Eugene Bauer

All Publications

• From the bench to the bedside and back: an essential journey. The Journal of investigative dermatology Bauer, E. A. 2015; 135 (3): 643–45

  View details for PubMedID 25666666

• Ruth Kimmelstiel Freinkel (1926-2014) IN MEMORIAM JOURNAL OF INVESTIGATIVE DERMATOLOGY Paller, A. S., Bauer, E. A. 2014; 134 (11): 2669–70

  View details for DOI 10.1038/jid.2014.386

  View details for Web of Science ID 000343271200002

  View details for PubMedID 25318427

• Inherited epidermolysis bullosa: Updated recommendations on diagnosis and classification JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Fine, J., Bruckner-Tuderman, L., Eady, R. A., Bauer, E. A., Bauer, J. W., Has, C., Heagerty, A., Hintner, H., Hovnanian, A., Jonkman, M. F., Leigh, I., Marinkovich, M. P., Martinez, A. E., McGrath, J. A., Mellerio, J. E., Moss, C., Murrell, D. F., Shimizu, H., Uitto, J., Woodley, D., Zambruno, G. 2014; 70 (6): 1103-1126

  Abstract

  Several new targeted genes and clinical subtypes have been identified since publication in 2008 of the report of the last international consensus meeting on diagnosis and classification of epidermolysis bullosa (EB). As a correlate, new clinical manifestations have been seen in several subtypes previously described.We sought to arrive at an updated consensus on the classification of EB subtypes, based on newer data, both clinical and molecular.In this latest consensus report, we introduce a new approach to classification ("onion skinning") that takes into account sequentially the major EB type present (based on identification of the level of skin cleavage), phenotypic characteristics (distribution and severity of disease activity; specific extracutaneous features; other), mode of inheritance, targeted protein and its relative expression in skin, gene involved and type(s) of mutation present, and--when possible--specific mutation(s) and their location(s).This classification scheme critically takes into account all published data through June 2013. Further modifications are likely in the future, as more is learned about this group of diseases.The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and molecular features of each EB subtype, and has sufficient flexibility incorporated in its structure to permit further modifications in the future.

  View details for DOI 10.1016/j.jaad.2014.01.903

  View details for Web of Science ID 000336030400032

• Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. Journal of the American Academy of Dermatology Fine, J., Bruckner-Tuderman, L., Eady, R. A., Bauer, E. A., Bauer, J. W., Has, C., Heagerty, A., Hintner, H., Hovnanian, A., Jonkman, M. F., Leigh, I., Marinkovich, M. P., Martinez, A. E., McGrath, J. A., Mellerio, J. E., Moss, C., Murrell, D. F., Shimizu, H., Uitto, J., Woodley, D., Zambruno, G. 2014; 70 (6): 1103-1126

  Abstract

  Several new targeted genes and clinical subtypes have been identified since publication in 2008 of the report of the last international consensus meeting on diagnosis and classification of epidermolysis bullosa (EB). As a correlate, new clinical manifestations have been seen in several subtypes previously described.We sought to arrive at an updated consensus on the classification of EB subtypes, based on newer data, both clinical and molecular.In this latest consensus report, we introduce a new approach to classification ("onion skinning") that takes into account sequentially the major EB type present (based on identification of the level of skin cleavage), phenotypic characteristics (distribution and severity of disease activity; specific extracutaneous features; other), mode of inheritance, targeted protein and its relative expression in skin, gene involved and type(s) of mutation present, and--when possible--specific mutation(s) and their location(s).This classification scheme critically takes into account all published data through June 2013. Further modifications are likely in the future, as more is learned about this group of diseases.The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and molecular features of each EB subtype, and has sufficient flexibility incorporated in its structure to permit further modifications in the future.

  View details for DOI 10.1016/j.jaad.2014.01.903

  View details for PubMedID 24690439

• The Changing Roles of Industry and Academia JOURNAL OF INVESTIGATIVE DERMATOLOGY Bauer, E. A., Cohen, D. E. 2012; 132 (3): 1033–36

  Abstract

  Over the past 25 years both the quality and quantity of pharmaceutical and biopharmaceutical research has changed. Formerly rigidly separated research efforts in academic institutions and the biopharmaceutical industry have become increasingly transparent to one another. Industry has in some cases scaled down its internal research efforts, while enhancing its outreach to basic research in academic institutions. In parallel, research at academic institutions has-in some cases-added a focus on application of discoveries to patient needs. This porosity between industry and academia has created opportunities for more rapid translation of basic discoveries to patient needs. Additionally, both physicians and fundamental scientists have broadened their career opportunities, and movement between industry and academia-almost unheard of two decades ago-now occurs regularly. At the same time, numerous examples exist of how these translational efforts have benefited not only patients but also investigators and academic institutions as well. Despite many potential advantages of closer interactions between industry and academia, other issues, such as conflicts of interest (both real and perceived), continue to pose challenges.

  View details for DOI 10.1038/jid.2011.368

  View details for Web of Science ID 000300374100034

  View details for PubMedID 22330271

• Skin biology DERMATOLOGIC THERAPY Hwa, C., Bauer, E. A., Cohen, D. E. 2011; 24 (5): 464-470

  Abstract

  The development of topical drug delivery systems has recently gained significant interest due to the ease of administration and lesser risks of systemic toxicity. The development of these new technologies utilizes the properties of the structure and function of the skin. The stratum corneum plays the largest role in affecting drug permeation, as the corneocytes and lipid matrix in this layer effectively prevent the diffusion of large molecules. In this review, we introduce the structure and function of the skin as it relates to topical drug delivery.

  View details for DOI 10.1111/j.1529-8019.2012.01460.x

  View details for Web of Science ID 000300678300002

  View details for PubMedID 22353152

• Revised classification system for inherited epidermolysis bullosa: Report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Fine, J. D., Eady, R. A., BAUER, E. A., Briggaman, R. A., Bruckner-Tuderman, L., Christiano, A., Heagerty, A., Hintner, H., Jonkman, M. F., McGrath, J., McGuire, J., Moshell, A., Shimizu, H., Tadini, G., UITTO, J. 2000; 42 (6): 1051-1066

  View details for Web of Science ID 000087448000016

  View details for PubMedID 10827412

• Dermatology - The importance of the intellectual base of the specialty ARCHIVES OF DERMATOLOGY BAUER, E. A. 2000; 136 (1): 24-24

  View details for Web of Science ID 000084661900005

  View details for PubMedID 10632181

• Gene therapy for a lethal genetic blistering disease: a status report. Transactions of the American Clinical and Climatological Association BAUER, E. A., Herron, G. S., Marinkovich, M. P., Khavari, P. A., Lane, A. T. 1999; 110: 86-92

  View details for PubMedID 10344009

• Cyclosporine as maintenance therapy in patients with severe psoriasis JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Shupack, J., Abel, E., Bauer, E., Brown, M., DRAKE, L., Freinkel, R., Guzzo, C., Koo, J., Levine, N., Lowe, N., McDonald, C., Margolis, D., Stiller, M., WINTROUB, B., Bainbridge, C., Evans, S., Hilss, S., Mietlowski, W., Winslow, C. 1997; 36 (3): 423-432

  Abstract

  Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated.Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis.After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases.During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group.Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

  View details for Web of Science ID A1997WM43300010

  View details for PubMedID 9091474

• Two-photon excitation of 4'-hydroxymethyl-4,5',8-trimethylpsoralen PHOTOCHEMISTRY AND PHOTOBIOLOGY Oh, D. H., Stanley, R. J., Lin, M., Hoeffler, W. K., Boxer, S. G., Berns, M. W., BAUER, E. A. 1997; 65 (1): 91-95

  Abstract

  Psoralens are a class of pharmaceutical agents commonly used to treat several cutaneous disorders. When irradiated with a mode-locked titanium: sapphire (Ti:sapphire) laser tuned to 730 nm, an aqueous solution of 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) emits blue light. The emission spectrum is centered at 452 nm and is identical to that obtained by one-photon excitation with UVA excitation, and its magnitude depends quadratically on the intensity of laser excitation. These results suggest that two-photon excitation occurs to a potentially photochemically active state. To estimate the two-photon absorption cross section, it was first necessary to measure the emission quantum yield of HMT using 365 nm excitation at room temperature that resulted in a value of 0.045 +/- 0.007. The two-photon absorption cross section of HMT at 730 nm is therefore estimated to be 20 x 10(-50) cm4 s (20 Göppert-Mayer). The excited-state photophysics and photochemistry of psoralens suggest potential applications to cutaneous phototherapy in diseases such as psoriasis and dystrophic epidermolysis bullosa.

  View details for Web of Science ID A1997WD16800021

  View details for PubMedID 9066288

• The merger of Stanford's and UCSF's clinical enterprises: impact on education. JAMA BAUER, E. A., Debas, H. T. 1996; 276 (21): 1770-1771

  View details for PubMedID 8940329

• GAMMA-2 CHAIN OF LAMININ-5 IS RECOGNIZED BY MONOCLONAL-ANTIBODY GB3 JOURNAL OF INVESTIGATIVE DERMATOLOGY Matsui, C., Nelson, C. F., Hernandez, G. T., Herron, G. S., BAUER, E. A., Hoeffler, W. K. 1995; 105 (5): 648-652

  Abstract

  Herlitz junctional epidermolysis bullosa is an autosomal recessive disorder characterized by generalized blistering at the lamina lucida of the cutaneous basement membrane. The monoclonal antibody GB3 has been used as a diagnostic probe because of its lack of reactivity in patient skin. The antigen recognized by GB3 has been identified as laminin-5, a glycoprotein consisting of three subunits (alpha 3, beta 3 and gamma 2). To identify the laminin-5 protein chain that contains the epitope recognized by GB3 and to determine if chain assembly is required for antibody recognition, we expressed a gamma 2 protein constructed from a full-length gamma 2 cDNA. Radioimmunoprecipitation of the culture medium from 293 cells revealed that both GB3 and anti-gamma 2 polyclonal antibodies were capable of directly precipitating recombinant gamma 2 without coprecipitation of other proteins. In immunodepletion experiments, each antibody removed most of the protein that was reactive with the other antibody. The epitope recognized by GB3 is present only when the complex is in the native conformation because GB3 reacted only with the non-reduced laminin-5, but not the reduced laminin-5 in immunoblots. Moreover, because GB3 reacted with laminin-5 of SCC25 cells (gamma 2 in the heterotrimer) but not recombinant gamma 2 in 293 cells (gamma 2 alone) during indirect immunofluorescence staining, this epitope may be dependent upon a less stable conformation of gamma 2. We conclude that GB3 recognizes the gamma 2 chain of laminin-5 and that the epitope is entirely contained in the native form of the gamma 2 chain.

  View details for Web of Science ID A1995TC99600003

  View details for PubMedID 7594636

• THE ASSEMBLY OF LAMININ-5 SUBUNITS JOURNAL OF BIOLOGICAL CHEMISTRY Matsui, C., Wang, C. K., Nelson, C. F., BAUER, E. A., Hoeffler, W. K. 1995; 270 (40): 23496-23503

  Abstract

  Laminin-5 is a heterotrimer composed of alpha 3, beta 3, and gamma 2 chains, produced by keratinocytes and the human squamous cell carcinoma line (SCC-25), and is one of the candidate proteins for the genetic lesion in junctional epidermolysis bullosa. Two-dimensional SDS-polyacrylamide gel electrophoresis (first dimension, nonreducing conditions; second dimension, reducing conditions) revealed that the immunoprecipitated laminin-5 from a SCC-25 cell fraction consisted of alpha 3, beta 3, and gamma 2 monomers, a beta 3 gamma 2 heterodimer, and an alpha 3 beta 3 gamma 2 heterotrimer. The presence of the beta 3 gamma 2 heterodimer, but not heterodimers containing an alpha 3 chain and any of the other chains, was suggestive of assembly of laminin-5 proceeding from a beta 3 gamma 2 heterodimer to an alpha 3 beta 3 gamma 2 heterotrimer. We showed, by cotransfection experiments using full-length recombinant beta 3 and gamma 2 chains in a human cell line devoid of endogenous laminin-5, that stable heterodimers can be formed in the absence of alpha 3 chain expression. In the SCC-25 cell fraction, the alpha 3 monomer pool was the smallest of the monomers. Pulse-chase experiments using the cell fraction also indicated that the heterotrimer was assembled after a 10-min pulse and was nearly absent after a 24-h chase. These results are consistent with the synthesis of alpha 3 being limiting for heterotrimer assembly, with rapid association of the alpha 3 chain with beta 3 gamma 2 heterodimers to form complete heterotrimers. Treatment with tunicamycin reduced the size of each of the laminin-5 subunits, indicating that all chains are glycosylated, but that N-linked glycosylation is not necessary for chain assembly and secretion.

  View details for Web of Science ID A1995RY90900042

  View details for PubMedID 7559513

• INHIBITION OF COLLAGENASE TYPE-I EXPRESSION BY PSORALEN ANTISENSE OLIGONUCLEOTIDES IN DERMAL FIBROBLASTS FASEB JOURNAL Lin, M., HULTQUIST, K. L., Oh, D. H., BAUER, E. A., Hoeffler, W. K. 1995; 9 (13): 1371-1377

  Abstract

  Type I collagenase plays an important role in both tumor metastasis and the remodeling of connective tissue in normal human skin, during wound healing, for example, and may participate in the pathophysiology of some dermatological diseases such as skin cancer and a chronic blistering disease, recessive dystrophic epidermolysis bullosa. In an effort specifically to inhibit collagenase expression, we have designed phosphorothioate antisense oligonucleotides, linked at the 5' ends with photoreactive 4'-(hydroxyethoxymethyl)-4,5',8-trimethyl-psoralen (HMT), and directed them against the 5' end of the collagenase mRNA. Two antisense-HMT molecules targeting a region overlapping the initiation codon were compared. Only one contained the HMT moiety targeting a 5'TpA on its complementary sense strand, and we observed greater than 50-fold improvement on the cross-linking of this antisense oligonucleotide to its target sequence after ultraviolet A (UVA) irradiation. Likewise, sequence complementary to the 5'TpA target was also required to demonstrate specific inhibition of in vitro translation of collagenase mRNA. Tissue culture experiments, conducted by incubation of collagenase-specific antisense-HMT oligonucleotides with fibroblasts in monolayer or in 3-dimensional dermal equivalents, showed lowered collagenase levels 24 h after UVA irradiation as compared to controls. Initial screening of antisense oligomers for specific hybridization and photo-cross-linking is a useful step in the design of antisense oligonucleotides, and allowed us to design an HMT-linked antisense phosphorothioate oligonucleotide that specifically inhibits the expression of fibroblastic collagenase.

  View details for Web of Science ID A1995TA37000017

  View details for PubMedID 7557028

• JUNCTIONAL EPIDERMOLYSIS-BULLOSA SKIN GRAFTED TO THE SCID MOUSE SHOWS PRESERVATION OF THE DISEASE PHENOTYPE MARINKOVICH, M. P., WOODLEY, D. T., WATANABE, G. L., JENSEN, R. A., CANTRELL, C. F., BANER, E. A., HOEFFLER, W. K., KIM, Y. H. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: 603

  View details for Web of Science ID A1995QR53200311

• BIOSYNTHESIS, ASSEMBLY AND SECRETION OF LAMININ-5 COMPONENTS MATSUI, C., HOEFFLER, W. K., CANTRELL, C. F., BAUER, E. A. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: 603

  View details for Web of Science ID A1995QR53200313

• AUTOIMMUNE EPIDERMOLYSIS-BULLOSA AQUISITA IS NOT ASSOCIATED WITH TYPE-VII COLLAGEN ALLELES WELSH, E. A., WU, D. W., FAIRCLOTH, E., BAUER, E. A., WOODLEY, D. T. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: 625

  View details for Web of Science ID A1995QR53200443

• CHARACTERIZATION OF NORMAL AND JEB KERATINOCYTES IMMORTALIZED WITH HPV E6, E7 GENES CANTRELL, C. F., LANIGAN, C., MARINKOVICH, P., BAUER, E. A., HOEFFLER, W. K. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: 628

  View details for Web of Science ID A1995QR53200463

• PHENOTYPIC REVERSION OF JUNCTIONAL EPIDERMOLYSIS-BULLOSA KERATINOCYTES BY THE INTRODUCTION OF A THERAPEUTIC LAMININ-5 CHAIN GENE HOEFFLER, W. K., WANG, C. K., MATSUI, C., CANTRELL, C. F., GERECKE, D., KIM, Y., HERRON, G. S., BAUER, E. A. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: 597

  View details for Web of Science ID A1995QR53200278

• CONSEQUENCES OF PREMATURE TERMINATION CODONS ON BOTH ALLELES OF THE TYPE-VII COLLAGEN GENE IN RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA - MARKEDLY REDUCED MESSENGER-RNA LEVELS AND ABSENCE OF TYPE-VII COLLAGEN Xu, Y. L., Christiano, A. M., Eichenfield, L. F., BAUER, E. A., Amano, S., Burgeson, R. E., UITTO, J. NATURE PUBLISHING GROUP. 1995: 631–31

  View details for Web of Science ID A1995QR53200482

• POTENTIALLY DIFFERENT SIGNALING PATHWAYS AND THRESHOLDS FOR NORMAL AND ACTIVATED RAS WANG, C. K., LEE, G. K., CANTRELL, C. F., BAUER, E. A., HOEFFLER, W. K. BLACKWELL SCIENCE PUBL INC CAMBRIDGE. 1995: 630

  View details for Web of Science ID A1995QR53200474

• GUIDELINES FOR CLINICAL-TRIALS IN SYSTEMIC-SCLEROSIS (SCLERODERMA) .1. DISEASE-MODIFYING INTERVENTIONS ARTHRITIS AND RHEUMATISM WHITE, B., BAUER, E. A., GOLDSMITH, L. A., HOCHBERG, M. C., KATZ, L. M., KORN, J. H., LACHENBRUCH, P. A., LEROY, E. C., MITRANE, M. P., PAULUS, H. E., POSTLETHWAITE, A. E., STEEN, V. D. 1995; 38 (3): 351–60

  Abstract

  To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death.A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used.Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage.Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

  View details for DOI 10.1002/art.1780380309

  View details for Web of Science ID A1995QL61500008

  View details for PubMedID 7880189

• PREMATURE TERMINATION CODONS IN THE TYPE-VII COLLAGEN GENE (COL7A1) UNDERLIE SEVERE, MUTILATING RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA GENOMICS Christiano, A. M., Anhalt, G., Gibbons, S., BAUER, E. A., UITTO, J. 1994; 21 (1): 160-168

  Abstract

  Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. The most severe, dystrophic (scarring) forms of EB demonstrate blister formation below the cutaneous basement membrane at the level of the anchoring fibrils. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the gene encoding type VII collagen (COL7A1), the major component of anchoring fibrils, have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. We have recently cloned the entire cDNA and gene for human COL7A1, which has been mapped to 3p21. In this study, we describe mutations in four COL7A1 alleles in three patients with severe, mutilating recessive dystrophic EB (Hallopeau-Siemens type, HS-RDEB). Each of these mutations resulted in a premature termination codon (PTC) in the amino-terminal portion of COL7A1. One of the patients was a compound heterozygote for two different mutations. The heterozygous carriers showed an approximately 50% reduction in anchoring fibrils, yet were clinically unaffected. Premature termination codons in both alleles of COL7A1 may thus be a major underlying cause of the severe, recessive dystrophic forms of EB.

  View details for Web of Science ID A1994NL71200022

  View details for PubMedID 8088783

• ACTIVATION OF C-JUN TRANSCRIPTION FACTOR BY SUBSTITUTION OF A CHARGED RESIDUE IN ITS N-TERMINAL DOMAIN NUCLEIC ACIDS RESEARCH Hoeffler, W. K., Levinson, A. D., BAUER, E. A. 1994; 22 (7): 1305-1312

  Abstract

  C-Jun is a cellular transcription factor that can control gene expression in response to treatment of cells with phorbol esters, growth factors, and expression of some oncogenes. The ability of c-Jun to catalyze the transcription of certain genes is controlled, in part, by changes in the phosphorylation state of specific amino acids in c-Jun. One of the major sites that is phosphorylated during signal response is Ser73. Here we show that substitution of a negatively charged aspartic acid residue at 73 constitutively increased transcriptional activity of c-Jun. The Asp73 substitution also enhanced its availability to bind to DNA in a whole cell extract without altering its intrinsic DNA binding activity since the intrinsic activity was unaltered for the c-Jun mutant proteins expressed in a bacterial system. The negatively charged Asp substitution may mimic the negative charge of a phosphorylated serine at 73. The substitution of an uncharged alanine at 73 resulted in lowered activities. The N-terminal end of c-Jun containing these substitutions was fused to the DNA-binding region of the bovine papilloma virus E2 protein, and was able to confer the same activation properties to the fusion protein at the heterologous E2 DNA-binding site. Ser73 lies in a region of c-Jun previously proposed to bind an uncharacterized inhibitor, perhaps related to a protein of approximately 17.5 kD that coprecipitates along with our c-Jun or the JunE2 fusion products.

  View details for Web of Science ID A1994NH13200027

  View details for PubMedID 8165146

  View details for PubMedCentralID PMC523657

• REGULATED EXPRESSION OF RECOMBINANT NICEIN/KALININ (NK) B-CHAINS IN CELLS FROM JUNCTIONAL EPIDERMOLYSIS-BULLOSA PATIENTS Hoeffler, W., Matsui, C., Cantrell, C., Herron, S., Lee, G., Rodriguez, J., Bauer, E. NATURE PUBLISHING GROUP. 1994: 542–42

  View details for Web of Science ID A1994NF40600132

• DETERMINATION OF HUMAN PAPILLOMA-VIRUS IN NON-ANOGENITAL SQUAMOUS-CELL CARCINOMAS BY POLYMERASE CHAIN-REACTION KIM, Y. H., SERKLAND, L. F., BAUER, E. A., PALEFSKY, J. M. BLACKWELL SCIENCE INC. 1994: 652

  View details for Web of Science ID A1994NF40600796

• PSORALEN ANTISENSE OLIGONUCLEOTIDE CONTROL OF COLLAGENASE EXPRESSION - FEASIBILITY OF A LASER 2-PHOTON EFFECT Hoeffler, W., Oh, D., Lin, M., Hultquist, K., Stanley, R., Boxer, S., Bauer, E. NATURE PUBLISHING GROUP. 1994: 650–50

  View details for Web of Science ID A1994NF40600781

• CONSTITUTIVE ACTIVATION OF THE COLLAGENASE PROMOTER IN RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA FIBROBLASTS - ROLE OF ENDOGENOUSLY ACTIVATED AP-1 EXPERIMENTAL CELL RESEARCH Unemori, E. N., Mauch, C., Hoeffler, W., Kim, Y., Amento, E. P., BAUER, E. A. 1994; 211 (2): 212-218

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a mutilating disease of the skin characterized by recurrent blistering and erosions that result from compromised integrity of the basement membrane zone. In this study, fibroblasts derived from the skin of RDEB patients were characterized for expression of the major metalloproteinases, particularly interstitial collagenase. Consistent with previous reports on increased collagenase protein levels in fibroblasts from some RDEB patients, we found that steady-state levels of collagenase mRNA were significantly increased in fibroblast strains derived from three of five RDEB patients compared to fibroblasts obtained from normal donors. Stromelysin mRNA was elevated in the same three fibroblast strains, whereas expression of neither the 72- nor the 92-kDa type IV collagenases was different from that of controls. Tissue inhibitor of metalloproteinases was expressed in RDEB fibroblasts at levels similar to those observed in normal fibroblasts. To investigate the mechanism behind the steady-state elevation in collagenase and stromelysin expression, AP-1 expression and activation were studied. Although levels of Jun expression were not different from those seen in normal fibroblasts, AP-1 activity, as assessed by ability to bind to a TPA response element-containing oligonucleotide, was endogenously elevated in RDEB fibroblasts compared to normal fibroblasts. Transfection studies using a plasmid construct containing the collagenase promoter linked to a CAT reporter gene demonstrated that RDEB fibroblasts were able to support active transcription of the promoter compared to normal fibroblasts. These studies support the hypothesis that RDEB fibroblasts contain chronically activated AP-1, and perhaps other transactivating factors, that contribute to the cellular phenotype of collagenase and stromelysin overexpression.

  View details for Web of Science ID A1994NE89700006

  View details for PubMedID 8143767

• EXPRESSION AND ASSEMBLY OF NICEIN/KALININ (NK) B-CHAINS MATSUI, C., HOEFFLER, W., CANTRELL, C., GERECKE, D., BURGESON, R., HERRON, S., HERNANDEZ, G., LANIGAN, C., BAUER, E. BLACKWELL SCIENCE INC. 1994: 549

  View details for Web of Science ID A1994NF40600176

• RAS INDUCTION OF RAT TRANSIN (STROMELYSIN) EXPRESSION IS MEDIATED BY ACTIVATED C-JUN LEE, G., BAUER, E., HOEFFLER, W. BLACKWELL SCIENCE INC. 1994: 626

  View details for Web of Science ID A1994NF40600640

• RAS INDUCTION OF RAT TRANSIN (STROMELYSIN) EXPRESSION IS MEDIATED BY ACTIVATED C-JUN LEE, G., BAUER, E., HOEFFLER, W. SLACK INC. 1994: A6

  View details for Web of Science ID A1994MR21400033

• THE 100-KDA CHAIN OF NICEIN/KALININ IS A LAMININ B2 CHAIN VARIANT EUROPEAN JOURNAL OF BIOCHEMISTRY VAILLY, J., VERRANDO, P., CHAMPLIAUD, M. F., GERECKE, D., WAGMAN, D. W., BAUDOIN, C., ABERDAM, D., BURGESON, R., BAUER, E., ORTONNE, J. P. 1994; 219 (1-2): 209–18

  Abstract

  We have isolated the basement membrane component nicein and performed rotary-shadow analyses using electron microscopy that showed the presence of two forms (I and II) of the protein. Molecular cloning of the cDNA that codes for the 100-kDa chain of the protein revealed that the sequence matches those independently identified for the 105-155-kDa subunit of kalinin, a recently identified basement membrane component. These data demonstrate that nicein and kalinin contain an identical chain. The length of the open reading frame in the cDNA (approximately 5200 nucleotides) and amino acid sequence obtained from the N-terminus of the 105-kDa kalinin chain showed the occurrence of a precursor polypeptide. This immature polypeptide is probably related to form I, observed by rotary shadowing, while the mature form is related to form II. It is noteworthy that nicein/kalinin subunits share discrete sequence similarities with the B2 chain of human laminin, but with a cleavage occurring within domain III that eliminates domains IV and V from the final product. The sequence of this subunit is nearly identical to that of B2t, a recently described polypeptide supposed to be related to a new laminin variant. Since nicein/kalinin expression is specifically impaired in the severe genodermatosis Herlitz junctional epidermolysis bullosa, the role and structure of this tissue-restricted laminin variant is crucial for the understanding of epidermal-dermal adhesion.

  View details for DOI 10.1111/j.1432-1033.1994.tb19932.x

  View details for Web of Science ID A1994MR85800024

  View details for PubMedID 8306988

• Activation of a c-jun transcription factor by substitution of a changed residue that may mimic phosphorylation Nucl. Acids Res Bauer E.A., Hoeffler W.K., Levinson A.D. 1994
• HUMAN RELAXIN DECREASES COLLAGEN ACCUMULATION IN-VIVO IN 2 RODENT MODELS OF FIBROSIS JOURNAL OF INVESTIGATIVE DERMATOLOGY Unemori, E. N., Beck, L. S., Lee, W. P., Xu, Y., Siegel, M., Keller, G., Liggitt, H. D., BAUER, E. A., Amento, E. P. 1993; 101 (3): 280-285

  Abstract

  The reproductive hormone, relaxin, inhibits collagen synthesis in vitro by normal human dermal fibroblast. In the present study, recombinant human relaxin is shown to modulate collagen accumulation and organization by mesenchymal cells in vivo in two rodent models of fibrosis: 1) fibrotic infiltration of polyvinyl alcohol sponge implants in rats, and 2) capsule formation around implanted osmotic pumps in mice. In the sponge, relaxin inhibits collagen accumulation, a measured by hydroxyproline content, in a dose-responsive manner by up to 25-29% in animals receiving 30 ng/ml relaxin, a finding supported by a decrease in collagen-specific trichrome staining in sections of sponges from relaxin-treated animals. In mice, the capsules surrounding relaxin-containing pumps are thinner and less dense than are capsules from control pumps. Ultrastructurally, control capsules are composed of densely packed parallel arrays of collagen fibrils, whereas fibrils more frequently are not packed in parallel arrays and are less abundant in treated capsules.

  View details for Web of Science ID A1993LX78600008

  View details for PubMedID 8370965

• 72 KDA TYPE-IV COLLAGENASE EXPRESSION IS ENHANCED BY ONCOGENIC VIRAL JUN HOEFFLER, W. K., HERNANDEZ, G., BAUER, E. A. BLACKWELL SCIENCE INC. 1993: 601

  View details for Web of Science ID A1993KW39500978

• DESIPRAMINE-INDUCED BLUE-GRAY PHOTOSENSITIVE PIGMENTATION ARCHIVES OF DERMATOLOGY Narurkar, V., SMOLLER, B. R., Hu, C. H., BAUER, E. A. 1993; 129 (4): 474-476

  Abstract

  Blue-gray pigmentation of the skin can be elicited by several medications. We report the first case (to our knowledge) of desipramine-induced photosensitive blue-gray pigmentation.Diffuse blue-gray pigmentation on sun-exposed surfaces was noted in a healthy 48-year-old woman who had been taking desipramine hydrochloride for 8 years. Ultrastructural studies demonstrated the presence of melanin and homogeneous electron-dense material in the dermis.We conclude that tricyclic antidepressant agents represent another class of medications responsible for blue-gray cutaneous pigmentation.

  View details for Web of Science ID A1993KW76500010

  View details for PubMedID 8466219

• Labeling of fractured human skin with antibodies to BM 600/nicein, epiligrin, kalinin and other matrix components. Journal of dermatological science Ceilley, E., Watanabe, N., Shapiro, D., Verrando, P., BAUER, E. A., Burgeson, R., Briggaman, R. A., Woodley, D. T. 1993; 5 (2): 97-103

  Abstract

  A variety of methods were used to fracture the dermal-epidermal junction (DEJ) of human skin. These included warm and hot phosphate buffered saline, trypsin, cold 1 M salt, potassium bromide and proteolytic digestion with dispase. The localization and sensitivity of basement membrane components (bullous pemphigoid antigen, BM 600/nicein, epiligrin, kalinin, laminin, collagens IV and VII (EBA antigen) and linkin) were determined after the DEJ was fractured by each method. We found that the basement membrane zone proteins, BM 600/nicein, epiligrin and kalinin remained with the dermal side of the DEJ fractured through the lamina lucida by cold salt, phosphate buffered saline and potassium bromide. BM 600/nicein, epiligrin and kalinin were not detected after treatment with trypsin. In contrast, laminin, another glycoprotein in the lamina lucida, was insensitive to all of the procedures, but co-localized to the dermal side of DEJ-fractured skin. We also found that separation of the DEJ with brief exposure of skin to 56 degrees C provided a useful substrate for testing the autoantibodies in the sera of patients with epidermolysis bullosa acquisita (EBA). Heat-separated skin can be prepared in a significantly shorter period of time than salt-separated skin.

  View details for PubMedID 8357788

• INHIBITION OF COLLAGENASE EXPRESSION BY PHOTO-ACTIVATABLE PHOSPHOROTHIOATE OLIGONUCLEOTIDES HULTQUIST, K. L., OH, D. H., LIU, T., PORKKA, S. J., HOEFFLER, W. K., BAUER, E. A. BLACKWELL SCIENCE INC. 1993: 499

  View details for Web of Science ID A1993KW39500366

• MELANOMA GROWTH-STIMULATORY ACTIVITY GRO DECREASES COLLAGEN EXPRESSION BY HUMAN FIBROBLASTS - REGULATION BY C-X-C BUT NOT C-C CYTOKINES JOURNAL OF BIOLOGICAL CHEMISTRY UNEMORI, E. N., AMENTO, E. P., BAUER, E. A., HORUK, R. 1993; 268 (2): 1338–42

  Abstract

  Melanoma growth-stimulatory activity (MGSA)/GRO is well characterized as a potent neutrophil chemoattractant. In the present study, we have demonstrated that MGSA induced a dose-dependent decrease in the expression of interstitial collagens by rheumatoid synovial fibroblasts. The decrease was observed over a dose range of 0.6-6.0 nM MGSA. This effect was specific, as MGSA had no demonstrable effect on the expression of collagen-degrading metalloproteinases, nor did it affect the collagenase inhibitor, tissue inhibitor of metalloproteinases. It also had no effect on the proliferation rate of these fibroblasts, unlike its mitogenic effect on melanoma cells. The ability to inhibit collagen expression was also demonstrated by another member of the C-X-C branch of the platelet factor 4 superfamily, interleukin-8 (IL-8), but not by RANTES, MIP-1 alpha, or MIP-1 beta, which belong to the C-C branch. Steady-state levels of expression of MGSA and IL-8 transcripts in normal adult tissues were dissimilar, suggesting that expression may be an important level at which the activity of these cytokines is regulated. Direct binding experiments with 125I-MGSA on synovial fibroblasts have allowed us to identify an MGSA receptor with a KD of 10.1 nM and approximately 75,000 binding sites/fibroblast. 125I-MGSA binding was specific and could not be displaced by unlabeled IL-8. These results suggest that MGSA, as well as IL-8, may play a role other than that of neutrophil chemo-attractant and more specifically, may be important in the regulation of collagen turnover.

  View details for Web of Science ID A1993KG07700086

  View details for PubMedID 8419336

• VASCULAR ENDOTHELIAL GROWTH-FACTOR INDUCES INTERSTITIAL COLLAGENASE EXPRESSION IN HUMAN ENDOTHELIAL-CELLS JOURNAL OF CELLULAR PHYSIOLOGY UNEMORI, E. N., FERRARA, N., BAUER, E. A., AMENTO, E. P. 1992; 153 (3): 557–62

  Abstract

  Vascular endothelial growth factor (VEGF) is a 45kDa secreted peptide that has potent mitogenic activity specific for endothelial cells in vitro and the ability to induce a strong angiogenic response in vivo. In the present study, 24 h treatment with VEGF resulted in a stimulation of expression of the metalloproteinase, interstitial collagenase, at the protein and mRNA levels 2.5-3.0-fold in human umbilical vein endothelial cells but not in human dermal fibroblasts. The dose response curve for collagenase induction was biphasic with the peak stimulatory response obtained by treatment of cells with 10-100 ng/ml (0.2-2 nM) VEGF. The dose response curve for collagenase induction overlapped with, but was not identical to, the response curve for proliferation, which showed VEGF mitogenic activity between < or = 0.1-50 ng/ml (< or = 0.002-1 nM). There was no induction seen in expression of other members of the matrix metalloproteinase family, including the 72kDa type IV collagenase, the 92kDa type V collagenase, or stromelysin. Expression of transcripts for the major metalloproteinase inhibitor, tissue inhibitor of metalloproteinases, was also unaltered by treatment with VEGF (1-200 ng/ml). These studies demonstrate that in addition to stimulating proliferation of endothelial cells, VEGF can also induce the expression of the only metalloproteinase that can initiate degradation of interstitial collagen types I-III under normal physiological conditions. Both responses are likely to contribute to the angiogenic potential of this peptide.

  View details for DOI 10.1002/jcp.1041530317

  View details for Web of Science ID A1992JZ90900016

  View details for PubMedID 1447317

• RELAXIN ALONE AND IN CONJUNCTION WITH INTERFERON-GAMMA DECREASES COLLAGEN-SYNTHESIS BY CULTURED HUMAN SCLERODERMA FIBROBLASTS JOURNAL OF INVESTIGATIVE DERMATOLOGY Unemori, E. N., BAUER, E. A., Amento, E. P. 1992; 99 (3): 337-342

  Abstract

  Fibroblasts derived from the involved skin of scleroderma patients frequently display a phenotype of supernormal collagen expression when cultured. Fibroblasts displaying this phenotype derived from seven patients were treated with relaxin (1-100 ng/ml) and interferon-gamma (1-100 U/ml), individually and in combination, to assess the relative abilities of these cytokines to down-modulate collagen synthesis and secretion. Scleroderma fibroblasts displayed varying sensitivities to both relaxin and interferon-gamma. Relaxin (100 ng/ml) decreased expression of collagen by six of seven lines tested from 8 to 59% compared to untreated cultures. Interferon-gamma (100 U/ml) depressed collagen secretion by all seven lines in a range from 7 to 89%. When relaxin and interferon-gamma were used in combination, relaxin augmented IFN-gamma-induced decreases in collagen secretion in four of seven lines. In three of these lines, the use of relaxin in conjunction with suboptimal doses of interferon-gamma resulted in decreases equivalent to or greater than that seen with a tenfold higher concentration of interferon-gamma. This study demonstrates the ability of relaxin to directly alter the excessive collagen-producing phenotype of scleroderma fibroblasts. In addition, in some cases, combining relaxin and interferon-gamma resulted in a cooperative effect in decreasing collagen expression by scleroderma cells in vitro.

  View details for Web of Science ID A1992JL54600016

  View details for PubMedID 1512471

• DERMAL MAST-CELL GRANULES BIND INTERSTITIAL PROCOLLAGENASE AND COLLAGENASE JOURNAL OF INVESTIGATIVE DERMATOLOGY KREJCI, N. C., Knapp, D. M., Rudd, R. J., BAUER, E. A., McGuire, J. 1992; 98 (5): 748-752

  Abstract

  In order to identify structures in human skin that bind collagenase, sections from frozen or paraffin-embedded skin were incubated with either procollagenase or activated collagenase. After washing, bound procollagenase or collagenase was detected by immunofluorescence microscopy. In normal skin, procollagenase bound only to isolated granular dermal cells that were identified as mast cells on the basis of staining with fluoresceinated avidin and pinacyanol erythrosinate. When mast cells were degranulated by exposure to the ionophore A23187, extracellular granules bound procollagenase. Of various pathologic conditions examined, the highest binding of procollagenase occurred in specimens of urticaria pigmentosa. Procollagenase bound to granular cells and to abundant granules scattered throughout the dermis. Binding could be abolished by pre-treatment of tissue sections with heparinase or by pre-incubation of procollagenase with soluble heparin, suggesting that heparin is the binding agent in the granules. Activated collagenase also bound to dermal mast cells but in addition bound strongly to the dermal collagen. Enzymatic activity of activated collagenase was not inhibited by heparin in concentrations up to 10 mg/ml. There is evidence that mast cell tryptase can contribute to procollagenase activation. This study further supports a role for mast cells in collagenolysis by demonstrating that heparin from mast cells binds procollagenase and possibly serves as a reservoir for procollagenase, which may then subsequently be activated.

  View details for Web of Science ID A1992HR03000014

  View details for PubMedID 1373747

• RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA PHENOTYPE IS PRESERVED IN XENOGRAFTS USING SCID MICE - DEVELOPMENT OF AN EXPERIMENTAL INVIVO MODEL JOURNAL OF INVESTIGATIVE DERMATOLOGY Kim, Y. H., Woodley, D. T., WYNN, K. C., GIOMI, W., BAUER, E. A. 1992; 98 (2): 191-197

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a subgroup of hereditary blistering diseases characterized by repetitive wounding and healing with subsequent extensive scarring. The purpose of this study was to establish a xenograft model that retains the RDEB phenotype and thus might be used as an experimental in vivo model to explore the molecular and biochemical mechanisms of the chronically wounded phenotype of RDEB. Full-thickness, tumor-free RDEB skin tissues were grafted onto the dorsum of severe combined immunodeficiency (SCID) mice. At 4, 8, 12, and 24 weeks after grafting, the xenografts were removed for examination. Immunofluorescence studies were performed using species-specific antibodies to human class I antigen, mouse class I antigen, human type IV and VII collagens and with cross-reacting antibody against bullous pemphigoid antigen (BPA). Staining with the antibody to human class I antigen, W6/32, and with the antibody to mouse class I antigen, 20.8.4s, confirmed the species-specific results obtained with the type IV and type VII collagen and laminin antibodies. The RDEB grafts showed essentially no staining with the type VII collagen antibody. Antibodies against laminin and BPA showed normal staining patterns in RDEB grafts. There was an overall paucity of anchoring fibrils in the grafts when examined with electron microscopy. Blisters could be induced in these grafts with minor trauma and showed a sublamina densa separation by immunomapping and electron microscopy. As late as 24 weeks post-transplantation, the RDEB grafts remain human, are not significantly replaced by mouse cells, and retain the RDEB disease phenotype.

  View details for Web of Science ID A1992HB07100012

  View details for PubMedID 1370678