bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Phosphorylation of Myosin Light Chain Kinase After an Increase in Cyclic AMP in Intact Smooth Muscle
Authors: de Lanerolle Primal , Nishikawa Masakatsu , Yost David A. , Adelstein Robert S.
Published: October 2006

The role of cyclic adenosine monophosphate-mediated phosphorylation of myosin light chain kinase in relaxing smooth muscle was examined. The kinase was immunoprecipitated from tissue extracts and the phosphate content was determined. The addition of forskolin to resting or methacholine-contracted muscles resulted in an increase in myosin light chain kinase phosphorylation and a relaxation of contracted muscles. These findings suggest that phosphorylation of myosin light chain kinase is one of the reactions in the process by which cyclic adenosine monophosphate causes relaxation of smooth muscle.
Elevated β-Endorphin in Cerebrospinal Fluid After Electrical Brain Stimulation: Artifact of Contrast Infusion?
Authors: Fessler Richard G. , Brown Frederick D. , Rachlin Jacob R. , Mullan Sean , Fang Victor S.
Published: October 2006

β-Endorphin-like immunoreactivity in cerebrospinal fluid was assayed in 11 patients receiving electrical stimulation of the brain for chronic pain. Immunoreactivity increased dramatically after contrast ventriculography prior to stimulation. No further elevations were observed after stimulation. The magnitude and time course of elevations were identical after placement of electrodes either in the thalamus or in the periventricular gray matter. These results suggest that previous findings of stimulation-induced elevation of β-endorphin-like immunoreactivity in cerebrospinal fluid are attributable to an artifact of contrast ventriculography.
Simian Sarcoma Virus—Transformed Cells Secrete a Mitogen Identical to Platelet-Derived Growth Factor
Authors: Owen Albert J. , Pantazis Panagiotis , Antoniades Harry N.
Published: October 2006

Normal rat kidney (NRK) cells transformed by simian sarcoma virus (SSV) release into the culture medium a biologically active mitogen with properties identical to those of human platelet-derived growth factor (PDGF). Like PDGF, the growth factor derived from SSV-NRK cells was shown to be stable to heat and sensitive to reducing agents. It was capable of inhibiting binding of labeled PDGF to the receptor on human fibroblasts. It also stimulated the phosphorylation of the same membrane protein (185 kilodaltons) in isolated plasma membranes from human fibroblasts. Immunoprecipitation of metabolically labeled proteins released by SSV-NRK cells showed that a 34-kilodalton protein was specifically precipitated by antiserum to PDGF. Upon reduction, this protein had a molecular size of 17 kilodaltons. PDGF has been shown to consist of two 14- to 18-kilodalton proteins linked by disulfide bonds.
Cytochrome a
3
Structure in Carbon Monoxide-Bound Cytochrome Oxidase
Authors: Argade P. V. , Ching Y. C. , Rousseau D. L.
Published: October 2006

The iron-carbon monoxide stretching mode and the iron-carbon-oxygen bending mode in carbon monoxide-bound cytochrome oxidase have been assigned at 520 and 578 cm
-1
, respectively. The frequencies, widths, and intensities of these modes show that the Fe-C-O grouping in carbon monoxide-cytochrome a
3
is linear but tilted from the normal to the heme plane; that the iron-histidine bond in both five- and six-coordinate cytochrome a
3
is strained; and that the carbon monoxide and the proximal histidine each have characteristic, well-defined orientations in all molecules. These data can account for the binding affinities of carbon monoxide and dioxygen under physiological conditions.
Voltage-Dependent Calcium Channels from
Paramecium
Cilia Incorporated into Planar Lipid Bilayers
Authors: Ehrlich Barbara E. , Finkelstein Alan , Forte Michael , Kung Ching
Published: October 2006

Two different divalent cation-selective channels from Paramecium cilia were incorporated into planar lipid bilayers. Both channels were much more permeable to divalent than univalent cations, and one of them discriminated significantly among the divalent cations. The selectivity and voltage dependence of the latter channel are comparable to those of voltage-dependent calcium channels found in a variety of cells. A combined biochemical, biophysical, and genetic study of calcium channels is now possible.
Alzheimer's Disease: A Disorder of Cortical Cholinergic Innervation
Authors: Coyle Joseph T. , Price Donald L. , DeLong Mahlon R.
Published: October 2006

Great emphasis is being placed on identification of neurotransmitter systems involved in the symptomatic manifestations of neurological and psychiatric disorders. In the case of Alzheimer's disease, which now seems to be one of the most common causes of mental deterioration in the elderly, compelling evidence has been developed that acetylcholine-releasing neurons, whose cell bodies lie in the basal forebrain, selectively degenerate. These cholinergic neurons provide widespread innervation of the cerebral cortex and related structures and appear to play an important role in cognitive functions, especially memory. These advances reflect a close interaction between experimental and clinical neuroscientists in which information derived from basic neurobiology is rapidly utilized to analyze disorders of the human brain.
Nucleotide Sequence and Expression of the Diphtheria
tox
228 Gene in
Escherichia coli
Authors: Kaczorek Michel , Delpeyroux Francis , Chenciner Nicole , Streeck Rolf E. , Murphy John R. , Boquet Patrice , Tiollais Pierre
Published: October 2006

The complete nucleotide sequence of the diphtheria
tox
228 gene encoding the nontoxic serologically related protein CRM228 has been determined. A comparison of the predicted amino acid sequence with the available amino acid sequences from the wild-type toxin made it possible to deduce essentially the entire nucleotide sequence of the wild-type
tox
gene. The signal peptide of pro-diphtheria toxin and the putative
tox
promoter have been identified, a highly symmetrical nucleotide sequence downstream of the toxin gene has been detected; this region may be the corynebacteriophage β attachment site (
att
P). The cloned toxin gene was expressed at a low level in
Escherichia coli
.
Relaxed Cellular Controls and Organelle Heredity
Authors: Birky C. William
Published: October 2006

Genes in mitochondria and chloroplasts behave quite differently from genes in the nucleus: they are often inherited from only one parent, and they segregate during mitotic cell divisions. Cells contain many copies of each mitochondrial or chloroplast gene, and the replication, recombination, and partitioning of these genes at cell division are much less stringently controlled than is the case for the one or two copies of each nuclear gene. Relaxed control results in random changes in gene frequencies inside single cells or lineages. This may have been the primitive mechanism behind the uniparental inheritance as well as the vegetative segregation of cytoplasmic genes and is still an important factor in many organisms.
Crankcase Oils: Are They a Major Mutagenic Burden in the Aquatic Environment?
Authors: Payne Jerry F. , Martins Isabel , Rahimtula Anver
Published: October 2006

Fractions from used crankcase oil enriched in polyaromatic hydrocarbons induced revertant colonies in
Salmonella typhimurium
strain TA 98 when activated by rat or trout liver extracts. The mutagenic activity was not due to benzopyrene or benzanthracene. Fractions from various crude and refined petroleums were nonmutagenic. Among various petroleum hydrocarbons entering inland and coastal waters, used crankcase oils may represent a major mutagenic burden.
Neurotrophic Protein Regulates Muscle Acetylcholinesterase in Culture
Authors: Oh T. H. , Markelonis G. J.
Published: October 2006

Skeletal muscles lose acetylcholinesterase in culture as a result of denervation. A protein fraction isolated from peripheral nerves maintained the level of acetylcholinesterase in cultures of aneural embryonic muscle or denervated adult chicken muscle. These results indicate that trophic regulation of muscle acetylcholinesterase might be mediated by a protein produced by nerves.
Translocations Among Antibody Genes in Human Cancer
Authors: Leder Philip , Battey Jim , Lenoir Gilbert , Moulding Christopher , Murphy William , Potter Huntington , Stewart Timothy , Taub Rebecca
Published: October 2006

The characteristic chromosomal translocations that occur in certain human malignancies offer opportunities to understand how two gene systems can affect one another when they are accidentally juxtaposed. In the case of Burkitt lymphoma, such a translocation joins the cellular oncogene, c-
myc
, to a region encoding one of the immunoglobulin genes. In at least one example, the coding sequence of the rearranged c-
myc
gene is identical to that of the normal gene, implying that the gene must be quantitatively, rather than qualitatively, altered in its expression if it is to play a role in transformation. One might expect to find the rearranged c-
myc
gene in a configuration that would allow it to take advantage of one of the known immunoglobulin promoters or enhancer elements. However, the rearranged c-
myc
gene is often placed so that it can utilize neither of these structures. Since the level of c-
myc
messenger RNA is often elevated in Burkitt cells, the translocation may lead to a deregulation of the c-
myc
gene. Further, since the normal allele in a Burkitt cell is often transcriptionally silent in the presence of a rearranged allele, a model for c-
myc
regulation is suggested that involves a trans-acting negative control element that might use as its target a highly conserved portion of the c-
myc
gene encoding two discrete transcriptional promoters.
Prolonged Survival and Remyelination After Hematopoietic Cell Transplantation in the Twitcher Mouse
Authors: Yeager Andrew M. , Brennan Susan , Tiffany Carol , Moser Hugo W. , Santos George W.
Published: October 2006

The twitcher mouse is an animal model of galactosylceramidase deficiency (Krabbe's disease), a human sphingolipidosis. The effects of hematopoietic cell transplantation as potential enzyme replacement therapy were examined in the twitcher mouse. Survival in twitcher mice with transplants was significantly prolonged and was associated with gradual repair of demyelination in peripheral nerves. In contrast, there was no improvement in the neurodegenerative process in the central nervous system after transplantation. These observations indicate that cellular transplantation may effectively provide in vivo enzyme replacement for the peripheral manifestations of genetic storage diseases. Strategies to perturb the blood-brain barrier may be necessary for enzyme replacement to be therapeutic in diseases with central nervous system manifestations.
Acetylcholine Receptor: An Allosteric Protein
Authors: Changeux Jean-Pierre , Devillers-Thiéry Anne , Chemouilli Phillippe
Published: October 2006

The nicotine receptor for the neurotransmitter acetylcholine is an allosteric protein composed of four different subunits assembled in a transmembrane pentamer α2 βγδ. The protein carries two acetylcholine sites at the level of the α subunits and contains the ion channel. The complete sequence of the four subunits is known. The membrane-bound protein undergoes conformational transitions that regulate the opening of the ion channel and are affected by various categories of pharmacologically active ligands.
Disulfide Bond Engineered into T4 Lysozyme: Stabilization of the Protein Toward Thermal Inactivation
Authors: Perry L. Jeanne , Wetzel Ronald
Published: October 2006

By recombinant DNA techniques, a disulfide bond was introduced at a specific site in T4 lysozyme, a disulfide-free enzyme. This derivative retained full enzymatic activity and was more stable toward thermal inactivation than the wild-type protein. The derivative, T4 lysozyme (Ile
3
→ Cys), was prepared by substituting a Cys codon for an Ile codon at position 3 in the cloned lysozyme gene by means of oligonucleotide-dependent, site-directed mutagenesis. The new gene was expressed in
Escherichia coli
under control of the (
trp-lac
) hybrid tac promoter, and the protein was purified. Mild oxidation generated a disulfide bond between the new Cys
3
and Cys
97
, one of the two unpaired cysteines of the native molecule. Oxidized T4 lysozyme (Ile
3
→ Cys) exhibited specific activity identical to that of the wild-type enzyme when measured at 20°C in a cell-clearing assay. The cross-linked protein was more stable than the wild type during incubation at elevated temperatures as determined by recovered enzymatic activity at 20°C.
Cigarette Craving, Smoking Withdrawal, and Clonidine
Authors: Glassman Alexander H. , Jackson Wynn K. , Walsh B. Timothy , Roose Steven P , Rosenfeld Bob
Published: October 2006

Clonidine, an α-2-adrenergic agonist, significantly reduces opiate withdrawal. Fifteen heavy smokers abstained from cigarettes on three separate occasions and received instead clonidine, placebo, or the benzodiazepine alprazolam. Clonidine and alprazolam diminished withdrawal symptoms. The two drugs suppressed anxiety, tension, irritability, and restlessness equally but clonidine had a greater effect than alprazolam on cigarette craving. These observations suggest that noradrenergic activity is a common feature in the pathophysiology of withdrawal and that a special relationship exists between central noradrenergic activity and craving.
Specific Sequence Homology and Three-Dimensional Structure of an Aminoacyl Transfer RNA Synthetase
Authors: Webster Teresa , Tsai Hsin , Kula Maria , Mackie George A. , Schimmel Paul
Published: October 2006

Few and limited amino acid sequence homologies have been found among eight bacterial aminoacyl transfer RNA (tRNA) synthetases whose primary structures are known. The entire 939-amino acid primary structure of
Escherichia coli
isoleucyl-tRNA synthetase is now reported. In a sequence of 11 consecutive amino acids matching a sequence in
E. coli
methionyl-tRNA synthetase, there are ten identical residues and one conservative change. This is the strongest homology recorded between any two aminoacyl tRNA synthetases. This part of the methionine enzyme's three-dimensional structure has been determined, and it occurs in a mononucleotide binding fold; a close three-dimensional structural homology of this part of the enzyme with
Bacillus stearothermophilus
tyrosyl-tRNA synthetase has also been reported. The three synthetases probably fold identically in this region.
Purified Human Granulocyte-Macrophage Colony-Stimulating Factor: Direct Action on Neutrophils
Authors: Gasson Judith C. , Weisbart Richard H. , Kaufman Susan E. , Clark Steven C. , Hewick Rodney M. , Wong Gordon G. , Golde David W.
Published: October 2006

Neutrophil migration inhibition factor from T lymphocytes (NIF-T) is a lymphokine that acts to localize granulocytes. Medium conditioned by the Mo human T-lymphoblast cell line was used to purify NIF-T, a glycoprotein with a molecular weight of 22,000. The NIF-T was found to potently stimulate the growth of granulocyte and macrophage colonies from human bone marrow and colony formation by the KG-1 myeloid leukemia cell line. Thus a human lymphokine (NIF-T) that modulates the activities of mature neutrophilic granulocytes is also a colony-stimulating factor acting on precursors to induce growth and differentiation of new effector cells.
Relative Brain Size and Metabolism in Mammals
Authors: Armstrong Este
Published: October 2006

Comparisons of the relation between brain and body weights among extant mammals show that brain sizes have not increased as much as body sizes. Interspecific increases in brain and body size appear to occur at the same rate, however, when the amount of available energy is taken into account. After this adjustment, brains of primates are slightly larger than expected from the overall mammalian data, but primates also use a larger proportion of their total energy reserves for their brains. Analyses of relative brain size must take into account the requirements that the metabolically active brain has for the body.
α-Difluoromethylornithine-Induced Polyamine Depletion of 9L Tumor Cells Modifies Drug-Induced DNA Cross-Link Formation
Authors: Tofilon Philip J. , Deen Dennis F. , Marton Laurence J.
Published: October 2006

Depletion of intracellular levels of polyamines, which are believed to have a role in the intranuclear stabilization of DNA, alters the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea and
cis
-diamminedichloroplatinum II in 9L rat brain tumor cells. Alkaline elution techniques were used to show that polyamine depletion alters the number of DNA cross-links formed by these cytotoxic agents.
Interruption of the Mammillothalamic Tract Prevents Seizures in Guinea Pigs
Authors: Mirski Marek A. , Ferrendelli James A.
Published: October 2006

Interruption of the connection between the mammillary bodies and the anterior nucleus of the thalamus in guinea pigs, by discrete bilateral electrolytic lesions of the mammillothalamic tract, resulted in essentially complete protection from the behavioral and electroencephalographic convulsant action and lethal effect of pentylenetetrazol. This result demonstrates that the mammillary bodies and their rostral efferent connections are important for the propagation and perhaps initiation of generalized seizures.
Cortical Neurons Sensitive to Combinations of Information-Bearing Elements of Biosonar Signals in the Mustache Bat
Authors: Suga Nobuo , O'Neill William E. , Manabe Toshiki
Published: October 2006

The auditory cortex of the mustache bat,
Pteronotus parnellii rubiginosus
, is composed of functional divisions which are differently organized to be suited for processing the elements of its biosonar signal according to their biological significance. Unlike the Doppler-shifted-CF (constant frequency) processing area, the area processing the frequency-modulated components does not show clear tonotopic and amplitopic representations, but consists of several clusters of neurons, each of which is sensitive to a particular combination (or combinations) of information-bearing elements of the biosonar signal and echoes. The response properties of neurons in the major clusters indicate that processing of information carried by the frequency-modulated components of echoes is facilitated by the first harmonic of the emitted biosonar signal. The properties of some of these neurons suggest that they are tuned to a target which has a particular cross-sectional area and which is located at a particular distance.
Risk Factor Intervention for Health Maintenance
Authors: Breslow Lester
Published: October 2006

Risk factors for disease consist of (i) personal habits, such as cigarette smoking and excessive alcohol consumption, and (ii) bodily characteristics, such as hypertension and high serum cholesterol. Progress in identifying and quantifying risk factors is opening the way to the prevention of disease and maintenance of health. Systematic, controlled trials of intervention against risk factors are beginning to produce evidence on the extent of success in reducing both the factors and the mortality from associated diseases.
Regressive Events in Neurogenesis
Authors: Cowan W. Maxwell , Fawcett James W. , O'Leary Dennis D. M. , Stanfield Brent B.
Published: October 2006

The development of most regions of the vertebrate nervous system includes a distinct phase of neuronal degeneration during which a substantial proportion of the neurons initially generated die. This degeneration primarily adjusts the magnitude of each neuronal population to the size or functional needs of its projection field, but in the process it seems also to eliminate many neurons whose axons have grown to either the wrong target or an inappropriate region within the target area. In addition, many connections that are initially formed are later eliminated without the death of the parent cell. In most cases such process elimination results in the removal of terminal axonal branches and hence serves as a mechanism to "fine-tune" neuronal wiring. However, there are now also several examples of the large-scale elimination of early-formed pathways as a result of the selective degeneration of long axon collaterals. Thus, far from being relatively minor aspects of neural development, these regressive phenomena are now recognized as playing a major role in determining the form of the mature nervous system.
Heroin-Related Deaths: New Epidemiologic Insights
Authors: Ruttenber A. James , Luke James L.
Published: October 2006

Deaths associated with injected street preparations of heroin increased substantially in the District of Columbia between April 1979 and December 1982. The 1981 population-based mortality rate (17.4 per 100,000) is possibly the highest ever reported. A case-control study based on toxicologic analyses of postmortem blood samples indicates that concentrations of both heroin and ethanol are substantial risk factors for heroin-related deaths. Analyses of the composition of street-level preparations of heroin and quarterly mortality indicate that the quantity of heroin in packages sold on the street, the price of heroin in these packages, and the quinine weight per package each predict deaths equally as well. An increase in the causal use of heroin in combination with ethanol and quinine is the probable cause of this epidemic.
Mating in Bighorn Sheep: Multiple Creative Male Strategies
Authors: Hogg John T.
Published: October 2006

Rocky Mountain bighorn rams obtained copulations by defending single estrous ewes (tending), fighting tending rams for temporary access to defended ewes (coursing), or moving and holding ewes away from other rams beyond the periphery of a traditional tending area (blocking). Coursing and blocking illustrate a feature of many male alternative mating strategies: the ability of males regularly to create mating opportunities.
Nucleotide Sequences of the Human and Mouse Atrial Natriuretic Factor Genes
Authors: Seidman Christine E. , Bloch Kenneth D. , Klein Karen A. , Smith John A. , Seidman J. G.
Published: October 2006

Mouse and human atrial natriuretic factor (ANF) genes have been cloned and their nucleotide sequences determined. Each ANF gene consists of three coding blocks separated by two intervening sequences. The 5′ flanking sequences and those encoding proANF are highly conserved between the two species, while the intervening sequences and 3′ untranslated regions are not. The conserved sequences 5′ of the gene may play an important role in the regulation of ANF gene expression.
Formation in Vitro of Sperm Pronuclei and Mitotic Chromosomes Induced by Amphibian Ooplasmic Components
Authors: Lohka Manfred J. , Masui Yoshio
Published: October 2006

A cell-free preparation of the cytoplasm from activated eggs of
Rana pipiens
induces, in demembranated sperm nuclei of
Xenopus laevis
, formation of a nuclear envelope, chromatin decondensation, initiation of DNA synthesis, and chromosome condensation. Both soluble and particulate cytoplasmic constituents are required to initiate these processes in vitro. The observed changes resemble processes occurring during fertilization and the mitotic cycle in early amphibian embryos. Therefore, this cell-free system may be useful in biochemical analysis of the interactions of nucleus and cytoplasm that control nuclear behavior.
Isolation of Human T-Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS)
Authors: Gallo Robert C. , Sarin Prem S. , Gelmann E. P. , Robert-Guroff Marjorie , Richardson Ersell , Kalyanaraman V. S. , Mann Dean , Sidhu Gurdip D. , Stahl Rosalyn E. , Zolla-Pazner Susan , Leibowitch Jacque , Popovic Mikulas
Published: October 2006

Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral blood lymphocytes from one patient in the United States and two in France were cultured with T-cell growth factor (TCGF) an shown to express HTLV antigens. Virus from the U.S. patient was isolated and characterized and shown to be related to HTLV subgroup I. The virus was also transmitted into normal human T cells from umbilical cord blood of a newborn. Whether or not HTLV-I or other retroviruses of this family with T-cell tropism cause AIDS, it is possible that patients from whom the virus can be isolated can also transmit it to others. If the target cell of AIDS is the mature T cell as suspected, the methods used in these studies may prove useful for the long-term growth of these cells and for the identification of antigens specific for the etiological agent of AIDS.
Endogenous Regulation of Macrophage Proliferative Expansion by Colony-Stimulating Factor-Induced Interferon
Authors: Moore Robert N. , Larsen Hal S. , Horohov David W. , Rouse Barry T.
Published: October 2006

Stimulation of cultures of murine bone-marrow cells with specific macrophage growth factor (colony-stimulating factor 1) resulted in the production of type 1 interferon. Neutralization of this endogenous interferon by antiserum directed against interferons α and β resulted in a significant enhancement of mononuclear phagocyte proliferation from committed marrow precursors. The effect of the antiserum was lost in cultures depleted of adherent cells, an indication that an adherent regulatory cell (or cells) in the marrow limits mononuclear phagocyte proliferation by producing antiproliferative interferon in response to high levels of specific growth factor.
Anticarcinoma Activity in Vivo of Rhodamine 123, a Mitochondrial-Specific Dye
Authors: Bernal Samuel D. , Lampidis Theodore J. , McIsaac Robert M. , Chen Lan Bo
Published: October 2006

Carcinoma cells and normal epithelial cells differ in the mitochondrial retention of a permeant cationic compound, rhodamine 123. The possibility of utilizing this difference in carcinoma chemotherapy was investigated. Rhodamine 123 exhibited anticarcinoma activity in mice, and this activity was potentiated by 2-deoxyglucose.
Infants' Discrimination of the Duration of a Rapid Spectrum Change in Nonspeech Signals
Authors: Jusczyk Peter W. , Pisoni David B. , Reed Marjorie A. , Fernald Anne , Myers Mary
Published: October 2006

Two-month-old infants discriminated complex sinusoidal patterns that varied in the duration of their initial frequency transitions. Discrimination of these nonspeech sinusoidal patterns was a function of both the duration of the transitions and the total duration of the stimulus pattern. This contextual effect was observed even though the information specifying stimulus duration occurred after the transitional information. These findings parallel those observed with infants for perception of synthetic speech stimuli. Specialized speech processing capacities are thus not required to account for infants' sensitivity to contextual effects in acoustic signals, whether speech or nonspeech.
Effect of Myasthenic Immunoglobulin on Acetylcholine Receptors of Intact Mammalian Neuromuscular Junctions
Authors: Stanley Elis F. , Drachman Daniel B.
Published: October 2006

Degradation of acetylcholine receptors of intact mouse neuromuscular junctions was determined in vivo and in vitro by the release of radioactivity from mouse diaphragms labeled with
125
I-α-bungarotoxin. Treatment of mice with immunoglobulin from myasthenic patients accelerated the degradation rate to approximately three times normal, in both intact animals and organ cultures. The released radioactivity was in the form of [
125
I]tyrosine, confirming the nature of the degradative process. Accelerated degradation of acetylcholine receptors at neuromuscular junctions may represent an important antibody-mediated mechanism in myasthenia gravis.
Biological Activity of Some Oxygenated Sterols
Authors: Kandutsch Andrew A. , Chen Harry W. , Heiniger Hans-Jörg
Published: October 2006

A group of oxygenated sterols has been identified as potent and specific inhibitors of sterol biosynthesis. The ability of these compounds to inhibit sterol synthesis in cultured cells and the ineffectiveness of cholesterol under the same conditions suggest that feedback regulation of sterol biosynthesis may be brought about by an oxygenated sterol rather than by cholesterol. The nature of the regulatory sterol may vary in different cells with their specific requirements for cholesterol as a structural component or as a precursor of other steroid products. The use of oxygenated sterols to block sterol synthesis in cultured cells provides new information regarding the role of sterol in cell membrane structure and function. For example, de novo sterol synthesis is required for DNA synthesis and cell division by some cultured cells. Studies with cultured cells, and with rats and mice in vivo, suggest that oxygenated sterols could be of value in the treatment of several important human diseases.
Disulfiram Enhances Pharmacological Activity of Barbital and Impairs Its Urinary Elimination
Authors: Sharkawi Mahmoud , Cianflone Denis
Published: October 2006

Disulfiram or diethyldithiocarbamate significantly enhanced the sleeping time induced by barbital in rats. At identical time intervals after rats were injected with barbital the concentration of barbital in the blood or brain of animals that had previously received disulfiram was significantly higher than the concentrations in the corresponding tissues of control animals. Urinary excretion of barbital was significantly reduced in disulfiram-treated animals.
Monoclonal Antibodies to a Synthetic Fibrin-Like Peptide Bind to Human Fibrin But Not Fibrinogen
Authors: Hui Kwan Y. , Haber Edgar , Matsueda Gary R.
Published: October 2006

A synthetic heptapeptide from the amino terminus of the β chain in human fibrin was used as an antigen to produce monoclonal antibodies that bind to fibrin even in the presence of human fibrinogen at the concentration found in plasma. As expected, the antifibrin activity was inhibited by the peptide antigen but not by a control heptapeptide. In a chicken ex vivo circulatory model for fibrin detection, intravenously administered monoclonal antibodies bound to human fibrin-coated disks placed in an extracorporeal chamber. These findings may lead to better methods for identifying deep vein and coronary artery thrombi.
Selenium Deficiency in Cattle Associated with Heinz Bodies and Anemia
Authors: Morris J. G. , Cripe W. S. , Chapman H. L. , Walker D. F. , Armstrong J. B. , Alexander J. D. , Miranda R. , Sanchez A. , Sanchez B. , Blair-West J. R. , Denton D. A.
Published: October 2006

Cattle grazing St. Augustine grass growing on peaty muck soils in the Florida Everglades developed anemia associated with the presence of Heinz bodies and suboptimal concentrations of selenium in blood. Selenium supplementation corrected the anemia, prevented Heinz body formation, increased the body weight of cows and calves, and elevated blood selenium. This may be the first recorded example of widespread anemia in a population due to selenium deficiency.
Adaptive Response of Human Lymphocytes to Low Concentrations of Radioactive Thymidine
Authors: Olivieri Gregorio , Bodycote Judy , Wolff Sheldon
Published: October 2006

When human lymphocytes were cultured with [
3
H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberrations induced by [
3
H]thymidine and x-rays separately. Often fewer aberrations were found after exposure to radiation from both sources than were found after exposure to x-rays alone. At the same fixation times, nonradioactive thymidine did not affect the yield of x-ray-induced aberrations. The same phenomenon occurred at earlier fixation times, after exposure to 30 or 40 rad of x-rays and [
3
H]thymidine. This response is analogous to the adaptive response to alkylating agents whereby prior treatment with small doses for a long period reduces the damage occurring from large doses of similar agents given for a short time.
Time-Varying Magnetic Fields: Effect on DNA Synthesis
Authors: Liboff A. R. , Williams T. , Strong D. M. , Wistar R.
Published: October 2006

Human fibroblasts have exhibited enhanced DNA synthesis when exposed to sinusoidally varying magnetic fields for a wide range of frequencies (15 hertz to 4 kilohertz) and amplitudes (2.3 × 10-6to 5.6 × 10-4tesla). This effect, which is at maximum during the middle of theSphase of the cell cycle, appears to be independent of the time derivative of the magnetic field, suggesting an underlying mechanism other than Faraday's law. The threshold is estimated to be between 0.5 × 10-5and 2.5 × 10-5tesla per second. These results bring into question the allegedly specific magnetic wave shapes now used in therapeutic devices for bone nonunion. The range of magnetic field amplitudes tested encompass the geomagnetic field, suggesting the possibility of mutagenic interactions directly arising from short-term changes in the earth's field.
Amblyomma americanum
: a Potential Vector of Lyme Disease in New Jersey
Authors: Schulze Terry L. , Bowen G. Stephen , Bosler Edward M. , Lakat Michael F. , Parkin William E. , Altman Ronald , Ormiston Brian G. , Shisler Joseph K.
Published: October 2006

Amblyomma americanum
is a likely secondary vector of Lyme disease in New Jersey. Ticks of this species were removed from the site of the characteristic skin lesion known as
erythema chronicum migrans
on two patients with the disease, and the Lyme disease spirochete was isolated from nymphs and adults of this species. That
A. americanum
is a potential vector is supported by its similarities to
Ixodes dammini
, the known tick vector, in seasonal distribution and host utilization. The extensive range of
A. americanum
may have great implications for potential Lyme disease transmission outside known endemic areas.
Complete Development of
Cryptosporidium
in Cell Culture
Authors: Current William L. , Haynes Thomas B.
Published: October 2006

Protozoan parasites of the genus
Cryptosporidium
cause a short-term, flu-like, gastrointestinal illness in immunocompetent persons and severe, persistent, life-threatening diarrhea in immunodeficient individuals. No effective therapy is available for the treatment of cryptosporidiosis in the immunodeficient host. Complete development (from sporozoite to sporulated oocyst) of a human isolate of
Cryptosporidium
was achieved in cultured human fetal lung cells and primary chicken kidney and porcine kidney cells. The growth of this newly recognized zoonotic agent in cell culture now provides a means of studying its behavior, development, and metabolism, and a mechanism for evaluation of potentially useful therapeutic agents.
Enzymatic Catalysis in Organic Media at 100°C
Authors: Zaks Aleksey , Klibanov Alexander M.
Published: October 2006

Porcine pancreatic lipase catalyzes the transesterification reaction between tributyrin and various primary and secondary alcohols in a 99 percent organic medium. Upon further dehydration, the enzyme becomes extremely thermostable. Not only can the dry lipase withstand heating at 100°C for many hours, but it exhibits a high catalytic activity at that temperature. Reduction in water content also alters the substrate specificity of the lipase: in contrast to its wet counterpart, the dry enzyme does not react with bulky tertiary alcohols.
Inhibitory Action of Gossypol on Enzymes and Growth of
Trypanosoma cruzi
Authors: Montamat Enrique E. , Burgos Carlos , Gerez de Burgos Nelia M. , Rovai Leonor E. , Blanco Antonio , Segura Elsa L.
Published: October 2006

Gossypol, a phenolic compound isolated from the cotton plant, is a powerful inhibitor of nicotinamide adenine dinucleotide-linked enzymes (α-hydroxyacid dehydrogenase and malate dehydrogenase) of "
Trypanosoma cruzi
, the parasite that causes Chagas' disease. Parasites at the epimastigote stage that were incubated for 5 minutes with 100 micromolar gossypol were completely immobilized. Concentrations of gossypol as low as 0.01 micromolar markedly reduced the growth rate of
T. cruzi
in culture.
Gap Junction Development Is Correlated with Insulin Content in the Pancreatic B Cell
Authors: Meda P. , Halban P. , Perrelet A. , Renold A. E. , Orci L.
Published: October 2006

The development of gap junctions between insulin-containing B cells was quantitatively analyzed in islets of Langerhans isolated from rats treated with the sulfonylurea glibenclamid for 1, 2, or 7 days. Glibenclamid treatment was associated with a marked depletion of the insulin content of B cells and with an increase in the number and size of gap junctions between these cells. A significant correlation was found between these two events.
Antireproductive Effects of a Potent Gonadotropin-Releasing Hormone Antagonist in the Male Rat
Authors: Rivier Catherine , Rivier Jean , Vale Wylie
Published: October 2006

Administration of a potent antagonist of gondadotropin-releasing hormone (GnRH) antagonist [Ac-dehydro-Pro
1
, pCl-D-Phe
2
, D-Trp
3,6
]-N
α
-MeLeu
7
-GnRH to adult male rats for 2 weeks resulted in decreased testosterone production and sexual organ weights and in disrupted spermatogenesis. The results demonstrate the essential role of gonadotropin-releasing hormone in the maintenance of reproductive functions and have implications for the regulation of male fertility.
Aspirin: an Unexpected Side Effect on Prostacyclin Synthesis in Cultured Vascular Smooth Muscle Cells
Authors: Whiting John , Salata Kalman , Bailey J. Martyn
Published: October 2006

Monolayer cultures of rat aorta smooth muscle cells synthesized the anti-aggregatory substance prostacyclin via the cyclooxygenase pathway from
14
C-labeled arachidonic acid. The product was identified both by bioassay and by mass spectrometry. Labeled cells produced prostacyclin only when exposed to the initiator thrombin: treatment with therapeutic concentrations of aspirin (0.2 millimolar) for 30 minutes completely destroyed the cells' ability to synthesize prostacyclin. Prostacyclin synthesis from exogenous arachidonic acid recovered fully within 1 to 2 hours by a cycloheximide-sensitive process. Thrombin responsiveness, which was permanently impaired in confluent nondividing cultures, recovered substantially and within 24 hours only when cells were stimulated to divide by subculturing. These results indicate that resting vascular cells can rapidly synthesize new cyclooxygenase, but that aspirin destroys additional components of the prostacyclin system which can only be replaced during cell division.
Age Determination of the Shanidar 3 Neanderthal
Authors: Thompson David D. , Trinkaus Erik
Published: October 2006

Close agreement between the age at death estimated by macroscopic and microscopic methods was obtained for the Shanidar 3 Neanderthal. This suggests the possibility of obtaining age at death estimates by microscopic methods in other fossil hominids where the skeletal remains are highly fragmentary and macroscopic methods are not applicable.
Thyrotropin-Releasing Hormone Effects in the Central Nervous System: Dependence on Arousal State
Authors: Stanton Toni L. , Bechman Alexander L. , Winokur Andrew
Published: October 2006

Thyrotropin-releasing hormone was microinjected into the dorsal hippocampus of ground squirrels (
Citellus lateralis
) when they were at different levels of arousal, as assessed by electrophysiological and behavioral criteria. When administered to the awake animal, thyrotropin-releasing hormone produced dose-dependent decreases in body temperature accompanied by behavioral quieting and reductions in metabolic rate and electromyographic activity. The magnitude of these effects was greater when the peptide was microinjected during a period of behavioral activation. In contrast, administration of the peptide during slow wave sleep produced increased thermogenesis, an increase in electromyographic activity, and an increase in the amount of electroencephalographic desynchronization.
Oxygen Delivery to the Brain Before and After Birth
Authors: Jones M. Douglas , Rosenberg Adam A. , Simmons Michael A. , Molteni Richard A. , Koehler Raymond C. , Traystman Richard J.
Published: October 2006

We studied the relationship between cerebral oxygen consumption and cerebral oxygen delivery (cerebral blood flow × arterial oxygen content) in fetal, newborn, and adult sheep, Relative to the amount of oxygen consumed, cerebral oxygen delivery in the fetus exceeds that in the lamb and adult by 70 percent. This may represent a protective advantage for the fetus or simply a necessary adaptation to the low arterial oxygen pressure in the intrauterine environment.
Interference with Dimethylhydrazine Induction of Colon Tumors in Mice by ε-Aminocaproic Acid
Authors: Corasanti James G. , Hobika Grant H. , Markus Gabor
Published: October 2006

The antifibrinolytic agent ε-aminocaproic acid given in the drinking water to Swiss ICR/Ha mice significantly counteracted the appearance of colorectal tumors induced by 21 weekly injections of 1,2-dimethylhydrazine. The drug affected both the number and the location of the tumors and, in some animals, altogether prevented their appearance. The low concentrations of ε-aminocaproic acid in the plasma of four control mice given the agent labeled with carbon-14 for 3 days suggest that the effect may depend not on inhibition of plasminogen activator activity, but on interference with the binding of some substance to the strong lysine binding site of plasminogen.
Identification of a Protein That Purifies with the Scrapie Prion
Authors: Bolton David C. , McKinley Michael P. , Prusiner Stanley B.
Published: October 2006

Purification of prions from scrapie-infected hamster brain yielded a protein that was not found in a similar fraction from uninfected brain. The protein migrated with an apparent molecular size of 27,000 to 30,000 daltons in sodium dodecyl sulfate polyacrylamide gels. The resistance of this protein to digestion by proteinase K distinguished it from proteins of similar molecular weight found in normal hamster brain. Initial results suggest that the amount of this protein correlates with the titer of the agent.
Exposure to Ethylene Oxide at Work Increases Sister Chromatid Exchanges in Human Peripheral Lymphocytes
Authors: Yager Janice W. , Hines Cynthia J. , Spear Robert C.
Published: October 2006

Sister chromatid exchange rates increased significantly in the peripheral lymphocytes of a small group of hospital workers exposed to ethylene oxide for as little as 3.6 minutes per day regularly over a period of months. Results based on breathing zone exposure and task frequency estimates over a 6-month period for 14 workers suggest that sister chromatid exchanges are a sensitive indicator of exposure and that cumulative dose and dose rate are important predictors of sister chromatid exchange response.
Specific Reading Disability: Identification of an Inherited Form Through Linkage Analysis
Authors: Smith Shelley D. , Kimberling William J. , Pennington Bruce F. , Lubs Herbert A.
Published: October 2006

Linkage analysis in families with apparent autosomal dominant reading disability produced a lod score of 3.241. Since the traditionally accepted significance level for linkage is a lod score of 3.0, these results strongly suggest that a gene playing a major etiologic role in one form of reading disability is on chromosome 15.
Liposomal Blockade of the Reticuloendothelial System: Improved Tumor Imaging with Small Unilamellar Vesicles
Authors: Proffitt Richard T. , Williams Lawrence E. , Presant Cary A. , Tin George W. , Uliana Joseph A. , Gamble Ronald C. , Baldeschwieler John D.
Published: October 2006

The reticuloendothelial system of mice bearing EMT6 tumors was effectively blocked by intravenous injections of small unilamellar vesicles that incorporated a 6-aminomannose derivative of cholesterol in the lipid bilayer. Neutral liposomes loaded with indium-111-nitrilotriacetic acid were then injected. Fifty percent more radioactivity was deposited in tumors of the animals with blocked reticuloendothelial systems than in controls. Twenty-four hours after the injection of radioactive vesicles, well-defined tumor images were observed in whole-body gamma camera scintigraphs. Biodistribution studies showed that tumors from animals with blocked reticuloendothelial systems had more than twice the radioactivity per gram than any other tissue analyzed.
Absence of Glycerol Teichoic Acids in Certain Oral Streptococci
Authors: Rosan Burton
Published: October 2006

Glycerol teichoic acids were not detected immunochemically or chemically in phenol-water, hot saline (Rantz and Randall), or supernatant fluids of disrupted cells of
Streptococcus mitis
. Thus, teichoic acids do not appear to be found in most Gram-positive bacteria, as has been suggested.
Rebound Insomnia: A New Clinical Syndrome
Authors: Kales Anthony , Scharf Martin B. , Kales Joyce D.
Published: October 2006

Rebound insomnia followed the withdrawal of three benzodiazepine hypnotic drugs, each of which had been administered in a single nightly dose for only short-term periods. The intense worsening of sleep is attributed to the short duration of the action of these drugs. A hypothesis involving benzodiazepine receptors in the brain is proposed in which there is a delay or lag in replacement of endogenous benzodiazepine-like molecules after the abrupt withdrawal of exogenous drugs.
Prolactin Binding Sites in the Rat Brain
Authors: Walsh Raymond J. , Posner Barry I. , Kopriwa Beatrix M. , Brawer James R.
Published: October 2006

The principles of the competitive-binding assay were used in conjunction with light microscopic radioautography to demonstrate specific prolactin binding sites localized on ependyma of the rat choroid plexus, a previously unknown prolactin target tissue.
Neural Crest Cells Contribute to Normal Aorticopulmonary Septation
Authors: Kirby Margaret L. , Gale Thomas F. , Stewart Donald E.
Published: October 2006

By analyzing the hearts of quail-chick chimeras, it was found that neural crest cells at the level of occipital somites 1 to 3 migrate to the region of the aorticopulmonary septum. Bilateral removal of this neural crest population prior to migration causes malformation of the aorticopulmonary septum resulting in common arterial outflow channels or transposition of the great vessels.
Endogenous Opiates Mediate Radiogenic Behavioral Change
Authors: Mickley G. Andrew , Stevens Karen E. , White Gerald A. , Gibbs Gregory L.
Published: October 2006

Exposure of C57BL/6J mice to ionizing radiation caused stereotypical locomotor hyperactivity similar to that produced by morphine. Naloxone administration prevented this radiation-induced behavioral activation. These results support the hypothesis that endorphins are involved in some aspects of radiogenic behavioral change.
Hypothalamic γ-Aminobutyric Acid Neurons Project to the Neocortex
Authors: Vincent Steven R. , Hökfelt Tomas , Skirboll Lana R. , Wu Jang-Yen
Published: October 2006

Three groups of γ-aminobutyric acid—containing neurons were found in the mammillary region of the posterior hypothalamus. The groups correspond to the tuberal, caudal, and postmammillary caudal magnocellular nuclei. Many cells in these nuclei were retrogradely labeled with fast blue after the injection of this fluorescent dye into the neocortex. Immunohistochemical experiments showed that these same neurons also contained the γ-aminobutyric acid-synthesizing enzyme glutamate decarboxylase. These results provide morphological evidence for a γ-aminobutyric acid pathway arising in magnocellular neurons of the posterior hypothalamus and innervating the neocortex.