ABSTRACT
Group B coxsackieviruses (CVBs) have a well-established association with type 1 diabetes but the mechanism of depletion of beta-cell mass following infection has not yet been defined. In this report we show that the major difference in pathogenesis between the E2 diabetogenic strain of CVB4 and the prototypic JVB strain in SJL mice is not in tropism for islet cells but in the degree of damage inflicted on the exocrine pancreas and the resulting capacity for regeneration of both acinar and islet tissue by the host. Both strains replicated to a high titre in acinar tissue up to day 3 post-infection (p.i.), while the islets of Langerhans were largely spared. However, the pancreas in the JVB-infected animals then regenerated and many small islets were seen throughout the tissue by day 10 p.i. In contrast, the acinar tissue in E2-infected mice became increasingly necrotic until all that remained by day 21 p.i. were large islets containing varying numbers of dead cells, caught up in strands of connective tissue. Surviving beta cells were found to synthesize little insulin, although islet amyloid polypeptide was detected and glucagon synthesis in alpha cells appeared normal or enhanced. Our results suggest that the key to CVB-E2-induced damage lies in the exocrine tissue and prevention of islet neogenesis rather than from direct effects on existing islets.
Subject(s)
Diabetes Mellitus, Type 1/etiology , Enterovirus B, Human/pathogenicity , Animals , Autoimmunity , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/virology , Enterovirus B, Human/classification , Glucose/metabolism , Glucose Transporter Type 2 , Homeostasis , Immune System/physiology , Male , Mice , Monosaccharide Transport Proteins/analysis , Species Specificity , Virus ReplicationABSTRACT
Pulmonary metastases from uterine leiomyomata are extremely rare and unpredictable, despite the high frequency of uterine leiomyoma. Review of the literature reveals seven previous examples of pulmonary metastasis from uterine leiomyomata; other cases may exist, but they were not considered because there was little evidence to distinguish them from leiomyosarcoma. The case we report is unusual in: 1) its prolonged course of 21 years, 2) its lack of pulmonary symptoms, despite extensive multiple nodules; and 3) the cystic change of the multiple lesions, which mimicked cystic lung disease.
