Digital Commons Network^™

Basic Fibroblast Growth Factor And Fibroblast Growth Factor Receptor I Are Implicated In The Growth Of Human Astrocytomas., R S Morrison, F Yamaguchi, H Saya, J M Bruner, Alan M. Yahanda Md, Facs, L A Donehower, M Berger

PCI Publications and Projects

Malignant astrocytomas are highly invasive, vascular neoplasms that comprise the majority of nervous system tumors in humans. A strong association has previously been made between malignancy in human astrocytic tumors and increased expression of certain fibroblast growth factor (FGF) family members, including basic and acidic FGF. The influence of endogenous basic FGF on glioblastoma cell growth in vitro was evaluated using basic FGF-specific antisense oligonucleotides. These studies indicated that human glioblastoma cell growth in vitro, can be inhibited by suppressing basic FGF expression. Human astrocytomas also exhibited changes in FGF receptor (FGFR) expression during the course of their progression from …

Sequencing Of Cdna From 50 Unrelated Patients Reveals That Mutations In The Triple-Helical Domain Of Type Iii Procollagen Are An Infrequent Cause Of Aortic Aneurysms., Gerard Tromp, Yuli Wu, Darwin J. Prockop, Swarna L. Madhatheri, Caren Kleinert, James J. Earley, Jiapiao Zhuang, Orjan Norrgård, R. Clement Darling, William M. Abbott, C. William Cole, Pekka Jaakkola, Markku Ryynanen, William H. Pearce, James S.T. Yao, Kari Majamaa, Stanton N. Smullens, Zoran Gatalica, Robert E. Ferrell, Sergio A. Jimenez, Charles E. Jackson, Virginia V. Michels, Michael Kaye, Helena Kuivaniemi

Department of Biochemistry and Molecular Biology Faculty Papers

Detailed DNA sequencing of the triple-helical domain of type III procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for …

Regulation Of Human Lung Fibroblast Alpha 1(I) Procollagen Gene Expression By Tumor Necrosis Factor Alpha, Interleukin-1 Beta, And Prostaglandin E2., Arturo Diaz, Elena Munoz, Rosemary Johnston, Joseph H. Korn, Sergio A. Jimenez

Department of Medicine Faculty Papers

We investigated the participation of prostaglandin (PG) E2 in the regulation of the alpha 1(I) procollagen gene expression by tumor necrosis factor alpha (TNF alpha), and interleukin-1 beta (IL-1 beta) in normal adult human lung fibroblasts. TNF alpha (100 units/ml) and IL-1 beta (100 units/ml) stimulated the production of PGE2 and caused a dose-dependent inhibition of up to 54 and 66%, respectively, of the production of type I procollagen. Preincubation of cultures with indomethacin partially reversed the inhibition of procollagen production induced by the cytokines. Cytokine-stimulated endogenous fibroblast PG accounted for 35 and 68% of the inhibition induced by TNF …

Can An Anesthesia Machine Flush Valve Provide For Effective Jet Ventilation?, S D Gaughan, J L Benumof, G T Ozaki

Faculty, Staff and Student Publications

Transtracheal jet ventilation (TTJV) using a percutaneously inserted intravenous (IV) catheter for the patient who cannot be ventilated or tracheally intubated or, using a jet stylet for changing endotracheal tubes (ETT) in patients for whom subsequent ventilation and/or tracheal reintubation may be difficult, are extremely valuable therapeutic options. The jet ventilation system must have a sufficiently high pressure-oxygen source to drive oxygen through noncompliant tubing and through relatively small IV catheters and/or jet stylets in order to achieve adequate ventilation and oxygenation. There is no evidence that using the common gas outlet of an anesthesia machine by activating the flush …

Plasma Total Glutathione In Humans And Its Association With Demographic And Health-Related Factors, Elaine W. Flagg, Ralph J. Coates, J. William Eley, Raymond S. Greenberg, Dean P. P. Jones, Elaine W. Gunter, Bethany Jackson

Faculty Publications

The tripeptide glutathione is proposed to be protective against a number of chronic diseases including cardiovascular disease and cancer. However, there have been few studies of plasma glutathione levels in humans and in those studies the numbers of participants have been very small. In an exploratory analysis the determinants of plasma total glutathione (GSHt) were investigated in a group of 100 volunteers aged 18–61 years in Atlanta, Georgia, USA during June and July 1989. Data on demographic and health-related factors were collected by interview and plasma GSHt was measured using a recently modified laboratory method. The mean concentration of plasma …

Indistinguishable Nuclear Factor Binding To Functional Core Sites Of The T-Cell Receptor Delta And Murine Leukemia Virus Enhancers., Juan M. Redondo, Jeffrey L. Pfohl, Cristina Hernandez-Munain, Shuwen Wang, Nancy A. Speck, Michael S. Krangel

Dartmouth Scholarship

We have previously shown that the delta E3 site is an essential element for transcriptional activation by the human T-cell receptor (TCR) delta enhancer and identified two factors, NF-delta E3A and NF-delta E3C, that bound to overlapping core (TGTGGTTT) and E-box motifs within delta E3. In this study, we show that protein binding to the core motif is necessary but not sufficient for transcriptional activation by the delta E3 element. In contrast, protein binding to the E-box motif does not contribute significantly to enhancer activity. A similar core motif present within the enhancers of T-cell-tropic murine retroviruses has been shown …

How To Make A Blastocyst., A J Watson, G M Kidder, G A Schultz

Obstetrics & Gynaecology Publications

Several of the new reproductive technologies have been cultivated from our current understanding of the genetic programming and cellular processes that are involved in the major morphogenetic events of mammalian preimplantation development. Research directed at characterizing the patterns of gene expression during early development has shown that the embryo is initially under maternal control and later superseded by new transcriptional activity provided by the activation of the embryonic genome. Several embryonic transcripts encoding: (i) growth factors, (ii) cell junctions, (iii) plasma membrane ion transporters, and (iv) cell adhesion molecules have been identified as contributing directly to the progression of the …

Modulation Of Cisplatin Sensitivity And Growth Rate Of An Ovarian Carcinoma Cell Line By Bombesin And Tumor Necrosis Factor-Alpha., Seiji Isonishi, Antti P. Jekunen, Doreen K. Hom, Alan Eastman, Peter S. Edelstein, Franz B. Thiebaut, Randolph D. Christen, Stephen B. Howell

Dartmouth Scholarship

A twofold change in the cisplatin (DDP) sensitivity of 2008 human ovarian carcinoma cells is sufficient to reduce tumor response in vivo. The DDP sensitivity of these cells can be enhanced by activation of the epidermal growth factor and protein kinase C signal transduction pathways. We report here that two endogenous growth factors, bombesin and tumor necrosis factor alpha (TNF alpha), enhanced DDP sensitivity by factors of 1.7 +/- 0.1 (SD)-fold and 1.8 +/- 0.1 (SD)-fold, respectively. Both agents also produced sensitization in an 11-fold DDP-resistant 2008 subline. Neither bombesin nor TNF alpha changed the accumulation of DDP, glutathione content, …

Alternative Splicing Of Human Prostaglandin G/H Synthase Mrna And Evidence Of Differential Regulation Of The Resulting Transcripts By Transforming Growth Factor Beta 1, Interleukin 1 Beta, And Tumor Necrosis Factor Alpha., Arturo Diaz, Anthony M. Reginato, Sergio A. Jimenez

Department of Medicine Faculty Papers

Prostaglandin G/H synthase (PGG/HS) is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and thromboxanes. We screened a human lung fibroblast cDNA library with an ovine PGG/HS cDNA and isolated a 2.3-kilobase clone (HCO-T9). Sequence analysis of this clone showed that (a) it contained the entire translated region of PGG/HS and (b) it displayed an in-frame splicing of the last 111 base pairs encoded by exon 9, which resulted in the elimination of the N-glycosylation site at residue 409. Polymerase chain reaction amplification with specific oligonucleotides of reverse-transcribed mRNA from diverse human tissues and cultured cells yielded …

The Future Of Dental Education, D L Allen

Faculty, Staff and Student Publications

No abstract provided.

Regulation Of Transforming Growth Factor-Beta 1 Gene Expression By Glucocorticoids In Normal Human T Lymphocytes., O. Ayanlarbatuman, A. P. Ferrero, Arturo Diaz, Sergio A. Jimenez

Department of Medicine Faculty Papers

Glucocorticoids (GC) modulate immune function in a number of ways, including suppression of T cell proliferation and other IL-2-mediated T cell functions. These inhibitory effects are similar to those induced by transforming growth factor-beta 1 (TGF-beta 1), a cytokine with potent T cell inhibiting activities. We examined the hypothesis that GC effects may be at least partially achieved through modulation of the expression of the TGF-beta 1 gene in activated T cells. Normal T cells were cultured with or without purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence or absence of the synthetic GC, dexamethasone (100-200 …

Statistical Interpretation Of Dna Typing Data, R Chakraborty

Faculty, Staff and Student Publications

No abstract provided.

Expression Of A Human Cartilage Procollagen Gene (Col2a1) In Mouse 3t3 Cells., Leena Ala-Kokko, James Hyland, Carol Smith, Kari I. Kivirikko, Sergio A. Jimenez, Darwin J. Prockop

Department of Medicine Faculty Papers

Expression in a recombinant system has been difficult to obtain for any of the major fibrillar collagens that require processing by eight or more post-translational enzymes. Here, two DNA constructs were designed so that the promoter region of the gene for the pro-alpha 1(I) chain of human type I procollagen drove expression of the human type II procollagen gene in mouse NIH 3T3 cells, a culture line that normally synthesizes type I procollagen but not any cartilage-specific protein such as type II procollagen. Both constructs were expressed as both mRNA and protein. In clones expressing the construct at high levels, …

Inclusion Of Data On Relatives For Estimation Of Allele Frequencies, R Chakraborty

Faculty, Staff and Student Publications

No abstract provided.

Interleukin-2-Triggered Raf-1 Expression, Phosphorylation, And Associated Kinase Activity Increase Through G1 And S In Cd3-Stimulated Primary Human T Cells., Antanina Zmuidzinas, Harvey J. Mamon, Thomas M. Roberts, Kendall A. Smith

Dartmouth Scholarship

To gain further insight into the role of Raf-1 in normal cell growth, c-raf-1 mRNA expression, Raf-1 protein production, and Raf-1-associated kinase activity in normal human T cells were analyzed. In contrast to the constitutive expression of Raf-1 in continuously proliferating cell lines, c-raf-1 mRNA and Raf-1 protein levels were barely detectable in freshly isolated G0 T lymphocytes. Previous work with fibroblasts has suggested that Raf-1 plays a signaling role in the G0-G1 phase transition. In T cells, triggering via the T-cell antigen receptor (TCR)-CD3 complex (TCR/CD3) resulted in an approximately fourfold increase in c-raf-1 mRNA. In addition, the promotion …

Association Of Circulating Receptor Fc Gamma Riii-Positive Monocytes In Aids Patients With Elevated Levels Of Transforming Growth Factor-Beta, J B. Allen, H L. Wong, P M. Guyre, G L. Simon

Dartmouth Scholarship

No abstract provided.

Religion And The Body: Rematerializing The Human Body In The Social Sciences Of Religion, Meredith B. Mcguire

Sociology & Anthropology Faculty Research

The social sciences of religion could be transformed by taking seriously the fact that humans are embodied. A new conceptualization of a mindful body has the potential to lead to profound shifts in how we view our subjects and their worlds. Our research strategies need to take into account that believers (and nonbelievers) are not merely disembodied spirits, but that they experience a material world in and through their bodies. Greater awareness of the social and political uses of human bodies should guide our research and theory.

An Experimental Analysis Of Higher-Order Stimulus Control In Humans, Michael B. Gatch

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This dissertation explored sane effects of context on the development of stimulus classes and the transfer of stimulus functions to novel stimuli. The research was also intended to demonstrate the utility of current behavioral theories for prediction and control of contextual effects on class formation. In Experiment lA, contextual control of stimulus classes was established successfully in all six college-student subjects. Matching-to-sample training successfully transferred the function of the contextual stimuli to four novel stimuli, whim resulted in the formation of two three-member classes of contextual stimuli. The first portion of Experiment 1B replicated Experiment 1A with three additional subjects. …

The Role Of Calcium Ions In Toxic Cell Injury., John L. Farber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium ions have been increasingly implicated as a mediator of the mechanisms generating lethal cell injury under a variety of pathologic circumstances. An overview of the various roles suggested for such alterations in cellular calcium homeostasis is presented. The central role of plasma membrane damage in the genesis of irreversible cell injury is used to divide the postulated roles for calcium ions into two major mechanisms. On the one hand, calcium ions have been proposed as mediators of the functional consequences of plasma membrane injury. An influx of extracellular calcium ions across a damaged permeability barrier and down a steep …

Identification And Characterization Of The Herpes Simplex Virus Type 2 Gene Encoding The Essential Capsid Protein Icp32/Vp19c, S P Yei, S I Chowdhury, B M Bhat, A J Conley, W S Wold, W Batterson

Faculty, Staff and Student Publications

We describe the characterization of the herpes simplex virus type 2 (HSV-2) gene encoding infected cell protein 32 (ICP32) and virion protein 19c (VP19c). We also demonstrate that the HSV-1 UL38/ORF.553 open reading frame (ORF), which has been shown to specify a viral protein essential for capsid formation (B. Pertuiset, M. Boccara, J. Cebrian, N. Berthelot, S. Chousterman, F. Puvian-Dutilleul, J. Sisman, and P. Sheldrick, J. Virol. 63: 2169-2179, 1989), must encode the cognate HSV type 1 (HSV-1) ICP32/VP19c protein. The region of the HSV-2 genome deduced to contain the gene specifying ICP32/VP19c was isolated and subcloned, and the nucleotide …

Induction Of Antigen-Specific Human Cytotoxic T Cells By Toxoplasma Gondii, I A. Khan, K A. Smith, L H. Kasper

Dartmouth Scholarship

No abstract provided.

Altered Expression Of Chondroitin Sulfate Proteoglycan In The Stroma Of Human Colon Carcinoma. Hypomethylation Of Pg-40 Gene Correlates With Increased Pg-40 Content And Mrna Levels., R Adany, R Heimer, B Caterson, Jm Sorrell, Rv Iozzo

Faculty & Staff Scholarship

No abstract provided.

Osteogenesis Imperfecta. The Position Of Substitution For Glycine By Cysteine In The Triple Helical Domain Of The Pro Alpha 1(I) Chains Of Type I Collagen Determines The Clinical Phenotype., Barbra J. Starman, David Eyre, Harry Charbonneau, Maria Harrylock, Mary Ann Weis, Lester Weiss, John M. Graham Jr., Peter H. Byers

Dartmouth Scholarship

Skin fibroblasts grown from three individuals with osteogenesis imperfecta (OI) each synthesized a population of normal type I collagen molecules and additional molecules that had one or two alpha 1(I) chains that contained a cysteine residue within the triple-helical domain, a region from which cysteine normally is excluded. The patients had very different phenotypes. One patient with OI type I had a population of alpha 1(I) chains in which glycine at position 94 of the triple helix was substituted by cysteine; a patient with OI type III had a population of alpha 1(I) chains in which glycine at position 526 …

Transforming Growth Factor-Beta Stimulation Of Lung Fibroblast Prostaglandin E2 Production., Arturo Diaz, John Varga, Sergio A. Jimenez

Department of Medicine Faculty Papers

Transforming growth factor-beta (TGF beta) stimulated the production of total protein, collagen, and fibronectin by normal human lung fibroblasts. The stimulatory response was maximal at 100 pM TGF beta and reversed toward control at higher concentrations. Inhibition of fibroblast prostaglandin (PG) synthesis enhanced TGF beta-induced stimulation of total protein, collagen, and fibronectin production and reversed the negative slope of the dose-response curve at high concentrations of TGF beta. Determination of the steady-state levels of Types I and III procollagens and fibronectin mRNAs employing specific cDNA probes demonstrated that inhibition of fibroblast PG production increased the stimulatory effect of TGF beta …

Effects Of Methylene Chloride On Immune Function In Mice And The In Vitro Effect Of Methylene Chloride In Immunologic Assays, Man-Ping Wang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A number of toxicities associated with methylene chloride have been found in both human subjects and mice. However, relatively few studies have probed immunotoxicities of methylene chloride. In order to examine possible immunotoxicities or immunomodulating effects of methylene chloride, several tests of cellular immune function were performed using both human in in vitro studies and a mouse model.

Body weights and specific organ weights of thymus, spleen, liver, and kidney were normal in CD-1 mice given various concentrations of methylenechloride. However, a significantly reduced mitogenic response to phytohemagglutinin (PHA} and reduced interleukin-2 (IL-2} production was found in these methylene-chloride-treated mice. …

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 …

Camp Antagonizes Interleukin 2-Promoted T-Cell Cycle Progression At A Discrete Point In Early G1., Kirk W. Johnson, Bruce H. Davis, Kendall A. Smith

Dartmouth Scholarship

T lymphocytes are stimulated to proliferate in an autocrine/paracrine manner by the lymphokine interleukin 2 (IL-2). In seeking further insight into the mechanisms by which IL-2 induces progression of T cells through the G1 phase of the cell cycle, studies were performed with agents that increase cellular adenosine 3',5'-cyclic monophosphate (cAMP), a well-known inhibitor of lymphocyte growth. The addition of dibutyryl-cAMP, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine to an IL-2-dependent murine T-cell line evoked a dose-related suppression of S-phase transition without affecting cellular viability. Moreover, elevation of cAMP levels led to an accumulation of uniformly small cells, suggesting an arrest in …

K+ Efflux In Nih Mouse 3t3 Cells And Transformed Derivatives: Dependence On Extracellular Ca2+ And Phorbol Esters., Martin Lubin

Dartmouth Scholarship

In culture medium deficient in Ca2+, NIH mouse 3T3 cells lose K+, gain Na+, and stop growing. A marked increase in the rate of K+ efflux accounts for this loss; Na+, K+-ATPase pump activity increases but does not fully compensate for enhanced K+ efflux. Phorbol esters and cycloheximide inhibit K+ loss in Ca2+-deficient medium. Phorbol esters inhibit K+ efflux from human fibroblasts as well, even at physiological levels of Ca2+. Two cell lines derived from NIH-3T3, one transformed by a simian virus 40 deletion mutant, the other by the polyoma virus oncogene encoding the middle-sized tumor antigen, retain K+ and …

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 …

Regulation Of Lymphokine Production And Human T Lymphocyte Activation By 1,25-Dihydroxyvitamin D3. Specific Inhibition At The Level Of Messenger Rna., William F.C. Rigby, Sylvia Denome, Michael W. Fanger

Dartmouth Scholarship

The steroid hormone, 1 alpha,25-dihydroxyvitamin D3 (calcitriol), has been shown to inhibit T cell proliferation, primarily through inhibition of interleukin 2 (IL-2) production. In these experiments, we show that calcitriol also markedly inhibited production of the lymphokine, gamma interferon (IFN-gamma), by activated human T lymphocytes. Regulation of both IL-2 and IFN-gamma production as well as transferrin receptor (TfR) expression by calcitriol was apparent at the messenger RNA (mRNA) level as determined by Northern blotting. The decrease in IL-2 and IFN-gamma mRNA that occurred with calcitriol treatment was coordinate and not apparent up to 12 h after phytohemagglutinin stimulation, whereas decreased …