bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutagenic Activity of Nitrite-Treated Foods: Human Stomach Cancer May Be Related to Dietary Factors
Authors: Marquardt Hildegard , Rufino Fred , Weisburger John H.
Published: October 2006

By the
Salmonella typhimurium
test, extracts of Japanese raw fish treated in the laboratory with nitrite showed mutagenic activity which is prevented by addition of ascorbate. Extracts from similarly treated beef and hot dogs were nonmutagenic. The data conform to a working concept that the high stomach cancer incidence in Japanese and certain other populations may be due to specific dietary factors of an alkylnitrosamide type.
Hemoglobin Ontogenesis: Test of the Gene Excision Hypothesis
Authors: Papayannopoulou Th. , Nute P. E. , Stamatoyannopoulos G. , McGuire T. C.
Published: October 2006

The gene excision hypothesis of hemoglobin ontogenesis was tested in persons with HbSC disease, with the use of monospecific fluorescent antibodies for the identification of hemoglobins S, C, and F in individual erythrocytes. The results are incompatible with the prediction that only one gamma- or beta-globin gene may be active in any single chromosome and provide further evidence for incomplete repression of gamma-globin genes lying
cis
to active beta-globin genes.
Signal Transduction Through the EGF Receptor Transfected in IL-3-Dependent Hematopoietic Cells
Authors: Pierce Jacalyn H. , Ruggiero Marco , Fleming Timothy P. , Di Fiore Pier Paolo , Greenberger Joel S. , Varticovski Lyuba , Schlessinger Joseph , Rovera Giovanni , Aaronson Stuart A.
Published: October 2006

An expression vector for the epidermal growth factor (EGF) receptor was introduced into the 32D myeloid cell line, which is devoid of EGF receptors and absolutely dependent on interleukin-3 (IL-3) for its proliferation and survival. Expression of the EGF receptor conferred the ability to utilize EGF for transduction of a mitogenic signal. When the transfected cells were propagated in EGF, they exhibited a more mature myeloid phenotype than was observed under conditions of IL-3-directed growth. Moreover, exposure to EGF led to a rapid stimulation of phosphoinositide metabolism, while IL-3 had no detectable effect on phosphoinositide turnover either in control or EGF receptor-transfected 32D cells. Although the transfected cells exhibited high levels of functional EGF receptors, they remained nontumorigenic. In contrast, transfection of v-
erb
B, an amino-terminal truncated form of the EGF receptor with constitutive tyrosine kinase activity, not only abrogated the IL-3 growth factor requirement of 32D cells, but caused them to become tumorigenic in nude mice. These results show that a naive hematopoietic cell expresses all of the intracellular components of the EGF-signaling pathway necessary to evoke a mitogenic response and sustain continuous proliferation.
Yeast
KEX2
Endopeptidase Correctly Cleaves a Neuroendocrine Prohormone in Mammalian Cells
Authors: Thomas Gary , Thorne Barbara A. , Thomas Laurel , Allen Richard G. , Hruby Dennis E. , Fuller Robert , Thorner Jeremy
Published: October 2006

Mammalian cell lines (BSC-40, NG108-15, and GH
4
C
1
) that cannot process the murine neuroendocrine peptide precursor prepro-opiomelanocortin (mPOMC) when its synthesis is directed by a vaccinia virus vector were coinfected with a second recombinant vaccinia virus carrying the yeast
KEX2
gene, which encodes an endopeptidase that cleaves at pairs of basic amino acid residues. mPOMC was cleaved intracellularly to a set of product peptides normally found in vivo, including mature γ-lipotropin and β-endorphin
1-31
. In GH
4
C
1
cells (a rat pituitary line), product peptides were incorporated into stored secretory granules. These results suggest that the inability of any particular cell line to process a prohormone precursor is due to the absence of a suitable endogenous processing enzyme.
The National Institutes of Health: Some Critical Years, 1955-1957
Authors: Shannon James A.
Published: October 2006

It has been my pleasure to participate in the conversion of a small but superb federal institution into a driving force for the development of excellence in the nation's biomedical sciences. The initial step was the establishment of an adequate science base for the developing enterprise. Given this, it was agreed that the nation's medical establishment could use the evolving support system effectively. What follows is a brief consideration of some events contributing to the reduction of a possibility to reality. Much of the material that follows was derived from a presentation to a presidential commission established by President Gerald Ford in 1975 and later published as a supplement to the
Journal of Medical Education
. The latter encompassed what happened during the critical years of development. But it seemed too recent at that time to discuss with grace the "how" of program changes. It is the "how of things" that will be treated in this article.
The Role of Protein Structure in Chromatographic Behavior
Authors: Regnier Fred E.
Published: October 2006

Chromatographic retention is determined by a relatively small number of amino acids located in a chromatographic contact region on the surface of a polypeptide. This region is determined by the mode of separation and the amino acid distribution within the polypeptide. The contact area may be as small as a few hundred square angstroms in bioaffinity chromatography. In contrast, the contact region in ion exchange, reversed phase, hydrophobic interaction and the other nonbioaffinity separation modes is much broader, ranging from one side to the whole external surface of a polypeptide. Furthermore, structural changes that alter the chromatographic contact region will alter chromatographic properties. Thus, although immunosorbents can be very useful in purifying proteins of similar primary structure, they will be ineffective in discriminating between small, random variations within a structure. Nonbioaffinity columns complement affinity columns in probing a much larger portion of solute surface and being able to discriminate between protein variants.
Development of the Primary Antibody Repertoire
Authors: Alt Frederick W. , Blackwell T. Keith , Yancopoulos George D.
Published: October 2006

The ability to generate a diverse immune response depends on the somatic assembly of genes that encode the antigen-binding portions of immunoglobulin molecules. In this article, we discuss the mechanism and control of these genomic rearrangement events and how aspects of this process are involved in generating the primary antibody repertoire.
Low Plasma Cholesterol Levels Caused by a Short Deletion in the Apolipoprotein B Gene
Authors: Young Stephen G. , Northey Susan T. , McCarthy Brian J.
Published: October 2006

Familial hypobetalipoproteinemia is a syndrome in which the plasma levels of apolipoprotein B (apo-B) and cholesterol are abnormally low. A truncated species of apo-B was identified in the plasma lipoproteins of members of a kindred with familial hypobetalipoproteinemia. DNA sequencing studies on genomic clones and enzymatically amplified genomic DNA samples revealed a four-base pair deletion in the apo-B gene. This short deletion, which results in a frameshift and a premature stop codon, accounts for the truncated apo-B species and explains the low apo-B and low cholesterol levels in this family.
Rejection of Male Skin Grafts by Splenectomized Female Mice
Authors: Coons Teresa A. , Goldberg Ellen H.
Published: October 2006

Female mice of the C3H strain normally do not reject skin grafts from males of the same strain; however, 40 percent of splenectomized C3H female mice completely rejected C3H male skin grafts applied 2 weeks later. All splenectomized females showed at least transitory signs of graft rejection.
Assemblage of Ortho Cleavage Route for Simultaneous Degradation of Chloro- and Methylaromatics
Authors: Rojo F. , Pieper D. H. , Engesser K.-H. , Knackmuss H.-J. , Timmis K. N.
Published: October 2006

Genetic engineering is a powerful means of accelerating the evolution of new biological activities and has considerable potential for constructing microorganisms that can degrade environmental pollutants. Critical enzymes from five different catabolic pathways of three distinct soil bacteria have been combined in patchwork fashion into a functional ortho cleavage route for the degradation of methylphenols and methylbenzoates. The new bacterium thereby evolved was able to degrade and grow on mixtures of chloro- and methylaromatics that were toxic even for the bacteria that could degrade the individual components of the mixtures. Except for one enzymatic step, the pathway was fully regulated and its component enzymes were only synthesized in response to the presence of pathway substrates.
Propolypeptide of von Willebrand Factor Circulates in Blood and Is Identical to von Willebrand Antigen II
Authors: Fay Philip J. , Kawai Yohko , Wagner Denisa D. , Ginsburg David , Bonthron David , Ohlsson-Wilhelm Betsy M. , Chavin Stephen I. , Abraham George N. , Handin Robert I. , Orkin Stuart H. , Montgomery Robert R. , Marder Victor J.
Published: October 2006

The generally mild bleeding disorder of von Willebrand disease is associated with abnormalities of two distinct plasma proteins, the large multimeric von Willebrand factor (vWF), which mediates platelet adhesion, and von Willebrand antigen II (vW AgII), which is of unknown function. The two proteins were found to have a common biosynthetic origin in endothelial cells and megakaryocytes, which explains their simultaneous absence in the severe form of this hereditary disease. Shared amino acid sequences from a 100-kilodalton plasma glycoprotein and from vW AgII are identical to amino acid sequences predicted from a complementary DNA clone encoding the 5′ end of vWF. In addition, these proteins have identical molecular weights and immunologic cross reactivities. Monoclonal antibodies prepared against both proteins recognize epitopes on the pro-vWF subunit and on a 100-kilodalton protein that are not present on the mature vWF subunit in endothelial cell lysates. In contrast, polyclonal antibodies against vWF recognize both pro-vWF and vWF subunits. Thus, the 100-kilodalton plasma glycoprotein and vW AgII are identical proteins and represent an extremely large propolypeptide that is first cleaved from pro-vWF during intracellular processing and then released into plasma.
Intracellular Accumulation of T-Cell Receptor Complex Molecules in a Human T-Cell Line
Authors: Tse Doris B. , Al-Haideri Maysoon , Pernis Benvenuto , Cantor Charles R. , Wang Chang Yi
Published: October 2006

This work was aimed at understanding the mechanisms of T-lymphocyte function by studying the cellular distribution and traffic of molecules of the T-cell receptor complex. The accumulation of specific molecules in intracytoplasmic vesicles is related to the activation of T lymphocytes. Some of these molecules include acid hydrolases, the transferrin receptor, and class I antigens of the major histocompatibility complex. Molecules of the T-cell receptor complex have now also been found in intracytoplasmic vesicles in a human T-cell line derived from a lymphoblastic leukemia. Such vesicles were tightly associated with the cytoplasmic microtubule network. One functional aspect of this association is a cellular pathway by which vesicles traveling to and from the cell surface converge in an area of the cells that is rich in processing enzymes.
Splicing of Messenger RNA Precursors
Authors: Sharp Phillip A.
Published: October 2006

A general mechanism for the splicing of nuclear messenger RNA precursors in eukaryotic cells has been widely accepted. This mechanism, which generates lariat RNAs possessing a branch site, seems related to the RNA-catalyzed reactions of self-splicing introns. The splicing of nuclear messenger RNA precursors involves the formation of a multicomponent complex, the spliceosome. This splicing body contains at least three different small nuclear ribonucleoprotein particles (snRNPs), U2, U5, and U4 + U6. A complex containing precursor RNA and the U2 snRNP particle is a likely intermediate in the formation of the spliceosome.
Cellular Localization of Somatomedin (Insulin-Like Growth Factor) Messenger RNA in the Human Fetus
Authors: Han Victor K. M. , D'Ercole A. Joseph , Lund P. Kay
Published: October 2006

The somatomedins or insulin-like growth factors (IGFs) are synthesized in many organs and tissues, but the specific cells that synthesize them in vivo have not been defined. By in situ hybridization histochemistry, IGF I (somatomedin C) and IGF II messenger RNAs were localized to connective tissues or cells of mesenchymal origin in 14 organs and tissues from human fetuses. IGF messenger RNAs were localized to perisinusoidal cells of liver, to perichondrium of cartilage, to sclera of eye, and to connective tissue layers, sheaths, septa, and capsules of each organ and tissue. All of the hybridizing regions are comprised predominantly of fibroblasts or other cells of mesenchymal origin. Because these cells are widely distributed and anatomically integrated into tissues and organs, they are ideally located for production of IGFs, which may exert paracrine effects on nearby target cells.
Selective Inactivation of Influenza C Esterase: A Probe for Detecting 9-
O
-Acetylated Sialic Acids
Authors: Muchmore Elaine A. , Varki Ajit
Published: October 2006

The influenza C virus (INF-C) hemagglutinin recognizes 9-
O
-acetyl-N-acetylneuraminic acid. The same protein contains the receptor-destroying enzyme (RDE), which is a 9-
O
-acetyl-esterase. The RDE was inactivated by the serine esterase inhibitor diisopropyl fluorophosphate (DFP). [
3
H]DFP-labeling localized the active site to the heavy chain of the glycoprotein. DFP did not alter the hemagglutination or fusion properties of the protein, but markedly decreased infectivity of the virus, demonstrating that the RDE is important for primary infection. Finally, DFP-treated INF-C bound specifically and irreversibly to cells expressing 9-
O
-acetylated sialic acids. This provides a probe for a molecule that was hitherto very difficult to study.
Does the Binding of Cyclosporine to Calmodulin Result in Immunosuppression?
Authors: LeGrue Stephen J. , Turner Rodney , Weisbrodt Norman , Dedman John R.
Published: October 2006

The cyclosporines are a family of cyclic endecapeptides that cause a profound suppression of primary immune stimulation both in vitro and in vivo. Recently, the regulatory protein calmodulin (CaM) has been implicated as a target for cyclosporin A (CsA) binding. This study utilized two less-active isomers of CsA to evaluate the specificity and biological significance of CaM binding. The three cyclosporines exhibited equivalent in vitro binding to CaM, regardless of immunosuppressive activity. Furthermore, CaM-dependent enzyme systems were inhibited equally by active and inactive cyclosporines, but only at concentrations 100 times those necessary to block lymphocyte activation. Thus the exquisite immunosuppressive stereospecificity displayed by cyclosporine isomers is not reflected in the binding to and inhibition of CaM, suggesting that inhibition of CaM-dependent processes is not sufficient to explain the immunosuppressive activity of CsA.
Computer Graphic Display Method for Visualizing Three-Dimensional Biological Structures
Authors: Jiménez Javier , Santisteban Antonio , Carazo José María , Carrascosa José L.
Published: October 2006

A computer graphic display method that produces two-dimensional perspective views of three-dimensional objects is presented. The method is applied to the reconstruction at a resolution of 2.2 nanometers of the neck of bacteriophage φ29, obtained from transmission electron micrographs processed by the direct Fourier method. The combined use of directed illumination, reflectance models, color, and different levels of transparency provides a powerful tool for a better interpretation of the three-dimensional structure, allowing improved correlation with genetic, structural, and biochemical data.
Structure of the GDP Domain of EF-Tu and Location of the Amino Acids Homologous to
ras
Oncogene Proteins
Authors: Jurnak Frances
Published: October 2006

A 2.7 angstrom resolution x-ray diffraction analysis of a trypsin-modified form of the
Escherichia coli
elongation factor Tu reveals that the GDP-binding domain has a structure similar to that of other nucleotide-binding proteins. The GDP ligand is located at the COOH-terminal end of the β sheet and is linked to the protein via a Mg
2+
ion salt bridge. The location of the guanine ring is unusual; the purine ring is located on the outer edge of the domain, not deep within a hydrophobic pocket. The amino acids from Pro
10
to Arg
44
and from Gly
59
to Glu
190
have been assigned to the electron density with computer graphic techniques, and the resulting model is consistent with all known biochemical data. An analysis of the structure reveals that four regions of the amino acid sequence that are homologous with the family of
ras
oncogene proteins, termed p21, are located in the vicinity of the GDP-binding site, and most of the invariant amino acids shared by the proteins interact directly with the GDP ligand.
Cell-Specific Expression of the Rat Insulin Gene: Evidence for Role of Two Distinct 5′ Flanking Elements
Authors: Edlund Thomas , Walker Michael D. , Barr Philip J , Rutter William J.
Published: October 2006

The 5′ flanking DNA of the rat insulin I gene contains sequences controlling cell-specific expression. Analysis of this region by replacement of specific portions with nondiscriminatory control elements from viral systems shows that a transcriptional enhancer is located in the distal portion of the 5′ flanking DNA; its position has been mapped by deletion analysis. Additional experiments suggest that another distinct regulatory element is located more proximal to the transcription start site. The activity of both elements is restricted to pancreatic B cells. The combinatorial effect of multiple control elements could explain the cell-specific expression of insulin genes.
Ethanol Neurotoxicity: Effects on Neurite Formation and Neurotrophic Factor Production in Vitro
Authors: Dow Kimberly E. , Riopelle Richard J.
Published: October 2006

The effects of ethanol on chick embryo sensory and spinal cord neurons growing on one of several biological substrates (poly-D-lysine, laminin, or neuron-produced neurite-promoting materials) were examined. Ethanol inhibited process formation by the neurons in a dose-dependent manner and inhibited the production of neurotrophic factors. Neuronal attachment to the substrates, survival of attached neurons, and receptor interactions of sensory neurons with nerve growth factor were not influenced by ethanol. It appears that ethanol alters certain metabolic characteristics of developing neurons.
Selective Inhibition of Fibronectin-Mediated Cell Adhesion by Monoclonal Antibodies to a Cell-Surface Glycoprotein
Authors: Brown Patricia J. , Juliano R. L.
Published: October 2006

Fibroblasts possess several distinct mechanisms that control cellular adhesion to extracellular matrix macromolecules. Monoclonal antibodies to a 140-kilodalton (kD) cell surface glycoprotein inhibited the adhesion of fibroblastic Chinese hamster ovary cells to fibronectin-coated substrata but did not inhibit adhesion to substrata coated with vitronectin, laminin, serum, or other adhesive macromolecules. Thus the 140-kD glycoprotein appears to be involved in the fibronectin-mediated adhesion mechanism but not in other adhesion processes.
Thyrotropin-Releasing Hormone: Stimulation of Colonic Activity Following Intracerebroventricular Administration
Authors: Smith John R. , La Hann Thomas R. , Chesnut Randolph M. , Carino Monserrat A. , Horita Akira
Published: October 2006

Intraventricularly administered thyrotropin-releasing hormone in rabbits elicited an increase in intraluminal pressure changes, a response commonly associated with muscular activity of the colon. The response appears to be central in origin with peripheral expression relying primarily on cholinergic receptors.
High-Resolution Soft X-Ray Microscopy
Authors: Feder R. , Spiller E. , Topalian J. , Broers A. N. , Gudat W. , Panessa B. J. , Zadunaisky Z. A. , Sedat J.
Published: October 2006

X-ray micrographs of biological materials have been obtained with a resolution better than 100 angstroms by using x-ray resist as the recording medium. A high-resolution scanning electron microscope with a short-focal-length final lens, operating in the "low-loss" mode, is used to make the smallest features in the x-ray replica visible.
Bacteriophages in Live Virus Vaccines: Lack of Evidence for Effects on the Genome of Rhesus Monkeys
Authors: Milstien Julie B. , Walker James R. , Petricciani John C.
Published: October 2006

Four juvenile rhesus monkeys were inoculated with 10
12
plaque-forming units of the bacteriophage φV1 isolated from live virus vaccines. After φV1 had been cleared from the blood, DNA's were isolated from the livers and kidneys and analyzed for the presence of bacteriophage by plaque assays, and for the presence of φV1 DNA by DNA-DNA reassociation kinetics. No evidence was found for persistence of the bacteriophage or for replication of the phage genome in these rhesus monkeys.
A Model for Fibrinogen: Domains and Sequence
Authors: Weisel John W. , Stauffacher Cynthia V. , Bullitt Ester , Cohen Carolyn
Published: October 2006

Electron microscopy of rotary-shadowed fibrinogen demonstrates that the molecules modified for crystallization by limited cleavage with a bacterial protease retain the major features of the native structure. This evidence, together with image processing and x-ray analysis of the crystals and of fibrin, has been used to develop a three-dimensional low resolution model for the molecule. The data indicate that the two large end domains of the molecule would be composed of the carboxyl-terminus of the Bβ chain (proximal) and γ chain (distal), respectively; the carboxyl-terminus of the Aα chain would fold back to form an additional central domain. On this basis, the carboxyl-terminal region of each of the three chains of fibrinogen is folded independently into a globular domain.
Medial Septal Lesions Retard Classical Conditioning of the Nictitating Membrane Response in Rabbits
Authors: Berry Stephen D. , Thompson Richard F.
Published: October 2006

Lesions of the medial septum were produced in 7 of 14 rabbits prior to classical conditioning of the nictitating membrane response. Lesions significantly altered the hippocampal electroencephalogram, attenuated conditioned hippocampal unit responses, and slowed the behavioral rate of acquisition. The contrast of the behavioral results with those of studies of massive septal or hippocampal ablation suggests a functional subdivision of the septo-hippocampal system in learning.
Viroids: Structure and Function
Authors: Diener T. O.
Published: October 2006

Viroids are nucleic acid species of relatively low molecular weight and unique structure that cause several important diseases of cultivated plants. Similar nucleic acid species may be responsible for certain diseases of animals and humans. Viroids are the smallest known agents of infectious disease. Unlike viral nucleic acids, viroids are not encapsidated. Despite their small size, viroids replicate autonomously in cells of susceptible plant species. Known viroids are single-stranded, covalently closed circular, as well as linear, RNA molecules with extensive regions of intramolecular complementarity; they exist in their native state as highly base-paired rods.
Regrowth of Severed Axons in the Neonatal Central Nervous System: Establishment of Normal Connections
Authors: Kalil Katherine , Reh Thomas
Published: October 2006

When pyramidal tract axons are cut in the adult hamster, fibers degenerate in both anterograde and retrograde directions from the lesion. If the same operation is performed on infant hamsters, however, there is massive regrowth of the severed axons via a new brainstem pathway to their appropriate terminal sites in the medulla and spinal cord. In contrast to previous studies, these results suggest that axons in the mammalian central nervous system damaged early in life may regenerate in a functionally useful way.
The Hyperactive Child Syndrome
Authors: Weiss Gabrielle , Hechtman Lily
Published: October 2006

The behavioral characteristics of the hyperactive child are described at different stages of development. Recent and sometimes controversial research findings are discussed with respect to prevalence, etiology, treatment, and outcome. It is concluded that this syndrome can best be understood in terms of interactions between social, psychological, and biological variables.
Exercise During Development Induces an Increase in Purkinje Cell Dendritic Tree Size
Authors: Pysh J. J. , Weiss G. M.
Published: October 2006

Mice allowed to exercise during the late postnatal period had Purkinje cells with larger dendritic trees and greater numbers of spines than littermates whose physical activity was severely restricted. These changes in Purkinje cells were accompanied by a selective reduction in the thickness of the cerebellar molecular layer. The data provide evidence for cerebellar plasticity during late development and demonstrate that physical activity can modify the development of Purkinje cell dendrites.
Microwaves: Effect on Thermoregulatory Behavior in Rats
Authors: Stern Sander , Margolin Leonid , Weiss Bernard , Lu Shin-Tsu , Michaelson Sol M.
Published: October 2006

Rats, with their fur clipped, pressed a lever to turn on an infrared lamp while in a cold chamber. When they were exposed to continuous-wave microwaves at 2450 megahertz for 15-minute periods, the rate at which they turned on the infrared lamp decreased as a function of the microwave power density, which ranged between 5 and 20 milliwatts per square centimeter. This result indicates that behaviorally significant levels of heating may occur at an exposure duration and intensities that do not produce measurable changes in many other behavioral measures or in colonic temperature. Further study of how microwaves affect thermoregulatory behavior may help us understand such phenomena as the reported "nonthermal" behavioral effects of microwaves.
Membrane Currents Examined Under Voltage Clamp in Cultured Neuroblastoma Cells
Authors: Moolenaar Wouter H. , Spector Ilan
Published: October 2006

Examination of ionic membrane currents in a voltage-clamped neuronal cell line derived from the mouse C1300 neuroblastoma disclosed four kinetically different components: sodium, potassium, calcium, and leakage current. The kinetics, voltage dependence, and pharmacological properties of the sodium and potassium currents qualitatively resemble those of the corresponding currents in squid giant axon and frog myelinated nerve fiber, suggesting that the molecular structures of the sodium and potassium channels in neuroblastoma are similar to those of the nonmammalian preparations.
Chlorpromazine and Its Metabolites Alter Polymerization and Gelation of Actin
Authors: Elias Elwyn , Boyer James L.
Published: October 2006

Hepatic hydroxylated metabolites of chlorpromazine (10
-5
M to 10
-4
M), a frequently used phenothiazine tranquilizer, produce solid gel formation with filamentous actin, but the less toxic chlorpromazine sulfoxide metabolite does not. At higher concentrations (5 × 10
-4
M) chlorpromazine inhibits actin polymerization. These dose-response relationships parallel the drug's hepatic toxicity in vivo and suggest that interactions between chlorpromazine or chlorpromazine metabolites and actin could be an underlying mechanism of cell injury.
Ion Channels in Plasmalemma of Wheat Protoplasts
Authors: Moran Nava , Ehrenstein Gerald , Iwasa Kunihiko , Bare Charles , Mischke Charles
Published: October 2006

The patch-clamp technique was used to study passive movements of ions through the plasmalemma of wheat leaf protoplasts. This method overcomes the problems inherent in conventional electrophysiological study of plant cells. Changes in conductance were recorded in patches excised from the plasmalemma. Two types of patches were observed: (i) regions of low channel density, where discrete single-channel currents could be resolved and conductance ranged from 10 to 200 picosiemens and (ii) regions of high channel density, where single-channel currents could not be resolved and conductance was on the order of a few nanosiemens. The results indicate a striking similarity between animal and plant cell membranes in the basic phenomena of transport. Moreover, the approach used constitutes a new degree of refinement in the study of processes of regulation, pathology, and toxicity in plants.
Functional Insertion of an Alu Type 2 (B2 SINE) Repetitive Sequence in Murine Class I Genes
Authors: Kress Michel , Barra Yves , Seidman J. G. , Khoury George , Jay Gilbert
Published: October 2006

The regulation of expression of the family of MHC (major histocompatibility complex) class I genes is complex. Sequence analysis has revealed that class I genes from the H-2D subregion of the MHC (which includes the D and L genes) differ from the class I gene from the H-2K subregion (the K gene) by the insertion of a type 2 Alu-like repetitive element (the murine B2 sequence) within the 3′ noncoding region of the D and L genes. The consequence of this insertion in the D and L genes is the introduction of a novel polyadenylation signal, which is preferentially used over the more distal signal, the analog of that found in the K gene. The insertion of the type 2 Alu-like sequence results in a change in the preferred site for endonucleolytic cleavage which is necessary for generating a correct 3′ terminus for polyadenylation. The data demonstrate that the type 2 Alu-like sequence has a function; the data also suggest a possible regulatory role of this sequence in the expression of class I genes.
Paradoxical Elevation of Growth Hormone by Intraventricular Somatostatin: Possible Ultrashort-Loop Feedback
Authors: Lumpkin Michael D. , Gegro-Vilar Andres , McCann Samuel M.
Published: October 2006

Somatostatin, the growth hormone-inhibiting factor, when microinjected into the third ventricle of the rat brain, paradoxically induced the release of growth hormone. A pituitary site of action having been ruled out, this result supports the concept that exogenous somatostatin within the hypothalamus acts either to suppress the release of somatostatin from somatostatin-containing neurons, possibly via an ultrashort-loop feedback mechanism, or to augment release of hypothalamic growth hormone-releasing factor, thereby inducing a release of growth hormone. Injection of somatostatin into the third ventricle also decreased plasma concentrations of luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone, probably by inhibiting the release of luteinizing hormone-releasing factor and thyrotropin-releasing factor.
The Opioid Peptide Dynorphin, Circadian Rhythms, and Starvation
Authors: Przewlocki R. , Lasón W. , Konecka A. M. , Gramsch C. , Herz A. , Reid L. D.
Published: October 2006

Dynorphin, an opioid peptide whose functions are unknown, is found in brain, pituitary, and peripheral organs. Specific radioimmunoassays were used to measure dynorphin in the hypothalamus and pituitary, during the day and at night, as a function of food and water deprivation. Immunoreactive dynorphin was increased in the hypothalamus and decreased in the pituitary at night. Water deprivation led to more than 50 percent reduction in daytime levels of pituitary dynorphin and concomitant increases in hypothalamic dynorphin.
Suppression of Epididymal Sperm Antigenicity in the Rabbit by Uteroglobin and Transglutaminase in Vitro
Authors: Mukherjee Diane C. , Agrawal Arun K. , Manjunath Ramanathapuram , Mukherjee Anil B.
Published: October 2006

There is evidence that the mammalian female genital tract is capable of responding immunologically when challenged with alloantigens. The antigenic properties of male gametes have been well delineated. However, it is only rarely that a female mammal ever responds immunologically to the male gametic antigens as a result of coitus. When a proposed mechanism of suppression of antigenicity of epididymal spermatozoa was tested experimentally, the results indicated that two proteins (uteroglobin and transglutaminase) present in the prostate may be responsible for suppressing sperm antigenicity in the rabbit.
Peptide Cotransmitter at a Neuromuscular Junction
Authors: Adams Michael E. , O'Shea Michael
Published: October 2006

The neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) is present in the nerve terminals of an identified slow skeletal motoneuron in the cockroach. Proctolin is released onto the target muscle, a coxal depressor, by neuron stimulation and by depolarization with potassium. The physiological action of the motoneuron suggests that proctolin acts as a cotransmitter. Proctolin and neural stimulation produce delayed and sustained contractile effects without muscle depolarization.
Retrograde Axonal Transport of Endogenous Proteins in Sciatic Nerve Demonstrated by Covalent Labeling in Vivo
Authors: Fink David J. , Gainer Harold
Published: October 2006

Extracellularly applied
N
-succinimidyl [2,3-
3
H]propionate was used in vivo to covalently label intra-axonal proteins in the rat sciatic nerve. This technique permitted a unique view of axonal transport of proteins independent of biosynthesis. The proteins detected in slow anterograde transport (1 to 2 millimeters per day) correspond to cytoskeletal proteins described in previous reports. The slowly retrogradely transported component (3 to 6 millimeters per day) was composed primarily of a single protein with a molecular weight of 68,000.
Mammoth Albumin
Authors: Prager Ellen M. , Wilson A. C. , Lowenstein Jerold M. , Sarich Vincent M.
Published: October 2006

Serum albumin was detected immunologically in muscle from a mammoth that died about 40,000 years ago. Rabbits injected with ground mammoth muscle produced antibodies that react strongly with elephant albumin, weakly with sea cow albumin, and still more weakly or not at all with other mammalian albumins. Since elephant albumin elicited antibodies with the same specificity, some of the surviving mammoth albumin molecules evidently have antigenic sites identical to those on native elephant albumin. Much of the mammoth albumin has, however, undergone postmortem change. The small amount of soluble albumin extractable from mammoth muscle is heterogeneous in size, charge, and antigenic properties.
Deficiency of Functional Messenger RNA for a Developmentally Regulated β-Crystallin Polypeptide in a Hereditary Cataract
Authors: Carper Deborah , Shinohara Toshimichi , Piatigorsky Joram , Kinoshita Jin H.
Published: October 2006

The messenger RNA for a β-crystallin polypeptide with a molecular size of 27 kilodaltons, first detected 5 to 10 days after birth in the normal mouse lens and the Nakano mouse cataract, was not detected in the Philly mouse cataract with translation in vitro. The heterozygous Philly lens had intermediate levels of the 27-kilodalton β-crystallin polypeptide and exhibited delayed onset of the cataract. The deficiency of functional 27-kilodalton β-crystallin messenger RNA is the earliest lesion reported yet for the Philly lens and points to a transcriptional or posttranscriptional developmental defect in this hereditary cataract.
Inherited Medullary Thyroid Carcinoma: A Final Monoclonal Mutation in One of Multiple Clones of Susceptible Cells
Authors: Baylin Stephen B. , Hsu Susan H. , Gann Donald S. , Smallridge Robert C. , Wells Samuel A.
Published: October 2006

Inherited medullary thyroid carcinomas contain one form of glucose-6-phosphate dehydrogenase (G6PD) in black female patients who are mosaic in normal tissues for G6PD types A and B. The same individual may have several tumors each containing either G6PD A or G6PD B. The data suggest that the inherited defect is an initial mutation producing multiple clones of defective cells; each tumor then arises as a final mutation in one clone of these cells.
Date of Channel Trenching (Arroyo Cutting) in the Arid Southwest
Authors: Bryan Kirk
Published: October 2006

Of the writers known to have considered the problem, Hough alone has attempted to give a date for the whole area. He says that the process began with the active occupancy of the region by white men thirty years before the date of his address, or in 1875. However, the foregoing review of the existing evidence as to the date when trenching began in southwestern United States indicates that these changes were initiated at slightly different times in each stream and occupied a considerable period in their accomplishment. The change from aggradation and the building of flood plains to dissection and the formation of arroyos in many streams of southern Arizona can be confidently placed in the decade 1880 to 1890, although many tributary streams were not affected until the 90's and some are still undissected. The date in southern Utah, northern Arizona and southern Colorado is apparently earlier, and cutting probably began at some time after 1860. The evidence as to the Rio Puerco in north-central New Mexico is conflicting and needs review. The statements of the early explorers indicate that the arroyos were already well formed at the time of the American conquest in 1846 and 47.
Lariat RNA's as Intermediates and Products in the Splicing of Messenger RNA precursors
Authors: Padgett Richard A. , Konarska Maria M. , Grabowski Paula J. , Hardy Steven F. , Sharp Phillip A.
Published: October 2006

The splicing of messenger RNA precursors in vitro proceeds through an intermediate that has the 5′ end of the intervening sequence joined to a site near the 3′ splice site. This lariat structure, which has been characterized for an adenovirus 2 major late transcript, has a branch point, with 2′-5′ and 3′-5′ phosphodiester bonds emanating from a single adenosine residue. The excised intervening sequence retains the branch site and terminates in a guanosine residue with a 3′ hydroxyl group. The phosphate group at the splice junction between the two exons originates from the 3′ splice site at the precursor.
Role of the Conserved AAUAAA Sequence: Four AAUAAA Point Mutants Prevent Messenger RNA 3′ End Formation
Authors: Wickens Marvin , Stephenson Pauline
Published: October 2006

A small region (220 bases) of SV40 sequence information—141 bases before the polyadenylation site and 79 beyond—are sufficient for cleavage of an messenger RNA precursor (that is, the formation of a mature 3′ terminus), the addition of polyadenylic acid, and the transport of messenger RNA from the nucleus to the cytoplasm. These 220 bases include a highly conserved sequence—AAUAAA (A, adenine; U, uracil). Four point mutations in this sequence—AACAAA, AAUUAA, AAUACA, and AAUGAA (C, cytosine; G, guanine)—prevent cleavage.
Amantadine: Neuromuscular Blockade by Suppression of Ionic Conductance of the Acetylcholine Receptor
Authors: Albuquerque Edson X. , Eldefrawi Amira T. , Eldefrawi Mohyee E. , Mansour Nabil A. , Tsai Ming-Cheng
Published: October 2006

Amantadine hydrochloride decreases the sensitivity of denervated mammalian muscle to iontophoretically applied acetylcholine. The drug depresses the amplitude of the end-plate current and reverses the slope of the relation between half-decay time and membrane potential suggesting that it alters the ionic conductance that is mediated by the acetylcholine receptor. Binding studies confirm that amantadine acts on the ion conductance modulator rather than the acetylcholine receptor.
Cyclic Polyether-Protonated Organic Amine Binding: Significance in Enzymatic and Ion Transport Processes
Authors: Izatt Reed M. , Izatt Neil E. , Rossiter Bryant E. , Christensen James J. , Haymore Barry L.
Published: October 2006

The cyclic polyether, 18-crown-6, reacts with protonated amines in methanol to form complexes whose formation constants (log
K
) decrease in the order NH
4
+
, RNH
3
+
> R
2
NH
2
+
> R
3
NH
+
. In the case of the organic amines, this stability order is identical to the earlier observed permeability sequence for protonated organic amines in glyceryl dioleate bilayers treated with valinomycin, nonactin, or gramicidin, and in bullfrog and rabbit gallbladder membranes. The decrease in log K values in the above series is primarily a result of decreased enthalpy change (ΔH) values, the entropy change (TΔS) term being essentially constant for the systems studied.
Efficient Metal-Ion Catalyzed Template-Directed Oligonucleotide Synthesis
Authors: Lohrmann R. , Bridson P. K. , Orgel L. E.
Published: October 2006

The Pb
2+
and Zn
2+
ions are efficient catalysts for the polycytidylic acid-directed polymerization of an activated guanylic acid derivative, guanosine 5′-phosphorimidazolide. The products include oligomers of 30 to 40 units in length. The nucleotide residues are predominantly 2′-5′ linked when Pb
2+
is the catalyst, and predominantly 3′-5′ linked in the presence of Zn
2+
. The significance of these results in the context of the prebiotic evolution of RNA polymerase is discussed.
Receptor for Albumin on the Liver Cell Surface May Mediate Uptake of Fatty Acids and Other Albumin-Bound Substances
Authors: Weisiger R. , Gollan J. , Ockner R.
Published: October 2006

Kinetic analysis of the uptake of carbon-14-labeled oleate in a single-pass perfusion of rat liver and saturable and specific binding of iodine-125-labeled albumin to hepatocytes in suspension suggest the existence of a receptor for albumin on the liver cell surface. The putative receptor appears to mediate uptake of albumin-bound fatty acids by the cell and may account for the efficient hepatic extraction of many other substances tightly bound to albumin.
Compartmentalization of Cyclic AMP During Phagocytosis by Human Neutrophilic Granulocytes
Authors: Pryzwansky Katherine B. , Steiner Alton L. , Spitznagel John K. , Kapoor Chiranjiv L.
Published: October 2006

Immunocytochemistry shows that early during phagocytosis of zymosan, adenosine 3′,5′-monophosphate (cyclic AMP) appears on the cell surface before the phagosome is internalized. The appearance of cyclic AMP on the cell surface is coincident with that of granule products and regulatory subunit of type I cyclic AMP-dependent protein kinase. Guanosine 3′,5′-monophosphate is not associated with the initiation site of phagocytosis, but is observed throughout the granular cytoplasmic region. This sharply localized accumulation of cyclic AMP may serve as a signal for the initiation of phagocytosis.
Nonhistone Proteins HMG
1
and HMG
2
Change the DNA Helical Structure
Authors: Javaherian Kashayar , Liu Leroy F. , Wang James C.
Published: October 2006

Two chromatin nonhistone proteins (from calf thymus) of the high mobility group, HMG
1
and HMG
2
, reduce the linking number (topological winding number) of a circular DNA if the covalent closure of the DNA is carried out in their presence. This indicates that these proteins can either unwind the double helix, or induce a supercoiling of the DNA.
The Chemistry of Vision
Authors: O'Brien David F.
Published: October 2006

The visual response is initiated by light reception and transduction into chemical and electrical energy in the outer-segment membranes of rod and cone cells. Recent research on the molecular events controlled by light has clarified the roles of some of the rod outer-segment biomolecules. These developments and the current unresolved questions are described.
Coupling of Dopamine D
1
Recognition Sites with Adenylate Cyclase in Nuclei Accumbens and Caudatus of Schizophrenics
Authors: Memo Maurizio , Kleinman Joel E. , Hanbauer Ingeborg
Published: October 2006

Sodium fluoride, guanylimidodiphosphate, and the D
1
dopamine receptor agonist SKF 38393 elicited a greater activation of adenylate cyclase in homogenates of caudate nucleus in schizophrenic than in nonschizophrenic subjects used as controls. Similarly, a greater activation of adenylate cyclase by sodium fluoride was observed in the nucleus accumbens of schizophrenics. These findings suggest that the coupling of dopamine D
1
recognition sites with adenylate cyclase is more efficient in the brain of the schizophrenic, presumably because of an increased affinity of the G/F protein for guanosine 5′-triphosphate.
Production of an Epidermal Growth Factor Receptor-Related Protein
Authors: Weber Wolfgang , Gill Gordon N. , Spiess Joachim
Published: October 2006

Human epidermoid carcinoma A431 cells in culture produce a soluble 105-kilodalton protein which, by the criteria of epidermal growth factor (EGF) binding, recognition by monoclonal and polyclonal antibodies to the EGF receptor, amino-terminal sequence analysis and carbohydrate content, is related to the cell surface domain of the EGF receptor. The high rate of production and the finding that with biosynthetic labeling the specific activity of this 105-kilodalton protein exceeds that of the intact receptor indicate that it is not derived from membrane-bound mature receptor but is separately produced by the cell. These cells thus separately synthesize an EGF receptor that is inserted into the membrane and an EGF receptor-related protein that is secreted.
Vitamin D
3
—Resistant Fibroblasts Have Immunoassayable 1,25-Dihydroxyvitamin D
3
Receptors
Authors: Pike J. Wesley , Dokoh Shigeharu , Haussler Mark R. , Liberman Uri A. , Marx Stephen J. , Eil Charles
Published: October 2006

Cultured fibroblasts obtained from patients with tissue resistance to 1,25-dihydroxyvitamin D
3
(vitamin D
3
-dependent rickets, type II) contain normal, low, or undetectable concentrations of this hormone's receptor protein as measured by a ligand-binding assay. Extracts from these cells were evaluated for receptors by immunoassay with a recently developed monoclonal antibody to the chick receptor. The results show that a protein sedimenting at 3.7
S
and recognizable by the antibody exists in comparable concentrations in cells from both normal and resistant patients, irrespective of the hormone-binding abnormalities of the cells. This implies that deficiencies in hormone binding associated with inherited tissue resistance to 1,25-dihydroxyvitamin D
3
probably arise from structural variations in the receptor molecule and not from defective receptor synthesis.
Sequencing the
erb
A Gene of Avian Erythroblastosis Virus Reveals a New Type of Oncogene
Authors: Debuire B. , Henry C. , Bernissa M. , Biserte G. , Claverie J. M. , Saule S. , Martin P. , Stehelin D.
Published: October 2006

Avian erythroblastosis virus (AEV) contains two distinct oncogenes,
erb
A and
erb
B. The
erb
B oncogene, which is homologous to a portion of the epidermal growth factor receptor, is related to the
src
family of oncogenes and efficiently transforms erythroblasts, whereas
erb
A potentiates the effects of
erb
B by blocking the differentiation of erythroblasts at an immature stage. This "potentiator" was sequenced; the amino acid sequence deduced from it was clearly different from the sequences of other known oncogene products and was related to carbonic anhydrases. These enzymes participate in the transport of carbon dioxide by erythrocytes, the precursors of which are main targets of avian erythroblastosis virus. A
src
-related oncogene such as
erb
B in synergy with an activated specific cell-derived gene such as
erb
A can profoundly affect early erythroid differentiation.
Anti-T-Cell Reagents for Human Bone Marrow Transplantation: Ricin Linked to Three Monoclonal Antibodies
Authors: Vallera Daniel A. , Ash Robert C. , Zanjani Esmail D. , Kersey John H. , LeBien Tucker W. , Beverley Peter C. L. , Neville David M. , Youle Richard J.
Published: October 2006

Three new reagents that react against human T cells were synthesized by covalently linking the toxin ricin to monoclonal antibodies recognizing differentiation antigens on the surface of T lymphocytes. Each of these immunotoxins selectively inhibited T-cell proliferation when the cells were incubated in the presence of lactose. Multipotent human stem cells were inhibited only at much higher concentrations. Mixtures of all three immunotoxins were more effective than any one alone. These reagents have the potential for preventing graft-versus-host disease in man.