bluuebunny/crossref_metadata_2025 huggingface dataset:
HTLV-I Tax Induces Cellular Proteins that Activate the κB Element in the IL-2 Receptor α Gene
Authors: Ballard Dean W. , Bohnlein Ernst , Lowenthal John W. , Wano Yuji , Franza B. Robert , Greene Warner C.
Published: October 2006

Jurkat T cell lines constitutively expressing Tax, the 40-kilodalton transactivator protein of human T lymphotropic virus type I (HTLV-I), were used to investigate the mechanism by which this viral product deregulates the expression of the interleukin-2 receptor α gene (IL-2Rα, Tac). Transfection of deleted forms of the IL-2Rα promoter and in vitro DNA-binding studies revealed that a 12-base pair promoter segment, which has homology with the binding site for NF-κB, was required for Tax-induced activation of the IL-2Rα promoter in vivo. An 18-base pair oligonucleotide containing this κB-like regulatory element proved sufficient to confer Tax inducibility upon a heterologous promoter. DNA affinity precipitation assays showed that Tax, like mitogenic stimuli, induced the expression of the 86-kilodalton cellular protein HIVEN86A, which specifically binds to the IL-2Rα κB element in vitro. Furthermore, DNA/protein cross-linking studies revealed that several polypeptides interact with this sequence motif. Thus, the deregulation of IL-2Rα gene expression encountered in HTLV-I leukemias appears to involve Tax activation of one or more cellular proteins that are normally induced by mitogens and that directly contribute to transcriptional activation of this receptor gene.
Spatially Resolved Calcium Dynamics of Mammalian Purkinje Cells in Cerebellar Slice
Authors: Tank David W. , Sugimori Mutsuyuki , Connor John A. , Llinás Rodolfo R.
Published: October 2006

Microfluorometric imaging was used to study the correlation of intracellular calcium concentration with voltage-dependent electrical activity in guinea pig cerebellar Purkinje cells. The spatiotemporal dynamics of intracellular calcium concentration are demonstrated during spontaneous and evoked activity. The results are in agreement with hypotheses of dendritic segregation of calcium conductances suggested by electrophysiological experiments. These in vitro slice fluorescence imaging methods are applicable to a wide range of problems in central nervous system biochemical and electrophysiological functions.
Two Types of Somatostatin Receptors Differentiated by Cyclic Somatostatin Analogs
Authors: Tran Vinh T. , Beal M. Flint , Martin Joseph B.
Published: October 2006

Somatostatin receptors in rat brain, pituitary, and pancreas were labeled with two radioiodinated analogs of somatostatins 14 and 28. Two cyclic analogs of somatostatin, SMS201-995 and cyclo(Ala-Cys-Phe-D-Trp-Lys-Thr-Cys), showed biphasic displacement of binding to somatostatin receptors by these radioligands. In contrast, all other somatostatin analogs, including somatostatin-14, competed for the receptor sites with monophasic displacement of radioligand receptor binding. Thus two types of somatostatin receptors were identified. It was found that the pituitary and pancreas have predominantly one type of somatostatin receptor whereas the brain has both, and that different regions of the brain have various proportions of the two types. These findings suggest methods to characterize other types of somatostatin receptors subserving somatostatin's diverse physiological functions, including a potential role in cognitive function and extrapyramidal motor system control.
Systemic Ethanol: Selective Enhancement of Responses to Acetylcholine and Somatostatin in Hippocampus
Authors: Mancillas Jorge R. , Siggins George R. , Bloom Floyd E.
Published: October 2006

In rat hippocampal pyramidal cells tested in situ by iontophoresis of several neurotransmitters, ethanol significantly enhanced excitatory responses to acetylcholine and inhibitory responses to somatostatin-14 but had no statistically significant effect on excitatory responses to glutamate or inhibitory responses to γ-aminobutyric acid or, in preliminary tests, to norepinephrine or serotonin. The effects of ethanol on responses to acetylcholine and somatostatin-14 may provide insight into synaptic mechanisms underlying the behavioral consequences of ethanol intoxication.
Positron Emission Tomography Reveals Elevated D
2
Dopamine Receptors in Drug-Naive Schizophrenics
Authors: Wong Dean F. , Wagner Henry N. , Tune Larry E. , Dannals Robert F , Pearlson Godfrey D. , Links Jonathan M. , Tamminga Carol A. , Broussolle Emmanuel P , Ravert Hayden T. , Wilson Alan A. , Toung J. K. Thomas , Malat Jan , Williams Jeffery A. , O'Tuama Lorcan A. , Snyder Solomon H. , Kuhar Michael J. , Gjedde Albert
Published: October 2006

In postmortem studies of patients with schizophrenia, D
2
dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D
2
dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D
2
dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia—one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D
2
dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D
2
dopamine receptor density.
HTLV-I—Associated B-Cell CLL: Indirect Role for Retrovirus in Leukemogenesis
Authors: Mann Dean L. , DeSantis Patricia , Mark George , Pfeifer Andrea , Newman Mark , Gibbs Nigel , Popovic Mikulas , Sarngadharan M. G. , Gallo Robert C. , Clark Jeffrey , Blattner William
Published: October 2006

Serum containing antibodies to the human T-lymphotropic virus type I (HTLV-I) has been observed at a higher than expected frequency in patients with B-cell chronic lymphocytic leukemia (CLL) in an area endemic for HTLV-I. An attempt was made to determine whether the cells from patients with this leukemia were HTLV-I antigen-committed B cells that had undergone malignant transformation. Cells from two HTLV-I seropositive Jamaican patients with CLL were fused with a human B-lymphoblastoid cell line. The hybridoma cells that resulted from the fusion of CLL cells from patient I.C. produced an immunoglobulin (IgM) that reacted with the p24
gag
protein from HTLV-I, HTLV-II, and HTLV-III (now referred to as HIV), but showed preferential reactivity with HTLV-I. The specific immunoglobulin gene rearrangement (IgM, κ) in the CLL cell was demonstrated in the hybridoma cell line, indicating that the captured immunoglobulin was from the CLL cells. The IgM secreted by the fusion of CLL cells from patient L.L. reacted only with HTLV-I-infected cells and with the HTLV-I large envelope protein (gp61) on Western blots. The CLL cells from these patients appear to be a malignant transformation of an antigen-committed B cell responding to HTLV-I infection, suggesting an indirect role for this retrovirus in leukemogenesis.
Quantal Release of Transmitter Is Not Associated with Channel Opening on the Neuronal Membrane
Authors: Young Steven H. , Chow Ida
Published: October 2006

The traditional view that quantal release of neurotransmitter results from the fusion of transmitter-containing vesicles with the neuronal membrane has been recently challenged. Although various alternative mechanisms have been proposed, a common element among them is the release of cytoplasmic transmitter, which, in one view, could occur through large conductance channels on the presynaptic membrane. Six nerve-muscle cell pairs were examined with a whole-cell patch clamp for the presence of such channels that are associated with the production of miniature end-plate potentials. Examination of the neuronal membrane current during the occurrence of 822 miniature end-plate potentials produced no evidence of large channels. Thus it is unlikely that quantal release is mediated by such channels in the neuromuscular junction.
Translocation and Rearrangement of Myeloperoxidase Gene in Acute Promyelocytic Leukemia
Authors: Weil Susan C. , Rosner Gayle L. , Reid Martha S. , Chisholm Rex L. , Lemons Richard S. , Swanson Maurice S. , Carrino John J. , Diaz Manuel O. , Le Beau Michelle M.
Published: October 2006

Acute promyelocytic leukemia (subtype M3) is characterized by malignant promyelocytes exhibiting an abundance of abnormally large or aberrant primary granules. Myeloperoxidase (MPO) activity of these azurophilic granules, as assessed by cytochemical staining, is unusually intense. In addition, M3 is universally associated with a chromosomal translocation, t(15;17)(q22;q11.2). In this report, the
MPO
gene was localized to human chromosome 17 (q12-q21), the region of the breakpoint on chromosome 17 in the t(15;17), by somatic cell hybrid analysis and in situ chromosomal hybridization. By means of
MPO
complementary DNA clones for in situ hybridization and Southern blot analysis, the effect of this specific translocation on the
MPO
gene was examined. In all cases of M3 examined,
MPO
is translocated to chromosome 15. Genomic blot analyses indicate rearrangement of
MPO
in leukemia cells of two of four cases examined. These findings suggest that
MPO
may be pivotal in the pathogenesis of acute promyelocytic leukemia.
Radioimmunotherapy with Alpha-Particle-Emitting Immunoconjugates
Authors: Macklis Roger M. , Kinsey Berma M. , Kassis Amin I. , Ferrara James L. M. , Atcher Robert W. , Hines John J. , Coleman C. Norman , Adelstein S. James , Burakoff Steven J.
Published: October 2006

Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An α-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2
+
EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [
3
H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy.
Observation of Individual DNA Molecules Undergoing Gel Electrophoresis
Authors: Smith Steven B. , Aldridge Paul K. , Callis James B.
Published: October 2006

Individual DNA molecules undergoing agarose gel electrophoresis were viewed with the aid of a fluorescence microscope. Molecular shape and orientation were studied in both steady and pulsed electric fields. It was observed that (i) DNA macromolecules advanced lengthwise through the gel in an extended configuration, (ii) the molecules alternately contracted and lengthened as they moved, (iii) the molecules often became hooked around obstacles in a U-shape for extended periods, and (iv) the molecules displayed elasticity as they extended from both ends at once. A computer model has been developed that simulates the migration of the molecules in a rotating-field gel electrophoresis experiment.
Atrial Natriuretic Factor: A Hormone Produced by the Heart
Authors: de Bold Adolfo J.
Published: October 2006

Systematic studies on the significance of the secretory-like morphological characteristic of cardiac atrial muscle cells of mammals led to the finding that these cells produce a polypeptide hormone. This hormone, described in 1981 as atrial natriuretic factor (ANF), is diuretic (natriuretic), hypotensive, and has an inhibitory effect on renin and aldosterone secretion. Thus, ANF probably intervenes in the short- and long-term control of water and electrolyte balance and of blood pressure. Phylogenetically, ANF appears early, suggesting different functions for this peptide in accordance with each species' environment. Knowledge of the properties of the hormone should provide insights into the pathophysiology of important clinical entities and lead to the development of new pharmaceutical products.
Colocalization of Band 3 with Ankyrin and Spectrin at the Basal Membrane of Intercalated Cells in the Rat Kidney
Authors: Drenckhahn Detlev , Schlüter Karen , Allen David P. , Bennett Vann
Published: October 2006

An immunoreactive form of the anion channel protein of erythrocytes, band 3, has been identified in the rat kidney. It is found in the intercalated cells of the distal tubule and collecting ducts. Immunostaining specific for band 3 is confined to the basolateral plasma membrane of these cells, where this protein probably mediates the transport of bicarbonate across the tubular wall. Double-immunolabeling studies demonstrate that band 3 is colocalized with immunoreactive forms of ankyrin and spectrin along the basolateral plasma membrane. The polarized distribution of band 3 may be the result of the association of its cytoplasmic domain with ankyrin, which in turn links band 3 to spectrin and the cytoskeleton. These observations help to explain how the collecting ducts of the kidney can direct the transport of bicarbonate ions, thus maintaining the acid-base balance.
The 3′ Splice Site of Pre-Messenger RNA Is Recognized by a Small Nuclear Ribonucleoprotein
Authors: Chabot Benoit , Black Douglas L. , LeMaster David M. , Steitz Joan A.
Published: October 2006

A component present in splicing extracts selectively binds the 3′ splice site of a precursor messenger RNA (pre-mRNA) transcript of a human beta-globin gene. Since this component can be immunoprecipitated by either autoantibodies of the Sm class or antibodies specifically directed against trimethylguanosine, it is a small nuclear ribonucleoprotein (snRNP). Its interaction with the 3′ splice site occurs rapidly even at 0°C, does not require adenosine triphosphate, and is altered by certain mutations in the 3′ splice site region. Binding is surprisingly insensitive to treatment of the extract with micrococcal nuclease. The U5 particle is the only abundant Sm snRNP with a capped 5′ end that is equally resistant to micrococcal nuclease. This suggests that, in addition to the U1 and U2 snRNP's, U5 snRNP's participate in pre-mRNA splicing.
E1A Transcription Induction: Enhanced Binding of a Factor to Upstream Promoter Sequences
Authors: Kovesdi Imre , Reichel Ronald , Nevins Joseph R.
Published: October 2006

The adenovirus E1A gene product
trans
-activates a number of viral and cellular promoters. The mechanism for this transcriptional induction was investigated with an in vivo exoIII mapping technique to assay for proteins that interact with an E1A-inducible promoter. A protein bound to the early E2 promoter was detected in wild-type infected cells. In the absence of E1A induction, specific interactions at the promoter could not be detected, as indicated by the absence of an exoIII-protected fragment. However, if conditions were established that allowed transcription of the E2 gene in the absence of E1A, the same exoIII protection was observed as was found in the presence of E1A. These results suggest a model in which the efficient utilization of the E2 promoter is mediated by a cellular transcription factor. In the absence of E1A, the interaction can take place, but slowly and inefficiently in comparison with the interaction in the presence of E1A.
Evolution of Human Influenza A Viruses Over 50 Years: Rapid, Uniform Rate of Change in NS Gene
Authors: Buonagurio Deborah A. , Nakada Susumu , Parvin Jeffrey D. , Krystal Mark , Palese Peter , Fitch Walter M.
Published: October 2006

Variation in influenza A viruses was examined by comparison of nucleotide sequences of the NS gene (890 bases) of 15 human viruses isolated over 53 years (1933 to 1985). Changes in the genes accumulate with time, and an evolutionary tree based on the maximum parsimony method can be constructed. The evolutionary rate is approximately 2 × 10
-3
substitution per site per year in the NS genes, which is about 10
6
times the evolutionary rate of germline genes in mammals. This uniform and rapid rate of evolution in the NS gene is a good molecular clock and is compatible with the hypothesis that positive selection is operating on the hemagglutinin (or perhaps some other viral genes) to preserve random mutations in the NS gene.
Structural Heterogeneity and Functional Domains of Murine Immunoglobulin G Fc Receptors
Authors: Ravetch Jeffrey V. , Luster Andrew D. , Weinshank Richard , Kochan Jarema , Pavlovec Amalia , Portnoy Daniel A. , Hulmes Jeffrey , Pan Yu-Ching E. , Unkeless Jay C.
Published: October 2006

Binding of antibodies to effector cells by way of receptors to their constant regions (Fc receptors) is central to the pathway that leads to clearance of antigens by the immune system. The structure and function of this important class of receptors on immune cells is addressed through the molecular characterization of Fc receptors (FcR) specific for the murine immunoglobulin G isotype. Structural diversity is encoded by two genes that by alternative splicing result in expression of molecules with highly conserved extracellular domains and different transmembrane and intracytoplasmic domains. The proteins encoded by these genes are members of the immunoglobulin supergene family, most homologous to the major histocompatibility complex molecule E
β
. Functional reconstitution of ligand binding by transfection of individual FcR genes demonstrates that the requirements for ligand binding are encoded in a single gene. These studies demonstrate the molecular basis for the functional heterogeneity of FcR's, accounting for the possible transduction of different signals in response to a single ligand.
The Urban Homeless: Estimating Composition and Size
Authors: Rossi Peter H. , Wright James D. , Fisher Gene A. , Willis Georgianna
Published: October 2006

Although homelessness has been recognized as a serious and growing urban social problem, scientifically acceptable methods for estimating the composition and size of the homeless population have been lacking. A new research approach to estimating the size and composition of undomiciled urban populations is presented, and its utility is illustrated through a description of the literal homeless of Chicago. The homeless in the Chicago sample are unaffiliated persons living in extreme poverty, with high levels of physical and mental disability. Homelessness is interpreted as a manifestation of extreme poverty among persons without families in housing markets with declining stocks of inexpensive dwelling units suitable for single persons.
Gene Dosage of the Amyloid β Precursor Protein in Alzheimer's Disease
Authors: Podlisny Marcia Berman , Lee Gloria , Selkoe Dennis J.
Published: October 2006

The progressive deposition in the human brain of amyloid filaments composed of the amyloid β protein is a principal feature of Alzheimer's disease (AD). Densitometric analysis of Southern blots probed with a complementary DNA for the amyloid protein has been carried out to determine the relative dosage of this gene in genomic DNA of 14 patients with AD, 12 aged normal subjects, and 10 patients with trisomy 21 (Down syndrome). Whereas patients in the last group showed the expected 1.5-fold increase in dosage of this gene, none of the patients with AD had a gene dosage higher than that of the normal controls. These results do not support the hypothesis that the genetic defect in AD involves duplication of a segment of chromosome 21 containing the amyloid gene. Alternative mechanisms for the brain-specific increase in amyloid protein deposition in AD should be considered.
Cyclic AMP-Responsive DNA-Binding Protein: Structure Based on a Cloned Placental cDNA
Authors: Hoeffler James P. , Meyer Terry E. , Yun Yungdae , Jameson J. Larry , Habener Joel F.
Published: October 2006

Cyclic AMP (cAMP) is an intracellular second messenger that activates transcription of many cellular genes. A palindromic consensus DNA sequence, TGACGTCA, functions as a cAMP-responsive transcriptional enhancer (CRE). The CRE binds a cellular protein of 38 kD in placental JEG-3 cells. A placental λgt11 library was screened for expression of specific CRE-binding proteins with the CRE sequence as a radioactive probe. A cDNA encoding a protein of 326 amino acids with the binding properties of a specific CRE-binding protein (CREB) was isolated. The protein contains a COOH-terminal basic region adjacent to a sequence similar to the "leucine zipper" sequence believed to be involved in DNA binding and in protein-protein contacts in several other DNA-associated transcriptional proteins including the products of the c-
myc
, c-
fos
, and c-
jun
oncogenes and GCN4. The CREB protein also contains an NH2-terminal acidic region proposed to be a potential transcriptional activation domain. The putative DNA-binding domain of CREB is structurally similar to the corresponding domains in the phorbol ester-responsive c-
jun
protein and the yeast transcription factor GCN4.
Oxidative Autoactivation of Latent Collagenase by Human Neutrophils
Authors: Weiss S. J. , Peppin G. , Ortiz X. , Ragsdale C. , Test S. T.
Published: October 2006

The pathological destruction of collagen plays a key role in the development of inflammatory disease states affecting every organ system in the human body. Neutrophils localized at inflammatory sites can potentially degrade collagen by releasing a metalloenzyme, collagenase, which is stored in a latent inactive form. Triggered human neutrophils were shown to release and simultaneously activate their latent collagenase. The activation of the latent enzyme was coupled to an oxidative process that required the generation of a highly reactive oxygen metabolite, hypochlorous acid. Oxidative regulation of latent collagenase activity may be important in the pathogenesis of connective tissue damage in vivo.
Protection Against Lethal Hyperoxia by Tracheal Insufflation of Erythrocytes: Role of Red Cell Glutathione
Authors: van Asbeck B. Sweder , Hoidal John , Vercellotti Gregory M. , Schwartz Bruce A. , Moldow Charles F. , Jacob Harry S.
Published: October 2006

Intact erythrocytes placed into the tracheobronchial tree of hyperoxic rats dramatically improved their chances for survival. Over 70 percent of the animals so treated survived more than 12 days during continuous exposure to 95 percent oxygen, whereas all of the control animals died within 96 hours. Lungs from erythrocyte-protected rats showed almost none of the morphologic damage suffered by untreated animals. Erythrocytes containing cyanomethemoglobin were as beneficial as normal erythrocytes, but cells in which glutathione was partially blocked were significantly less protective. Analogous results were obtained in vitro:
51
Cr-labeled target cells released 70 to 90 percent of their label when exposed briefly to hydrogen peroxide or to toxic oxygen species generated by phorbol ester-stimulated neutrophils. Addition of intact erythrocytes decreased release by approximately 75 percent, but significantly less than this if red blood cell glutathione was partially blocked. These results suggest that insufflated erythrocytes, through their recyclable glutathione, protect rats from toxic oxygen species engendered by hyperoxia.
Expression in
Escherichia coli
of Open Reading Frame Gene Segments of HTLV-III
Authors: Chang N. T. , Chanda P. K. , Barone A. D. , McKinney S. , Rhodes D. P. , Tam S. H. , Shearman C. W. , Huang J. , Chang T. W. , Gallo R. C. , Wong-Staal F.
Published: October 2006

Human T-cell lymphotropic virus type III (HTLV-III), the causative agent of the acquired immune deficiency syndrome (AIDS), was recently isolated and its genomic structure analyzed by DNA cloning methods. In the studies reported here a combined cloning and expression system was used to identify HTLV-III encoded peptides that react immunologically with antibodies in sera from AIDS patients. Cloned HTLV-III DNA was sheared into approximately 500-base-pair fragments and inserted into an "open reading frame" expression vector, pMR100. The inserted DNA was expressed in
Escherichia coli
transformants as a polypeptide fused to the λCI protein at its amino terminus and to β-galactosidase at its carboxyl terminus. Sera from AIDS patients containing antibodies to HTLV-III were then used to screen for immunoreactive fusion proteins. Twenty clones, each specifying a fusion protein strongly reactive with AIDS serum, were identified. DNA sequence analysis indicated that the HTLV-III fragments were derived from the open reading frame DNA segments corresponding to the gag and pol gene coding regions and also the large open reading frame region (env-lor) located near the 3′ end of the viral genome.
Construction and Recovery of Viable Retroviral Genomes Carrying a Bacterial Suppressor Transfer RNA Gene
Authors: Lobel Leslie I. , Patel Mayuri , King Walter , Nguyen-Huu M. Chi , Goff Stephen P.
Published: October 2006

The integration of retroviral genomes into cellular DNA can induce mutations by altering the expression of nearby cellular genes and can serve to identify the gene affected. The construction of a retrovirus that stably carries a suppressor transfer RNA gene from
Escherichia coli
has allowed facile recovery of the viral genome in vectors marked with amber mutations. This virus can be used for rapid isolation of cellular sequences at the site of proviral insertion.
Protection of Mice Against Fatal Herpes Simplex Type 2 Infection by Liposomes Containing Muramyl Tripeptide
Authors: Koff Wayne C. , Showalter Stephen D. , Hampar Berge , Fidler Isaiah J.
Published: October 2006

Intravenous administration of liposomes containing muramyl tripeptide phosphatidylethanolamine, a lipophilic derivative of muramyl dipeptide that activates macrophages to a cytolytic state in situ, significantly protected mice against lethal challenge with herpes simplex virus type 2. These findings suggest that the systemic activation of macrophages by liposomes containing an immunomodulator can lead to prophylaxis of severe infections caused by herpesviruses.
The LDL Receptor Gene: A Mosaic of Exons Shared with Different Proteins
Authors: Südhof Thomas C. , Goldstein Joseph L. , Brown Michael S. , Russell David W.
Published: October 2006

The multifunctional nature of coated pit receptors predicts that these proteins will contain multiple domains. To establish the genetic basis for these domains, we have determined the exon organization of the gene for the low-density lipoprotein (LDL) receptor. This gene is more than 45 kilobases in length and contains 18 exons, most of which correlate with functional domains previously defined at the protein level. Thirteen of the 18 exons encode protein sequences that are homologous to sequences in other proteins: five of these exons encode a sequence similar to one in the C9 component of complement; three exons encode a sequence similar to a repeat sequence in the precursor for epidermal growth factor (EGF) and in three proteins of the blood clotting system (factor IX, factor X, and protein C); and five other exons encode nonrepeated sequences that are shared only with the EGF precursor. The LDL receptor appears to be a mosaic protein built up of exons shared with different proteins, and it therefore belongs to several supergene families.
The
x
Gene Is Essential for HTLV Replication
Authors: Chen Irvin S. Y. , Slamon Dennis J. , Rosenblatt Joseph D. , Shah Neil P. , Quan Shirley G. , Wachsman William
Published: October 2006

The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in man and will transform normal human T cells in vitro. The mechanism of malignant transformation by HTLV is unknown but appears to be distinct from that of other classes of retroviruses, which induce malignant transformation through viral or cellular oncogenes. Recently a new gene, termed
x
, was identified in HTLV. This gene has been hypothesized to be the transforming gene of HTLV because of its conservation within the HTLV class of retroviruses. By in vitro mutagenesis of the HTLV-II
x
gene, it is now demonstrated that the presence of a functional
x
gene product is necessary for efficient HTLV transcription. Therefore, these studies provide direct evidence for an important function of the
x
gene in HTLV replication. The functional analogies between the
x
gene and transcriptional regulatory genes of some DNA viruses suggest that these viruses share similar mechanisms for cellular transformation.
An RNA Processing Activity That Debranches RNA Lariats
Authors: Ruskin Barbara , Green Michael R.
Published: October 2006

The excised introns of pre-messenger RNA's (pre-mRNA's) and intron-containing splicing intermediates are in a lariat configuration in which the 5′ end of the intron is covalently joined by a 2′,5′-phosphodiester bond to a specific adenosine residue near the 3′ end of the intron. A 2′,5′-phosphodiesterase activity in HeLa cell extracts has been detected that debranches RNA lariats, converting them to linear RNA molecules by specific cleavage of the 2′,5′-phosphodiester bond. This lariat debranching activity is distinct from previously reported 2′,5′-phosphodiesterases with regard to its biochemical and substrate requirements as well as its stringent cleavage specificity. The debranching activity is observed only if the RNA lariats generated during in vitro processing are deproteinized and added back to the extract. These results suggest that during the normal in vitro splicing reaction the 2′,5′-phosphodiester bond of RNA lariats is protected from cleavage by the lariat debranching activity.
The
neu
Gene: an
erb
B-Homologous Gene Distinct from and Unlinked to the Gene Encoding the EGF Receptor
Authors: Schechter Alan L. , Hung Mien-Chie , Vaidyanathan Lalitha , Weinberg Robert A. , Yang-Feng Teresa L. , Francke Uta , Ullrich Axel , Coussens Lisa
Published: October 2006

The
neu
oncogene, identified in ethylnitrosourea-induced rat neuroglioblastomas, had strong homology with the
erb
B gene that encodes the epidermal growth factor receptor. This homology was limited to the region of
erb
B encoding the tyrosine kinase domain. It was concluded that the
neu
gene is a distinct novel gene, as it is not coamplified with sequences encoding the EGF receptor in the genome of the A431 tumor line and it maps to human chromosome 17.
Benzodiazepine Receptor-Mediated Chemotaxis of Human Monocytes
Authors: Ruff Michael R. , Pert Candace B. , Weber Richard J. , Wahl Larry M. , Wahl Sharon M. , Paul Steven M.
Published: October 2006

Benzodiazepines, which are widely prescribed for their antianxiety effects, are shown to be potent stimulators of human monocyte chemotaxis. The chemotactic effects of benzodiazepine receptor agonists were blocked by the peripheral benzodiazepine receptor antagonist PK-11195, suggesting that these effects are mediated by the peripheral-type benzodiazepine receptor. Diazepam was also active in inducing chemotaxis. Binding studies on purified monocytes revealed high-affinity peripheral benzodiazepine receptors, and the displacement potencies of various benzodiazepines correlated with their relative potencies in mediating chemotaxis. The demonstration of functional benzodiazepine receptors on human monocytes, together with recent evidence of receptor-mediated monocyte chemotaxis by other psychoactive peptides (such as opiate peptides), suggests a biochemical substrate for psychosomatic communication.
The Epidemiology of AIDS: Current Status and Future Prospects
Authors: Curran James W. , Morgan W. Meade , Hardy Ann M. , Jaffe Harold W. , Darrow William W. , Dowdle Walter R.
Published: October 2006

The reported incidence of acquired immune deficiency syndrome (AIDS) continues to increase in countries throughout the world. On the basis of a polynomial model for extrapolation, the cumulative number of cases diagnosed and reported since 1981 in the United States is expected to double during the next year with over 12,000 additional cases projected to be diagnosed by July 1986. The annual incidence rates for single (never-married) men in Manhattan and San Francisco, intravenous drug users in New York City and New Jersey, and persons with hemophilia A ranged from 261 to 350 per 100,000 population during 1984. For single men aged 25 to 44 years in Manhattan and San Francisco, AIDS was the leading cause of premature mortality in 1984 as measured by years of potential life lost. Infection with HTLV-III/LAV is considerably more common than reported AIDS in high-risk populations and can persist at least for several years, so the presence of specific antibody should be considered presumptive evidence of current infection. The screening of donated blood and plasma for antibody to HTLV-III/LAV and use of safer clotting factor concentrates should greatly reduce HTLV-III/LAV transmission through blood and blood products. Most HTLV-III/LAV infections occur through sexual transmission, use of contaminated needles, and as a result of infected mothers passing the virus to newborns. Continued research commitment is needed to develop an HTLV-III/LAV vaccine and therapy for this infection. In the interim, widespread community efforts are needed to minimize transmission.
Intercontinental Spread of a New Antibiotic Resistance Gene on an Epidemic Plasmid
Authors: O'Brien Thomas F. , del Pilar Pla Maria , Mayer Kenneth H. , Kishi Hiroichi , Gilleece Elaine , Syvanen Michael , Hopkins John D.
Published: October 2006

Bacteria of different genera isolated at nine medical centers in different parts of the United States and at one center in Venezuela during the first decade of gentamicin usage carried the gentamicin resistance gene 2"-aminoglycoside nucleotidyltransferase on the same transferable plasmid. Such widespread dissemination of a newly observed resistance gene on one plasmid suggests that a new resistance gene may emerge once on a single plasmid, which then carries it to other centers and other plasmids. The resistance gene might, therefore, be contained if detected early.
Cystic Fibrosis Locus Defined by a Genetically Linked Polymorphic DNA Marker
Authors: Tsui Lap-Chee , Buchwald Manuel , Barker David , Braman Jeffrey C. , Knowlton Robert , Schumm James W. , Eiberg Hans , Mohr Jan , Kennedy Dara , Plavsic Natasa , Zsiga Martha , Markiewicz Danuta , Akots Gita , Brown Valerie , Helms Cynthia , Gravius Thomas , Parker Carol , Rediker Kenneth , Donis-Keller Helen
Published: October 2006

A polymorphic DNA marker has been found genetically linked, in a set of 39 human families, to an autosomal recessive gene that causes cystic fibrosis (CF), a disease affecting one in 2000 Caucasian children. The DNA marker (called
D0CRI-917
) is also linked to the PON locus, which by independent evidence is linked to the CF locus. The best estimates of the genetic distances are 5 centimorgans between the DNA marker and PON and 15 centimorgans between the DNA marker and the CF locus, meaning that the location of the disease gene has been narrowed to about 1 percent of the human genome (about 30 million base pairs). Although the data are consistent with the interpretation that a single locus causes cystic fibrosis, the possibility of genetic heterogeneity remains. The discovery of a linked DNA polymorphism is the first step in molecular analysis of the CF gene and its causative role in the disease.
Ribavirin: Efficacy in the Treatment of Murine Autoimmune Disease
Authors: Klassen Lynell W. , Budman Daniel R. , Williams Gary W. , Steinberg Alfred D. , Gerber N. Lynn
Published: October 2006

Ribavirin, a drug with known antiviral activity, was given to mice with established lupus nephritis. Ribavirin was effective in prolonging survival, reducing the titer of antibodies to DNA, and reversing proteinuria. Other antiviral agents were not effective in the dosages used.
Binding of HTLV-III/LAV to T4
+
T Cells by a Complex of the 110K Viral Protein and the T4 Molecule
Authors: McDougal J. S. , Kennedy M. S. , Sligh J. M. , Cort S. P. , Mawle A. , Nicholson J. K. A.
Published: October 2006

Human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV) is tropic for human T cells with the helper-inducer phenotype, as defined by reactivity with monoclonal antibodies specific for the T4 molecule. Treatment of T4
+
T cells with monoclonal antibodies to T4 antigen blocks HTLV-III/LAV binding, syncytia formation, and infectivity. Thus, it has been inferred that the T4 molecule itself is a virus receptor. In the present studies, the surfaces of T4
+
T cells were labeled radioactively, and then the cells were exposed to virus. After the cells were lysed, HTLV-III/LAV antibodies were found to precipitate a surface protein with a molecular weight of 58,000 (58K). By blocking and absorption experiments, this 58K protein was identified as the T4 molecule. No cell-surface structures other than the T4 molecule were involved in the antibody-antigen complex formation. Two monoclonal antibodies, each reactive with a separate epitope of the T4 molecule, were tested for their binding capacities in the presence of HTLV-III/LAV. When HTLV-III/LAV was bound to T4
+
T cells, the virus blocked the binding of one of the monoclonal antibodies, T4A (OKT4A), but not of the other, T4 (OKT4). When HTLV-III/LAV was internally radiolabeled and bound to T4
+
T cells which were then lysed, a viral glycoprotein of 110K (gp110) coprecipitated with the T4 molecule. The binding of gp110 to the T4 molecule may thus be a major factor in HTLV-III/LAV tropism and may prove useful in developing therapeutic or preventive measures for the acquired immune deficiency syndrome.
A Mutation in the R Body-Coding Sequence Destroys Expression of the Killer Trait in
P. tetraurelia
Authors: Dilts Judith A. , Quackenbush Robert L.
Published: October 2006

This report describes a mutant strain of
Caedibacter taeniospiralis
169 that does not produce refractile (R) bodies or kill sensitive paramecia, but still renders its host resistant to killing by wild-type strains of
Caedibacter taeniospiralis
. The mutation is due to insertion of a 7.5-kilobase, transposon-like element into the R body-coding region of the plasmid pKAP169. The results provide strong evidence that R body synthesis is required for expression of the killer trait.
The Structure, Function, and Expression of Interleukin-2 Receptors on Normal and Malignant Lymphocytes
Authors: Waldmann Thomas A.
Published: October 2006

Antigen or mitogen-induced activation of resting T cells induces the synthesis of interleukin-2 (IL-2) as well as the expression of specific cell surface receptors for this lymphokine. Failure of the production of either IL-2 or its receptor results in a failure of the T-cell immune response. The receptor is composed of a 33,000-dalton (251-amino acid) peptide precursor that is post-translationally glycosylated into the mature 55,000-dalton form. In contrast to resting T cells, human T-cell lymphotrophic virus I (HTLV-I)-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL-2 receptors are present on the malignant T cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are treated with a monoclonal antibody that binds to the IL-2 receptor.
Activation of the AIDS Retrovirus Promoter by the Cellular Transcription Factor, Sp1
Authors: Jones Katherine A. , Kadonaga James T. , Luciw Paul A. , Tjian Robert
Published: October 2006

The nature and position of transcriptional control elements responsible for the expression of genes encoded by the retrovirus associated with acquired immune deficiency syndrome (AIDS) have not been precisely defined. In this study it is shown that the mammalian Sp1 transcription factor binds to promoter sequences within the AIDS retrovirus long terminal repeat (LTR) and activates RNA synthesis five- to eightfold in reconstituted reactions in vitro. Experiments in which regions of DNA were protected from added reagents by specifically bound proteins (footprinting) indicated that the upstream promoter region of the AIDS virus LTR lies between -45 and -77 (relative to the RNA start site, +1) and contains three tandem, closely spaced Sp1 binding sites of variable affinity. Base-substitution mutations targeted to one or all three Sp1 binding sites were found both to eliminate the binding of Sp1 and to cause up to a tenfold reduction in transcriptional efficiency in vitro. These findings suggest that one important component of the AIDS virus transcriptional control region interacts with a cellular transcription factor, Sp1, and that this factor must function in conjunction with transcriptional elements located downstream of the RNA cap site to mediate the response of the LTR to viral
trans
-activation.
Identification and Characterization of the Protein Encoded by the Human N-
myc
Oncogene
Authors: Slamon Dennis J. , Boone Thomas C. , Seeger Robert C. , Keith Duane E. , Chazin Vicki , Lee Hyun C. , Souza Lawrence M.
Published: October 2006

The human N-
myc
gene is related to the c-
myc
proto-oncogene, and has been shown to have transforming potential in vitro. Many studies have reported amplification of N-
myc
in human neuroblastoma and retinoblastoma cell lines. In primary tumors, amplification of the gene was found to correlate directly with behavior of the tumor. Specific restriction fragments of a partial complementary DNA clone of N-
myc
from LA-N-5 human neuroblastoma cells were placed into a bacterial expression vector for the purpose of producing antigens representative of the N-
myc
protein. Rabbits immunized with these antigens produced antisera that recognized a protein of 62-64 kilodaltons in neuroblastoma cells. By several criteria, this protein appears to be part of the same proto-oncogene family as the c-
myc
protein. Moreover, the antisera to fragments of this protein were capable of histochemically identifying malignant cells in clinical specimens.
Coronavirus Infection Induces H-2 Antigen Expression on Oligodendrocytes and Astrocytes
Authors: Suzumura Akio , Lavi Ehud , Weiss Susan R. , Silberberg Donald H.
Published: October 2006

Infection of the central nervous system by mouse hepatitis virus strain A59, a murine neurotropic coronavirus, induces class I major histocompatibility complex antigens on mouse oligodendrocytes and astrocytes, cells that do not normally express these antigens on their surfaces. This induction, which occurs through soluble factors elaborated by infected glial cells, potentially allows immunocytes to interact with the glial cells and may play a critical role in the pathogenesis of virus-induced, immune-mediated demyelination in the central nervous system.
Neutralization of HTLV-III/LAV Replication by Antiserum to Thymosin α
1
Authors: Sarin Prem S. , Sun Daisy K. , Thornton Arthur H. , Naylor Paul H. , Goldstein Allan L.
Published: October 2006

An antiserum prepared against thymosin α
1
, a hormone secreted by the thymus gland, effectively neutralized the AIDS-associated virus [HTLV-III/LAV (clone BH-10)] and blocked its replication in H9 cells. Reverse transcriptase activity and expression of the HTLV-III/LAV antigens p15 and p24 were inhibited by purified immunoglobulin G preparations of antisera to thymosin α
1
. The antiviral activity of the antiserum was found to be due to a region of homology between thymosin α
1
and p17, a product of the
gag
gene of HTLV-III/LAV. Comparison of the primary sequences of thymosin α
1
and the
gag
protein revealed a 44% to 50% homology in an 18-amino acid region, between positions 11 and 28 on thymosin α
1
and 92 and 109 on the
gag
protein. The effectiveness of the thymosin α
1
antiserum and of immunoglobulin G-enriched preparations in blocking replication of HTLV-III(BH-10) in H9 cells suggests a novel approach to the development of an AIDS vaccine. A vaccine directed against the
gag
protein might overcome the problem of genetic drift in the envelope region of the virus and be useful against all genetic variants of HTLV-III/LAV.
Studies and Perspectives of Protein Kinase C
Authors: Nishizuka Yasutomi
Published: October 2006

Protein kinase C, an enzyme that is activated by the receptor-mediated hydrolysis of inositol phospholipids, relays information in the form of a variety of extracellular signals across the membrane to regulate many Ca
2+
-dependent processes. At an early phase of cellular responses, the enzyme appears to have a dual effect, providing positive forward as well as negative feedback controls over various steps of its own and other signaling pathways, such as the receptors that are coupled to inositol phospholipid hydrolysis and those of some growth factors. In biological systems, a positive signal is frequently followed by immediate negative feedback regulation. Such a novel role of this protein kinase system seems to give a logical basis for clarifying the biochemical mechanism of signal transduction, and to add a new dimension essential to our understanding of cell-to-cell communication.
Psychotomimesis Mediated by κ Opiate Receptors
Authors: Pfeiffer Andreas , Brantl Victor , Herz Albert , Emrich Hinderk M.
Published: October 2006

The κ opioid agonists are analgesics that seem to be free of undesired morphine-like effects. Their dysphoric actions observed with the κ agonist cyclazocine are thought to be mediated by an action at σ-phencyclidine receptors. The benzomorphan κ agonist MR 2033 is inactive at σ-phencyclidine receptors. In male subjects, the opiate-active (-)-isomer, but not the (+)-isomer, elicited dose-dependent dysphoric and psychotomimetic effects that were antagonized by naloxone. Thus, κ opiate receptors seem to mediate psychotomimetic effects. In view of the euphorigenic properties of μ agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.
Chromosomal Localization of Muscle Nicotinic Acetylcholine Receptor Genes in the Mouse
Authors: Heidmann Odile , Buonanno Andrés , Geoffroy Brigitte , Robert Benoît , Guénet Jean-Louis , Merlie John P. , Changeux Jean-Pierre
Published: October 2006

The chromosomal localization of the genes encoding the four subunits of muscle nicotinic receptor was determined by analyzing restriction fragment length polymorphisms between two mouse species
Mus musculus domesticus
(DBA/2) and
Mus spretus
(SPE). Analysis of the progeny of the interspecies mouse backcross (DBA/2 × SPE) × DBA/2 showed that the α-subunit gene cosegregates with the α-cardiac actin gene on chromosome 17, that the β-subunit gene is located on chromosome 11, and that the γ- and δ-subunit genes cosegregate and are located on chromosome 1.
AIDS in Africa: An Epidemiologic Paradigm
Authors: Quinn Thomas C. , Mann Jonathan M. , Curran James W. , Piot Peter
Published: October 2006

Cases of the acquired immune deficiency syndrome (AIDS) have been reported in countries throughout the world. Initial surveillance studies in Central Africa suggest an annual incidence of AIDS of 550 to 1000 cases per million adults. The male to female ratio of cases is 1:1, with age- and sex-specific rates greater in females less than 30 years of age and greater in males over age 40. Clinically, AIDS in Africans is often characterized by a diarrhea-wasting syndrome, opportunistic infections, such as tuberculosis, cryptococcosis, and cryptosporidiosis, or disseminated Kaposi's sarcoma. From 1 to 18% of healthy blood donors and pregnant women and as many as 27 to 88% of female prostitutes have antibodies to human immunodeficiency virus (HIV). The present annual incidence of infection is approximately 0.75% among the general population of Central and East Africa. The disease is transmitted predominantly by heterosexual activity, parenteral exposure to blood transfusions and unsterilized needles, and perinatally from infected mothers to their newborns, and will continue to spread rapidly where economic and cultural factors favor these modes of transmission. Prevention and control of HIV infection through educational programs and blood bank screening should be an immediate public health priority for all African countries.