paget’s bone disease. (Hiruma, Kurihara, Subler, Zhou, Boykin, Zhang, Ishizuka, Dempster, Roodman & Wi...
Osgood-Schlatter Disease or syndrome (OSD) is an irritation of the patellar ligament at the tibial tuberosity (Dhar). Osgood-Schlatter Disease is claimed by some to not actually be a disease (Sims). But is rather a collection of symptoms that involves the tibial tubercle epiphysis (Sims). Osgood-Schlatter Disease affects as many as 1 in 5 adolescent athletes (Diseases and Conditions: Osgood-Schlatter Disease). Some other common names for this disease are Osteochondrosis, Tibial Aponphysitis, Tibial Tubercle Apophyseal Traction Injury, Morbus Osgood- Schlatter, and Rugby Knee (Dhar). “This can cause multiple sub-acute avulsion fractures along with inflammation of the tendon, leading to excess bone growth in the tuberosity and producing a visible lump which can be very painful when hit (Dhar). Activities such as kneeling may irritate the tendon further (Dhar).”
Osteogenesis Imperfecta (OI), also called fragile bone ailment or Lobstein disorder, is an inherent bone issue portrayed by weak bones that are inclined to break effortlessly with practically zero cause. A arrangement of various sorts of OI is regularly used to depict how seriously a man with OI is affected.OI is brought on by hereditary deformities that influence the body's capacity to make solid bones. In predominant established OI, a man has too little sort I collagen or a low quality of sort I collagen because of a transformation in one of the sort I collagen qualities which makes the bones
Emery-Dreifuss muscular dystrophy is a rare form of muscular dystrophy characterized by early onset contractures of the elbows, achilles tendons and post-cervical muscles with progressive muscle wasting and weakness It is also associated with heart complications like cardiomyopathy and arrhythmia which in both cases can lead to death. Cardiomyopathy is a heart disease which affects the muscles of the heart. In cardiomyopathy is muscles get rigid, enlarged or thick. They also sometimes changed by scar tissues. On the other hand arrhythmia is a disorder with the rhythm or rate of heartbeat. The heart can beat fast, which is called tachycardia or it could be beating too slow, which is called bradycardia. Emery-Dreifuss muscular dystrophy is characterized by early onset of contractures and humeroperoneal distribution. Humeroperoneal refers to effects on the humerus and fibula. The genes known to be responsible for EDMD encode proteins associated with the nuclear envelope: the emerin and the lamins A and C.
So far, various techniques have been used for reconstruction and regeneration of maxillary and mandibular bone defects. Autogenous bone grafting, guided bone regeneration (GBR), distraction osteogenesis and nerve transpositioning are among these regenerative techniques (1-8). Decision making for the treatment could be influenced by the type, size and location of the bone defects (2, 3, 9, 10). GBR had high success rate in treating small alveolar defects such as dehiscence or fenestration. Regenerative bony walls around the defect with ingrowing blood vessels can begin osteogenesis (11) larger bone defects with insufficient regenerative walls and an low quality avascular bed need varied amount of autogeneous bone graft from extra oral or intra oral donor sites, however, the patient may suffer from complications in donor site as well as bone graft resorption.(10, 12-15)
Schulman, Joshua M., and David E. Fisher. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 28 Aug. 0005. Web. 24 Apr. 2014.
It is estimated that 1 out of every 5,600-7,700 boys ages 5-24 have Duchene or Becker muscular dystrophy. (“Data & Statistics,” 2012 April 6) Muscular dystrophy is a group of genetic diseases defined by muscle fibers that are unusually susceptible to damage. There are several different types of muscular dystrophy some of which shorten the affected person’s lifespan. (“Muscular dystrophy: Types and Causes of each form,” n.d.) There is a long history of the disorder but until recently there wasn’t much knowledge of the cause. (“Muscular Dystrophy: Hope through Research,” 16 April 2014) Symptoms are obvious and can be seen as soon as a child starts walking. (“Muscular Dystrophy,” 2012 January 19) Although muscular dystrophy mostly affects boys, girls can get it too. (“Muscular Dystrophy,” 2012 January 19) There is no cure for muscular dystrophy but there are several types of therapy and most types of muscular dystrophy are still fatal. (“Muscular Dystrophy: Hope through Research,” 16 April 2014)
Hoffmeister, Ellen. "Gene Therapy and Pharmaceuticals Offer Hope for Many Patients With Brittle Bones." Bone and Joint 11.5 (2005): 49-51. eBook.
The most common musculoskeletal disorder and a major cause of disability in people over 65 years is osteoarthritis (OA) (Felson DT et al, 1987) (1). According to World Health Organization (WHO) report, OA of knee is more likely to become the fourth most important cause of disability in women, and the eighth most important cause in men (Murray CJL, Lopez AD, 1997)(2) . Primary prevention of knee OA has become a major health care aim and a clear understanding of the risk factors is required to design preventive strategies. Many investigations reported obesity, previous history of knee injury, sedentary life style, hand OA (Heberden’s nodes), and a familial history of the disease are major risk factors for OA of knee (Cyrus Cooper et al, 2000) (3). In spite of recent advancements the causes and pathogenesis of knee OA remains largely unknown (A Teichtahl, A Wluka, F M Cicuttini, 2003) (4) but however there is increasing research interest in the contribution of biomechanical variables on progression and management of the disease (Andriacchi TP, 1991) (5).
The big picture. Where the two schools of medicine differ is in philosophy. Doctors of osteopathy "treat people, not just symptoms," says Karen Nichols, dean of the Chicago College of Osteopathic Medicine. "The course list looks exactly the same, but the M.D.'s focus is on discrete organs. The osteopathic focus is that all of those pieces are interrelated. You can't affect one with out affecting another." That means paying more than simple lip service to the idea of the "whole" patient: It means that diagnosis and treatment rely on an examination of a person's environment and family and general situation as well as his or her body. Not surprisingly, about 65 percent of the nation's 52,000 licensed osteopaths (by comparison, the country boasts at least 900,000 M.D.'s) are primary-care physicians. The American Association of Colleges of Osteopathic Medicine has a description of osteopathic training, as well as short profiles of 20 schools, at www.aacom.org. The D.O. programs and their contact information are listed in the directory section of this book.
The musculoskeletal system is comprised of bones, joints, cartilage, tendons, ligaments, fascia and muscles. Together these body parts work to establish a framework that is the musculoskeletal system. This framework is what gives the body its shape, form, and figure. It stabilizes the body as well as supplies the structural support. The musculoskeletal body features not only provide a framework for your body but allows your ability to create movement. These movements are monitored by the musculoskeletal components which then determine your degree of flexibility. Overall the amount of energy your body uses comes almost entirely from these musculoskeletal functions. Which makes sense because it
Rheumatoid arthritis, also commonly known as RA, is one of the most severe forms of arthritis an individual can have. About 1.3 million people in the United States suffer from this autoimmune disease that attacks one’s joints. The immune system will mistakenly attack normal cells within the body which can lead to inflammation in certain areas. RA is a chronic long term disease that cause edema, stiffness, pain and limited function of many joints. Many patient who suffer from rheumatoid arthritis state that their symptoms become worse in the morning or very late in the evening. RA may be hard to detect in many patients because of its subtle symptoms. Because many diseases behave like RA, it is hard to tell if achy joints and stiffness is a reliable symptom for this disease. Weakness, low grade fevers, loss of appetite are some of the first symptoms patients’ experience. Some other major signs and symptoms to look for are dryness of the eyes, mouth, nose and throat, stiff, locked joints particularly in the knees and elbows, and numbness or tingling in the hands. Although RA is a progressive disease that cannot be cured it is best that patients begin their treatment during the early stages; otherwise it can lead to permanent damage of the bones, joints, and cartilage. There are many treatment forms that are used in treating this disease. Disease modifying antirhumatic drugs such as Methotrexate and anti-inflammatories such as Mobic, are two classes of drugs that are highly effective for treating rheumatoid arthritis.
The skeletal system is composed of two hundred and six bones in the human body. Functions such as the tendons, cartilage, and ligaments connect the bones and tissues together. Bone tissues make up about 18% of the weight of the human body. There are two types of tissue inside the bones. They consist of; compact bone and spongy bone. First, compact bone depicts the main shaft of long bones in the human body such as the arms and legs. Its tissue is dense and hard and it also makes up the outer layer of most bones in our body. Meanwhile, spongy bone tissue is made up of smaller plates occupied with red bone marrow. Mostly, it is found at the ends of long bones such as the head of the femur.
The Skeletal System, also known as the Skeleton make up a framework that support the body and protect the organs. The Skeleton consists of the bones and joints of the body. In the human body there is 300 bones at birth, these then fuse together to make 206 bones in a fully grown adult. The Skeleton is made up of two divisions: The axial and appendicular Skeleton.