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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The origin of idiopathic acute pancreatitis has not been well defined. Several enteroviruses, including coxsackievirus, have been implicated. We report the case of a 21-year-old woman with severe, acute pancreatitis with no classic risk factors. Initial evaluation failed to show choledocholithiasis. Her condition improved with conservative treatment, but symptoms recurred after resumption of oral intake. Computed tomography (CT) of the abdomen revealed an atypical pseudocyst and omental nodules suggestive of a metastatic malignancy. An acute coxsackievirus B5 titer delayed CT-guided omental biopsy. The patient showed improvement, but progression of the omental nodules prompted open laparotomy. No malignant or inflammatory process was identified. This is the first reported case of presumed viral pancreatitis causing reactive omental nodules. This case shows a benign process mimicking malignancy, requiring an extensive, potentially dangerous workup. It also emphasizes the need to consider viral causes for unusual presentations of common problems.
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PMID:Coxsackievirus-associated pancreatitis mimicking metastatic carcinoma. 861 92

While alcohol abuse and biliary disease can result in the development of pancreatitis, the factors that contribute to the idiopathic form of the disease are not well understood. I propose that coxsackievirus infections account for a subset of cases of pancreatitis of unknown etiology. Evidence to support this concept is derived from serological studies, case reports and animal models. In reviewing the available data, it is obvious that the relationship between coxsackievirus infection and the development of pancreatitis is not a simple one. Many elements contribute to the development of the disease including the strain of the infecting virus, the genetic predisposition of the host and additional environmental factors that maintain the disease process. Studies that show an association between coxsackievirus infection and acute pancreatitis in humans are given additional support by the extensive data from mouse studies demonstrating that some serotypes (B4,B3) are tropic for the exocrine pancreas. Some viral strains may cause limited pancreatic tissue injury which is compatible with tissue repair followed by full restoration of pancreatic function. Other viral strains may cause more extensive tissue damage giving rise to chronic pancreatitis which, on a genetic background that predisposes to autoimmunity, may result in an autoimmune chronic pancreatitis. A multi-disciplinary approach is required to increase our understanding of the complex relationship between coxsackievirus infection and pancreatic diseases. Such studies should address the biology of viral replication, the immune response to infection, the role of viruses in the development of autoimmunity, the biology of pancreatic tissue injury and the underlying repair process.
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PMID:Coxsackieviruses and pancreatitis. 925 48

Two genetically similar variants of coxsackievirus B4, CB4-P and CB4-V, cause distinct disease syndromes in mice. A multidisciplinary approach was used to examine the events occurring in situ. The CB4-P variant induced acute pancreatitis, followed by repair of the exocrine tissues, while the CB4-V variant induced chronic pancreatitis, characterized by extensive destruction of the exocrine tissues. Since CB4-V replicated more efficiently than CB4-P in vivo, the more extensive tissue injury associated with CB4-V infection could be explained as the result of a higher level of viral replication. However, the fact that CB4-V replicated more efficiently in a mouse strain that survives infection than in a strain that succumbs to infection suggests that immune-mediated mechanisms as well as viral cytolysis may contribute to pancreatic tissue injury. To address the role of the immune system in virus-induced pancreatitis, the cell types within the inflammatory infiltrate were analyzed by flow cytometry. B cells (34 to 75%) were the most abundant, followed by T cells (10 to 30%), natural killer cells (4 to 8%), and macrophages (0 to 6%). Recruitment (and perhaps proliferation) of B and T cells to the pancreatic tissues was influenced by viral strain. Differential recruitment of T and B cells may reflect altered antigenic sites between CB4-P and CB4-V. The viral sequence that affected T- and B-cell recruitment was identified as a threonine residue at position 129 of the VP1 capsid protein.
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PMID:Differential recruitment of B and T cells in coxsackievirus B4-induced pancreatitis is influenced by a capsid protein. 934 27

Coxsackievirus infection causes severe pancreatitis and myocarditis in humans, often leading to death in young or immunocompromised individuals. In susceptible strains of mice, coxsackievirus strain CB4 causes lethal hypoglycemia. To investigate the potential of gamma interferon (IFN-gamma) in protection and clearance of the viral infection, IFN-gamma knockout mice and transgenic (Tg) mice specifically expressing IFN-gamma in their pancreatic beta cells were infected with CB4. Lack of IFN-gamma in mice normally resistant to CB4-mediated disease resulted in hypoglycemia and rapid death. However, expression of IFN-gamma in the beta cells of Tg mice otherwise susceptible to lethal infection allowed for survival and protected them from developing the accompanying hypoglycemia. While all the mice had high levels of viral replication in their pancreata and comparable tissue pathology following viral infection, the Tg mice had significantly lower levels of virus at the peak of infection, significantly higher numbers of activated macrophages before and after infection, and less damage to their acinar tissue. Additionally, despite having increased levels of inducible nitric oxide synthetase (iNOS) expression, treatment of Tg mice with the iNOS inhibitor aminoguanidine did not alter the level of protection afforded by IFN-gamma expression. In conclusion, IFN-gamma protects from lethal coxsackievirus infection by activating macrophages in an iNOS-independent manner.
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PMID:Protection from lethal coxsackievirus-induced pancreatitis by expression of gamma interferon. 997 52

Coxsackieviruses are important human pathogens, frequently causing myocarditis, pancreatitis, and a variety of less severe diseases. B lymphocytes appear central to the interaction between these viruses and their mammalian hosts, because agammaglobulinemic humans, genetically incapable of antibody production, are susceptible to chronic infections by coxsackieviruses and related enteroviruses, such as poliovirus and echovirus. However, recent studies show that Type B coxsackievirus (CVB) infects B lymphocytes soon after infection, suggesting the possibility that these cells may play some role in virus dissemination and/or that the virus may be able to modulate the host immune response. We analyzed the role of B lymphocytes in CVB infection and confirmed that CVB infects B lymphocytes, and extended these findings to show that this is a productive infection involving approximately 1 to 10% of the cells; however, infectious center assays show that other splenocytes are infected at approximately the same frequency. Virus is readily detectable by in situ hybridization in the spleen of immunocompetent mice but is difficult to detect in mice deficient in B cells (BcKO mice), consistent with much of the splenic signal being the result of B cell infection. Surprisingly, given the extent of their infection, B cells express barely detectable levels of the murine coxsackievirus-adenovirus receptor (mCAR), suggesting that another means of cell entry may be used. We found no evidence of B cell depletion following CVB infection, indicating that this is not the explanation for the transient immunosuppression previously reported. Virus replication and dissemination are slightly delayed in BcKO mice, consistent with B cells' playing a role as an important early target of infection and/or a means to distribute the virus to many tissues. In addition, we show that BcKO mice recapitulate a central feature of human agammaglobulinemia: CVB establishes chronic infection in a variety of organs (heart, liver, brain, kidney, lung, pancreas, spleen). In most of these tissues the viral titers remain high (10(5)-10(8) plaque forming units (pfu) per gram of tissue) for the life of the mouse, and in several there is severe pathology, particularly severe myocardial fibrosis with ventricular dilation, reminiscent of the dilated cardiomyopathy seen in humans with chronic enteroviral myocarditis. Transfer of B and/or T cells from non-immune mice had no discernible effect, whereas equivalent transfers from immune mice often resulted in transient or permanent disappearance of detectable CVB.
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PMID:The role of B lymphocytes in coxsackievirus B3 infection. 1051 3

An association of enterovirus infection with endemic cardiomyopathy (Keshan disease [KD]) and outbreaks of myocarditis in selenium-deficient rural areas of southwestern China has been established. Enteroviruses have been isolated from patients with KD or during outbreaks of myocarditis in last two decades. Six of these isolates grew readily in cell lines (Vero or HEp-2) and were investigated by a novel molecular typing method apart from serotyping and pathogenicity. A neutralization assay identified two isolates from KD as coxsackievirus serotype B2 (CVB2) and two isolates from myocarditis as coxsackievirus serotype B6 (CVB6) but failed to type the remaining two isolates, also from myocarditis. Direct nucleotide sequencing of reverse transcription-PCR products amplified from the 5' nontranslated region (5'NTR) of these viruses confirmed that they belong to a phylogenetic cluster consisting of coxsackie B-like viruses, including some echovirus serotypes. Sequence analysis of the coding region for viral capsid protein VP1 showed that two isolates serotyped as CVB2 have the highest amino acid sequence homology with CVB2 and that the remaining four isolates, two CVB6 and the two unknown serotypes, are most closely related to the sequence of CVB6. Sequences among these isolates varied from 82.3 to 99% in the 5'NTR and from 69 to 99% in VP1, indicating no cross contamination. The pathogenicity of these viruses in adult and suckling mice was assessed. None caused pathologic changes in the hearts of adult MF-1 or SWR mice, although pancreatitis was evident. However, the four CVB6-like viruses caused death in suckling mice, similar to a virulent coxsackievirus group B3 laboratory strain. In conclusion, the sequence data confirm that coxsackievirus group B serotypes are predominant in the region in which KD is endemic and may be the etiological agents in outbreaks of myocarditis. VP1 genotyping of enteroviruses is accurate and reliable. Animal experiments indicate that isolates may differ in pathogenicity.
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PMID:Characterization of enterovirus isolates from patients with heart muscle disease in a selenium-deficient area of China. 1101 60

Group B coxsackieviruses (CVBs) are a major cause of viral myocarditis and pancreatitis in humans and produce a similar pattern of disease in inbred strains of mice. As there are six strains of CVBs, individuals can be infected with multiple serotypes. This raises the possibility of antibody enhancement of infectivity (AEI) by cross-reactive but non-neutralizing antibody to a different strain from a prior infection. To determine whether AEI plays a role in coxsackievirus pathogenesis, an in vitro system using the murine macrophage cell line J774.1 was tested for enhanced infection when incubated with CVB3 plus anti-CVB2 antibody. Yields of virus were found to increase by 10-50-fold and the percentage of infected cells increased proportionately. The effect was Fc-mediated as F(ab')2 fragments of the antibody could not mediate the effect. To determine whether AEI could also be demonstrated in vivo CVB3 was injected into 5-week-old mice together with mouse polyclonal anti-CVB2. Controls included mice injected with PBS or CVB3 alone. Results showed that the titres of virus in tissues of animals injected with virus plus antibody were 1-2 logs higher than when virus was injected alone. This was accompanied by greater histopathological damage, particularly in the heart. These results have implications for human disease as infection with multiple strains likely occurs during the lifetime of an individual.
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PMID:Enhancement of coxsackievirus B3 infection by antibody to a different coxsackievirus strain. 1180 28

Infections with the group B coxsackieviruses either can be asymptomatic or can lead to debilitating chronic diseases. To elucidate the mechanism by which these viruses cause chronic disease, we developed a mouse model of chronic pancreatitis by using a virulent variant of coxsackievirus B4, CVB4-V. Infection with CVB4-V results in an early, severe pancreatitis, which can lead to mortality or progress to chronic pancreatitis. Chronic pancreatitis, in this model, is due to immunopathological mechanisms. We investigated whether interleukin-12 (IL-12) could modulate the outcome of CVB4-V infection. Eighty-five percent of the infected mice treated with 500 ng of IL-12 survived, whereas all untreated mice succumbed. To understand the mechanism underlying the beneficial effect of IL-12, we investigated the role of gamma interferon (IFN-gamma). Three lines of evidence suggest that the protective effect of IL-12 is due to IFN-gamma. First, administration of IL-12 increased the production of endogenous IFN-gamma in CVB4-V-infected mice. Both NK and NKT cells were identified as the source of IFN-gamma. Second, IFN-gamma knockout mice treated with IL-12 succumbed to infection with CVB4-V. Third, wild-type mice treated with IFN-gamma survived infection with CVB4-V. Due to the antiviral effects of IFN-gamma, we examined whether IL-12 treatment affected viral replication. Administration of IL-12 did not decrease viral replication in the pancreas, but it did prevent extensive tissue damage and the subsequent development of chronic pancreatitis. The data suggest that IL-12 treatment during CVB4-V infection is able to suppress the immunopathological mechanisms that lead to chronic disease.
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PMID:Exogenous interleukin-12 protects against lethal infection with coxsackievirus B4. 1285 96

Long-term, heavy alcohol consumption is associated with both acute and chronic pancreatitis. Progression of pancreatitis may lead to multiple comorbidities including maldigestion, diabetes, and pancreatic cancer. Understanding the underlying molecular, biochemical, and cellular mechanisms by which alcohol ingestion leads to the development of pancreatitis may help to develop strategies for the treatment and prevention of the disease. The National Institute on Alcohol Abuse and Alcoholism and the Office of Rare Diseases of National Institutes of Health sponsored a satellite symposium on "Mechanisms of Alcoholic Pancreatitis" at the annual meeting of the American Pancreatic Association, Chicago, IL, November 2002. For this symposium, 8 speakers were invited to address the following issues: (1) epidemiology of alcoholic pancreatitis; (2) pathophysiology of alcoholic pancreatitis; (3) animal models of alcoholic pancreatitis--roles of cholecystokinin (CCK) and viral infections; (4) alcohol and zymogen activation in the pancreatic acinar cell; (5) role of alcohol metabolism in alcoholic pancreatitis; (6) pancreatic stellate cell activation in alcoholic pancreatitis; and (7) genetic predisposition to alcoholic chronic pancreatitis. It was concluded that alcohol abuse is a major contributory factor to the development of both acute and chronic pancreatitis. The injurious effects of ethanol on the pancreas may be mediated through (1) sensitization of acinar cells to CCK-induced premature activation of zymogens; (2) potentiation of the effect of CCK on the activation of transcription factors, nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1); (3) generation of toxic metabolites such as acetaldehyde and fatty acid ethyl esters; (4) sensitization of the pancreas to the toxic effects of coxsackievirus B3; and (5) activation of pancreatic stellate cells by acetaldehyde and oxidative stress and subsequent increased production of collagen and other matrix proteins.
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PMID:Mechanisms of alcoholic pancreatitis. Proceedings of a conference. Chicago, Illinois, USA, November 2002. 1457 87

Pancreatitis is clearly associated with alcohol abuse, but only a relatively small percentage of people who abuse alcohol develops obvious pancreatitis. These observations have led to the concept that the development of alcoholic pancreatitis requires cofactors. Although diet and smoking have been studied, a clear cofactor has not been identified. The study results presented in this paper were obtained to determine whether viral infection of the pancreas would be a cofactor for alcoholic pancreatitis similar to the role of hepatitis virus infections in the development of alcoholic liver disease. To test this hypothesis, mice were fed ethanol with a liquid diet protocol and infected with coxsackievirus B3 (CVB3). It was found that consumption of alcohol alone did not result in pancreatitis as determined by serum levels of amylase or histologic changes in the pancreas. Two strains of CVB3 that are tropic for the pancreas were used; a virulent and an avirulent strain. Infection of alcohol-fed animals with the virulent CVB3 strain 28 resulted in a more severe pancreatitis than the pancreatitis noted in control animals. Alcohol-fed mice infected with the avirulent strain (GA) showed severe pancreatitis, whereas the infection of control mice did not result in obvious pathologic effects in the pancreas. This model allows mechanistic studies to define the role of viral infection as a cofactor for alcoholic pancreatitis.
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PMID:Animal model of alcoholic pancreatitis: role of viral infections. 1457 91


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