Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion... more Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion and proliferation whose tightly regulated expression in B lymphocytes is likely important for their normal development and/or function. To examine the physiologic role of mouse CD43 (mCD43) in vivo, we exploited transgenic (TG) mice whose developmental expression of mCD43 was extended during B cell differentiation so that mCD43 was now expressed on peripheral B cells. Despite having increased B cells, localization of lymphocytes in the TG spleens appeared normal by immunocytochemistry with anti-CD4, anti-CD8, and anti-B220 mAbs. However, the numbers of splenic germinal centers and the resting sera Ig levels were decreased in the TG mice compared with littermate controls. TG mice had decreased humoral responses to the T-dependent Ags keyhole limpet hemocyanin and OVA, as well as reduced Ag-specific B cell numbers. In contrast, in vitro LPS stimulation of purified TG or control B cells re...
Although fibroblasts are traditionally described as static cells providing framework and support ... more Although fibroblasts are traditionally described as static cells providing framework and support for tissues, there is an accumulating body of evidence showing that fibroblasts are a dynamic cell type which exist in functionally and morphologically heterogeneous subpopulations. Fibroblast subsets have been shown to play a critical role in the production and regulation of extracellular matrix components, in wound repair and regeneration, and have been implicated in the pathogenesis of fibrotic conditions. We have reviewed the evidence supporting heterogeneity of fibroblasts from pulmonary, periodontal, and dermal tissues. In addition, we will explore the role fibroblast subpopulations may play in the complex process of wound repair and regeneration.
Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologou... more Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologous to the transforming gene of avian myelocytomatosis virus, resides on mouse chromosome 15 and in many plasmacytomas is translocated to the antibody heavy chain gene locus on chromosome 12. The transcriptional orientation of the translocated c-myc sequence is opposite the orientation of the adjacent Calpha gene that
Since mouse keratinocytes are tolerogenic antigen presenting cells for T cell activation, the exp... more Since mouse keratinocytes are tolerogenic antigen presenting cells for T cell activation, the expression of second signal molecules such as B7-1 was targeted to epidermal keratino-cytes (KC) in vivo in transgenic mice. The expression vector
The mouse liver contains a group of 10-12 dif- ferent tissue-specific mRNAs, each present at an a... more The mouse liver contains a group of 10-12 dif- ferent tissue-specific mRNAs, each present at an average concen- tration of 12,000-15,000 copies per cell (Hastie, N. D. & Bishop, J. 0. (1976) Cell 9, 761-774). We have determined, by translation in vitro, that these mRNAs are developmentally regulated in the liver. We have also used specific cloned probes to quantitate the developmental time course of expression of five different abun- dant liver mRNAs. We have found that there are at least three periods during liver development when specific abundant mRNAs are first detectable: prior to 14 days postconception, at birth, and during the onset of sexual maturity. These results indicate that all the members of this mRNA group are not under common devel- opmental regulation. One of the abundant liver mRNAs (p54 mRNA) increases more than 1000-fold in the liver 1 day before birth. We discuss factors that may be involved in the develop- mental regulation of expression of the genes encoding t...
We have combined three different methods, deletion mapping of T-cell lines, field-inversion gel e... more We have combined three different methods, deletion mapping of T-cell lines, field-inversion gel electrophoresis, and the restriction mapping of a cosmid clone, to construct a physical map of the murine T-cell receptor flchain gene family. We have mapped 19 variable (Va) gene segments and the two clusters of diversity (Do) and joining (p) gene segments and constant (Cp) genes. These members of the fl-chain gene family span %450 kilobases of DNA, excluding one potential gap in the DNA fragment alignments. The antigen-binding T-cell receptors are encoded in mice by two families of genes-the a-chain gene located on murine chromosome 14 and the p-chain genes on chromosome 6 (1-5). The p chains are encoded by a constant gene (C,3) and variable (1,9), diversity (D.8), and joining (4) gene segments, which rearrange and are joined together at the DNA level during T-cell differentiation to generate an assembled Vat gene (6-10). The ,-chain gene family of murine T-cell receptors contains just ...
Susceptibility of mice to the induction of pulmonary fibrosis by bleomycin sulfate is inbred stra... more Susceptibility of mice to the induction of pulmonary fibrosis by bleomycin sulfate is inbred strain dependent, with C57BL/6 mice exhibiting high sensitivity to the drug and BALB/c mice demonstrating a resistant phenotype. The lungs of bleomycin treated C57BL/6J and BALB/cBy mice were analyzed for their mRNA expression level of a panel of cytokines using a semi-quantitative polymerase chain reaction (SQ-PCR) assay. Transforming growth factor-beta 1 (TGF-beta 1) mRNA was found to increase sevenfold by 5 days after bleomycin treatment of C57BL/6J (sensitive) mice. BALB/cBy (resistant) animals demonstrated a lower level of TGF-beta 1 mRNA induction, approximately threefold, after bleomycin administration. Analysis of interleukin-1 beta (IL-1 beta) mRNA levels also revealed a difference between the two strains, with BALB/cBy mice expressing approximately fourfold higher IL-1 beta mRNA levels than C57BL/6J mice. This result suggested possible protection by IL-1 beta. Analysis of (C57BL/6JxBALB/cBy)F1 hybrids, which are shown in this report to be sensitive to bleomycin-induced fibrosis, revealed a high IL-1 beta mRNA level, similar to that in the resistant parent. Thus, the observed strain variation in the level of IL-1 beta mRNA is not associated with differences in susceptibility to the induction of pulmonary fibrosis. In contrast, strain variation in interleukin-6 (IL-6) mRNA levels was observed that was completely concordant with the segregation of susceptibility phenotypes between the parental and F1 strains. This result indicates a possible association between sensitivity to bleomycin-induced fibrosis and inducibility of IL-6 mRNA upon drug treatment. Analysis of TGF-beta 2, interferon-gamma, interleukin-2, interleukin-3, and interleukin-4 (IL-4) mRNA showed no detectable strain variation in steady state mRNA levels in the lung as a consequence of bleomycin treatment. In contrast, the level of IL-4 receptor mRNA was induced to a higher degree in both sensitive groups (C57BL/6J and F1) than in resistant mice (BALB/cBy). Therefore, modulation of the IL-4 response, not at the level of IL-4 but through regulation of the IL-4 receptor, may play a role in pulmonary fibrogenesis.
The human prostate-specific antigen (PSA) and glandular kallikrein-1 (hGK-1, also known as hK2) g... more The human prostate-specific antigen (PSA) and glandular kallikrein-1 (hGK-1, also known as hK2) genes are tandemly located on chromosome 19, separated by a 12-kb intergenic region. The coordinate regulation of these two genes suggests the presence of common regulatory elements responsible for tissue specificity and/or levels of expression within this region. To identify such regulatory elements, we generated two sets of transgenic mice, which had incorporated either the PSA gene alone or together with the intergenic region. Both sets of transgenics exhibit remarkably prostate-specific expression of the transgene. However, the presence of the intergenic region abrogates the dependence on high PSA gene copy-number for high levels of PSA expression. This suggests the existence of a positive regulatory element in the intergenic region. By using a previously identified distal enhancer element of PSA (termed DEE 1) as a probe, we identified a cross-hybridizing fragment, which we termed DE...
Transgenic (Tg) mice whose epidermal keratinocytes constitutively overexpress either B7-1 (CD80) ... more Transgenic (Tg) mice whose epidermal keratinocytes constitutively overexpress either B7-1 (CD80) or B7-2 (CD86) exhibited exaggerated cutaneous delayed type hypersensitivity (DTH) to haptens compared to non-Tg mice. To determine whether enhanced DTH in these Tg mice is seen in response to cutaneous fungal infections, a primary infection with Candida albicans was established by inoculating this organism on the occluded skin of Tg and non-Tg mice. These infections resolved 7 days after removal of occlusive dressing in all three groups of mice, without evidence of exaggerated inflammation in either the Tg or non-Tg mice. Only B7-2 Tg mice developed enhanced Th1-lymphocyte-mediated immune responses to C. albicans antigens after resolving this infection: enhanced footpad swelling in response to intradermal C. albicans antigens, enhanced production of mRNA encoding Th1 lymphokines in draining lymph nodes, and increased gamma interferon secreted into culture supernatants by lymph node T ly...
B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs tha... more B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase p...
Proceedings of the National Academy of Sciences of the United States of America, Jan 17, 1995
Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein... more Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apop...
Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologou... more Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologous to the transforming gene of avian myelocytomatosis virus, resides on mouse chromosome 15 and in many plasmacytomas is translocated to the antibody heavy chain gene locus on chromosome 12. The transcriptional orientation of the translocated c-myc sequence is opposite the orientation of the adjacent C alpha gene that codes for the heavy chain of immunoglobulin A. The translocated c-myc sequence is not the same oncogene detected in urine plasmacytomas by the NIH-3T3 cell transformation assay.
The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), pu... more The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), putative inhibitor of neutrophil elastase, and contrapsin, an inhibitor in vitro of trypsinlike proteases. We have shown by nucleotide sequence analysis that these two inhibitors are related (R. E. Hill, P. H. Shaw, P. A. Boyd, H. Baumann, and N. D. Hastie, Nature (London) 311:175-177, 1984). Here, we show that the contrapsin and alpha 1-PI genes are members of two different multigene families, each containing at least three genes in mice and rats. We established the chromosomal locations of these genes by analyzing the segregation of restriction fragment length polymorphisms in recombinant inbred mouse strains. These experiments show that the multiple genes in each family are clustered and that the two gene families are closely linked on chromosome 12. Thus the genes for contrapsin and alpha 1-PI are likely to have evolved by duplication of a common ancestral gene. The contrapsin multigen...
Platelet-derived growth factor (PDGF) has been previously shown to be homologous to the transform... more Platelet-derived growth factor (PDGF) has been previously shown to be homologous to the transforming gene of simian sarcoma virus (v-sis), and inappropriate expression of the cellular counterpart of the v-sis gene (c-sis) has been implicated in the generation of mesenchymal tumors. The U-2 OS human osteosarcoma line was shown to contain multiple c-sis transcripts. Immunoprecipitation experiments with antiserum to PDGF identified a variety of polypeptides ranging in size from 18,000 to 165,000 daltons that were immunoprecipitated specifically from U-2 OS cell extracts. The osteosarcoma also was shown to secrete a 29,000-dalton protein having the serological and structural characteristics of PDGF.
... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Alla... more ... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Allan, Alicia Linares, Valentina N. Suchkova, Gennady Sukhikh, Gennady Grechko,Yuri Blidchenko, Eugenia A ... Heufelder, AE; Smith, TJ; Gorman, CA; Bahn, RSJ Clin. ...
... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Alla... more ... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Allan, Alicia Linares, Valentina N. Suchkova, Gennady Sukhikh, Gennady Grechko,Yuri Blidchenko, Eugenia A ... Heufelder, AE; Smith, TJ; Gorman, CA; Bahn, RSJ Clin. ...
Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion... more Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion and proliferation whose tightly regulated expression in B lymphocytes is likely important for their normal development and/or function. To examine the physiologic role of mouse CD43 (mCD43) in vivo, we exploited transgenic (TG) mice whose developmental expression of mCD43 was extended during B cell differentiation so that mCD43 was now expressed on peripheral B cells. Despite having increased B cells, localization of lymphocytes in the TG spleens appeared normal by immunocytochemistry with anti-CD4, anti-CD8, and anti-B220 mAbs. However, the numbers of splenic germinal centers and the resting sera Ig levels were decreased in the TG mice compared with littermate controls. TG mice had decreased humoral responses to the T-dependent Ags keyhole limpet hemocyanin and OVA, as well as reduced Ag-specific B cell numbers. In contrast, in vitro LPS stimulation of purified TG or control B cells re...
Although fibroblasts are traditionally described as static cells providing framework and support ... more Although fibroblasts are traditionally described as static cells providing framework and support for tissues, there is an accumulating body of evidence showing that fibroblasts are a dynamic cell type which exist in functionally and morphologically heterogeneous subpopulations. Fibroblast subsets have been shown to play a critical role in the production and regulation of extracellular matrix components, in wound repair and regeneration, and have been implicated in the pathogenesis of fibrotic conditions. We have reviewed the evidence supporting heterogeneity of fibroblasts from pulmonary, periodontal, and dermal tissues. In addition, we will explore the role fibroblast subpopulations may play in the complex process of wound repair and regeneration.
Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologou... more Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologous to the transforming gene of avian myelocytomatosis virus, resides on mouse chromosome 15 and in many plasmacytomas is translocated to the antibody heavy chain gene locus on chromosome 12. The transcriptional orientation of the translocated c-myc sequence is opposite the orientation of the adjacent Calpha gene that
Since mouse keratinocytes are tolerogenic antigen presenting cells for T cell activation, the exp... more Since mouse keratinocytes are tolerogenic antigen presenting cells for T cell activation, the expression of second signal molecules such as B7-1 was targeted to epidermal keratino-cytes (KC) in vivo in transgenic mice. The expression vector
The mouse liver contains a group of 10-12 dif- ferent tissue-specific mRNAs, each present at an a... more The mouse liver contains a group of 10-12 dif- ferent tissue-specific mRNAs, each present at an average concen- tration of 12,000-15,000 copies per cell (Hastie, N. D. & Bishop, J. 0. (1976) Cell 9, 761-774). We have determined, by translation in vitro, that these mRNAs are developmentally regulated in the liver. We have also used specific cloned probes to quantitate the developmental time course of expression of five different abun- dant liver mRNAs. We have found that there are at least three periods during liver development when specific abundant mRNAs are first detectable: prior to 14 days postconception, at birth, and during the onset of sexual maturity. These results indicate that all the members of this mRNA group are not under common devel- opmental regulation. One of the abundant liver mRNAs (p54 mRNA) increases more than 1000-fold in the liver 1 day before birth. We discuss factors that may be involved in the develop- mental regulation of expression of the genes encoding t...
We have combined three different methods, deletion mapping of T-cell lines, field-inversion gel e... more We have combined three different methods, deletion mapping of T-cell lines, field-inversion gel electrophoresis, and the restriction mapping of a cosmid clone, to construct a physical map of the murine T-cell receptor flchain gene family. We have mapped 19 variable (Va) gene segments and the two clusters of diversity (Do) and joining (p) gene segments and constant (Cp) genes. These members of the fl-chain gene family span %450 kilobases of DNA, excluding one potential gap in the DNA fragment alignments. The antigen-binding T-cell receptors are encoded in mice by two families of genes-the a-chain gene located on murine chromosome 14 and the p-chain genes on chromosome 6 (1-5). The p chains are encoded by a constant gene (C,3) and variable (1,9), diversity (D.8), and joining (4) gene segments, which rearrange and are joined together at the DNA level during T-cell differentiation to generate an assembled Vat gene (6-10). The ,-chain gene family of murine T-cell receptors contains just ...
Susceptibility of mice to the induction of pulmonary fibrosis by bleomycin sulfate is inbred stra... more Susceptibility of mice to the induction of pulmonary fibrosis by bleomycin sulfate is inbred strain dependent, with C57BL/6 mice exhibiting high sensitivity to the drug and BALB/c mice demonstrating a resistant phenotype. The lungs of bleomycin treated C57BL/6J and BALB/cBy mice were analyzed for their mRNA expression level of a panel of cytokines using a semi-quantitative polymerase chain reaction (SQ-PCR) assay. Transforming growth factor-beta 1 (TGF-beta 1) mRNA was found to increase sevenfold by 5 days after bleomycin treatment of C57BL/6J (sensitive) mice. BALB/cBy (resistant) animals demonstrated a lower level of TGF-beta 1 mRNA induction, approximately threefold, after bleomycin administration. Analysis of interleukin-1 beta (IL-1 beta) mRNA levels also revealed a difference between the two strains, with BALB/cBy mice expressing approximately fourfold higher IL-1 beta mRNA levels than C57BL/6J mice. This result suggested possible protection by IL-1 beta. Analysis of (C57BL/6JxBALB/cBy)F1 hybrids, which are shown in this report to be sensitive to bleomycin-induced fibrosis, revealed a high IL-1 beta mRNA level, similar to that in the resistant parent. Thus, the observed strain variation in the level of IL-1 beta mRNA is not associated with differences in susceptibility to the induction of pulmonary fibrosis. In contrast, strain variation in interleukin-6 (IL-6) mRNA levels was observed that was completely concordant with the segregation of susceptibility phenotypes between the parental and F1 strains. This result indicates a possible association between sensitivity to bleomycin-induced fibrosis and inducibility of IL-6 mRNA upon drug treatment. Analysis of TGF-beta 2, interferon-gamma, interleukin-2, interleukin-3, and interleukin-4 (IL-4) mRNA showed no detectable strain variation in steady state mRNA levels in the lung as a consequence of bleomycin treatment. In contrast, the level of IL-4 receptor mRNA was induced to a higher degree in both sensitive groups (C57BL/6J and F1) than in resistant mice (BALB/cBy). Therefore, modulation of the IL-4 response, not at the level of IL-4 but through regulation of the IL-4 receptor, may play a role in pulmonary fibrogenesis.
The human prostate-specific antigen (PSA) and glandular kallikrein-1 (hGK-1, also known as hK2) g... more The human prostate-specific antigen (PSA) and glandular kallikrein-1 (hGK-1, also known as hK2) genes are tandemly located on chromosome 19, separated by a 12-kb intergenic region. The coordinate regulation of these two genes suggests the presence of common regulatory elements responsible for tissue specificity and/or levels of expression within this region. To identify such regulatory elements, we generated two sets of transgenic mice, which had incorporated either the PSA gene alone or together with the intergenic region. Both sets of transgenics exhibit remarkably prostate-specific expression of the transgene. However, the presence of the intergenic region abrogates the dependence on high PSA gene copy-number for high levels of PSA expression. This suggests the existence of a positive regulatory element in the intergenic region. By using a previously identified distal enhancer element of PSA (termed DEE 1) as a probe, we identified a cross-hybridizing fragment, which we termed DE...
Transgenic (Tg) mice whose epidermal keratinocytes constitutively overexpress either B7-1 (CD80) ... more Transgenic (Tg) mice whose epidermal keratinocytes constitutively overexpress either B7-1 (CD80) or B7-2 (CD86) exhibited exaggerated cutaneous delayed type hypersensitivity (DTH) to haptens compared to non-Tg mice. To determine whether enhanced DTH in these Tg mice is seen in response to cutaneous fungal infections, a primary infection with Candida albicans was established by inoculating this organism on the occluded skin of Tg and non-Tg mice. These infections resolved 7 days after removal of occlusive dressing in all three groups of mice, without evidence of exaggerated inflammation in either the Tg or non-Tg mice. Only B7-2 Tg mice developed enhanced Th1-lymphocyte-mediated immune responses to C. albicans antigens after resolving this infection: enhanced footpad swelling in response to intradermal C. albicans antigens, enhanced production of mRNA encoding Th1 lymphokines in draining lymph nodes, and increased gamma interferon secreted into culture supernatants by lymph node T ly...
B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs tha... more B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase p...
Proceedings of the National Academy of Sciences of the United States of America, Jan 17, 1995
Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein... more Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apop...
Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologou... more Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologous to the transforming gene of avian myelocytomatosis virus, resides on mouse chromosome 15 and in many plasmacytomas is translocated to the antibody heavy chain gene locus on chromosome 12. The transcriptional orientation of the translocated c-myc sequence is opposite the orientation of the adjacent C alpha gene that codes for the heavy chain of immunoglobulin A. The translocated c-myc sequence is not the same oncogene detected in urine plasmacytomas by the NIH-3T3 cell transformation assay.
The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), pu... more The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), putative inhibitor of neutrophil elastase, and contrapsin, an inhibitor in vitro of trypsinlike proteases. We have shown by nucleotide sequence analysis that these two inhibitors are related (R. E. Hill, P. H. Shaw, P. A. Boyd, H. Baumann, and N. D. Hastie, Nature (London) 311:175-177, 1984). Here, we show that the contrapsin and alpha 1-PI genes are members of two different multigene families, each containing at least three genes in mice and rats. We established the chromosomal locations of these genes by analyzing the segregation of restriction fragment length polymorphisms in recombinant inbred mouse strains. These experiments show that the multiple genes in each family are clustered and that the two gene families are closely linked on chromosome 12. Thus the genes for contrapsin and alpha 1-PI are likely to have evolved by duplication of a common ancestral gene. The contrapsin multigen...
Platelet-derived growth factor (PDGF) has been previously shown to be homologous to the transform... more Platelet-derived growth factor (PDGF) has been previously shown to be homologous to the transforming gene of simian sarcoma virus (v-sis), and inappropriate expression of the cellular counterpart of the v-sis gene (c-sis) has been implicated in the generation of mesenchymal tumors. The U-2 OS human osteosarcoma line was shown to contain multiple c-sis transcripts. Immunoprecipitation experiments with antiserum to PDGF identified a variety of polypeptides ranging in size from 18,000 to 165,000 daltons that were immunoprecipitated specifically from U-2 OS cell extracts. The osteosarcoma also was shown to secrete a 29,000-dalton protein having the serological and structural characteristics of PDGF.
... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Alla... more ... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Allan, Alicia Linares, Valentina N. Suchkova, Gennady Sukhikh, Gennady Grechko,Yuri Blidchenko, Eugenia A ... Heufelder, AE; Smith, TJ; Gorman, CA; Bahn, RSJ Clin. ...
... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Alla... more ... FIBROSIS, AND THE CONCEPT OF FIBROBLAST HETEROGENEITY Richard K. Barth, Clare M. Baecher-Allan, Alicia Linares, Valentina N. Suchkova, Gennady Sukhikh, Gennady Grechko,Yuri Blidchenko, Eugenia A ... Heufelder, AE; Smith, TJ; Gorman, CA; Bahn, RSJ Clin. ...
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