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D Gu

Publications and source records attributed to D Gu.

28 records · Page 2Linked to original sources
PubMed1995

Treatment of IFN-gamma transgenic mice with anti-IFN-gamma reveals the remodeling capacity of the adult pancreas.

Pancreatic expression of gamma-interferon (IFN-gamma) initiates a cascade of pathogenic changes that include pancreatic inflammation, islet cell destruction, hyperglycemia, and islet regeneration. In this study, we explore the developmental plasticity of the adult pancreas and particularly its ability to return to normoglycemia and to remodel itself from an advanced pathogenic state. This was approached by treating adult transgenic mice with a pulse of anti-IFN-gamma antibody and determining the functional and morphological status of the pancreas. We demonstrated that anti-IFN-gamma antibody administration led to the reduction of hyperglycemic blood glucose levels in transgenic mice. We also observed that the pancreas returned from a profoundly perturbed state toward normality. Analysis of the mitotic index indicated that cell proliferation previously associated with islet cell regeneration was greatly reduced after anti-IFN-gamma administration. Our results highlight the ability of the adult pancreas to remodel itself and return from a complex pathological state to normalcy once the trophic signal inducing this pathology is removed. These data also suggest that anti-IFN-gamma administration may have important clinical implications for treatment of chronic pancreatitis in humans.

Animals↗
PubMed1995

Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factor-beta 1.

Transgenic mice expressing transforming growth factor-beta 1 (TGF-beta 1) in the pancreatic beta-islet cells directed by human insulin promoter were produced to study in vivo effects of TGF-beta 1. Fibroblast proliferation and abnormal deposition of extracellular matrix were observed from birth onward, finally replacing almost all the exocrine pancreas. Cellular infiltrates comprising macrophages and neutrophils were also observed. Plasminogen activator inhibitor was induced in the transgenic pancreas as well as fibronectin and laminin, partly explaining accumulation of extracellular matrix. TGF-beta 1 inhibited proliferation of acinar cells in vivo as evidenced by decreased bromodeoxyuridine incorporation. Development of pancreatic islets was dysregulated, resulting in small islet cell clusters without formation of normal adult islets; however, the overall islet cell mass was not significantly diminished. Additional transgenic lines with less pronounced phenotypes had less expression of TGF-beta 1 transgene. These findings suggest that TGF-beta 1 might be a mediator of diseases associated with extracellular matrix deposition such as chronic pancreatitis, and this mouse model will be useful for further analysis of the in vivo effects of TGF-beta 1, including its potential for immunosuppression.

Animals↗
PubMed1994

A transgenic model for studying islet development.

The regeneration of islet cells in a transgenic mouse strain harboring the interferon-gamma gene (IFN-gamma) linked to the insulin promoter DNA fragment (ins-IFN-gamma) is described. The regeneration follows the loss of islets by an immune response provoked by IFN-gamma and manifests in the proliferation of duct cells, the presence of progenitor cells, and the formation of buds and isletlike structure. All three types (A, B, and D) of four endocrine cells identified by immunolabeling are present. The progenitor cells express neuronal enzymes, tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD), as revealed by specific antibodies. The results indicate that the islet regeneration closely resembles the embryonic islet differentiation and serves as a model for studying islet development. The expression of neuronal enzymes by islet progenitor cells signifies yet unknown relationships to the nervous tissue. GAD, recognized as an autoantigen in insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome, may provide a clue to the mechanism of autoimmune disease.

Animals↗
PubMed1994

Postnatal anti-interferon-gamma treatment prevents pancreatic inflammation in transgenic mice with beta-cell expression of interferon-gamma.

beta-Cell-targeted expression of interferon-gamma (IFN-gamma) leads to pancreatitis and immune sensitization to beta-cells. This transgenic model is used to explore the possible role of locally produced IFN-gamma in loss of tolerance to beta-cell-specific antigens in insulin-dependent diabetes mellitus (IDDM). The aim of the present study was to test if postnatal treatment with antibodies against IFN-gamma could inhibit morphological changes in the IFN-gamma transgenic pancreas, even though the transgene is expressed during embryogenesis. Treatment with a monoclonal rat anti-mouse IFN-gamma antibody for 6 weeks, starting from 5 to 7 days of age, completely inhibited IFN-gamma-induced morphological changes in the pancreas, and only a modest inflammatory reaction emerged after prolonged treatment for 12 weeks. The lack of morphological changes may reflect the ability of nonterminally differentiated neonatal pancreatic cells to compensate for transgene-induced pathological alterations occurring in utero prior to the antibody treatment. We conclude that inflammation and altered pancreas morphology in the transgenic mice is the result of the biological actions of IFN-gamma and not by disrupted islet development due to transgene overexpression in the pancreatic beta-cells. Furthermore, our treatment schedule can serve as a model for future intervention studies in the transgenic mice, elaborating the role of IFN-gamma in localized inflammatory reactions, IDDM in particular.

Animals↗
PubMed1994

Transitional cells in the regenerating pancreas.

We examined the spectrum of intermediate cell types in the regenerating pancreas as duct epithelial cells progressed through their differentiation pathway to become mature endocrine cells. The model used was transgenic mice in which the pancreatic islets continue to grow during adulthood, unlike normal mice whose islet cell formation ceases early in life. Because the intermediate cells migrated into islet-like clusters at specific locations, we propose a specific pathway for islet development. Endocrine cells are derived from duct cells co-expressing a duct cell antigen, carbonic anhydrase II (CA II) and an exocrine enzyme, amylase. The CA II/amylase cells become amylase/endocrine intermediate cells as they exited from their lumenal location. The abluminal amylase/endocrine cells continue to differentiate to multihormone-bearing young endocrine cells, which migrated to form clusters with other differentiating endocrine cells.

Amylases↗
PubMed1993

Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice.

We have identified a model system for the study of pancreatic islet development and regeneration in transgenic mice bearing the interferon-gamma (IFN-g) gene expressed in the pancreatic islets. Previous studies showed that the locally produced IFN-g causes lymphocyte infiltration and islet cell destruction. Here we demonstrate that new islet cells are formed continuously from duct cells as evidenced by (1) the dramatic proliferation of duct cells, (2) the appearance of primitive cells and (3) their subsequent differentiation to endocrine cells. The IFN-g induced islet neogenesis is similar to embryonic islet morphogenesis and offers a model system for studying factors modulating islet development. Additionally, the duct cells occasionally transdifferentiate to gastrointestinal-like cell types and hepatocytes. These results underscore the lymphokine's ability to initiate a complex 'transdifferentiation' pathway, providing a window for understanding lineage interrelationships within a terminally differentiated structure.

Animals↗
PubMed1993

[Research on anti-idiotypic antibodies to bovine abortus].

Based on the establishment of McAbs to a local Brucella strain S85A, the McAb A7 was selected and tested as a protective one. Using A7 to immunize rabbits, we got high titer anti-idiotypic antibodies which were then proved to possess internal image by competitive inhibiting ELISA and catch blocking ELISA. The anti-idiotypic antibodies were then purified and mixed with glycerin to immunize guinea pigs and mice. The results showed that: immunized guinea pigs and mice had produced certain titer antibodies to Brucella. 79.2% of immunized guinea pigs had been protected from the challenge of 544A 4 months later from primary immunization. The number of T ANAE+ in peripheral blood of immunized mice had increased significantly compared to controls. These results suggest that the anti-idiotypic antibodies not only possess the antigen internal image but have the available immunogenicity stimulate animals producing Ab3 and make them get free from the infection.

Animals↗
PubMed1992

Regeneration of pancreatic endocrine cells in interferon-gamma transgenic mice.

We have shown that the pancreatic duct cells of IFN-gamma mouse are actively multiplying and that many duct cells differentiate to become endocrine cells. This islet regenerating process closely parallels the islet development during normal organogenesis in the fetus and offers a model for studying the cell lineage relationships of islet cells. The subject has received wide interest and intensive research in recent years. One of the noteworthy results of this study is the finding that duct cells retain the ability to proliferate and to differentiate into islet cells. Under normal conditions, duct cells do not continue to multiply or to differentiate. The results suggest that in the transgenic mice, the progenitor cells of embryonic multipotential duct cells transform into adult cells, but in the presence of appropriate signals or stimuli can resume their multipotential property. The appearance of hepatocytes indicates that while the cell proliferation observed largely results in endocrine cells, other differentiation pathways are occasionally possible. We also detect a few large cells containing albumin and alpha-fetoprotein in the periductal area. Pancreatic hepatocytes have also been observed in the rat after recovery from copper deficiency diet. Thus, the regeneration of islet cells in transgenic mice provides a model system for the study of factors modulating the growth pattern as well as the differentiation pathway.

Animals↗
PubMed1992

Diagnostic exploration of enlarged peripheral nerves in suspected cases of leprosy. An analysis of 55 cases.

In 55 cases presenting with enlarged peripheral nerves without any skin lesions, a rice grain-sized biopsy of the nerve lesion was taken for histopathological examination. As a result definitive diagnoses could be established: leprosy was diagnosed in 32 cases. In 23 cases the cause of nerve enlargement was not leprosy: post-traumatic neuritis 9, cysts 5, hypertrophic neuritis 3, nonspecific 4, neurofibroma 1, and amyloidosis 1. In all of these cases there was a deficit of the nerve function and postoperatively there were no complications. The authors, as a result of this experience, believe that surgical exploration and biopsy is a harmless diagnostic tool for establishing a definitive diagnosis of leprosy in cases presenting with enlarged peripheral nerves without any skin lesions. In 23 out of 55 such cases the nerve enlargement was proved to be other causes than leprosy.

Adolescent↗