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PubMed1995

Transgenic animal models of renal development and pathogenesis.

The use of transgenic animals represents a powerful tool with which to address the role of particular gene products in vivo. Recent technical and biological advances have simplified the process of creating both transgenic mice and null-mutation mice. Increasing numbers of genetic control elements are available to direct transgene expression to particular renal cell types and to enhance the consistency of expression. These approaches have contributed significantly to our understanding of renal development and pathogenesis, in particular in the following areas: the roles of various oncogenes, homeobox genes, and growth factors in renal development and the pathogenesis of cystic renal diseases; the contribution of systemic and local expression of the renin-angiotensin system to blood pressure control; the role of growth factors and cytokines in progressive glomerular disease; the role of viral proteins in the pathogenesis of glomerular and tubular disease; and mechanisms of immune-mediated renal disease.

Animals↗
PubMed2006

Potential biomarkers found by protein profiling may provide insight for the macrovascular pathogenesis of diabetes mellitus.

Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

Animals↗
PubMed2004

Mitochondrial DNA mutation at the D310 (displacement loop) mononucleotide sequence in the pathogenesis of gallbladder carcinoma.

PURPOSE: Mutations in the mitochondrial DNA (mtDNA) have been observed frequently in human neoplasia, in both coding and noncoding regions. A mononucleotide repeat (poly-C) between 303 and 315 nucleotides (D310) within the regulatory displacement loop has been identified recently as a frequent hot spot of deletion/insertion mutations in tumors. We investigated the frequency and pattern of D310 abnormalities in the pathogenesis of gallbladder carcinoma (GBC). EXPERIMENTAL DESIGN: DNA extracted from neoplastic and nonneoplastic archival gallbladder tissue including 123 tumors, 53 dysplastic areas, and 90 histologically normal epithelia adjacent to GBC, chronic cholecystitis, and 15 normal gallbladders were examined by PCR-based assay for D310 mutations, followed by sequencing in a subset of cases. RESULTS: D310 mutation was a relatively frequent (47 of 123; 38%) abnormality in GBC. A very high frequency of mutations were detected in dysplastic (8 of 14; 57%) and normal-appearing gallbladder epithelia (10 of 22; 46%) accompanying GBC, showing a clonal relationship compared with the corresponding tumors. D310 mutations were also detected in dysplastic (8 of 39; 21%) and normal (17 of 68; 25%) epithelia obtained from chronic cholecystitis. A single case of 15 normal gallbladders showed a D310 abnormality. Overall, deletions (67 of 91; 74%) at D310 were more frequent than insertions. CONCLUSIONS: D310 mutation at the mtDNA displacement loop is a relatively frequent and early event in the sequential pathogenesis of GBC, being detected in normal-appearing epithelium from chronic cholecystitis. Our findings suggest that mtDNA mutations should be additionally investigated in GBC pathogenesis, and D310 mononucleotide abnormalities could be included in a panel of molecular biomarkers for GBC early detection strategy.

Aged↗
PubMed2000

Molecular genetic parameters in pathogenesis and prognosis of testicular germ cell tumors.

Aim of this review article was to critically analyze the recently described cytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosme i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromosomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies the percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in the research for prgnosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it will also define new approaches to classification and management of germ cell tumors

Carrier Proteins↗
PubMed1997

Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas' disease.

The major goal of studies on immunity to Trypanosoma cruzi is the understanding of immunological mechanisms involved in resistance to this protozoan as well as the pathogenesis of Chagas' disease. Different studies have defined CD8+ T lymphocytes, IFN-gamma and macrophages as important elements controlling parasite replication during the acute phase of infection. In contrast, during the chronic stage of the disease parasite-specific antibodies that fix complement and lyse the blood from trypomastigotes are thought to be the main effector molecules responsible for maintaining latent infection. In both acute and chronic infection with T. cruzi CD4+ Th1 lymphocytes appear to be the main cells responsible for induction of protective immunity. The immunological mechanisms involved in the pathogenesis of Chagas' disease are much more controversial. CD8+ lymphocytes are thought to be the main effector cells responsible for cardiac tissue destruction. Although many experiments suggest the involvement of autoimmunity in the pathogenesis of Chagas' disease, recent studies both in mice and humans indicate a positive association of tissue parasitism, inflammation and severity of pathology induced by T. cruzi. Finally, T. cruzi has emerged as an important opportunistic pathogen in patients infected with HIV and presenting low numbers of CD4+ T lymphocytes. These clinical findings indicate the essential requirement of CD4+ T-helper cells in mediating resistance during chronic Chagas' disease; however, the effector mechanisms that control the reactivation of chronic infection in vivo are not completely defined.

Acute Disease↗
PubMed1996

Distinctive ultrastructural pathology of nonulcerative interstitial cystitis: new observations and their potential significance in pathogenesis.

Ultrastructural study of the bladder in interstitial cystitis has, so far, been limited, mainly to the urothelium. The present study was conducted first to study in detail the ultrastructural features of all tissue components of the bladder wall in nonulcerative interstitial cystitis and second to derive clues from the observed changes to pathogenesis of the disease. Endoscopic biopsies of urothelium with attached suburothelium, and muscularis, were obtained from both lesional and nonlesional areas in 5 female patients with unequivocal clinical diagnosis of interstitial cystitis. The specimens were processed for electron microscopic study by standard methods and subjected to comprehensive ultrastructural study of urothelium, suburothelium, detrusor muscle cells, intrinsic blood vessels, and intrinsic nerves. A distinctive combination of peculiar muscle cell profiles, injury of intrinsic vessels and nerves in muscularis and suburothelium, and discohesive urothelium was observed in lesional and less markedly in nonlesional samples of all specimens. Marked edema of various tissue elements and cells appeared to be a common denominator of many observed changes. Edema of muscle cells resulted in characteristic querciphylloid profiles, so designated because of peripheral bosselation of cell sarcoplasm with a lobed perimeter resembling that of an oak leaf. Urothelial changes disrupted the true permeability barrier, consisting of asymmetric unit membrane and triple epithelial junctions of surface (umbrella) cells. Vascular lesions included endothelial cell injury and suggested sluggishness of intrinsic microcirculation. Neural changes included a combination of degenerative and regenerative features, some expressing neural plasticity. The observed ultrastructural changes appear to be sufficiently distinctive to be diagnostic in specimens submitted for pathologic confirmation of nonulcerative interstitial cystitis. The changes do not support a primary pathogenetic role of mast cells or a selectively deficient glycosaminoglycan layer. They do suggest, however, a pathogenesis based on a potentially self-perpetuating process of neurogenic inflammation that can trigger a biologically potent cascade of events, including a leaky urothelium and mast cell activation. As proposed, neurogenic inflammation consolidates various proposals advanced as the pathogenesis of interstitial cystitis and can readily accommodate infectious, immunologic, and autoimmunologic mechanisms as factors that contribute to development or chronicity of the disease.

Adult↗
PubMed2007

Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms.

The role of inflammation in the pathogenesis of abdominal aortic aneurysms (AAA) is well established. The inflammatory process leads to protease-mediated degradation of the extracellular matrix and apoptosis of smooth muscle cells (SMC), which are the predominant matrix synthesizing cells of the vascular wall. These processes act in concert to progressively weaken the aortic wall, resulting in dilatation and aneurysm formation. Oxidative stress is invariably increased in, and contributes importantly to, the pathophysiology of inflammation. Moreover, reactive oxygen species (ROS) play a key role in regulation of matrix metalloproteinases and induction of SMC apoptosis. ROS may also contribute to the pathogenesis of hypertension, a risk factor for AAA. Emerging evidence suggests that ROS and reactive nitrogen species (RNS) are associated with AAA formation in animal models and in humans. Although experimental data are limited, several studies suggest that modulation of ROS production or activity may suppress AAA formation and improve experimental outcome in rodent models. Although a number of enzymes can produce injurious ROS in the vasculature, increasing evidence points toward a role for NADPH oxidase as a source of oxidative stress in the pathogenesis of AAA.

Animals↗
PubMed1996

Distinct roles for pneumolysin's cytotoxic and complement activities in the pathogenesis of pneumococcal pneumonia.

Pneumolysin, the major Streptococcus pneumoniae cytotoxin, contributes to the early pathogenesis of invasive pneumococcal pneumonia by facilitating intrapulmonary bacterial growth and invasion into the blood. Pneumolysin is a multifunctional toxin, with distinct cytolytic ("hemolytic") and complement-activation ("complement") activities that have been mapped to several regions of the molecule. To characterize the specific contributions of pneumolysin's hemolytic and complement properties to the pathogenesis of pneumococcal pneumonia, we compared the in vivo effects of type 2 S. pneumoniae mutant strains, which produce pneumolysins deficient in these activities. The absence of either pneumolysin's hemolytic or complement activities rendered mutant strains less virulent than the wild-type strain during pulmonary infection. Pneumolysin's hemolytic activity correlated with acute lung injury and bacterial growth at 3 and 6 h after endotracheal instillation. In contrast, pneumolysin's complement activity correlated with bacterial growth and bacteremia at 24 h after pulmonary infection. Pneumolysin's complement activity was not associated with the degree of alveolar-capillary injury or recruitment of leukocytes during initial pulmonary infection. However, pneumolysin's complement activity inhibited killing of mutant bacteria in an in vitro complement-dependent neutrophil killing assay. Thus, both pneumolysin's hemolytic and complement activities made specific contributions to the early pathogenesis of pneumococcal pneumonia at different stages of infection and by different mechanisms.

Animals↗
PubMed2005

Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma pathogenesis?

The potential role of atypical bacterial infection in the pathogenesis of asthma is a subject of continuing debate. There is an increasing body of literature concerning the association between the atypical bacteria Chlamydophila pneumoniae and Mycoplasma pneumoniae and asthma pathogenesis; however, many studies investigating such a link have been uncontrolled and have provided conflicting evidence, in part due to the difficulty in accurately diagnosing infection with these atypical pathogens. This article reviews the evidence for an association between atypical bacterial respiratory pathogens and the pathogenesis of asthma, and discusses the biological mechanisms that could account for such a link. The possible role of antibacterial therapy in the management of asthma and the need for well-designed studies to investigate this is also discussed.

Anti-Bacterial Agents↗
PubMed1980

Evaluation of a role for 1,25-dihydroxyvitamin D3 in the pathogenesis and treatment of X-linked hypophosphatemic rickets and osteomalacia.

Although a defect in renal transport of phosphate seems well established as the primary abnormality underlying the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia, several observations indicate that renal phosphate wasting and hypophosphatemia cannot solely account for the spectrum of abnormalities characteristic of this disease. Thus, in the present study, we investigated the potential role of abnormal vitamin D metabolism in the pathogenesis of this disorder and the effect of 1,25-dihydroxyvitamin D(3) therapy on both the biochemical abnormalities characteristic of this disease and the osteomalacia. Four untreated patients, ages 14-30 yr, had normocalcemia (9.22+/-0.06 mg/dl); hypophosphatemia (2.25+/-0.11 mg/dl); a decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate (2.12+/-0.09 mg/dl); normal serum immunoreactive parathyroid hormone concentration; negative phosphate balance; and bone biopsy evidence of osteomalacia. The serum 25-hydroxyvitamin D(3) concentration was 33.9+/-7.2 ng/ml and, despite hypophosphatemia, the serum level of 1,25-dihydroxyvitamin D(3) was not increased, but was normal at 30.3+/-2.8 pg/ml. These data suggested that abnormal homeostasis of vitamin D metabolism might be a second defect central to the phenotypic expression of X-linked hypophosphatemic rickets/osteomalacia. This hypothesis was supported by evaluation of the long-term response to pharmacological amounts of 1,25-dihydroxyvitamin D(3) therapy in three subjects. The treatment regimen resulted in elevation of the serum 1,25-dihydroxyvitamin D levels to values in the supraphysiological range. Moreover, the serum phosphate and renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate increased towards normal whereas the phosphate balance became markedly positive. Most importantly, however, repeat bone biopsies revealed that therapy had positively affected the osteomalacic component of the disease, resulting in normalization of the mineralization front activity. Indeed, a central role for 1,25-dihydroxyvitamin D(3) in the mineralization of the osteomalacic bone is suggested by the linear relationship between the serum level of this active vitamin D metabolite and the mineralization front activity. We, therefore, suggest that a relative deficiency of 1,25-dihydroxyvitamin D(3) is a factor in the pathogenesis of X-linked hypophosphatemic rickets and osteomalacia and may modulate the phenotypic expression of this disease.

Adolescent↗
PubMed2006

Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury.

Periventricular white-matter injury is the major form of brain injury associated with prematurity and the leading cause of cerebral palsy in survivors of premature birth. Progress in understanding the pathogenesis of periventricular white-matter injury requires the development of animal models that are relevant to the unique physiology of the preterm human brain and that replicate the major neuropathologic features of human injury. The sheep is the most extensively studied true fetal preparation. The neurodevelopment of the preterm sheep fetus (0.65 gestation) is comparable to that of the preterm human between approximately 24 and 28 weeks. The size of the fetal sheep permits chronic instrumentation so that well-defined insults can be studied with reliable measurements of blood flow and metabolism in cerebral white-matter. We review here recent developments in the understanding of the role of cerebral hypoxia-ischemia and vulnerable oligodendrocyte progenitors in the pathogenesis of periventricular white-matter injury in the immature sheep fetus. We focus on recent developments in high-resolution spatially defined cerebral blood flow measurements in utero. We determined ovine white-matter maturation between 90 and 120 days' gestation, as defined by immunohistochemical localization of oligodendrocyte lineage-specific antibodies. There was considerable spatial and temporal heterogeneity in oligodendrocyte maturation in the immature periventricular white-matter. Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided with that of the preterm human during the high-risk period for white-matter injury. Hence, the immature state of the 90- to 105-day fetal periventricular white-matter is an optimal and dynamic developmental window to study the role of cellular-maturational factors in the pathogenesis of white-matter injury. We conclude with a review of the significant advantages of the instrumented fetal sheep to accelerate progress in the translation of preventive therapies for periventricular white-matter injury and cerebral palsy.

Animals↗
PubMed2004

Pathogenesis of brain and spinal cord atrophy in multiple sclerosis.

For more than a century, multiple sclerosis was viewed as a disease process characterized by oligodendrocyte and myelin loss, and research into the pathogenesis of multiple sclerosis was mainly focused on the mechanisms of inflammation. However, with development of more sophisticated neuroimaging and molecular biology techniques, attention has shifted to new aspects of pathogenesis of multiple sclerosis: axonal loss and neurodegeneration. Evidence is increasing that tissue destruction, primarily axonal loss and neurodegeneration, is a key element in the pathogenesis of multiple sclerosis. In addition, it is now known that brain and spinal cord atrophy begins early in the disease process of multiple sclerosis and advances relentlessly throughout the course of the disease. Cumulative data suggest that axonal loss is the major determinant of progressive neurologic disability in patients with multiple sclerosis. Magnetic resonance imaging and magnetic resonance spectroscopy in patients with multiple sclerosis for < 5 years indicate brain atrophy and loss of axonal integrity. Neurodegeneration and axonal loss in patients with multiple sclerosis are initially accompanied by a local response from oligodendrocyte progenitor cells and some remyelination. However, these repair mechanisms eventually fail, and patients typically develop generalized brain atrophy, cognitive decline, and permanent disability. Although the exact mechanisms underlying central nervous system atrophy in patients with multiple sclerosis are largely unknown, evidence exists that atrophy may represent an epiphenomenon related to the effects of dynamic inflammation within the central nervous system, including demyelination, axonal injury, neuronal loss, Wallerian degeneration, and possibly iron deposition. This article summarizes the potential mechanisms involved in central nervous system atrophy in patients with multiple sclerosis.

Apoptosis↗
PubMed2002

The pathogenesis of oral lichen planus.

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta 1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.

Animals↗
PubMed2003

The pathogenesis of Leishmania/HIV co-infection: cellular and immunological mechanisms.

The intracellular protozoan parasites of the genus Leishmania have been recognized as opportunistic pathogens in immunosuppressed individuals, including those infected with human immunodeficiency virus type-1 (HIV-1). Leishmaniasis and AIDS overlap in several sub-tropical and tropical regions around the world, including the Mediterranean area. In 1994, 3%-7% of HIV-1-infected individuals in southern Europe developed visceral leishmaniasis. In humans, interestingly, both HIV-1 and Leishmania interact with, invade, and multiply within cells of myeloid or lymphoid origin. The combined modulation of Leishmania - and HIV-1-related pathogenesis in the co-infected cases is therefore probably a realistic goal. In the light of the recent demonstration that L. donovani can up-regulate HIV-1 replication, both in monocytoid and lymphoid cells in vitro and in co-infected individuals, it is clear from the epidemiological data available that Leishmania can probably act as a powerful co-factor in the pathogenesis of HIV-1 infection. In those who are co-infected, complex mechanisms involving cytokine secretion and cellular-signalling events play pivotal roles in the Leishmania-mediated activation and pathogenesis of HIV-1. An overview of the recent findings concerning this Leishmania/HIV-1 interaction is presented here.

AIDS-Related Opportunistic Infections↗
PubMed2006

Rhinosinusitis derived Staphylococcal enterotoxin B plays a possible role in pathogenesis of food allergy.

BACKGROUND: Staphylococcal enterotoxin B (SEB) is a potent immunomodulator and implicated with pathogenesis of inflammatory diseases mediated by Th1 or Th2 dominant immune responses. The objective of this study is to determine a possible association between rhinosinusitis derived SEB and pathogenesis of food allergy (FA). METHODS: The study included chronic rhinosinusitis (CRS) patients with FA (N = 46) or without FA (N = 33). Controls included FA patients without CRS (N = 26) and healthy volunteers (N = 25). In CRS patients, we assessed the parameters associated with FA including prick skin test (PST) reactivity to food allergens, serum levels of allergen-specific IgE and cytokines (IL-4, IL-13, IFN-I3), and the number/reactivity of food-allergen specific Th1/Th2 cells in the peripheral blood before and 2 months after sinus surgery. Changes of these parameters were evaluated in comparison with changes in SEB concentration in the sinus lavage and stool samples and also in vitro reactivity to SEB. In CRS patients with FA, we also assessed changes in reactivity to oral challenge of offending food before and after sinus surgery. RESULTS: Two months following sinus surgery, we observed statistically significant reduction in PST and oral challenge reactivity in CRS patients with FA in parallel to decrease in serum levels of Th2 cytokines (IL-4 and IL-13) and allergen specific IgE. Improvement of reactivity to food allergens was positively associated with decline in SEB concentrations in the sinus lavage and stool samples. In vitro study results also indicated a role of SEB in aggravation of Th2 skewed responses to food allergens. Such changes were not observed in CRS-non FA patients or control FA patients. CONCLUSION: The rhinosinusitis derived SEB plays a certain role in the pathogenesis of FA by augmenting and/or maintaining polarized Th2 responses. Removal of SEB-producing pathogens from the rhinosinuses may be beneficial for attenuating the FA symptoms in patients with CRS-FA.

Adult↗
PubMed2000

What you should know about PR3-ANCA. Evidence for the role of T cells in the pathogenesis of systemic vasculitis.

The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. There is a growing body of evidence that T cells may contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Predominantly, T cells and monocytes are found in inflammatory infiltrates in patients with Wegener's granulomatosis (WG). The production of ANCA appears to be T-cell-dependent. T lymphocytes from the peripheral blood of patients with ANCA-associated vasculitis have been shown to proliferate in response to proteinase 3 (PR3). These and other findings outlined in this review indicate T-cell involvement, although further studies are still needed to elucidate the exact contribution of T cells to the pathogenesis of systemic vasculitis.

Animals↗
PubMed2005

Molecular pathogenesis of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathologic entity accounting for 30% of non-Hodgkin's lymphomas. The pathogenesis of DLBCL is complex and heterogeneous. Recent studies using analysis of global gene expression with DNA microarrays and the classical molecular approaches demonstrate presence of several DLBCL subtypes characterized by different cells of origin, cytogenetic and molecular aberrations, and distinct pathogenesis. This review summarizes the progress in understanding of DLBCL biology and presents a state-of-the-art overview of DLBCL molecular pathogenesis.

Female↗
PubMed2001

Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome.

The aim of this review is to examine recent advances in experimental and clinical research relevant to the pathogenesis of diarrhea-associated hemolytic uremic syndrome with special reference to histopathologic findings, virulence factors of Shiga toxin-producing Escherichia coli, the host response, and the prothrombotic state. Despite significant advances during the past decade, the exact mechanism by which Shiga toxin-producing E. coli leads to hemolytic uremic syndrome remains unclear. Factors such as Shiga toxin, lipopolysaccharide, the adhesins intimin and E. coli-secreted proteins A, B, and D, the 60-MD plasmid, and enterohemolysin likely contribute to the pathogenesis. Data on the inflammatory response of the host, including leukocytes and inflammatory mediators, are updated. The pathogenesis of the prothrombotic state leading to thrombocytopenia secondary to endothelial cell damage and platelet activation is also discussed. A hypothetical sequence of events from ingestion of the bacteria to the development of full-blown hemolytic uremic syndrome is proposed.

Adhesins, Bacterial↗