Medical Sciences Commons^™

Human Muc4 Mucin Induces Ultra-Structural Changes And Tumorigenicity In Pancreatic Cancer Cells., N. Moniaux, P. Chaturvedi, G. C. Varshney, Jane L. Meza, J. F. Rodriguez-Sierra, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is …

Diarrea Viral Bovina Y Animales Portadores Del Virus En Hatos Productores De Leche De La Irrigación De Majes, Arequipa, John C. Huaman G., Hermelinda G. Rivera, Mariluz Araínga, Cesar Gavidia Ch., Alberto Manchego S.

Journal Articles: Pharmacology & Experimental Neuroscience

The objective of this study was to determine the prevalence of bovine viral diarrhea virus (BVDV) and persistently infected (PI) animals in dairy herds located in Majes, Arequipa, Peru. In the first phase, 204 bulk tank milk samples from herds were collected and sent to the local commercial processing plant in Majes for detection of antibodies against BVDV by indirect ELISA test. In the second phase, 286 blood samples from 57 were collected strong positive (Optical Density [OD] ≥ 0.900) for the detection of herds antibodies against BVDV and in PI animals by the indirect and capture ELISAs respectively. In …

The Notch Regulator Maml1 Interacts With P53 And Functions As A Coactivator., Yongtong Zhao, Rebecca B. Katzman, Laurie M. Delmolino, Ishfaq Bhat, Ying Zhang, Channabasavaiah B. Gurumurthy, Aleksandra Germaniuk-Kurowska, Honey V. Reddi, Aharon Solomon, Mu-Sheng Zeng, Aisha Kung, Hui Ma, Qingshen Gao, Goberdhan Dimri, Adina Stanculescu, Lucio Miele, Lizi Wu, James D. Griffin, David E. Wazer, Hamid Band, Vimla Band

Journal Articles: Biochemistry & Molecular Biology

Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that …

Clinical Implication Of Genome-Wide Profiling In Diffuse Large B-Cell Lymphoma And Other Subtypes Of B-Cell Lymphoma., Javeed Iqbal, Shantaram Joshi, Kavita N. Patel, Sofi I. Javed, Can Kucuk, Afeera Aabida, Francesco D'Amore, Kai Fu

Journal Articles: Pathology and Microbiology

The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely …

An Essential Role Of Human Ada3 In P53 Acetylation., Alo Nag, Aleksandra Germaniuk-Kurowska, Manjari Dimri, Michael A. Sassack, Channabasavaiah B. Gurumurthy, Qingshen Gao, Goberdhan Dimri, Hamid Band, Vimla Band

Journal Articles: Biochemistry & Molecular Biology

The p53 tumor suppressor protein functions as a critical component of genotoxic stress response by regulating the expression of effector gene products that control the fate of a cell following DNA damage. Unstressed cells maintain p53 at low levels through regulated degradation, and p53 levels and activity are rapidly elevated upon genotoxic stress. Biochemical mechanisms that control the levels and activity of p53 are therefore of great interest. We and others have recently identified hAda3 (human homologue of yeast alteration/deficiency in activation 3) as a p53-interacting protein and enhancer of p53 activity. Here, we show that endogenous levels of p53 …

Effects Of Low Dose Gm-Csf On Microglial Inflammatory Profiles To Diverse Pathogen-Associated Molecular Patterns (Pamps)., Nilufer Esen, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: It is well appreciated that obtaining sufficient numbers of primary microglia for in vitro experiments has always been a challenge for scientists studying the biological properties of these cells. Supplementing culture medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) partially alleviates this problem by increasing microglial yield. However, GM-CSF has also been reported to transition microglia into a dendritic cell (DC)-like phenotype and consequently, affect their immune properties.

METHODS: Although the concentration of GM-CSF used in our protocol for mouse microglial expansion (0.5 ng/ml) is at least 10-fold less compared to doses reported to affect microglial maturation and function (>/= …

Intercenter Reliability And Validity Of The Rhesus Macaque Genechip, Fenghai Duan, Eliot R. Spindel, Yu-Hua Li, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The non-human primate (NHP) research community has been intensely interested in obtaining whole-genome expression arrays for their work. Recently, novel approaches were used to generate the DNA sequence information for a rhesus GeneChip. To test the reliability of the rhesus GeneChip across different centers, RNA was isolated from five sources: cerebral cortex, pancreas, thymus, testis, and an immortalized fibroblast cell line. Aliquots of this RNA were sent to each of three centers: Yerkes National Primate Research Center, Oregon National Primate Research Center and the University of Nebraska Medical Center. Each center labeled the samples and hybridized them with two …

Sustained Il-6/Stat-3 Signaling In Cholangiocarcinoma Cells Due To Socs-3 Epigenetic Silencing., Hajime Isomoto, Justin L. Mott, Shogo Kobayashi, Nathan W. Werneburg, Steve F. Bronk, Serge Haan, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Interleukin 6 (IL-6)-mediated signal transducers and activators of transcription 3 (STAT-3) phosphorylation (activation) is aberrantly sustained in cholangiocarcinoma cells resulting in enhanced myeloid cell leukemia 1 (Mcl-1) expression and resistance to apoptosis. Because suppressor of cytokine signaling 3 (SOCS) controls the IL-6/STAT-3 signaling pathway by a classic feedback loop, the aims of this study were to examine SOCS-3 regulation in human cholangiocarcinoma.

METHODS: SOCS-3 expression was assessed in human cholangiocarcinoma tissue and the Mz-ChA-1 and CCLP1 human cholangiocarcinoma cell lines.

RESULTS: An inverse correlation was observed between phospho-STAT-3 and SOCS-3 protein expression in cholangiocarcinoma. In those cancers …

Single Nucleotide Polymorphisms (Snps) Distinguish Indian-Origin And Chinese-Origin Rhesus Macaques (Macaca Mulatta), Betsy Ferguson, Summer L. Street, Hollis Wright, Carlo Pearson, Yibing Jia, Shaun L. Thompson, Patrick Allibone, Christopher J. Dubay, Eliot Spindel, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis.

RESULTS: We surveyed the …

Androgen-Regulated Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Shalini Mitra, Lakshmanan Annamalai, Souvik Chakraborty, Kristen E. Johnson, Xiao-Hong Song, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate …

Molecular Diagnosis Of Burkitt's Lymphoma., Sandeep S. Dave, Kai Fu, George W. Wright, Lloyd T. Lam, Philip Kluin, Evert-Jan Boerma, Timothy Greiner, Dennis D. Weisenburger, Andreas Rosenwald, German Ott, Hans-Konrad Müller-Hermelink, Randy D. Gascoyne, Jan Delabie, Lisa M. Rimsza, Rita M. Braziel, Thomas M. Grogan, Elias Campo, Elaine S. Jaffe, Bhavana J. Dave, Warren Sanger, M Bast, Julie M. Vose, James O. Armitage, Joseph M. Connors, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Richard I. Fisher, Thomas P. Miller, Emilio Montserrat, Wyndham H. Wilson, Manisha Bahl, Hong Zhao, Liming Yang, John Powell, Richard Simon, Wing C. Chan, Louis M. Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.

RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target …

Evaluación De Anticuerpos Contra El Virus De La Diarrea Viral Bovina De Un Hato En Proceso De Erradicación De La Enfermedad., Zuniga Alfonso H., Hermelinda G. Rivera, Mariluz Araínga, Alberto Manchego S.

Journal Articles: Pharmacology & Experimental Neuroscience

Antibodies against viral bovine diarrhea virus (BVDV) and of BVDV antigen in serum samples Were evaluated from cattle aged 10 to 23 months (n = 148) from a dairy herd disease eradication where the has-been carrying out since 2002. The herd is located in Santa Rita, Arequipa, Peru, and samples were collected twice on a 30-day interval. Antibodies against BVDV and BVDV antigen were analyzed by viral neutralization and capture ELISA tests respectively. Neutralising antibodies against BVDV were detected in 6.8% (10/148) of animals, and most reactors were 19 to 23 months of age. The antibody titer ranged from 8 …

The Human Paf Complex Coordinates Transcription With Events Downstream Of Rna Synthesis., Bing Zhu, Subhrangsu S. Mandal, Anh-Dung Pham, Yong Zheng, Hediye Erdjument-Bromage, Surinder K. Batra, Paul Tempst, Danny Reinberg

Journal Articles: Biochemistry & Molecular Biology

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates …

Anticuerpos Contra El Virus De La Estomatitis Vesicularen Sajinos (Tayassu Tajacu) De Zoocriaderos De Iquitos Y Pucallpa, Aldo D. Wilson, Mariluz Araínga, Hugo Galvez C., Alberto Manchego S., Hermelinda G. Rivera

Journal Articles: Pharmacology & Experimental Neuroscience

The objetive of this study was to detect antibodies against vesicular stomatitis virus (VSV) collared peccaries in (Tayassu tajacu) from farms of Iquitos and Pucallpa, Peru. Blood samples were collected in animals olders than 6 months of age (pregnant females were not included) from a farm in Iquitos (n = 21) and from four farms in Pucallpa (n = 47), for detection of antibodies against Indiana 1 and New Jersey serotype of VSV by viral neutralization test. No specific antibodies against both serotypes of VSV were detected, indicating that the peccaries were not exposed to VSV, and suggesting absence of …

Dinámica De Seroconversión En Hembras Bovinas Post Eliminación De Animales Portadores Del Virus De La Diarrea Viral Bovina., Jayashi Cesar F., Gavidia Cesar C., Mariluz Araínga, Alberto Manchego, Hermelinda G. Rivera

Journal Articles: Pharmacology & Experimental Neuroscience

A study was conducted to determine the effect of culling BVDV carrier animals on the seroconversion against BVDV in the new generation of heifers from a dairy herd located in Arequipa, Peru. Blood samples were collected from 6-12 month old females in four sampling periods: January (n = 73), June (n = 48), October 2003 (n = 48), and January 2004 (n = 35) to evaluate their serological against BVDV status and to screen for carrier animals using the virus neutralization and antigen-capture ELISA tests, respectively. The prevalence of BVDV was 80.8 ± 9.0, 56.3 ± 14.0, 50.0 ± 14.2 …

Mitochondrial Dna Mutations, Apoptosis, And The Misfolded Protein Response., Justin L. Mott, Dekui Zhang, Hans Peter Zassenhaus

Journal Articles: Biochemistry & Molecular Biology

Studies of transgenic mice with accelerated accumulation of mtDNA mutations specifically in the heart lead us to propose that apoptotic signaling and cell death is central to the pathogenesis of mtDNA mutations in aging. It is the cellular response to that apoptotic signaling and the organ?s compensatory response to a loss of cells that specify the phenotype of an accumulation of mtDNA mutations. In the heart, cardiomyocytes induce a vigorous anti-apoptotic, pro-survival response to counteract mitochondrial apoptotic signaling. The heart up-regulates contractility of remaining myocytes in order to maintain cardiac output. We hypothesize that mutant mitochondrial proteins originate apoptotic signaling …

Multiple Roles Of Mucins In Pancreatic Cancer, A Lethal And Challenging Malignancy., N. Moniaux, M. Andrianifahanana, R. E. Brand, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin production is a hallmark of inflammatory and neoplastic disorders of the pancreas. Herein, we discuss the factors that contribute to the lethality of pancreatic cancer as well as the key role played by mucins, particularly MUC1 and MUC4, in the development and progression of the disease. Aspects pertaining to the aberrant expression and glycosylation of …

Immunopathogenesis Of Brain Abscess., Tammy Kielian

Journal Articles: Pathology and Microbiology

Brain abscess represents a significant medical problem despite recent advances made in detection and therapy. Due to the emergence of multi-drug resistant strains and the ubiquitous nature of bacteria, the occurrence of brain abscess is likely to persist. Our laboratory has developed a mouse experimental brain abscess model allowing for the identification of key mediators in the CNS anti-bacterial immune response through the use of cytokine and chemokine knockout mice. Studies of primary microglia and astrocytes from neonatal mice have revealed that S. aureus, one of the main etiologic agents of brain abscess in humans, is a potent stimulus for …

Transcriptional Activation Of The Human Prostatic Acid Phosphatase Gene By Nf-Kappab Via A Novel Hexanucleotide-Binding Site., Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed that a 577 bp fragment (-1356/-779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, …

Muc4 Mucin Expression In Human Pancreatic Tumours Is Affected By Organ Environment: The Possible Role Of Tgfbeta2., A. Choudhury, N. Moniaux, A. B. Ulrich, B. M. Schmied, J. Standop, Parviz M. Pour, S. J. Gendler, Michael A. Hollingsworth, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (P

Creation Of Non-Human Primate Neurogenetic Disease Models By Gene Targeting And Nuclear Transfer, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Genetically modified rhesus macaques are necessary because mouse models are not suitable for a number of important neurogenetic disorders; for example, Kallmann's syndrome, Lesch-Nyhan's disease and Ataxia-Telangiectasia. Mouse models may not be suitable because there may be no mouse ortholog of the human gene of interest, as is the case for Kallmann's syndrome, or because mutant mice do not exhibit the same phenotype observed in humans, as is the the case for Lesch-Nyhan's disease and Ataxia-Telangiectasia. Non-human primate models of neurogenetic diseases are expected to more closely resemble human diseases than existing mouse models. Genetically modified rhesus macaques can be …

Efecto De La Gnrh En El Proceso Del Reconocimiento Maternal De La Preñez Sobre La Supervivencia Embrionaria En Alpacas., Mariluz Araínga, Victor Leyva V., Wilber Garcia V., Enrique Franco Li.

Journal Articles: Pharmacology & Experimental Neuroscience

The effect of GnRH administered around the time of maternal recognition of prenancy on the embryonic survival rate was studied. This study used 67 adult female alpacas sexually receptive to the male, and bearing a preovulatory follicle ≥ 7mm, detected by rectal ultrasonography. Animals were distributed in three groups: Go (n=23) as control; G1 (n=22) received 6 µg GnRH on day 4 after ovulation; and G2 (n=22) received 4 µg GnRH on days 8 and 9 after ovulation. The ocurrence of ovulation was confirmed through the detection of a corpus luteum (CL) on day 5 after ovulation. Fertilization and gestation …

Actinomyces Pyogenes Causante De Aborto En Bovinos, Mariluz Araínga, Nieves Sandoval Ch., Erik R. Zacharias, Hermelinda Rivera G.

Journal Articles: Pharmacology & Experimental Neuroscience

A case of fetal bovine abortion due to Actinomyces pyogenes in a dairy herd of Cieneguilla valley of Lima, Peru is reported. A bovine fetus of four months of gestation was aborted and submitted for laboratory examination. Macroscopic lesions in fetal tissues were not found with the exception of numerous white foci up to 1mm in diameter in the lungs. Various fetal tissue samples were collected for virologic, bacteriologic and histopathologic examinations. Bovine viral diarrhea virus (BVDV) and Neospora caninum antigen were ruled out by immunohistochemistry but, pure colonies of A. pyogenes were isolated from the lung and other fetal …

Expression Of Tumor-Associated Glycoprotein-72 (Tag-72) Antigen In Human Prostatic Adenocarcinomas., Dev Karan, Sonny L. Johansson, Ming-Fong Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Tumor-specific antigens are usually defined by monoclonal antibodies (MAbs) and can play critical roles in the diagnosis and therapy of carcinomas. Despite advances in the understanding of the molecular genetics of human prostate carcinomas, therapeutic approaches require that tumor-specific markers, preferably on the cell surface, should be defined. In this study, we examined the expression of an oncofetal antigen tumor-associated glycoprotein-72 (TAG-72) in prostatic adenocarcinomas with a Gleason grade of six or higher. Using a second generation MAb CC49 against TAG-72, immunoreactivity was detected in 88% (29/33) of the prostatic cancer tissues. Occasionally, the benign epithelium showed a very faint …

Genomic Structure Of Murine Mitochondrial Dna Polymerase-Gamma., Justin L. Mott, Grace Denniger, Steve J. Zullo, H. Peter Zassenhaus

Journal Articles: Biochemistry & Molecular Biology

We have sequenced a genomic clone of the gene encoding the mouse mitochondrial DNA polymerase. The gene consists of 23 exons, which span approximately 13.2 kb, with exons ranging in size from 53 to 768 bp. All intron-exon boundaries conform to the GT-AG rule. By comparison with the human genomic sequence, we found remarkable conservation of the gene structure; the intron-exon borders are in almost identical locations for the 22 introns. The 5' upstream region contains approximately 300 bp of homology between the mouse and human sequences that presumably contain the promoter element. This region lacks any obvious TATA domain …

Interaction Between Fgf And Bmp Signaling Pathways Regulates Development Of Metanephric Mesenchyme., Andrew T. Dudley, R. E. Godin, E. J. Robertson

Journal Articles: Genetics, Cell Biology & Anatomy

Nephrogenesis in the mouse kidney begins at embryonic day 11 and ends approximately 10 days postpartum. During this period, new nephrons are continually being generated from a stem-cell population-the nephrogenic mesenchyme-in response to signals emanating from the tips of the branching ureter. Relatively little is known about the mechanism by which the nephrogenic mesenchyme cell population is maintained at the tips of the ureter in the presence of signals promoting tubulogenesis. Previous studies have shown that a loss of Bmp7 function leads to kidney defects that are a likely result of progressive loss of nephrogenic mesenchyme by apoptosis. The studies …

Analysis Of The Effects Of Overexpression Of Metallothionein-I In Transgenic Mice On The Reproductive Toxicology Of Cadmium., T Dalton, Kai Fu, G C Enders, R D Palmiter, G K Andrews

Journal Articles: Pathology and Microbiology

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. …

A Requirement For Bone Morphogenetic Protein-7 During Development Of The Mammalian Kidney And Eye., Andrew T. Dudley, K. M. Lyons, E. J. Robertson

Journal Articles: Genetics, Cell Biology & Anatomy

BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of secreted growth factors, is expressed during mouse embryogenesis in a pattern suggesting potential roles in a variety of inductive tissue interactions. The present study demonstrates that mice lacking BMP-7 display severe defects confined to the developing kidney and eye. Surprisingly, the early inductive tissue interactions responsible for establishing both organs appear largely unaffected. However, the absence of BMP-7 disrupts the subsequent cellular interactions required for their continued growth and development. Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential …

The Epidermal Growth Factor Receptor From Prostate Cells Is Dephosphorylated By A Prostate-Specific Phosphotyrosyl Phosphatase., Ming-Fong Lin, Gail M. Clinton

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) has been found to have phosphotyrosyl-protein phosphatase activity (H. C. Li, J. Chernoff, L. B. Chen, and A. Kirschonbaun, Eur. J. Biochem. 138:45-51, 1984; M.-F. Lin and G. M. Clinton, Biochem. J. 235:351-357, 1986) and has been suggested to negatively regulate phosphotyrosine levels, at least in part, by inhibition of tyrosine protein kinase activity (M.-F. Lin and G. M. Clinton, Adv. Protein Phosphatases 4:199-228, 1987; M.-F. Lin, C. L. Lee, and G. M. Clinton, Mol. Cell. Biol. 6:4753-4757, 1986). We investigated the molecular interaction of PAcP with a specific tyrosine kinase, the epidermal growth factor …

Developmental Expression Of Tyrosyl Kinase Activity In Human Serum., Ming-Fong Lin, Joan E. Bailey-Wilson, Robert C. Elston, Gail M. Clinton

Journal Articles: Biochemistry & Molecular Biology

Tyrosine protein kinases, in addition to their roles as viral transforming proteins and growth factor receptors, have been suggested to have specialized functions in tissue specific processes and in differentiation. High levels of soluble tyrosine kinases have been found in human serum and plasma. To determine if the level of tyrosine kinase activity is development tally expressed in human serum, we assayed sera from 214 individuals of different ages from newborns to 90 years. We found that serum tyrosine kinase levels are high in newborns and the levels closely parallel skeletal growth until late adolescence. The serum tyrosine kinase levels …