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At least 721 records · Page 40Linked to original sources
PubMed2002

[Neuropsychiatric involvement in systemic lupus erythematosus. Part 1: clinical presentation and pathogenesis].

BACKGROUND: Central nervous system (CNS) involvement is a frequent complication of systemic lupus erythematosus (SLE) ranging from a subclinical to a severe disabling disease. Neuropsychiatric manifestations have been described in 18-67% of cases depending on the diagnostic criteria. The cerebral involvement may precede the full-blown picture of SLE or may develop in the course of disease, most frequently within the first 3 years. CLINICAL PRESENTATION: Neuropsychiatric manifestations in SLE comprise diffuse psychiatric symptoms, focal neurologic symptoms, and the involvement of the peripheral nervous system. Numerous CNS syndroms have been described: migraine, seizure, stroke, chorea, transverse myelopathy, psychosis, mood disorders, acute confusional state, and cognitive dysfunction. The diagnosis of cerebral involvement can be difficult and has to be differentiated from neurologic complications which may be, for instance, due to uremia, hypertension, drug toxicity, and infection. PATHOGENESIS: A large number of etiopathophysiologic processes are involved: antineuronal antibodies, antibodies against ribosimal P-protein, and cytokines have been implicated in the pathogenesis of diffuse neuropsychiatric symptoms. Focal neurologic symptoms are the consequence of vascular injury induced by circulating immune complex, occlusive vasculopathy as a result of endothelial cell activation induced by cytokines and complement activation, or macro- and microvascular thrombosis induced by antiphospholipid antibodies. In the later stages of disease, cerebrovascular manifestations are often related to accelerated atherosclerosis, which is entertained by increased intravascular complement turnover and antiphospholipid antibodies.

Diagnosis, Differential↗
PubMed2003

[Hepatocellular carcinoma. Pathogenesis and multicentricity].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world, with an extremely poor prognosis. The clinical and molecular pathogenesis of HCC is very complex and involves alterations in the structure or expression of several tumor suppressor genes, oncogenes and, possibly, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation. Central to the molecular pathogenesis of HCC are mutations of various genes and a genetic instability which, in most cases, result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. The prognosis is generally very poor. Most studies report a 5-year survival rate of less than 5% in symptomatic HCC patients. Therapeutic strategies include resection, liver transplantation, and nonsurgical interventions such as percutaneous ethanol injection, radiofrequency thermal ablation, transarterial embolization, and chemoembolization. HCC has been shown to be quite resistant to radio- and chemotherapy.

Antineoplastic Agents↗
PubMed2003

[Latest aspects in psoriasis pathogenesis].

During recent years the understanding of psoriasis pathogenesis has changed essentially. Psoriasis is now considered as a T cell mediated inflammation of the skin. Genetic predisposition and microbial environment cooperate in the induction of an antigen-specific T cell mediated immune response which may persist lifelong. The phenotype of the psoriatic inflammation is determined by the particular functional differentiation of the pathogenic T cells. The progress in understanding the pathogenesis of psoriasis has identified T cells and T cell-derived cytokines as targets for causal treatment approaches that in the near future will change psoriasis therapy considerably.

Autoimmune Diseases↗
PubMed2003

[Cutaneous epithelial tumors. Molecular biology and pathogenesis-based therapy].

Basal cell carcinomas and squamous cell carcinomas are the most common human cancers and increasing in incidence. The development of novel, pathogenesis-based therapies requires a better knowledge of the molecular mechanisms leading to the development of these tumors. Basal cell carcinomas are characterized by aberrant activation of Sonic-Hedgehog (SHH) signaling due to mutations in the PTCH or SMOH genes. In addition, about 50% of the cases carry mutations in the TP53 tumor suppressor gene. Squamous cell carcinomas lack alterations of SHH signaling, while TP53 mutations are detectable in virtually all cases. Alterations in cell cycle regulatory genes, such as CDKN2A, are also common. Recently, specific inhibitors of the SHH-signaling pathway have been developed and shown promising results in preclinical studies on experimental basal cell carcinomas. However, the clinical significance of such targeted molecular therapy remains to be evaluated. Another successful pathogenesis-based therapy, which is already in clinical use, is the administration of topic immune response modifier imiquimod. This drug can eradicate non-melanoma skin cancers by different mechanisms, including cytokine-mediated stimulation of the anti-tumor immune response, as well as the induction of tumor cell apoptosis.

Adjuvants, Immunologic↗
PubMed2006

[Advances in the pathogenesis of atopic dermatitis].

The incidence of atopic dermatitis (AD) is noticeably increasing in industrialized countries. New insights into the pathogenesis of this disease are mirrored by a changed terminology suggested by the World Allergy Organization: a distinction between a so-called atopic and non-atopic dermatitis. The pathogenesis of the AD, which this article concentrates on, is highly complex. Genetic and environmental factors play a pivotal role in triggering AD. The complex pattern of cytokines and chemokines, reflecting a deviated immune response in AD patients, is a focus of research, as are the involvement of various cells and the epidermal barrier. Research concerning T cells with regulatory features as well as IgE-mediated autoreactivity will soon give insight into the defective tolerance of atopic patients and might possibly lead to new concepts in the management of the disease.

Adult↗
PubMed2003

[Adverse effects of antiretroviral therapy. Aspects of pathogenesis].

Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia, diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolic alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin, leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future.

Anti-HIV Agents↗
PubMed2004

Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease.

Rare monogenic forms of Parkinson's disease (PD) are promoting our understanding of the molecular pathways involved in the common, non-Mendelian forms of the disease. Here, we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics of this form and the rapidly expanding knowledge about the structure and biochemical properties of the DJ-1 protein. We also discuss how DJ-1 dysfunction might lead to neurodegeneration, and the implications of this novel piece of information for the pathogenesis of the common PD forms. Although much work remains to be done to clarify the biology of DJ-1, its proposed activity as a molecular chaperone and/or as oxidative sensor appear intriguing in the light of the current theories on the pathogenesis of PD.

Adolescent↗
PubMed1998

The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease.

This contribution reviews the structure and organization of collagen molecules found in cartilage and the roles that they may play in rheumatic diseases. Cartilage is unique in its physical properties and molecular composition, and contains sufficient amounts of types II, IX, X, and XI collagen to deem these molecules as "cartilage-specific." The vitreous body of the eye, a "cartilage-like" tissue is also rich in the same collagens but is type X deficient. Types VI and XII collagen are present in cartilage as well as noncartilaginous tissues. Types II, IX, and XI collagen are organized into matrix fibrils, where type II constitutes the bulk of the fibril, type XI regulates fibril size, and type IX facilitates fibril interaction with proteoglycan macromolecules. Genetic defects in these collagens can produce mild to severe developmental abnormalities, including spondyloepiphyseal dysplasia often accompanied by an accelerated form of osteoarthritis. Sensitization with collagen can produce experimental rheumatic diseases. Type II collagen induces an erosive polyarthritis in certain strains of rats, mice, and higher primates which can resemble rheumatoid arthritis and relapsing polychondritis. Type XI collagen is arthritogenic in rats but not mice; type IX induces autoimmunity in both species but not arthritis. Arthritis is initiated by complement fixing antibodies that bind to type II collagen in autologous cartilage, and the production of these antibodies is MHC restricted and T cell dependent. It is unclear whether T cells alone can induce arthritis, although they probably help sustain it. Mapping and characterizing the of T cell epitopes on type II collagen has resulted in the synthesis of small homolog and substituted peptides of type II collagen which suppress arthritis in an antigen-specific manner by a variety of routes, including mucosal. Moreover, collagen-induced arthritis has proven a valuable model to study the contribution of cytokines and other biological agents in the pathogenesis of joint injury and how they might be used to develop new therapies. Collagen autoimmunity has been implicated in the pathogenesis rheumatoid arthritis and polychondritis. Circulating antibodies to type II collagen are found in both diseases. Antibodies to types IX and XI collagen are also present in rheumatoid sera but are less prevalent. Rheumatoid cartilage and synovium contain antibodies to type II collagen at a prevalence far greater than serum, suggesting an intra-articular antigen-driven immune process. Although effective in animal models, attempts to treat rheumatoid arthritis with orally administered type II collagen have proven elusive. Different approaches using newer formulations and selected or modified oligopeptides remain to be tested and could prove effective in the treatment of the human rheumatic diseases.

Animals↗
PubMed2000

[The pathogenesis of interstitial cystitis--many hypotheses, but etiology remains uncertain].

Pathogenic aspects of interstitial cystitis (IC) are reviewed on the basis of the current literature applying the criteria of evidence-based medicine (EBM). Three hundred forty-six peer-reviewed publications of the past 30 years were retrieved via MEDLINE employing the key words "interstitial cystitis and pathogenesis or etiology" and classified according to EBM criteria and subject categories. The papers were then reviewed and summarized and are discussed considering the theory of acute and chronic inflammatory responses. In the literature, nearly all steps of the normal inflammatory response are considered pathogenically important in development of the IC syndrome. Applying EBM criteria, all studies fail to meet the criteria for sound statistical evaluation and to demonstrate reproducibly a reliable pathogenic factor. Most publications report only small numbers of patients. Control groups are frequently lacking or too small. Clinically useful criteria for the diagnosis of IC are not properly defined. There is no commonly accepted animal model in which IC occurs naturally or can be artificially induced. Of the 683 IC papers studied, 346 (50.7%) deal with pathogenic or etiological aspects of IC. The inflationary use of the terms pathogenesis or etiology in one out of every two papers calls for more prudent application of terminology in the future. As yet, none of the published pathogenic factors was found to represent the main trigger of the IC syndrome. Some of them seem to be part of a vicious cycle of the inflammatory reaction present. Detailed knowledge of the process of chronic inflammation can lead to treatments that may interrupt an inflammatory response. This might contribute to solving the pathogenic issue of IC and could be helpful in designing further investigations. Advances in understanding the causes of IC require objective criteria to subclassify the heterogenous patient cohort presently referred to as IC syndrome. Such subclassifications are a predisposition for pathogenic investigations and determining future treatment strategies.

Cystitis, Interstitial↗
PubMed2003

The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure.

Type 1 diabetes mellitus results from a T-cell mediated autoimmune destruction of the pancreatic beta cells in genetically predisposed individuals. The knowledge of the immunopathogenesis has increased enormously in the last two decades. The contribution of T-cells in the pathogenesis is beyond doubt. Therapies directed against T-cells have been shown to halt the disease process and prevent recurrent beta-cell destruction after islet transplantation. Less is known about the nature and function of these T-cells, the cause of the loss of tolerance to islet autoantigens, why the immune system apparently fails to suppress autoreactivity, and whether (or which) autoantigen(s) are critically involved in the initiation or progression of the disease. The contribution of dendritic cells in directing the immune response is clear, while the contribution of B-cells and autoantibodies is subject to reconsideration. Autoreactive T-cells have proven to be valuable tools to study pathogenic or diabetes-related processes. Measuring T-cell autoreactivity has also provided critical information to determine the fate of islet allografts transplanted to Type 1 diabetic patients. Cellular autoimmunity is a difficult study subject, but it has been a worthwhile quest to unravel the role of T-cells in the pathogenesis of Type 1 diabetes. The challenge for the future is to determine which factors contribute to the loss of tolerance to beta-cell antigens, and to define what measures T-cells can provide to suppress autoreactivity, since it is becoming increasingly evident that T-cells provide a two-edged sword: some T-cells could be pathogenic, but others can regulate the disease process and thus form new targets for immunointervention.

Animals↗
PubMed2004

Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice.

AIMS/HYPOTHESIS: During the pathogenesis of type 2 diabetes insulin resistance causes compensatory proliferation of beta cells. As beta cells have a limited replication potential, this compensatory proliferation might accelerate cellular senescence and lead to diabetes. We examined the cellular senescence of beta cells after proliferation during lipoglucotoxicity. METHODS: Senescence-associated markers in beta cells were examined in nutrient-induced diabetic C57BL/6J mice that were fed a high-fat diet. After 4 and 12 months of the high-fat diet, intraperitoneal glucose tolerance tests (IPGTTs) and histochemical analyses of Ki-67, p38, senescence-associated beta-galactosidase, and beta cell mass were performed. RESULTS: At 4 months, the AUC for plasma insulin levels during the IPGTT (AUC(insulin)) was higher, beta cell mass was 3.1-fold greater, and the proliferation of beta cells was 2.2-fold higher than in the control group. However, at 12 months, AUC(insulin) declined, the frequency of Ki-67-positive beta cells decreased to one-third that of the control group, and the senescence-associated, beta-galactosidase-positive area increased to 4.7-fold that of the control group. Moreover, small amounts of p38, which is induced by oxidative stress and mediates cellular senescence, were found in beta cells from the high-fat diet group, but not in beta cells from the control group. Furthermore, the senescence-associated, beta-galactosidase-positive area in the high-fat diet group had a highly significant negative correlation with AUC(insulin) (r=-0.852, p<0.01). CONCLUSIONS/INTERPRETATION: Beta cell senescence occurred in diet-induced type 2 diabetes and led to insufficient insulin release. These findings suggest that cellular senescence contributes to the pathogenesis of diet-induced diabetes.

Animals↗
PubMed2005

Roles of estrogen receptor, progesterone receptor, p53 and p21 in pathogenesis of pelvic organ prolapse.

The aim of this study is to compare the levels of estrogen receptor (ER), progesterone receptor (PR), p53 and p21 between pelvic organ prolapse (POP) and control groups in order to evaluate their roles in pathogenesis of POP, and to find out the relationship among these proteins. Through the year of 2002, uterosacral ligaments were obtained from 20 prolapsus and 24 non-prolapsus hysterectomized uteruses. ER, PR, p53, and p21 proteins were extracted by Western blot analysis and relative levels of proteins were compared by Student t-test and Pearson correlation coefficient. P value <0.05 was considered statistically significant. All patients were postmenopausal and had never taken hormone replacement therapy. ER, PR, p53, and p21 were significantly lower in the study than control group (p<0.0001). Positive correlations were found among all proteins in the prolapse group. Further researches are needed to elucidate the interrelationship among these proteins and their precise roles in pathogenesis of POP.

Aged↗
PubMed2004

Involvement of pulmonary endothelial cell injury in the pathogenesis of pulmonary fibrosis: clinical assessment by 123I-MIBG lung scintigraphy.

PURPOSE: Pulmonary microvascular endothelial injury may be involved in the pathogenesis of pulmonary fibrosis (PF). The aim of this study was to evaluate the pulmonary vascular status in patients with PF by lung scintigraphic assessment of 123I-metaiodobenzylguanidine (123I-MIBG), which reflects latent endothelial cell lesions. METHODS: We assessed lung 123I-MIBG kinetics and clinical indices in 23 PF patients and 16 controls. Mean uptake ratios of lung to mediastinum (L/M) were calculated in anterior planar images at 30 (early image) and 270 (delayed image) min after intravenous injection of 123I-MIBG. The pulmonary mean washout rate (WR) of 123I-MIBG was also calculated. RESULTS: The L/M ratio in early images, but not in delayed images, was significantly lower in the PF patients than in the controls (L/M(early) 1.41+/-0.14 vs 1.53+/-0.10, p<0.01; L/M(delayed) 1.28+/-0.10 vs 1.33+/-0.07, p=NS). WR was significantly reduced in the PF patients compared with the controls (28.6%+/-3.1% vs 34.2%+/-5.1%, p<0.001). In the study subjects (PF patients plus controls) there were significant relationships between lung WR of (123)I-MIBG and other diagnostic parameters for the severity of PF, such as vital capacity (r=0.625, p<0.0001), total lung capacity (r=0.691, p<0.0001), carbon monoxide diffusing capacity (r=0.622, p<0.0001), serum angiotensin-converting enzyme activity (r=0.422, p<0.01), carbohydrate antigen KL-6 levels (r=-0.495, p<0.01) and surfactant protein-D levels (r=-0.461, p<0.01). When control subjects were excluded, similar significant correlations were observed between WR and %TLC (r=0.508, p<0.05), DL(CO) (r=0.593, p<0.01) and serum ACE activity (r=0.515, p<0.05) in the PF patients. CONCLUSION: These results suggest that endothelial cell injury plays a significant role in the pathogenesis of PF, and that lung WR of 123I-MIBG, which is a specific marker of endothelial damage, can serve as a novel diagnostic tool to evaluate the functional severity of PF.

3-Iodobenzylguanidine↗
PubMed2006

Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster.

INTRODUCTION: Mucositis induced by antineoplastic drugs is an important, dose-limiting, and costly side effect of cancer therapy. AIM: To investigate the role of nitric oxide (NO) on the pathogenesis of 5-fluorouracil (5-FU)-induced oral mucositis. MATERIALS AND METHODS: Oral mucositis was induced by two intraperitoneal (i.p) administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) in male hamsters. Animals were treated subcutaneously with saline (0.4 ml), 1,400 W (1 mg/kg), aminoguanidine (5 or 10 mg/kg) or Nphi-Nitro-L-Arginine Methyl Ester (L-NAME) (5, 10, or 20 mg/kg) 1 h before the injections of 5-FU and daily until sacrifice, on the tenth day. Macroscopic and histopathological analyses were evaluated and graded. Tissues from the cheek pouches were harvested for measurement of myeloperoxidase (MPO) activity, nitrite level, and immunohistochemistry for induced nitric oxide synthase (iNOS). RESULTS: Treatment with 1,400 W or aminoguanidine reduced macroscopic and histological parameters of oral mucositis, and reduced the inflammatory cell infiltration as detected by histopathology and by MPO activity. In contrast, the administration of L-NAME did not significantly reverse the inflammatory alterations induced by experimental mucositis. Increased NOS activity, nitrite level and immunostaining for iNOS were detected on the check pouch tissue of animals submitted to 5-FU-induced oral mucositis on the tenth day. CONCLUSION: These results suggest an important role of NO produced by iNOS in the pathogenesis of oral mucositis induced by 5-FU.

Animals↗
PubMed1997

[Neuroendocrine tumors of the stomach. Pathogenesis, classification and clinical aspects].

Neuroendocrine tumors of the stomach are classified into four types mostly on the basis of their pathological associations: 1) carcinoid type I, associated with atrophic corporal gastritis, 2) carcinoid type II, associated with multiple endocrine neoplasia type 1, 3) carcinoid type III, sporadic, and 4) neuroendocrine carcinoma. The first two types develop through a histologically recognizable sequence hyperplasia--dysplasia--neoplasia. Their pathogenesis depends on the combined action of promoting agents, mostly hypergastrinemia, and of transforming agents, the role of which is currently under investigation. Their prognosis is generally favourable in sharp contrast with that of the other two types of tumors, which is usually poor. The pathogenesis and the precursor lesions of the latter neoplasms have not been clarified yet.

Carcinoid Tumor↗
PubMed1997

Cloning and characterisation of glutamine synthetase from Colletotrichum gloeosporioides and demonstration of elevated expression during pathogenesis on Stylosanthes guianensis.

Experiments were designed to clone and identify genes of the fungal phytopathogen Colletotrichum gloeosporioides expressed at high levels during growth on the compatible host Stylosanthes guianensis when compared with expression in axenic culture. A cDNA clone (pCgGS) that hybridised preferentially to a cDNA probe prepared from infected leaves was isolated by the differential screening of a cDNA library from a nitrogen-starved axenic culture of C. gloeosporioides. The DNA sequence of pCgGS is highly homologous to genes for glutamine synthetase (GS) in other organisms. pCgGS contained all of the conserved regions assigned as catalytic domains in GS enzymes. Comparison with genomic sequences indicated that in C. gloeosporioides the GS gene is present as a single copy with three introns. To our knowledge this is the first report of the cloning of a GS from a filamentous fungus. A second clone (pCgRL1) was also isolated and represented a partial cDNA of the 25s rRNA of C. gloeosporioides. Because pCgRL1 did not hybridise to plant rRNA under high-stringency hybridisation conditions, it was used as a reference to quantify the expression of fungal GS mRNA during pathogenesis in S. guianensis compared to fungal growth in axenic culture. The results indicated that elevated expression of GS occurred during pathogenesis of C. gloeosporioides on S. guianensis, particularly at early stages of infection where expression was about six-times higher than during growth in rich culture media. This work also demonstrates that fungal-specific 25s rRNA fragments, such as pCgRL1, have considerable utility as a reference for quantifying pathogen gene expression in infected plants.

Amino Acid Sequence↗
PubMed2002

Alterations in diffusion and perfusion in the pathogenesis of peritumoral brain edema in meningiomas.

Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant ( p<0.0005) lower rrCBV and rrCBFi. The edema index (EI) correlated strongly with the rrCBV. A fitting procedure resulted into the following mathematical relation: EI=0.1/rrCBV(2). The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10(-3) vs 1.55 x 10(-3) mm(2)/s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema.

Adult↗
PubMed2005

The pathogenesis of craniopharyngiomas.

OBJECTIVE: The objective of the study is to review the pathogenesis of craniopharyngiomas. METHODS: A literature review of articles relating to the embryogenesis of the pituitary gland and sella and the pathogenesis of craniopharyngiomas was performed. CONCLUSIONS: Craniopharyngiomas are benign, epithelial neoplasms of the sella and parasellar region seen in children and adults that may arise from neoplastic transformation of ectoderm-derived epithelial cell remnants of Rathke's pouch and the craniopharyngeal duct.

Craniopharyngioma↗