• Title/Summary/Keyword: cause of disease and pathogenesis

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Function and dysfunction of leucine-rich repeat kinase 2 (LRRK2): Parkinson's disease and beyond

  • Bae, Jae Ryul;Lee, Byoung Dae
    • BMB Reports
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    • v.48 no.5
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    • pp.243-248
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    • 2015
  • Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). As such, functions and dysfunctions of LRRK2 in PD have been the subject of extensive investigation. In addition to PD, increasing evidence is suggesting that LRRK2 is associated with a wide range of diseases. Genome-wide association studies have implicated LRRK2 in Crohn's disease (CD) and leprosy, and the carriers with pathogenic mutations of LRRK2 show increased risk to develop particular types of cancer. LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. The association of LRRK2 with the pathogenesis of apparently unrelated diseases remains enigmatic, but it might be related to the yet unknown diverse functions of LRRK2. Here, we reviewed current knowledge on the link between LRRK2 and several diseases, including PD, AD, CD, leprosy, and cancer, and discussed the possibility of targeting LRRK2 in such diseases. [BMB Reports 2015; 48(5): 243-248]

UNUSUAL OSSIFICATION IN TMJ OSTEOARTHRITIS (측두하악관절염에서 발생한 희귀한 골화현상)

  • Ahn, Sang-Hun;Kim, Jong-Pil;Chang, Heon-Soo;Park, Jae-Bum;Ann, Jye-Jynn;Shin, Mi-Jung
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.18 no.2
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    • pp.308-315
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    • 1996
  • Osteoarthritis is a noninflammatory degenerative disease affecting the articular surfaces and is accompanied by remodeling of the underlying bone. The sympotms of osteoarthritis of the temporomandibular joint are pain in the joint and muscles of mastication, limitation. Osteoarthritis is generally accepted that several factors can contribute to the trauma, aging process, internal derangement and MPDS. Radiographic features of the osteoarthritis are seen flattening of joint, sclerosis on flattened area and osteophyte or anterior lipping. In the past, osteoarthritis was considered to self-limiting disease. Currently, synovial chondromembrane is part of the process of osteoarthritis secondary to trauma. Synovial chondromatosis is an uncommon disease of cartilaginous transformation of synovial membrane with formation of loose bodies within the joint space. The pathogenesis is more an active metaplastic than a neoplastic process. The cause of synovial chondromatosis is unknown. Although trauma and inflammation have all been cited as possible factors in tis pathogenesis. The clinical sign and symptoms are unilateral swelling of the joint region, pain in the joint area and crepitus seem to be the most reliable signs and symptoms. Radiographic evidence of loose bodies may or may not be present. This is a case report of 66 year old female with synovial chondromatosis, that is advanced disease of the osteoarthrits. We treated patient with surgical excision of lose bodies, diskectomy and synovectomy. The defected articular fossa area was reconstructed with temporalis fascia flap. The result was satisfactory.

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A Case of Erythema Nodosum Associated with Mycoplasma pneumoniae Infection: Pathologic Findings and a Presumed Pathogenesis (마이코플라즈마 폐렴균 감염에 의한 결절성 홍반; 조직병리학적 소견과 병인론의 고찰)

  • Ju, Hee Young;Kim, Gou Young;Choi, Sun Hee
    • Pediatric Infection and Vaccine
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    • v.23 no.1
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    • pp.67-71
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    • 2016
  • Erythema nodosum (EN) is a painful skin disease characterized by erythematous tender nodules located predominantly over the extensor aspects of the legs. Various etiological factors, including infection, drug administration, and systemic illness have been implicated as causes of EN. Mycoplasma pneumoniae is one of rare infectious agents to cause EN in children. We report a case of a 7-year-old boy with context of respiratory illness and skin lesions with arthralgia. From stepwise approaches, IgM antibody against M. pneumoniae was positive with titers of 12.18, consistent with respiratory infection of M. pneumoniae and histopathology showed findings of septal and lobular inflammation without vasculitis consistent with EN. In addition, we reviewed the pathogenesis of this disease based on our case and the previous reports.

Experimental In Vivo Models of Bacterial Shiga Toxin-Associated Hemolytic Uremic Syndrome

  • Jeong, Yu-Jin;Park, Sung-Kyun;Yoon, Sung-Jin;Park, Young-Jun;Lee, Moo-Seung
    • Journal of Microbiology and Biotechnology
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    • v.28 no.9
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    • pp.1413-1425
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    • 2018
  • Shiga toxins (Stxs) are the main virulence factors expressed by the pathogenic Stx-producing bacteria, namely, Shigella dysenteriae serotype 1 and certain Escherichia coli strains. These bacteria cause widespread outbreaks of bloody diarrhea (hemorrhagic colitis) that in severe cases can progress to life-threatening systemic complications, including hemolytic uremic syndrome (HUS) characterized by the acute onset of microangiopathic hemolytic anemia and kidney dysfunction. Shiga toxicosis has a distinct pathogenesis and animal models of Stx-associated HUS have allowed us to investigate this. Since these models will also be useful for developing effective countermeasures to Stx-associated HUS, it is important to have clinically relevant animal models of this disease. Multiple studies over the last few decades have shown that mice injected with purified Stxs develop some of the pathophysiological features seen in HUS patients infected with the Stx-producing bacteria. These features are also efficiently recapitulated in a non-human primate model (baboons). In addition, rats, calves, chicks, piglets, and rabbits have been used as models to study symptoms of HUS that are characteristic of each animal. These models have been very useful for testing hypotheses about how Stx induces HUS and its neurological sequelae. In this review, we describe in detail the current knowledge about the most well-studied in vivo models of Stx-induced HUS; namely, those in mice, piglets, non-human primates, and rabbits. The aim of this review is to show how each human clinical outcome-mimicking animal model can serve as an experimental tool to promote our understanding of Stx-induced pathogenesis.

Current progress on development of respiratory syncytial virus vaccine

  • Chang, Jun
    • BMB Reports
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    • v.44 no.4
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    • pp.232-237
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    • 2011
  • Human respiratory syncytial virus (HRSV) is a major cause of upper and lower respiratory tract illness in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for prophylaxis of HRSV infection. There are several hurdles complicating the development of a RSV vaccine: 1) incomplete immunity to natural RSV infection leading to frequent re-infection, 2) immature immune system and maternal antibodies of newborn infants who are the primary subject population, and 3) imbalanced Th2-biased immune responses to certain vaccine candidates leading to exacerbated pulmonary disease. After the failure of an initial trial featuring formalin-inactivated virus as a RSV vaccine, more careful and deliberate efforts have been made towards the development of safe and effective RSV vaccines without vaccine-enhanced disease. A wide array of RSV vaccine strategies is being developed, including live-attenuated viruses, protein subunit-based, and vector-based candidates. Though licensed vaccines remain to be developed, our great efforts will lead us to reach the goal of attaining safe and effective RSV vaccines in the near future.

Management of Diabetic Foot Problems (당뇨병성 족부병변의 관리)

  • Park, Yoon-Jeong;Yun, So-Young
    • Physical Therapy Korea
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    • v.5 no.2
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    • pp.98-105
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    • 1998
  • The purposes of this article are to review the pathogenesis, prevention, and management of amputation due to diabetes mel1itus complications, and to report one case who had lost his toes due to diabetes mellitus. A primary cause for hospital admission of the patient was foot ulcer. Since many amputations in diabetic patients are precipitated by such ulcers, a program for active prevention and optimal treatment of diabetic foot lesions might decrease the risk of amputation. Diabetic foot ulcers and, ultimately, amputation can stem from a variety of pathways. The combination of peripheral neuropathy, peripheral vascular disease and infections is the harbinger of the final cataclysmic events of gangrene and amputation. As the physical therapist is often involved in the treatment of diabetic patients, the therapist should be aware of the followings: the patient's type of diabetes and the severity of the diabetes, the complications of the disease, the effects of exercise, the importance of wearing proper shoes and education to patients about appropriate diabetic foot care.

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New Perspectives in Pediatric Nonalcoholic Fatty Liver Disease: Epidemiology, Genetics, Diagnosis, and Natural History

  • Ko, Jae Sung
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.6
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    • pp.501-510
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    • 2019
  • Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The global prevalence of pediatric NAFLD from general populations is 7.6%. In obese children, the prevalence is higher in Asia. NAFLD has a strong heritable component based on ethnic difference in the prevalence and clustering within families. Genetic polymorphisms of patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2, and glucokinase regulatory protein (GCKR) are associated with the risk of NAFLD in children. Variants of PNPLA3 and GCKR are more common in Asians. Alterations of the gut microbiome might contribute to the pathogenesis of NAFLD. High fructose intake increases the risk of NAFLD. Liver fibrosis is a poor prognostic factor for disease progression to cirrhosis. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction are more accurate for steatosis quantification than ultrasound. Noninvasive imaging methods to assess liver fibrosis, such as transient elastography, shear-wave elastography, and magnetic resonance elastography are useful in predicting advanced fibrosis, but they need further validation. Longitudinal follow-up studies into adulthood are needed to better understand the natural history of pediatric NAFLD.

Role of tea catechins in prevention of aging and age-related disorders

  • Khanna, Arjun;Maurya, Pawan Kumar
    • CELLMED
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    • v.2 no.1
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    • pp.2.1-2.11
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    • 2012
  • Tea polyphenols especially catechins have long been studied for their antioxidant and radical scavenging properties. Scientists throughout the world have investigated the usefulness of the regular green tea consumption in several disease conditions. In-vitro and in-vivo experiments on catechins especially epigallocatechingallate have revealed a significant role in many ways. Reactive oxygen species have been increasingly implicated in the pathogenesis of many diseases and important biological processes. Toxic effects of these oxidants, commonly referred to as oxidative stress, can cause cellular damage by oxidizing nucleic acids, proteins, and membrane lipids. Oxidative stress has been related to aging and age related disorders. It is found that in a wide variety of pathological processes, including cancer, atherosclerosis, neurological degeneration, Alzheimer's disease, ageing and autoimmune disorders, oxidative stress has its implications. Catechins have been reported to be useful in combating aging and age related disorders like cancer, cardiovascular disorders and neurodegenerative diseases. In this mini review we will discuss such studies done across the globe.

Necrotizing enterocolitis in newborns: update in pathophysiology and newly emerging therapeutic strategies

  • Choi, Young Youn
    • Clinical and Experimental Pediatrics
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    • v.57 no.12
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    • pp.505-513
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    • 2014
  • While the survival of extremely premature infants with respiratory distress syndrome has increased due to advanced respiratory care in recent years, necrotizing enterocolitis (NEC) remains the leading cause of neonatal mortality and morbidity. NEC is more prevalent in lower gestational age and lower birth weight groups. It is characterized by various degrees of mucosal or transmural necrosis of the intestine. Its exact pathogenesis remains unclear, but prematurity, enteral feeding, bacterial products, and intestinal ischemia have all been shown to cause activation of the inflammatory cascade, which is known as the final common pathway of intestinal injury. Awareness of the risk factors for NEC; practices to reduce the risk, including early trophic feeding with breast milk and following the established feeding guidelines; and administration of probiotics have been shown to reduce the incidence of NEC. Despite advancements in the knowledge and understanding of the pathophysiology of NEC, there is currently no universal prevention measure for this serious and often fatal disease. Therefore, new potential techniques to detect early biomarkers or factors specific to intestinal inflammation, as well as further strategies to prevent the activation of the inflammatory cascade, which is important for disease progression, should be investigated.

Molecular Characterization of Survival and Toxigenesis of Vibrio vulnificus

  • Choi Sang Ho
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2002.10a
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    • pp.56-58
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    • 2002
  • Understanding the molecular pathogenesis of the multifaceted host-pathogen interaction is critical in the development of improved treatment and prevention, as well as elucidating how certain bacteria can circumvent host defenses, multiply in the host, and cause such extensive damage. Disease caused by infection with V. vulnificus is remarkable for the invasive nature of the infection, ensuing severe tissue damage, and rapidly fulminating course. The characterization of somatic as well as secreted products of V. vulnificus has yielded a large list of putative virulence attributes, whose known functions are easily imagined to explain the pathology of disease. These putative virulence factors include a carbohydrate capsule, lipopolysaccharide, a cytolysin/hemolysin, elastolytic metalloprotease, iron sequestering systems, lipase, and pili. However, only few among the putative virulence factors has been confirmed to be essential for virulence by the use of molecular Koch's postulates. This presentation describes molecular biological characterization of the virulence factors contributing to survival as well as to toxigenesis of V. vulnificus.

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