Advances In Pathogenesis Research Articles

Pulmonary Complications of Hemoglobinopathies

Hemoglobinopathies are diseases caused by genetic mutations that result in abnormal, dysfunctional hemoglobin molecules or lower levels of normal hemoglobin molecules. The most common hemoglobinopathies are sickle cell disease (SCD) and the thalassemias. In SCD, an abnormal hemoglobin alters the erythrocyte, causing a chronic hemolytic anemia, which can lead to pulmonary parenchymal damage and impaired vascular function. Pulmonary complications of SCD include the acute chest syndrome (ACS), reactive airways disease, pulmonary hypertension (PH), and pulmonary fibrosis. Episodes of ACS and the development of PH both increase the risk of death in patients with SCD. Both α and β thalassemia are characterized by impaired production of hemoglobin subunits, and severity of disease varies widely. Although screening studies suggest that PH is a common complication for patients with thalassemia, its impact on survival is unknown. Understanding the pathogenesis, diagnostic options, and prevention and treatment strategies for such complications is critical for clinicians who care for these patients. In this review, we discuss the mechanisms and clinical presentation of pulmonary complications associated with hemoglobinopathies, with a focus on recent advances in pathogenesis and treatment.

Limited Joint Mobility in Diabetes and Ageing: Recent Advances in Pathogenesis and Therapy

Limited joint mobility is frequently observed in elderly people and in patients suffering from diabetes, who represent a growing segment of the population of western countries. Our review wishes to offer the state of art about this interesting topic, which may have important clinical implications, leading to impairment of both basic and instrumental activities of daily living. The main causes of a reduced range of motion are degenerative joint diseases and increased stiffness of collagen tissue. The main biochemical abnormality, common to aging and diabetes, is the non-enzymatic glycosilation of collagen, with advanced glycation end product (AGE) formation, which in turn leads to an increase of collagen cross-links. The most extensive accumulation of AGEs occurs in tissues that contain proteins with low turnover, such as the collagen in the extracellular matrix of articular capsule, ligaments and muscle-tendon units. The increase in collagen cross-linking alters the mechanical properties of these tissues with a decrease in elasticity and tensile strength, and an increase in mechanical stiffness. Besides this, AGEs react with specific cell surface receptors (RAGEs). The engagement of the ligand by RAGEs triggers cell-specific signalling, resulting in enhanced generation of reactive oxygen species and sustained up-regulation of pro-inflammatory mediators and adhesion molecules. An appropriate control of the glucose levels and a diet rich in antioxidant agents are recommended in patients with diabetes. Stretching and strengthening programmes are widely used, in order to prevent and to reduce joint stiffness, but the improvements with physiotherapy are little and short-lasting. Several drugs, which can interfere with AGE formation and removal, or with the cellular effects of AGEs, are under study (among them pyridoxamine, an active form of Vitamin B6, AGE-breaker compounds, glucosamine, rutin and derivatives, soluble RAGE isoforms, and statins). In experimental animal models, these drugs are effective in reducing diabetic complications due to AGE formation; however, further study is necessary before their extensive use in the clinical setting.

Acute exacerbations of interstitial lung diseases

This review aims to highlight recent advances in pathogenesis, clinical presentation and treatment of interstitial lung diseases (ILDs). Acute exacerbation is increasingly recognized as a major complication in the course of idiopathic pulmonary fibrosis. It is precipitated by a variety of intrinsic and extrinsic factors. Moreover, acute exacerbation is an apparently equally frequent event in hypersensitivity pneumonitis and collagen-vascular diseases associated ILDs, especially the rheumatoid pulmonary fibrosis. Treatment of acute exacerbations is unsatisfactory and prognosis extremely poor. In a critically ill patient proper recognition of an acute exacerbation and of the underlying chronic ILD is warranted because treatment approach varies with the type of ILD. Advances in the understanding of the pathogenesis and treatment of this 'idiopathic' phenomenon are reviewed.

A sperm viability test using SYBR-14/propidium iodide flow cytometry as a tool for rapid screening of primary ciliary dyskinesia patients and for choosing sperm sources for intracytoplasmic sperm injection

Spermatozoa viability tests based on dual-color flow cytometry after staining with Sybr-14/propidium iodide were performed on 44 men with complete asthenospermia for primary ciliary dyskinesia (PCD) screening, and seven were identified with PCD by electron microscopy of ultrastructural ciliary defects. Six PCD patients underwent eight intracytoplasmic sperm injection therapy cycles using ejaculated sperm or testicular sperm, obtaining a mean fertilization rate of 46.6%, with three healthy babies born and one in utero at the time of writing.

Immunological advances in pathogenesis of psoriasis

The pathogenesis of psoriasis is closely associated with immune system. Most of recent studies have suggested that psoriasis is a mixed Thl/Thl7 immunological disease. Besides dendritic cells, T cells, keratinocytes and Thl type cytokines such as interleukin (IL)-12 and IL-18, Thl7 type cytokines such as IL-23 and IL-22 also participate in the development of psoriasis. Thl7 type immune response may play an essential role in the pathogenesis of psoriasis. Key words: Psoriasis; Immunology; Cytokines

Pulmonary hypertension: advances in pathogenesis and treatment

Pulmonary hypertension is an orphan disease that until recently has received limited attention within the wider medical community. This has changed distinctly in the last 10 years with the advent of new classes of therapy and a renewed interest in mechanisms of pathogenesis. This review utilized information gathered from recent conferences, and a review of the literature was conducted using MedLine and Pubmed. Accepted mechanisms of pathogenesis and currently available treatments are presented. We will discuss interesting new concepts in pathogenesis, including the importance of genetic forms of the disease and in particular the transforming growth factor receptor superfamily and the evolving evidence of the contribution of dysregulated immunity. Areas of research may yield therapeutic benefits in the not-too-distant future, including anti-proliferative therapies and stem cell therapy.

Nipah and Hendra Viruses: Recent Advances in Pathogenesis

Nipah and Hendra Viruses: Recent Advances in Pathogenesis

중이염 병인의 최신지견

중이염 병인의 최신지견

2007 Workshop of the Society for Hematopathology and European Association for Haematopathology

The August and September issues of the Journal will include a series of proceedings from the Workshop of the Society for Hematopathology and European Association for Haematopathology, which was held in Indianapolis, IN, in November 2007. The Workshop focused on chronic myeloproliferative neoplasms (MPNs), myeloproliferative/myelodysplastic neoplasms, de novo and therapy-related myelodysplastic syndromes (MDS), extramedullary myeloid tumors, and mastocytosis. Cases of de novo acute myeloid leukemia were excluded. The goals of the Workshop were to correlate diagnostic hematopathology practice to the most recent discoveries in myeloid neoplasms and address diagnostic challenges through case discussions. The Workshop and preparation of the proceedings coincided with the update of the World Health Organization (WHO) classification of hematopoietic and lymphoid neoplasms; thus, the articles discuss the individual diagnostic entities and submitted cases in light of this updated classification published in September 2008.1 The Workshop included plenary sessions and scientific lectures. The latter aimed to review recent advances in pathogenesis of my-eloid neoplasms and developments in molecularly targeted therapies and to outline the role of molecular pathology and cytogenetics in determining the prognosis and monitoring of myeloid neoplasms. The plenary sessions included interesting cases selected to represent current issues in the diagnosis of myeloid neoplasms. The diagnostic approach was based on a careful integration of morphologic assessment with ancillary …

Stiff person syndrome: Advances in pathogenesis and therapeutic interventions

Stiff person syndrome (SPS) varies from mild to severe, but if untreated it can be progressive and disabling. Although progress has been made in understanding and treating SPS, the disease remains underdiagnosed, delaying treatment. Antibodies against glutamic acid decarboxylase provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is an antigenic target. Circulating anti-GABARAP antibodies that inhibit GABA(A) receptor expression on GABAergic neurons have been found in up to 65% of SPS patients. The impairment of GABAergic pathways and reduction of brain GABA results in clinical manifestations of stiffness, spasms, and phobias. Increased awareness of SPS among practicing physicians is necessary to recognize the disease early and prevent permanent disability. Most patients with SPS respond to GABA-enhancing drugs, but the high doses required cause unacceptable adverse effects. The disease clearly responds to intravenous immunoglobulin, but repeated infusions are needed to maintain response. New immunomodulating agents are being explored to treat difficult cases and to induce long-lasting remissions.

ドライマウス研究の現状と展望

ドライマウス研究の現状と展望

Campylobacter, 3rd edition

This valuable new edition documents advances in Campylobacter spp. molecular biology, epidemiology, immunology, and food safety interventions over the past quarter century. It is an easy-to-read resource for both lay readers and scientists who are active in these research fields. The book contains 6 complementary sections. The first section provides an overview of the taxonomy of Campylobacter and related species, followed by in-depth chapters on population biology and molecular techniques. The second section reviews clinical and epidemiologic aspects of human infections. The next 3 sections describe advances in pathogenesis, immunity, glycobiology, and gene expression. Food safety interventions are discussed in the final section. Throughout the book, current references are cited, such as one that describes a recent finding of a possible link between C. rectus and C. concisus infections and Barrett’s esophagitis, a precursor of esophageal adenocarcinoma. One chapter provides an up-to-date summary of risk factors associated with human campylobacteriosis. Other chapters describe current methods for examining antibiotic resistance, mechanisms of resistance, and subtyping infectious strains. The center of the book is dedicated to technical research areas that may eventually lead to new prevention technologies. The final chapters relate to policies for enhancing food safety. The third edition of this book is a valuable reference. It provides a history of the science for this field, a review of current understanding, and expert guidance on avenues for future research. Its theme can be summarized by paraphrasing Stephen On and colleagues: With the integration of statistics, epidemiology, biology, and a risk-based paradigm Campylobacter, science is coming of age. Future discoveries are likely to be as thrilling, challenging, and surprising as the developments of the past 25 years (On et al., Chapter 10, p. 207).

Overexpression of Interleukin-1β in the Murine Pancreas Results in Chronic Pancreatitis

Chronic pancreatitis is a significant cause of morbidity and a known risk factor for pancreatic adenocarcinoma. Interleukin-1beta is a proinflammatory cytokine involved in pancreatic inflammation. We sought to determine whether targeted overexpression of interleukin-1beta in the pancreas could elicit localized inflammatory responses and chronic pancreatitis. We created a transgenic mouse model (elastase sshIL-1beta) in which the rat elastase promoter drives the expression of human interleukin-1beta. Mice were followed up for up to 2 years. Pancreata of elastase sshIL-1beta mice were analyzed for chronic pancreatitis-associated histologic and molecular changes. To study the potential effect of p53 mutation in chronic pancreatitis, elastase sshIL-1beta mice were crossed with p53(R172H) mice. Three transgenic lines were generated, and in each line the pancreas was atrophic and occasionally showed dilation of pancreatic and biliary ducts secondary to proximal fibrotic stenosis. Pancreatic histology showed typical features of chronic pancreatitis. There was evidence for increased acinar proliferation and apoptosis, along with prominent expression of tumor necrosis factor-alpha; chemokine (C-X-C motif) ligand 1; stromal cell-derived factor 1; transforming growth factor-beta1; matrix metallopeptidase 2, 7, and 9; inhibitor of metalloproteinase 1; and cyclooxygenase 2. The severity of the lesions correlated well with the level of human interleukin-1beta expression. Older mice displayed acinar-ductal metaplasia but did not develop mouse pancreatic intraepithelial neoplasia or tumors. Elastase sshIL-1beta*p53(R172H/+) mice had increased frequency of tubular complexes, some of which were acinar-ductal metaplasia. Overexpression of interleukin-1beta in the murine pancreas induces chronic pancreatitis. Elastase sshIL-1beta mice consistently develop severe chronic pancreatitis and constitute a promising model for studying chronic pancreatitis and its relationship with pancreatic adenocarcinoma.

Advances in pathogenesis of hyperlipidemic acute pancreatitis and its diagnosis and treatment

Advances in pathogenesis of hyperlipidemic acute pancreatitis and its diagnosis and treatment

Advances in pathogenesis of pruritis in atopic dermatitis

瘙痒是特应性皮炎的一个基本特征.因为瘙痒严重地影响着生活质量,大部分患者判断特应性皮炎的严重程度是通过瘙痒的剧烈程度而不是皮疹的表现.但其发生机制尚不完全清楚.最近,在研究特应性皮炎瘙痒的机制方面已取得很大的进展,既有神经系统的兴奋,又有一些介质的作用.这些进展为特应性皮炎患者瘙痒的研究和治疗提供新的思路。

Future directions in therapeutic interventions for conjunctival inflammatory disorders

To review recent advances in pathogenesis and treatment of conjunctival inflammatory disorders. The conjunctiva becomes inflamed in a number of conditions, including allergy, atopy, dry eye, mucus membrane pemphigoid, Stevens-Johnson syndrome and surgical manipulation. Basic and clinical studies have identified a number of inflammatory mediators as potential therapeutic targets in these conditions. Additionally, new therapeutic agents and enhanced delivery systems have been evaluated. Increased understanding of the key mediators of conjunctival inflammation coupled with improved drug delivery methods are leading to more effective therapy for conjunctival inflammatory disorders.

Advances in pathogenesis and management of sepsis

The rationale for therapeutic targets in sepsis has arisen from the concept of pathogenesis. This review focuses on recent advances in pathogenesis of sepsis that can aid in management of sepsis patients. Cellular survival in sepsis is related to the magnitude of the stimulus, the stage of the cell cycle and the type of microbe. While phenotypic modification of the endothelium (procoagulant and proadhesive properties, increased endothelial permeability, endothelial apoptosis and changes in vasomotor properties) leads to vasoplegia as a direct correlate to septic shock mortality, phenotypic changes in the epithelium cause activation of the virulence of the opportunistic pathogens and loss of mucosal barrier function, the latter causing a vicious circle in severe sepsis. Early identification of sepsis with protocolized screening, triggering evidence-based protocolized care, is anticipated to reduce sepsis morbidity and mortality. Current treatment of sepsis includes early antibiotic therapy, early aggressive goal-directed resuscitation targeting tissue hypoperfusion, steroids (for refractory shock), activated protein C (for high risk of death) and maintaining support of organ systems. A better understanding of pathogenesis of sepsis has led to specific proven management tools that are likely to improve clinical outcome once incorporated into protocolized care.

Advance in pathogenesis of fungal keratitis

Fungal keratitis is the most common and severe infectious corneal diseases in many developing countries. The disease has become the leading cause of corneal blindness in China. It is imperative to study deeply on pathogenesis of fungal keratitis for lowering its incidence, increasing therapeutic option and enhancing therapeutic efficacy. This article reviewed the advances of related factors in pathogenesis of fungal keratitis including fungal virulence factors and host defense mechanisms.

Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy

Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential 'disease modifier' role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usually conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient's quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.

VASCULAR CALCIFICATION IN PATIENTS WITH KIDNEY DISEASE: Calcific Uremic Arteriolopathy: Advances in Pathogenesis and Treatment

AbstractCalcific uremic arteriolopathy (CUA) is a rare but serious life‐threatening complication of CRF that manifests as painful nonhealing eschars in association with panniculitis and dermal necrosis. This condition is being increasingly recognized and reported as a contributing factor to death in dialysis patients. The pathognomic lesion is vascular calcification with intimal arterial hypertrophy and superimposed small vessel thrombosis. Hyperparathyroidism and elevated concentrations of serum phosphate remain consistent clinical features of most cases reported. Controversy still exists regarding the role of parathyroidectomy in this condition with some studies suggesting improved outcome with surgical intervention. A number of potential new etiological factors have been identified including reduced serum levels of a calcification inhibitory protein α,2‐Heremans–Schmid glycoprotein (Fetuin‐A) and abnormalities in smooth muscle cell biology in uremia. Promising new treatment options including hyperbaric oxygen therapy and sodium thiosulfate infusion have been reported in case series. Benefits from biphosphonates and tissue plasminogen activator have also been reported. Overall these new treatment approaches and understanding of potential mechanisms underlying this important severe clinical condition offer new hope in the diagnosis and management of this severely morbid and often fatal condition.