bluuebunny/crossref_metadata_2025 huggingface dataset:
A Transgenic Mouse Model of the Chronic Hepatitis B Surface Antigen Carrier State
Authors: Chisari F. V. , Pinkert C. A. , Milich D. R. , Filippi P. , McLachlan A. , Palmiter R. D. , Brinster R. L.
Published: October 2006

In an attempt to establish a model of the healthy carrier state in hepatitis B virus (HBV) infections, transgenic mice expressing HBV genes were produced. Fertilized one-cell eggs were microinjected with subgenomic fragments of HBV DNA containing the coding regions for the HBV surface antigen (HBsAg) and pre-S and X antigens. Either the normal (HBV) or metallothionein promoters were used to obtain expression of the HBV genes. There was no evidence of viral replication or tissue pathology. The integrated HBV DNA sequences were inherited in a normal Mendelian fashion. Three of 16 transgenic mice expressed HBV-encoded gene products to which they were immunologically tolerant. Expression was not tissue specific and may be influenced by the genomic integration site and cellular factors. Both HBsAg and pre-S antigen were detectable within the cytoplasm of hepatocytes and renal tubular epithelial cells. High serum concentrations of HBsAg were detectable and the secreted product appeared authentic as judged by mean density, morphology, mean particle diameter, polypeptide composition, and antigenicity. The absence of tissue pathology in these immunologically tolerant animals supports the hypothesis that cellular injury under these conditions is not a direct consequence of expression of the pre-S or HBs regions of the HBV genome.
Gene for Human Insulin Receptor: Localization to Site on Chromosome 19 Involved in Pre-B-Cell Leukemia
Authors: Yang-Feng Teresa L. , Francke Uta , Ullrich Axel
Published: October 2006

Consistent chromosomal translocations in neoplastic cells may alter the expression of proto-oncogenes that are located near the breakpoints. The complementary DNA sequence of the human insulin receptor is similar to those of the EGF receptor (
erbB
oncogene) and products of the src family of oncogenes. With in situ hybridization and Southern blot analysis of somatic cell hybrid DNA, the human insulin receptor gene was mapped to the distal short arm of chromosome 19 (bands p13.2→p13.3), a site involved in a nonrandom translocation in pre-B-cell acute leukemia.
Serologic Identification and Characterization of a Macaque T-Lymphotropic Retrovirus Closely Related to HTLV-III
Authors: Kanki P. J. , McLane M. F. , King N. W. , Letvin N. L. , Hunt R. D. , Sehgal P. , Daniel M. D. , Desrosiers R. C. , Essex M.
Published: October 2006

Human T-lymphotropic virus type III (HTLV-III) is thought to play an etiologic role in the development of the acquired immune deficiency syndrome (AIDS). In this study the serologic characterization of a new simian retrovirus that is related to HTLV-III is described. This new virus, here referred to as STLV-III, was isolated from sick macaques at the New England Regional Primate Research Center. Radioimmunoprecipitation analysis revealed STLV-III-specific proteins of 160, 120, 55, and 24 kilodaltons, all similar in size to the majorgagandenvproteins of HTLV-III. These antigens were recognized by representative macaque serum samples and human reference serum samples positive for HTLV-III antibodies. Monoclonal antibodies directed to p24, the major core protein of HTLV-III, also immunoprecipitated a 24-kilodalton species in lysates of cells infected with the macaque virus. This HTLV-III-related virus, which naturally infects a nonhuman primate species, may provide a useful model for the study of HTLV-III and the pathogenesis of AIDS.
Distribution of Enkephalin Immunoreactivity in Germinative Cells of Developing Rat Cerebellum
Authors: Zagon Ian S. , Rhodes Randall E. , McLaughlin Patricia J.
Published: October 2006

The cellular distribution of enkephalin, an endogenous opioid, in the developing rat cerebellum was determined by immunocytochemistry. Methionine and leucine enkephalin were concentrated in the external germinal layer, a matrix of proliferative cells; staining was confined to the cortical cytoplasm. Enkephalin was not detected by immunocytochemistry in differentiated neural cells. These results indicate that endogenous opioids are involved specifically in early phases of nervous system development, particularly cell proliferation and differentiation.
Trypanothione: A Novel Bis(glutathionyl)spermidine Cofactor for Glutathione Reductase in Trypanosomatids
Authors: Fairlamb Alan H. , Blackburn Peter , Ulrich Peter , Chait Brian T. , Cerami Anthony
Published: October 2006

Glutathione reductase from trypanosomes and leishmanias, unlike glutathione reductase from other organisms, requires an unusual low molecular weight cofactor for activity. The cofactor was purified from the insect trypanosomatid
Crithidia fasciculata
and identified as a novel glutathione-spermidine conjugate, N
1
,N
8
-bis(L-γ-glutamyl-L-hemicystinyl-glycyl)spermidine, for which the trivial name trypanothione is proposed. This discovery may open a new chemotherapeutic approach to trypanosomiasis and leishmaniasis.
Amino Acid Replacements that Compensate for a Large Polypeptide Deletion in an Enzyme
Authors: Ho Calvin , Jasin Maria , Schimmel Paul
Published: October 2006

Deletion of more than 400 amino acids from the carboxyl terminus of an enzyme causes a severe reduction in catalytic activity. Selected point mutations within the residual protein partially reverse the effects of the missing segment. The selection can yield mutants with activities at least ten times as high as those of the starting polypeptides. One well-characterized mutation, a single amino acid replacement in the residual polypeptide, increases the catalytic activity of the polypeptide by a factor of 5. The results suggest substantial potential for design of protein elements to compensate for missing polypeptide sequences. They also may reflect that progenitors of large aminoacyl-tRNA (transfer RNA) synthetases—one of which was used in these studies—were themselves much smaller.
A Neuroendocrine Marker in Tissues of the Immune System
Authors: Angeletti Ruth Hogue , Hickey William F.
Published: October 2006

Antibodies to chromogranin, a secretory protein marker for the diffuse neuroendocrine system, were used to analyze rat lymphoreticular tissues by means of immunochemistry and immunohistochemistry. Chromogranin-positive cells were present in spleen, lymph node, thymus, and fetal liver. When these organs were gently dispersed and separated on a Ficoll gradient, the chromogranin-immunoreactive cells became enriched in the dense red-cell pellets. The unexpected distribution of these neuroendocrine cells in all immunologically relevant structures suggests that they may link the nervous and immunological systems.
B Lineage—Specific Interactions of an Immunoglobulin Enhancer with Cellular Factors in Vivo
Authors: Ephrussi Anne , Church George M. , Tonegawa Susumu , Gilbert Walter
Published: October 2006

The mouse heavy chain immunoglobulin gene contains a tissue-specific enhancer. The enhancer and flanking sequences were studied in vivo by carrying out dimethyl sulfate protection experiments on living cells, in combination with genomic sequencing. Relative to reactions on naked DNA, there are changes (protections and enhancements) in the reactivity of guanine residues to dimethyl sulfate within the enhancer sequence in myeloma, B, and early B cells, whereas virtually no alterations appear in cells of non-B lineage. Most of the affected residues are in four clusters, in sequences homologous to the octamer 5′CAGGTGGC 3′ (C, cytosine; A, adenine; G. guanine; T, thymine). The alterations in the pattern of G reactivity are consistent with the tissue-specific binding of molecules to the mouse immunoglobulin heavy chain enhancer.
Vitamin E Reversal of the Effect of Extracellular Calcium on Chemically Induced Toxicity in Hepatocytes
Authors: Fariss Marc W. , Pascoe Gary A. , Reed Donald J.
Published: October 2006

Isolated rat hepatocytes were incubated in the presence or absence of extracellular calcium and α-tocopherol succinate with three different toxic chemicals; namely, adriamycin in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea, ethyl methanesulfonate, and the calcium ionophore A23187. In the absence of extracellular calcium these three compounds were far more toxic to the cells than in its presence. The addition of vitamin E to calcium-free medium, however, protected hepatocytes against toxic injury, whereas cells incubated in medium containing calcium were not protected. Hepatocyte viability during each toxic insult correlated well with the cellular α-tocopherol content but not with the presence or absence of extracellular calcium. These results suggest that cellular α-tocopherol maintains the viability of the cell during a toxic insult and that the presence or absence of vitamin E in the incubation medium probably explains the conflicting reports on the role of extracellular calcium in toxic cell death.
Stereostructure of the Archaebacterial C
40
Diol
Authors: Heathcock Clayton H. , Finkelstein Bruce L. , Aoki Tadashi , Poulter C. Dale
Published: October 2006

The stereostructure of the archaebacterial C
40
diol has been established as (3
R
,7
R
,11
R
,15
S
,18
S
,22
R
,26
R
,30
R
)-3,7,11,15,18,22,26,30- octamethyldotriacontane-1,32-diol by stereorational total synthesis. This provides the final evidence necessary to establish the structure of an archaebacterial membrane substance that is a 72-membered-ring tetraether with 18 stereocenters.
Presence of Nonoxidative Ethanol Metabolism in Human Organs Commonly Damaged by Ethanol Abuse
Authors: Laposata Elizabeth A. , Lange Louis G.
Published: October 2006

Acetaldehyde, the end product of oxidative ethanol metabolism, contributes to alcohol-induced disease in the liver, but cannot account for damage in organs such as the pancreas, heart, or brain, where oxidative metabolism is minimal or absent; nor can it account for the varied patterns of organ damage found in chronic alcoholics. Thus other biochemical mediators may be important in the pathogenesis of alcohol-induced organ damage. Many human organs were found to metabolize ethanol through a recently described nonoxidative pathway to form fatty acid ethyl esters. Organs lacking oxidative alcohol metabolism yet frequently damaged by ethanol abuse have high fatty acid ethyl ester synthetic activities and show substantial transient accumulations of fatty acid ethyl esters. Thus nonoxidative ethanol metabolism in addition to the oxidative pathway may be important in the pathophysiology of ethanol-induced disease in humans.
Optical Image Quality and the Cone Mosaic
Authors: Snyder Allan W. , Bossomaier Terry R. J. , Hughes Austin
Published: October 2006

Contrary to the orthodox view that optical image quality should "match" the photoreceptor grain, anatomical data from the eyes of various animals suggest that the image quality is significantly superior to the potential resolution of the cone mosaic in most retinal regions. A new theory is presented to explain the existence of this relation and to better appreciate eye design. It predicts that photoreceptors are potentially visible through the natural optics.
Structure of Tobacco Mosaic Virus at 3.6 Å Resolution: Implications for Assembly
Authors: Namba Keiichi , Stubbs Gerald
Published: October 2006

X-ray fiber diffraction analysis of tobacco mosaic virus (TMV) has led to the building of a molecular model of the intact virus, based on a map at 3.6 Å resolution derived from five separated Bessel orders. This has been made possible by advances in the solution of the fiber diffraction phase problem. It is now possible to understand much of the chemical basis of TMV assembly, particularly in terms of intersubunit electrostatic interactions and RNA binding. Consideration of the molecular structure in conjunction with physical chemical studies by several groups of investigators suggests that the nucleating aggregate for initiation of TMV assembly is a short (about two turns) helix of protein subunits, probably inhibited from further polymerization in the absence of RNA by the disordering of a peptide loop near the inner surface of the virus.
Descending Efferents from the Superior Colliculus Relay Integrated Multisensory Information
Authors: Meredith M. Alex , Stein Barry E.
Published: October 2006

By means of their efferent projections to motor and premotor structures, the cells in the deep superior colliculus are intimately involved in behaviors that control the orientation of the eyes, pinnae, and head. These same efferent cells receive multiple sensory inputs, thereby apparently enabling an animal to orient its receptor organs in response to a wide variety of cues. This sensory convergence also provides a system in which motor responses need not be immutably linked to individual stimuli but can vary in reaction to the multitude of stimuli present in the environment at any given moment.
Genetic Origin of Mutations Predisposing to Retinoblastoma
Authors: Cavenee Webster K. , Hansen Marc F. , Nordenskjold Magnus , Kock Eric , Maumenee Irene , Squire Jeremy A. , Phillips Robert A. , Gallie Brenda L.
Published: October 2006

Retinoblastoma is one of several human tumors to which predisposition can be inherited. Molecular genetic analysis of several nonheritable cases has led to the hypothesis that this tumor develops after the occurrence of specific mitotic events involving human chromosome 13. These events reveal initial predisposing recessive mutations. Evidence is presented that similar chromosomal events occur in tumors from heritable cases. The chromosome 13 found in the tumors was the one carrying the predisposing germline mutation and not the homolog containing the wild-type allele at the
Rb-1
locus. These results suggest a new approach for identifying recessive mutant genes that lead to cancer and a conceptual basis for accurate prenatal predictions of cancer predisposition.
Involvement of Sialic Acid on Endothelial Cells in Organ-Specific Lymphocyte Recirculation
Authors: Rosen Steven D. , Singer Mark S. , Yednock Ted A. , Stoolman Lloyd M.
Published: October 2006

Mouse lymphocytes incubated on cryostat-cut sections of lymphoid organs (lymph nodes and Peyer's patches) specifically adhere to the endothelium of high endothelial venules (HEV), the specialized blood vessels to which recirculating lymphocytes attach as they migrate from the blood into the parenchyma of the lymphoid organs. Treatment of sections with sialidase eliminated the binding of lymphocytes to peripheral lymph node HEV, had no effect on binding to Peyer's patch HEV, and had an intermediate effect on mesenteric lymph node HEV. These results suggest that sialic acid on endothelial cells may be an organ-specific recognition determinant for lymphocyte attachment.
Angiogenesis: A Marker for Neoplastic Transformation of Mammary Papillary Hyperplasia
Authors: Brem Steven S. , Gullino Pietro M. , Medina Daniel
Published: October 2006

Mouse mammary papillomas elicit new formation of vessels when transplanted onto the rabbit iris. This angiogenic capacity is a property of carcinomas but not of the resting mammary gland. In mouse papillary hyperplasias, however, this property appears much earlier than any morphological or clinical sign of carcinoma. A test for angiogenic capacity may reveal a step in the progression toward clinical malignancy and thus could be used to screen for neoplastic potential of hyperplastic epithelium in biopsy tissues.
Multiple Mechanisms of Protein Insertion into and Across Membranes
Authors: Wickner William T. , Lodish Harvey F.
Published: October 2006

Protein localization in cells is initiated by the binding of characteristic leader (signal) peptides to specific receptors on the membranes of mitochondria or endoplasmic reticulum or, in bacteria, to the plasma membrane. There are differences in the timing of protein synthesis and translocation into or across the bilayer and in the requirement for a transmembrane electrochemical potential. Comparisons of protein localization in these different membranes suggest underlying common mechanisms.
Intracellular Free Calcium Localization in Neutrophils During Phagocytosis
Authors: Sawyer Daniel W. , Sullivan James A. , Mandell Gerald L.
Published: October 2006

Intracellular free calcium (Ca
2+
i
) is thought to be an important second messenger for phagocyte functions. The fluorescent indicator Quin2 was used to measure and visualize [Ca
2+
]
i
in human neutrophils during chemotaxis toward, and phagocytosis of, opsonized zymosan. In neutrophils migrating toward zymosan, [Ca
2+
]
i
was highest in the lamellipodium. Neutrophils ingesting opsonized zymosan had the highest [Ca
2+
]
i
in the pseudopods and periphagosomal cytoplasm. Most of the increase in [Ca
2+
]
i
was from extracellular sources. Regional increments in [Ca
2+
]
i
are strategically located to modulate such cellular functions as chemotaxis, oxidative activity, and degranulation.
Premotor Cortical Ablations in Monkeys: Contralateral Changes in Visually Guided Reaching Behavior
Authors: Moll L. , Kuypers H. G. J. M.
Published: October 2006

In rhesus monkeys (
Macaca mulatta
), ablation of the premotor and supplementary motor areas and the adjoining rostral half of the precentral gyrus impairs the capacity of the contralateral arm to reach around a transparent obstacle to a visible food reward, and results in a tendency of this arm to reach straight to where the food is visible. This may reflect a disinhibition of brainstem pathways which steer the arm and hand straight to a visual target.
Nitrite Promotes Lymphoma Incidence in Rats
Authors: Newberne Paul M.
Published: October 2006

Rats were exposed to sodium nitrite in food or water at concentrations of 0, 250, 500, 1000, and 2000 parts per million. Lymphoma was increased in all groups fed nitrite; the overall combined incidence was 5.4 percent in 573 control rats and 10.2 percent in 1383 treated rats. The mechanism of cancer induction did not appear to be through the formation of nitrosamines but through a more direct effect of nitrite on the lymphocyte.
Racial Differences in Blood Pressure Control
Authors: Voors A. W. , Berenson G. S. , Dalferes E. R. , Webber L. S. , Shuler S. E.
Published: October 2006

Children from an entire biracial geographical population were examined for blood pressure. A sample of 278 children, stratified by diastolic blood pressure, was reexamined 1 to 2 years later. Dopamine β-hydroxylase, renin activity, and resting heart rate were observed in black and white children. In the group with high blood pressure, whites had higher heart rates and greater renin activity than blacks. Dopamine β-hydroxylase concentrations in blacks were lower than in whites over the entire spectrum of blood pressure levels. High blood pressure seems to have a different metabolic background in the two races which may influence the early natural history of essential hypertension. Therefore, the rationale of prevention, and possibly treatment, of early hypertension in blacks and whites may differ.
Experimental Allergic Neuritis Induced by Sensitization with Galactocerebroside
Authors: Saida Takahiko , Saida Kyoko , Dorfman Susan H. , Silberberg Donald H. , Sumner Austin J. , Manning Margaret C. , Lisak Robert P. , Brown Mark J.
Published: October 2006

Thirteen of 31 rabbits immunized repeatedly with bovine brain galactocerebroside developed experimental allergic neuritis, manifested by flaccid paresis and hypesthesia of four limbs, 2 to 11 months after the initial inoculation. Electrophysiological studies revealed multifocal conduction block of peripheral nerves. Perivenular demyelinative lesions associated with phagocytic mononuclear cells occurred in spinal ganglia, roots, and less frequently in distal nerves.
Appetitive Learning in 1-Day-Old Rat Pups
Authors: Johanson Ingrid B. , Hall W. G.
Published: October 2006

One-day-old rat pups learned to probe upward into a terry-cloth-covered paddle when they were rewarded with small infusions of milk into their mouths. In the presence of two paddles, discriminable on the basis of odor and position in the test container, the pups learned to probe into the paddle that provided them with milk. These experiments demonstrate (i) that milk may serve as a reinforcer to deprived rat pups and (ii) that pups as young as 1 day are capable of appetitive learning.
Enhanced 5-Fluorouracil Nucleotide Formation After Methotrexate Administration: Explanation for Drug Synergism
Authors: Cadman Ed , Heimer Robert , Davis Lynn
Published: October 2006

Exposure of L1210 leukemia cells first to 0.1 to 100 micromolar methotrexate and then to 10 micromolar 5-fluorouracil produces a synergistic effect on the number of cells killed in culture. Methotrexate dose-related increases occur in the concentrations of intracellular 5-fluorouracil ribonucleotides and 5-fluoro-2′-deoxyuridylate and in the incorporation of 5-fluorouracil into RNA. These increases are correlated with increased concentrations of intracellular phosphoribosylpyrophosphate. It is proposed that the enhanced formation of ribonucleotides of 5-fluorouracil and the subsequent incorporation of these compounds into RNA in methotrexate-treated cells may account for synergism between these agents.
RNA Processing and RNA Tumor Virus Origin and Evolution
Authors: Gillespie David , Gallo Robert C.
Published: October 2006

The results of molecular hybridization experiments with high-molecular-weight RNA isolated from RNA tumor viruses and DNA from normal cells suggest that RNA tumor virus genomes originate from cell genes. Some RNA tumor viruses (here called class 1) appear to have been generated in recent times in that their RNA is closely related in nucleotide sequence to certain cell genes (class 1 genes). A second class of RNA tumor viruses (here called class 2) is more distantly related to genomic information of normal cells. Structural properties of the RNA of RNA tumor viruses lead us to propose that the tumor virus RNA is originated when RNA transcripts of class 1 genes are processed by a mechanism we call "paraprocessing." We postulate that RNA paraprocessing is normally used only at particular times during differentiation and is characterized by the cytoplasmic appearance of high-molecular-weight RNA chains containing terminal polyadenylic acid (200 residues). Paraprocessing of class 1 gene transcripts in committed or differentiated cells is considered to be aberrant in transcription that can lead to the generation of an RNA tumor virus genome. If the paraprocessed class 1 gene transcript codes for a reverse transcriptase, replication of the RNA becomes possible. Transfer of the replicating RNA to a new cell can result in genetic change such that the virus genome mutates, differing from the original progenitor genes. We propose that this genetic change causes class 1 viruses to become class 2. These ideas are applied to evidence concerning the biology of infection of RNA tumor viruses and concerning the involvement of RNA tumor viruses in human cancer.

Genetic change can also occur during the origination of an RNA tumor virus genome by repeated reverse transcription and recombination or by genetic alteration of particularly changeable cell genes ("hot spots").
Candidiasis: Detection by Gas-Liquid Chromatography of D-Arabinitol, a Fungal Metabolite, in Human Serum
Authors: Kiehn Timothy E. , Bernard Edward M. , Gold Jonathan W. M. , Armstrong Donald
Published: October 2006

D-Arabinitol was identified as a major metabolite of
Candida
species in human subjects. Gas-liquid chromatography was used to measure the concentration of D-arabinitol in serum. The study included subjects who were healthy and cancer patients who had proven invasive candidiasis or were colonized with
Candida
. D-Arabinitol concentrations greater than 1.0 microgram per milliliter were found in serum from patients with invasive infection. This technique may prove valuable in the diagnosis of invasive candidiasis.
Microsecond Sensitivity of the Human Visual System to Irregular Flicker
Authors: Diamond A. Leonard
Published: October 2006

A flickering light presented to the eye produces a small alternating voltage at the scalp of a subject. This alternating voltage indicates the following response of the brain to the flicker. If every other flash in the flicker is displaced temporally by as little as 30 microseconds, an asymmetry appears in the brain's alternating voltage. The results suggest an underlying mechanism that may enhance visual detection of high-frequency flicker.
Dendritic Growth in the Aged Human Brain and Failure of Growth in Senile Dementia
Authors: Buell Stephen J. , Coleman Paul D.
Published: October 2006

Golgi-stained dendrites of single randomly chosen layer-II pyramidal neurons in the human parahippocampal gyrus were quantified with a computer-microscope system. In nondemented aged cases (average age, 79.6 years), dendritic trees were more extensive than in adult cases (average age, 51.2), with most of the difference resulting from increases in the number and average length of terminal segments of the dendritic tree. These results provide morphological evidence for plasticity in the mature and aged human brain. In senile dementia (average age, 76.0), dendritic trees were less extensive than in adult brains, largely because their terminal segments were fewer and shorter. Cells with shrunken dendritic trees were found in all brains. These data suggest a model of aging in the central nervous system in which one population of neurons dies and regresses and the other survives and grows. The latter appears to be the dominant population in aging without dementia.
Inbreeding and Juvenile Mortality in Small Populations of Ungulates
Authors: Ralls Katherine , Brugger Kristin , Ballou Jonathan
Published: October 2006

Juvenile mortality of inbred young was higher than that of noninbred young in 15 of 16 species of captive ungulates. In 19 of 25 individual females, belonging to ten species, a larger percentage of young died when the female was mated to a related male than when she was mated to an unrelated male.
Goblet Cells in Embryonic Intestine: Accelerated Differentiation in Culture
Authors: Black Betty L. , Moog Florence
Published: October 2006

If duodenal tissue from 14-day chick embryos is cultured in chemically defined medium, more than twice as many goblet cells appear within 48 hours as in intact embryos during the same time. The increase in goblet cell number is further accelerated by 10
-9
molar thyroxine but is prevented by 10
-6
molar hydrocortisone. The results suggest that differentiation of intestinal epithelium is regulated in part by a circulating inhibitor.
Diurnal Rhythm: Effects on Hepatic Regeneration and Hepatic Regenerative Stimulator Substance
Authors: LaBrecque Douglas R. , Feigenbaum Alan , Bachur Nicholas R.
Published: October 2006

The effect of a controlled lighting schedule on the activity of a weanling rat liver extract that stimulates DNA synthesis in regenerating adult rat liver, and on the response of the test animals to the extract, has been investigated. Both activity of the extract and endogenous DNA synthesis in the weanling animals follow the same distinct diurnal rhythm. Reversal of the lighting schedule reverses the rhythm of endogenous DNA synthesis but activity of the extract no longer correlates with the peak of DNA synthesis. Diurnal rhythm also has a striking effect on DNA synthesis in the regenerating test animal, but the extract increases DNA synthesis to the same relative degree, regardless of the time of day the hepatectomy is performed.
Brain Noradrenergic Systems as a Prerequisite for Developing Tolerance to Barbiturates
Authors: Tabakoff Boris , Yanai Joseph , Ritzmann Ronald F.
Published: October 2006

Mice treated with 6-hydroxydopamine before they were chronically fed phenobarbital did not develop functional barbiturate tolerance, measured by duration of the loss of righting reflex and hypothermia. Injection of 6-hydroxydopamine caused significant depletion of brain norepinephrine, while brain dopamine levels were not significantly depleted. Intact brain noradrenergic systems seem to be necessary for developing tolerance to the hypnotic and hypothermic effects of the barbiturates.
In Vitro Model for Stretch-Induced Hypertrophy of Skeletal Muscle
Authors: Vandenburgh Herman , Kaufman Seymour
Published: October 2006

Mechanical stretch of embryonic chicken skeletal myotubes developed in vitro leads to many of the biochemical changes seen in skeletal muscle hypertrophy. These include increased amino acid accumulation, increased incorporation of amino acids into general cellular proteins and myosin heavy chains, and increased accumulation of total protein and myosin heavy chains. This model system should aid in understanding how the growth rate of skeletal muscle is regulated by its activity.
Strong Electrical Currents Leave the Primitive Streak of Chick Embryos
Authors: Jaffe Lionel F. , Stern Claudio D.
Published: October 2006

The electrical fields above chick embryos were explored with a vibrating probe. These fields indicate that steady currents with exit densities of the order of 100 microamperes per square centimeter leave the whole streak and return elsewhere through the epiblast. The epicenter of these strong exit currents lies near Hensen's node. They are probably pumped into the intraembryonic space by the epiblast and then leak out of the streak because it is a zone of junctional disruption.
Infectious and Selectable Retrovirus Containing an Inducible Rat Growth Hormone Minigene
Authors: Miller A. Dusty , Ong Estelita S. , Rosenfeld Michael G. , Verma Inder M. , Evans Ronald M.
Published: October 2006

A growth hormone minigene carrying its natural promoter (237 nucleotides of chromosomal DNA) was stably propagated in a murine retrovirus containing hypoxanthine-guanine phosphoribosyltransferase as a selectable marker. Glucocorticoid and thyroid hormone inducibility was transferred with the growth hormone gene. Recombinant virus with titers of 10
6
per milliliter was recovered. This demonstration that retroviruses can be used to transfer a nonselectable gene under its own regulatory control enlarges the scope of retroviral vectors as potent tools for gene transfer.
Surface-Active Biomaterials
Authors: Hench Larry L. , Wilson June
Published: October 2006

Since the discovery in 1969 of a man-made surface-active material that would bond to bone, a range of materials with the same ability has been developed. These include glass, glass-ceramic, and ceramic materials which have a range of reaction rates and from which it should be possible to select a surface-active material for a specific application. The available materials and their similarities, differences, and current clinical applications are reviewed.
Receptors for the Age of Anxiety: Pharmacology of the Benzodiazepines
Authors: Tallman John F. , Paul Steven M. , Skolnick Phil , Gallager Dorothy W.
Published: October 2006

Investigation of the actions of the benzodiazepines has provided insights into the neurochemical mechanisms underlying anxiety, seizures, muscle relaxation, and sedation. Behavioral, electrophysiological, pharmacological, and biochemical evidence indicates that the benzodiazepines exert their therapeutic effects by interacting with a high-affinity binding site (receptor) in the brain. The benzodiazepine receptor interacts with a receptor for γ-aminobutyric acid, a major inhibitory neurotransmitter, and enhances its inhibitory effects. The benzodiazepine receptor may also interact with endogenous substances and several naturally occurring compounds, including the purines and nicotinamide, are candidates for this role. Both the purines and nicotinamide possess some benzodiazepine-like properties in vivo, although further work will be required to confirm their possible roles as endogenous benzodiazepines.
Depolarization- and Ionophore-Induced Release of Octacosa Somatostatin from Stalk Median Eminence Synaptosomes
Authors: Kewley C. F. , Millar R. P. , Berman M. C. , Schally A. V.
Published: October 2006

Species of somatostatin of higher molecular weight were present in the nerve terminals (synaptosomes) of ovine stalk median eminences and were released by depolarizing stimuli. One of these species was identified as the biologically active molecule octacosa somatostatin. Octacosa somatostatin appears therefore to be secreted into the hypothalamic-hypophyseal system, supporting the concept of a role for this peptide in regulating pituitary hormone secretion.
Inhibition of Idiotype—Anti-Idiotype Interaction for Detection of a Parasite Antigen: a New Immunoassay
Authors: Potocnjak Pedro , Zavala Fidel , Nussenzweig Ruth , Nussenzweig Victor
Published: October 2006

Described in this report is an immunoradiometric assay of general applicability that is based on a new principle: the inhibition of the interaction between monoclonal antibodies by an antigen. The advantages of this assay are that it measures concentrations of single epitopes, purified antigen is not required, and the reagents can be obtained in unlimited amounts and are homogeneous. Its features are particularly attractive when the antigen has not been purified and is a minor component of a complex mixture of molecule.
Central Regulation of Intestinal Motility by Somatostatin and Cholecystokinin Octapeptide
Authors: Bueno Lionel , Ferre Jean-Pierre
Published: October 2006

When injected continuously into the lateral ventricles of the rat, somatostatin increased the frequency of the migrating myoelectric complexes of the small intestine in a dose-related manner. A significant increase was obtained at a dose as low as 0.066 picomole per minute. In contrast, cholecystokinin octapeptide decreased the frequency of the migrating myoelectric complex of the small intestine or disrupted this pattern when injected into the lateral ventricle at rates of 0.073 to 0.23 picomole per minute. These findings support the hypothesis that somatostatin and cholecystokinin octapeptide act on central nervous system structures that are involved in the control of intestinal motility.
Destruction of Noradrenergic Neurons in Rabbit Brainstem Elevates Plasma Vasopressin, Causing Hypertension
Authors: Blessing W. W. , Sved A. F. , Reis D. J.
Published: October 2006

When A1 noradrenergic neurons in the caudal ventrolateral medulla of rabbits are destroyed electrolytically or by local injection of the neurotoxin kainic acid, the concentration of vasopressin in plasma increases, causing hypertension. The A1 neurons may tonically inhibit the activity of vasopressin-secreting neuroendocrine cells through a direct hypothalamic projection.
Inhibition of Collagen Fibril Formation in Vitro and Subsequent Cross-Linking by Glucose
Authors: Lien Yeong-Hau , Stern Robert , Fu Joseph C. C. , Siegel Robert C.
Published: October 2006

Glucose inhibits collagen fibril formation in vitro. A linear dose response was observed, with half-maximum inhibition of fibril formation occurring at 50 m
M
glucose. Nonfibrillar collagen cannot be cross-linked by lysyl oxidase, an enzyme that catalyzes the initial cross-linking reaction. The degree of decreased fibril formation correlated with the loss of ability of the collagen to serve as a substrate for lysyl oxidase. Collagen that is not cross-linked is unstable and more susceptible to collagenolytic attack. Interference with collagen cross-linking and more rapid degradation may explain the decreased amounts of interstitial collagen and the poor healing of wounds associated with diabetes mellitus.
A Substance P Antagonist, [D-Pro
2
, D-Trp
7,9
]SP, Inhibits Inflammatory Responses in the Rabbit Eye
Authors: Holmdahl G. , Håkanson R. , Leander S. , Rosell S. , Folkers K. , Sundler F.
Published: October 2006

Neurogenic factors released by antidromic nerve stimulation are thought to be in part responsible for the vasodilation and breakdown of the blood-aqueous barrier that follows trauma to the eye. Substance P is one candidate for the mediation of the inflammatory response since it is thought to be a neurotransmitter in sensory afferents and since exogenous substance P is capable of eliciting a response characteristic of inflammation. In rabbits, intravitreal or topical application onto the eye of a specific substance P antagonist, [D-Pro
2
, D-Trp
7,9
]SP, inhibited not only the irritant effects of exogenous substance P but also the inflammatory response to a standardized trauma (infrared irradiation of the iris). These observations suggest that substance P, or a related peptide, is a neurogenic mediator of the inflammatory response in the eye.
Transformation Induced by Abelson Murine Leukemia Virus Involves Production of a Polypeptide Growth Factor
Authors: Twardzik Daniel R. , Todaro George J. , Marquardt Hans , Reynolds Fred H. , Stephenson John R.
Published: October 2006

Rat embryo fibroblasts transformed by Abelson murine leukemia virus (MuLV) produce and release a transforming growth factor (TGF). Production of this factor is correlated with a tyrosine-specific protein kinase that is functionally active and is associated with the major Abelson MuLV gene product, P120. Transformation-defective mutants of Abelson MuLV do not transform cells, do not have their virus coded transforming gene product phosphorylated in tyrosine, and do not induce TGF production. Abelson MuLV-induced TGF morphologically transforms cells in culture, competes with
125
I-labeled epidermal growth factor (EGF) for binding to cell receptors, and induces phosphorylation of tyrosine acceptor sites in the 160,000-dalton EGF membrane receptor. After purification to homogeneity, Abelson virus-induced TGF migrates as a single polypeptide with an apparent size of 7400 daltons as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Differential Breakdown of Phylogenetically Diverse Ribosomal RNA's Inserted via Liposomes into Mammalian Cells
Authors: Lavelle Donald , Ostro Marc J. , Giacomoni Dario
Published: October 2006

Liposomes were used to deliver ribosomal RNA's from three different organisms into cultivated mouse plasmacytoma cells. Ribosomal RNA from
Escherichia coli
was degraded intracellularly within 1 hour, whereas mouse and yeast ribosomal RNA's were degraded more slowly. This indicates that cells can discriminate between different ribosomal RNA's.
Substance P: A Putative Sensory Transmitter in Mammalian Autonomic Ganglia
Authors: Jiang Zhi-Gen , Dun Nae J. , Karczmar Alexander G.
Published: October 2006

Repetitive presynaptic stimulation elicited slow membrane depolarization in neurons of inferior mesenteric ganglia from guinea pigs. This response was not blocked by cholinergic antagonists but was specifically and reversibly inhibited by a substance P analog, (D-Pro2, D-Phe7, D-Trp9)-substance P, which also depressed the depolarization induced by exogenously applied substance P. The atropine-sensitive slow excitatory and slow inhibitory postsynaptic potentials evoked in neurons of rabbit superior cervical ganglia were not affected by the substance P analog. These and previous results provide strong support for the hypothesis that substance P or a closely related peptide is the transmitter mediating the slow depolarization. The latter may represent a sensory input from the gastrointestinal tract to neurons of the prevertebral ganglia.
Amplification and Enhanced Expression of the Epidermal Growth Factor Receptor Gene in A431 Human Carcinoma Cells
Authors: Merlino Glenn T. , Xu Young-Hua , Ishii Shunsuke , Clark Adrian J. L. , Semba Kentaro , Toyoshima Kumao , Yamamoto Tadashi , Pastan Ira
Published: October 2006

The sequence of the human epidermal growth factor (EGF) receptor shows great homology with the avian erythroblastosis virus v-
erb
B oncogene, raising the possibility that the receptor gene is identical to the c-
erb
B protooncogene. Human A431 epidermoid carcinoma cells, which have an unusually high number of EGF receptors, were examined to determine whether elevated EGF receptor levels correlate with gene amplification. Southern blots of genomic DNA's from A431 and other human cell lines were probed with either a v-
erb
B gene fragment or a human EGF receptor complementary DNA clone (pE7), previously isolated from an A431 complementary DNA library. When either probe was used to analyze Eco RI- or Hind III-generated DNA fragments, EGF receptor DNA sequences were amplified about 30-fold in A431. Differences in the banding pattern of A431 DNA fragments relative to normal fibroblast DNA indicate the occurrence of a rearrangement in the region of the receptor gene. Furthermore, A431 cells contain a characteristic, prominent 2.9-kilobase RNA. These results are consistent with the hypothesis that, in A431 cells, gene amplification, possibly associated with a translocation event, may result in the overproduction of EGF receptor protein or the appearance of the transformed phenotype (or both).
Structure of the Gene Encoding the Immunodominant Surface Antigen on the Sporozoite of the Human Malaria Parasite
Plasmodium falciparum
Authors: Dame John B. , Williams Jackie L. , McCutchan Thomas F. , Weber James L. , Wirtz Robert A. , Hockmeyer Wayne T. , Maloy W. Lee , Haynes J. David , Schneider Imogene , Roberts Donald , Sanders Greg S. , Reddy E. Premkumar , Diggs Carter L. , Miller Louis H.
Published: October 2006

The gene for the circumsporozoite (CS) protein of
Plasmodium falciparum
has been cloned and its nucleotide sequence determined. The gene encodes a protein of 412 amino acids as deduced from the nucleotide sequence. The protein contains 41 tandem repeats of a tetrapeptide, 37 of which are Asn-Ala-Asn-Pro and four of which are Asn-Val-Asp-Pro. Monoclonal antibodies against the CS protein of
Plasmodium falciparum
were inhibited from binding to the protein by synthetic peptides of the repeat sequence. The CS protein of
Plasmodium falciparum
and the CS protein of a simian malaria parasite,
Plasmodium knowlesi
, have two regions of homology, one of which is present on either side of the repeat. One region contains 12 of 13 identical amino acids. Within the nucleotide sequence of this region, 25 of 27 nucleotides are conserved. The conservation of these regions in parasites widely separated in evolution suggests that they may have a function such as binding to liver cells and may represent an invariant target for immunity.
Command Neurons in
Pleurobranchaea
Receive Synaptic Feedback from the Motor Network They Excite
Authors: Gillette Rhanor , Kovac Mark P. , Davis William J.
Published: October 2006

Command neurons that cause rhythmic feeding behavior in the marine mollusc
Pleurobranchaea californica
have been identified in the cerebropleural ganglion (brain). Intracellular stimulation of single command neurons in isolated nervous systems, semi-intact preparations, and restrained whole animals causes the same rhythmic motor output pattern as occurs during feeding. During this motor output pattern, action potentials recorded intracellularly from the command neurons occur in cyclic bursts that are phase-locked with the feeding rhythm. This modulation results from repetitive, alternating bursts of excitatory and inhibitory postsynaptic potentials, which are caused at least in part by synaptic feedback to the command neurons from identified classes of neurons in the feeding network. Central feedback to command neurons from the motor network they excite provides a possible general physiological mechanism for the sustained oscillation of neural networks controlling cyclic behavior.
Supplemental Lighting Stimulates Growth and Lactation in Cattle
Authors: Peters R. R. , Chapin L. T. , Leining K. B. , Tucker H. A.
Published: October 2006

Sixteen hours of light daily (114 to 207 lux) increased weight gains and milk yield 10 to 15 percent in Holstein cattle in comparison with cattle exposed to natural-length photoperiods (39 to 93 lux) of 9 to 12 hours. The weight gain was accomplished without increased consumption of feed. Manipulation of supplemental light may thus cause dramatic increases in food supplies from animals.
A Potential Second Messenger Role for Unsaturated Fatty Acids: Activation of Ca
2+
-Dependent Protein Kinase
Authors: McPhail Linda C. , Clayton Christine C. , Snyderman Ralph
Published: October 2006

Arachidonate and other unsaturated long-chain fatty acids were found to activate protein kinase C from human neutrophils. Kinase activation by arachidonate required calcium and was enhanced by diolein but did not require exogenous phosphatidylserine. Submaximal levels of arachidonate also enhanced the affinity of the kinase for calcium during activation by phosphatidylserine. Thus the release of arachidonate, which is triggered in many cell types by ligand-receptor interactions, could play a second messenger role in the regulation of cellular function by activation of protein kinase C.
Prevalence of Antibodies to Lymphadenopathy-Associated Retrovirus in African Patients with AIDS
Authors: Brun-Vézinet F. , Rouzioux C. , Montagnier L. , Chamaret S. , Gruest J. , Barré-Sinoussi F. , Geroldi D. , Chermann J. C. , McCormick J. , Mitchell S. , Piot P. , Taelman H. , Mirlangu Kapita Bila , Wobin Odio , Miazebo P. Mbendi N. , Kalambayi Kayembe , Bridts C. , Desmyter J. , Feinsod F. M. , Quinn T. C.
Published: October 2006

The presence of antibodies to lymphadenopathy-associated retrovirus (LAV) was determined by a radioimmunoprecipitation assay and by an enzyme-linked immunosorbent solid assay of sera from Zairian patients with the acquired immune deficiency syndrome (AIDS) in 1983. Thirty-five of 37 patients (94 percent) and 32 of 36 patients (88 percent), respectively, were seropositive by the two tests. In a control group of 26 patients, six (23 percent) showed positive results in these tests. Of these six control patients, five had clinically demonstrable infectious diseases and a low ratio of T4 to T8 lymphocytes. In addition, sera collected from a control group of Zairian mothers in 1980 were positive for LAV in 5 of 100 cases. Other serologic data suggest that LAV was present as early as 1977 in Zaire.
Chemical Mutation of Enzyme Active Sites
Authors: Kaiser E. T. , Lawrence D. S.
Published: October 2006

New active sites can be introduced into naturally occurring enzymes by the chemical modification of specific amino acid residues with the use of appropriately designed coenzyme analogs. The resultant semisynthetic enzymes can have catalytic activities very different from those of the corresponding native enzymes. For example, papain has been converted into a highly effective oxidoreductase by covalent modification of the sulfhydryl group of the active site cysteine residue (Cys25) with flavins such as 8-bromoacetyl-10-methylisoalloxazine. Thus, it is now possible to enhance the catalytic versatility of existing enzymes through the process of "chemical mutation" of the active site.
Conformational Variability of NAD
+
in the Free and Bound States: a Nicotinamide Sandwich in NAD
+
Crystals
Authors: Parthasarathy R. , Fridey Susan M.
Published: October 2006

X-ray analysis of the free-acid crystal form of the coenzyme nicotinamide adenine dinucleotide (NAD
+
) revealed a conformational difference between the free NAD
+
molecule and one bound in enzymes or complexed to Li
+
ions. The pyrophosphate group showed asymmetry in the phosphate-oxygen bonds of the phosphate-oxygen-phosphate link; this bond at the nicotinamide side of the link is longer than that at the adenosine side by 0.04 angstrom. The crystal structure showed a novel intermolecular stacking of adenine and water molecules on opposite sides of nicotinamide that gives rise to a nicotinamide sandwich.