bluuebunny/crossref_metadata_2025 huggingface dataset:
Saturnine Gout: Lead-Induced Formation of Guanine Crystals
Authors: Farkas Walter R. , Stanawitz Tom , Schneider Morris
Published: October 2006

Intravenous injection of a sublethal dose of lead acetate into a domestic pig resulted in a 4.5-fold increase of guanine in the urine, indicating an impairment in the conversion of guanine to xanthine. This impairment is probably due to the inhibition of guanine aminohydrolase (guanase), since the activity of this enzyme is inhibited by Pb
2+
(the inhibition constant being 3.0 × 10
-6
M
). Postmortem histological examination revealed concretions of crystalline material in the epiphyseal plate of the femoral head. Extraction of the section containing the concretions showed that they were guanine. The relation of these findings to saturnine gout is discussed.
Immunologic Inhibition of Ultraviolet Radiation-Induced Tumor Suppressor Cell Activity
Authors: Granstein Richard D. , Parrish John A. , McAuliffe Daniel J. , Waltenbaugh Carl , Greene Mark I
Published: October 2006

Long-term exposure of C3H mice to ultraviolet radiation resulted in the formation of suppressor T cells that recognize ultraviolet radiation-induced regressor skin cancers as a class before the appearance of overt tumors. Administration of monoclonal antibodies to the product of the I-J
k
subregion of the major histocompatibility complex or low doses of cyclophosphamide in vivo inhibited the development or activity of these cells. This activity of the monoclonal antibody was eliminated by adsorption on B10.BR (I-J
k
) but not B10.D2 (I-J
d
) splenocytes. These findings provide evidence that elements expressing the I-J determinant are important in regulating the host response prior to the overt development of ultraviolet radiation-induced skin cancers and suggest novel therapeutic approaches to malignancies or other diseases involving suppressor T cells in their pathogenesis.
Cyclophilin: A Specific Cytosolic Binding Protein for Cyclosporin A
Authors: Handschumacher Robert E. , Harding Matthew W. , Rice Jeffrey , Drugge Rhett J. , Speicher David W.
Published: October 2006

Cyclophilin, a specific cytosolic binding protein responsible for the concentration of the immunosuppressant cyclosporin A by lymphoid cells, was purified to homogeneity from bovine thymocytes. Cation-exchange high-performance liquid chromatography resolved a major and minor cyclophilin species that bind cyclosporin A with a dissociation constant of about 2 × 10
-7
moles per liter and specific activities of 77 and 67 micrograms per milligram of protein, respectively. Both cyclophilin species have an apparent molecular weight of 15,000, an isoelectric point of 9.6, and nearly identical amino acid compositions. A portion of the NH
2
-terminal amino acid sequence of the major species was determined. The cyclosporin A-binding activity of cyclophilin is sulfhydryl dependent, unstable at 56°C and at
p
H 4 or 9.5, and sensitive to trypsin but not to chymotrypsin digestion. Cyclophilin specifically binds a series of cyclosporin analogs in proportion to their activity in a mixed lymphocyte reaction. Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism.
Revertants of Human Cells Transformed by Murine Sarcoma Virus
Authors: Cho Han Yong , Cutchins Ernest C. , Rhim Johng Sik , Huebner Robert J.
Published: October 2006

Revertants of nonproducer human osteosarcoma (NP/KHOS) cells induced by Kirsten murine sarcoma virus were isolated after incubating at high temperature (40.5°C) overnight and subcloning at 36°C. The morphologic variants, from which murine sarcoma virus could no longer be rescued, had growth properties similar to those of the nontransformed, parent human osteosarcoma cells and did not release RNA-dependent DNA polymerase activity. These revertants were nontumorigenic in nude mice. The revertants supported leukemia virus growth and showed an enhanced sensitivity to murine sarcoma virus superinfection. Thus, the revertants were from human cells transformed by an oncogenic RNA virus.
Photosynthesis of Previtamin D
3
in Human Skin and the Physiologic Consequences
Authors: Holick M. F. , MacLaughlin J. A. , Clark M. B. , Holick S. A. , Potts J. T. , Anderson R. R. , Blank I. H. , Parrish J. A. , Elias P.
Published: October 2006

Photosynthesis of previtamin D
3
can occur throughout the epidermis and in the dermis when hypopigmented Caucasian skin is exposed to solar ultraviolet radiation. Once previtamin D
3
is formed in the skin, it undergoes a temperature-dependent thermal isomerization that takes at least 3 days to complete. The vitamin D-binding protein preferentially translocates the thermal product, vitamin D
3
, into the circulation. These processes suggest a unique mechanism for the synthesis, storage, and slow, steady release of vitamin D
3
from the skin into the circulation.
Endogenous Substrate for Cyclic AMP-Dependent Protein Kinase in Adrenocortical Polyadenylated Messenger Ribonucleoproteins
Authors: Moore Robert E. , Sharma Rameshwar K.
Published: October 2006

An endogenous polysomal cyclic AMP-dependent protein kinase specifically phosphorylates a 150,000-dalton peptide bound to an adrenocortical polyadenylated messenger ribonucleoprotein complex. There is a possibility that this protein is a physiological substrate of cyclic AMP-dependent protein kinase and that the phosphorylation and dephosphorylation of this substrate may be important in the translational control of adrenal polyadenylated messenger RNA.
Pituitary Intermediate Lobe in Dog: Two Cell Types and High Bioactive Adrenocorticotropin Content
Authors: Halmi Nicholas S. , Peterson Mark E. , Colurso Gloria J. , Liotta Anthony S. , Krieger Dorothy T.
Published: October 2006

The pituitary intermediate lobe of most species is cytologically monotonous, but that of the dog is composed of two immunocytochemically distinct cell types. The predominant A cells are typical pars intermedia cells: they stain immunocytochemically for α-melanotropin and, more weakly, for adrenocorticotropin and β-lipotropin. The B cells are like the corticotrophs of the anterior lobe: they stain intensely for adrenocorticotropin and β-lipotropin but not for α-melanotropin. The B cells may account for the high concentration of bioactive adrenocorticotropin measured in the canine pars intermedia, and may explain why in dogs adenomas causing Cushing's disease through hypersecretion of adrenocorticotropin can arise from the intermediate as well as the anterior pituitary lobe.
Epidermal Growth Factors Enhances Viral Transformation of Granulosa Cells
Authors: Harrison J. , Auersperg N.
Published: October 2006

Kirsten sarcoma virus produced a low incidence of transient morphological transformation in primary cultures of rat ovarian granulosa cells. In the presence of epidermal growth factor, the incidence of transient transformation increased severalfold and two continuous cell lines were established. Epidermal growth factor, a naturally occurring polypeptide hormone, appears to act here as a tumor promoter in the retrovirus-induced transformation of a mesodermally derived epithelium.
Fluctuating Responses at a Central Synapse:
n
of Binomial Fit Predicts Number of Stained Presynaptic Boutons
Authors: Korn Henri , Triller Antoine , Mallet Alain , Faber Donald S.
Published: October 2006

Binomial predictions provided a better description than the Poisson law of fluctuating unitary inhibitory postsynaptic potentials evoked in the goldfish Mauthner cell by impulses in presynaptic interneurons. The number of terminal boutons established on this target cell by each horseradish peroxidase-filled interneuron corresponded to the value of the binomial parameter
n
.
Morphine in Cow and Human Milk: Could Dietary Morphine Constitute a Ligand for Specific Morphine (μ) Receptors?
Authors: Hazum Eli , Sabatka Julie J. , Chang Kwen-Jen , Brent David A. , Findlay John W. A. , Cuatrecasas Pedro
Published: October 2006

Morphine has been found in cow and human milk at concentrations of 200 to 500 nanograms per liter. Multistep purification yields a material that has immunological, biological, pharmacological, and chemical properties identical to those of morphine. Similar morphine-like material, which has been tentatively identified in some common plant sources, may be a ubiquitous dietary constituent and a possible source for the material in milk. Since morphine (μ) receptors have a low affinity for enkephalins, and since morphine-like materials have been described in brain and intestine, it is possible that morphine in food may be the source of this material and a normal ligand specific for μ receptors.
Differentiation of Respiratory and Abortigenic Isolates of Equine Herpesvirus 1 by Restriction Endonucleases
Authors: Studdert M. J. , Simpson T. , Roizman B.
Published: October 2006

Viruses classified by immunologic criteria as equine herpesvirus 1 cause respiratory disease and abortion in horses. Restriction endonuclease analyses of the DNA's of viruses from animals with respiratory disease and from aborted fetuses show that the patterns for respiratory viruses, while similar to each other, are entirely different from the patterns for fetal viruses. It is therefore proposed that the DNA restriction endonuclease patterns of fetal and respiratory viruses analyzed in this study be designated as prototypic of equine herpesvirus 1 and 4, respectively.
Epinephrine Reduction of Heme: Implication for Understanding the Transmission of an Agonist Stimulus
Authors: Peterson Douglas A. , Gerrard Jonathan M. , Glover Sheila M. , Rao Gundu H. R. , White James G.
Published: October 2006

Alpha-adrenergic agonists that promote platelet aggregation were found to reduce ferric heme to ferrous heme. Agents that bind iron in heme inhibited epinephrine-induced platelet aggregation. It is proposed that epinephrine first binds to its receptor and then reduces an adjacent heme group to transmit its agonist stimulus.
Intracellular
p
H of Mitogen-Stimulated Lymphocytes
Authors: Gerson Donald F. , Kiefer Hansruedi , Eufe Wolfgang
Published: October 2006

Mitogenic stimulation of mouse lymphocytes results in two sequential intracellular alkalinizations. The first shift of intracellular
p
H from 7.18 to 7.35 coincides with early biochemical events following mitogenic stimulation. The second alkalinization begins 12 hours after stimulation and rises in parallel with the rate of thymidine incorporation. The results suggest that intracellular alkalinization following stimulation may play a key role in the enhancement of cellular activation and mitogenesis.
Organization of Endogenous Opiate and Nonopiate Pain Control Systems
Authors: Watkins Linda R. , Mayer David J.
Published: October 2006

Research during the past decade has revealed the existence of neural systems that modulate pain transmission. Much of this work has focused on the role of endogenous opiate systems, but recent research indicates the involvement of nonopiate mechanisms as well. In this article, we present data demonstrating that opiate and nonopiate analgesia systems can be selectively activated by different environmental manipulations and describe the neural circuitry involved. Both neural and hormonal pathways and both opiate and nonopiate substances play roles in the complex modulation of pain transmission. The existence and description of these modulatory mechanisms have important clinical implications for the treatment of pain.
Significance of Tissue
myo
-Inositol Concentrations in Metabolic Regulation in Nerve
Authors: Simmons David A. , Winegrad Albert I. , Martin Donald B.
Published: October 2006

Approximately 25 percent of resting energy utilization in isolated nerve endoneurium is inhibited by medium containing defatted albumin and selectively restored by arachidonic acid but is unaffected by indomethacin or nordihydroguaiaretic acid. The same component of energy utilization is inhibited by small decreases in endoneurial
myo
-inositol, which decrease incorporation of carbon-14-labeled arachidonic acid into phosphatidylinositol. The fraction of the resting oxygen uptake inhibited by ouabain is decreased 40 to 50 percent by a reduced tissue
myo
-inositol concentration or by defatted albumin. Metabolic regulation by rapid, basal phosphatidylinositol turnover is dependent on the maintenance of normal tissue
myo
-inositol concentrations.
Precipitated Withdrawal by a Benzodiazepine Receptor Antagonist (Ro 15-1788) After 7 Days of Diazepam
Authors: Lukas Scott E. , Griffiths Roland R.
Published: October 2006

Baboons implanted with intragastric catheters were given diazepam (10 milligrams per kilogram of body weight) twice daily for 45 consecutive days. On days 7 and 35, they were given intramuscular injections of the benzodiazepine receptor antagonist Ro 15-1788. Mild and intermediate withdrawal signs, including retching and vomiting, were observed after 7 days of diazepam, and more frequent and intense withdrawal signs, including tremor and convulsion, occurred after 35 days of diazepam. With the termination of the diazepam injections after 45 days, a mild to intermediate withdrawal syndrome was observed over the next 15-day period.
Naloxone Antagonism of the Thermoregulatory Effects of Phencyclidine
Authors: Glick Stanley D. , Guido Ronald A.
Published: October 2006

Phencyclidine elicits hyperthermia at low doses and hypothermia at high doses in rats. Naloxone antagonizes both effects. Phencyclidine's effects on thermoregulation are probably mediated by an interaction with a mu opiate receptor.
Cat Color Vision: The Effect of Stimulus Size
Authors: Loop Michael S. , Bruce Laura L.
Published: October 2006

Adult cats were trained to discriminate blue from green and gray. Although the cats could discriminate the intensity of stimuli whose areas ranged from 33 to 0.36 square centimeters they could not discriminate color when the stimulus was 0.36 square centimeter (<20° visual angle). This influence of stimulus size may account for both positive and negative results of previous studies.
Hormonal Regulation of Gonadotropin Receptors and Steroidogenesis in Cultured Fetal Rat Tests
Authors: Warren Dwight W. , Dufau Maria L. , Catt Kevin J.
Published: October 2006

Gonadotropic activation of the adult rat testis in vitro and in vivo is followed by down-regulation of luteinizing hormone receptors and decreased androgen responses to subsequent hormonal stimulation. In contrast, treatment of cultured fetal testes with gonadotropins and dibutyryl adenosine 3′,5′-monophosphate enhanced steroidogenic responsiveness and did not cause the luteinizing hormone-receptor loss and desensitization that is characteristic of the adult gonad. The analysis of gonadotropin receptors and action in cultured fetal testis cells facilitates developmental studies of gonadal function, and has revealed significant differences in the responses of fetal and adult Leydig cells to gonadotropic regulation.
New Method for Detecting Cellular Transforming Genes
Authors: Blair D. G. , Cooper C. S. , Oskarsson M. K. , Eader L. A. , Vande Woude G. F.
Published: October 2006

Tumor induction in athymic nude mice can be used to detect dominant transforming genes in cellular DNA. Mouse NIH 3T3 cells freshly transfected with either cloned Moloney sarcoma proviral DNA or cellular DNA's derived from virally transformed cells induced tumors when injected into athymic nu/nu mice. Tumors were also induced by cells transfected with DNA from two tumor-derived and one chemically transformed human cell lines. The mouse tumors induced by human cell line DNA's contained human DNA sequences, and DNA derived from these tumors was capable of inducing both tumors and foci on subsequent transfection. Tumor induction in nude mice represents a useful new method for the detection and selection of cells transformed by cellular oncogenes.
Oncogene from Human EJ Bladder Carcinoma Is Located on the Short Arm of Chromosome 11
Authors: de Martinville Bérengère , Giacalone Joseph , Shih Chiaho , Weinberg Robert A. , Francke Uta
Published: October 2006

The human cellular homolog of the transforming DNA sequence isolated from the bladder carcinoma cell line EJ was localized on the short arm of human chromosome 11 by Southern blot analysis of human-rodent hybrid cell DNA. This locus contains human sequences homologous to the Harvey murine sarcoma virus v-Ha-
ras
oncogene.
Ammonium Chloride Prevents Lytic Growth of Reovirus and Helps to Establish Persistent Infection in Mouse L Cells
Authors: Canning W. Michael , Fields Bernard N.
Published: October 2006

Ammonium chloride, a lysosomotropic agent that raises intralysosomal
p
H, reduces the yield of reovirus during infection of mouse L cells. Subsequent removal of ammonium chloride results in the rapid establishment of a persistent infection.
Swine Influenza-Like Viruses in Turkeys: Potential Source of Virus for Humans?
Authors: Hinshaw V. S. , Webster R. G. , Bean W. J. , Downie J. , Senne D. A.
Published: October 2006

Influenza A viruses (subtype H1N1), recently isolated from turkeys in different areas of the United States, were determined to be closely related to strains typically associated with pigs. This conclusion was based on comparisons of H1N1 isolates from pigs, humans, ducks, and turkeys with polyclonal and monoclonal antibodies, RNA-RNA competitive hybridization, and replication studies. One of the H1N1 isolates from turkeys caused influenza in a laboratory technician, who displayed fever, respiratory illness, virus shedding, and seroconversion. These results suggest that turkeys as well as pigs are involved in the maintenance of these viruses and their transmission to humans.
Hemagglutinin Variants of Reovirus Type 3 Have Altered Central Nervous System Tropism
Authors: Spriggs Dale R. , Bronson Roderick T. , Fields Bernard N.
Published: October 2006

Variants of the Dearing strain of reovirus type 3 with antigenically altered hemagglutinin proteins are much less neurovirulent than the parental virus. When injected intracerebrally into mice these variants infected a subset of the brain neurons that were infected by the parental virus. When injected intraperitoneally, the variants did not spread to the brain. These results indicate that minor modifications of the reovirus hemagglutinin dramatically alter the ability of the virus to spread into and injure the central nervous system.
High-Efficiency Ligation and Recombination of DNA Fragments by Vertebrate Cells
Authors: Miller Cynthia K. , Temin Howard M.
Published: October 2006

DNA-mediated gene transfer (transfection) is used to introduce specific genes into vertebrate cells. Events soon after transfection were quantitatively analyzed by determining the infectivity of the DNA from an avian retrovirus and of mixtures of subgenomic fragments of this DNA. The limiting step of transfection with two DNA molecules is the uptake by a single cell of both DNA's in a biologically active state. Transfected cells mediate ligation and recombination of physically unlinked DNA's at nearly 100 percent efficiency.
Frequent Activation of c-
kis
as a Transforming Gene in Fibrosarcomas Induced by Methylcholanthrene
Authors: Eva Alessandra , Aaronson Stuart A.
Published: October 2006

The DNA's from two of four methylcholanthrene-induced mouse fibrosarcomas contained transforming genes that were identical in their pattern of restriction endonuclease resistance to inactivation of biologic activity. This transforming gene was identified as the activated homolog of the Kirsten murine sarcoma virus
onc
gene, v-
kis
. The finding that a defined carcinogen reproducibly leads to activation of
kis
as a transforming gene should be of value in elucidating the role of oncogenes in the neoplastic process.
A Parathyroid Hormone Inhibitor in Vivo: Design and Biological Evaluation of a Hormone Analog
Authors: Horiuchi Noboru , Holick Michael F. , Potts John T. , Rosenblatt Michael
Published: October 2006

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34]bPTH-(7-34)NH
2
, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3′,5′-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.
Metabolism of Polycyclic Aromatic Hydrocarbon Derivatives to Ultimate Carcinogens During Lipid Peroxidation
Authors: Dix Thomas A. , Marnett Lawrence J.
Published: October 2006

Lipid peroxidation triggered by ascorbate or reduced nicotinamide adenine dinucleotide in rat liver microsomes can initiate the epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene. The stereochemistry of epoxidation is indicative of a peroxide-dependent free radical process. Since the epoxides formed may be the most carcinogenic derivatives of benzo[a]pyrene yet identified, lipid peroxidation can effect the metabolic activation of proximate carcinogens to ultimate carcinogens.
Ribonucleotide Reductase—a Radical Enzyme
Authors: Reichard Peter , Ehrenberg Anders
Published: October 2006

Ribonucleotide reductases catalyze the enzymatic formation of deoxyribonucleotides, an obligatory step in DNA synthesis. The native form of the enzyme from
Escherichia coli
or from mammalian sources contains as part of its polypeptide structure a free tyrosyl radical, stabilized by an iron center. The radical participates in all probability in the catalytic process during the substitution of the hydroxyl group at C-2 of ribose by a hydrogen atom. A second, inactive form of the
E. coli
reductase lacks the tyrosyl radical. Extracts from
E. coli
contain activities that interconvert the two forms. The tyrosyl radical is introduced in the presence of oxygen, while anaerobiosis favors its removal, suggesting a regulatory role in DNA synthesis for oxygen.
An Opiate Binding Site in the Rat Brain Is Highly Selective for 4,5-Epoxymorphinans
Authors: Grevel Joachim , Sadée Wolfgang
Published: October 2006

In vitro binding studies have demonstrated the existence of multiple opiate receptor types. An additional site in the rat brain (termed the λ site) is distinct from the established types by its selectivity for 4,5-epoxymorphinans (such as naloxone and morphine). While the λ site displays a high affinity for naloxone in vivo and in vitro in fresh brain membrane homogenates, these sites rapidly convert in vitro to a state of low affinity. The regional distribution of the λ site in the brain is strikingly different from that of the classic opiate receptor types.
Detection of Antibodies to Herpes Simplex Virus with a Continuous Cell Line Expressing Cloned Glycoprotein D
Authors: Berman Phillip W. , Dowbenko Donald , Lasky Laurence A. , Simonsen Christian C.
Published: October 2006

The gene for glycoprotein D of herpes simplex virus type 1 (HSV-1) was expressed in stable mammalian cell lines. Glycoprotein D produced in these cells has a number of antigenic determinants in common with the native glycoprotein. Cell lines expressing glycoprotein D were used in an enzyme-linked immunosorbent assay to detect human antibodies to glycoprotein D. This strategy should prove useful in determining the extent to which the immune response to HSV-1 is directed toward glycoprotein D.
Action of the
e
Locus of Mice in the Response of Phaeomelanic Hair Follicles to α-Melanocyte-Stimulating Hormone in Vitro
Authors: Tamate Hidetoshi B. , Takeuchi Takuji
Published: October 2006

Dibutyryl adenosine 3′,5′-monophosphate (dibutyryl cyclic AMP) induced eumelanin synthesis in hair bulb melanocytes of recessive yellow (
e
/
e
) mice in vitro, whereas α-melanocyte-stimulating hormone (α-MSH) did not. In contrast, the melanocytes of lethal yellow (
A
y
/
a
) mice produced eumelanin in response to both dibutyryl cyclic AMP and α-MSH. These results suggest that the
e
locus controls a mechanism that determines the function of an α-MSH receptor.
Identification of Common Interneurons Mediating Pre- and Postsynaptic Inhibition in the Cat Spinal Cord
Authors: Solodkin M. , Jiménez I. , Rudomin P.
Published: October 2006

The spike-triggered averaging of dorsal and ventral root potentials permits the identification of two populations of interneurons in the intermediate nucleus of the cat spinal cord. One produced negative dorsal root potentials and inhibitory ventral root potentials, in some cases with monosynaptic latencies, suggesting that they mediate presynaptic inhibition of group I afferent fibers from muscles and postsynaptic inhibition of motoneurons. The other population mediated only nonreciprocal postsynaptic inhibition of motoneurons.
Adaptation of Lymphadenopathy Associated Virus (LAV) to Replication in EBV-Transformed B Lymphoblastoid Cell Lines
Authors: Montagnier L. , Gruest J. , Chamaret S. , Dauguet C. , Axler C. , Guétard D. , Nugeyre M. T. , Barré-Sinoussi F. , Chermann J.-C. , Brunet J. B. , Klatzmann D. , Gluckman J. C.
Published: October 2006

A strain of lymphadenopathy associated retrovirus (LAV) passaged in vitro was used to infect a lymphoblastoid cell line obtained by transformation with Epstein-Barr virus of B lymphocytes from a healthy donor. The virus produced from this line (B-LAV) was also able to grow at a high rate in some other lymphoblastoid lines and in a Burkitt lymphoma line. This adapted strain retained the biochemical, ultrastructural, and antigenic characteristics of the original strain, as well as its tropism for normal T4
+
lymphocytes. It is thus possible to grow LAV in large quantities that can be used for the preparation of diagnostic reagents. The interaction between such a human retrovirus and Epstein-Barr virus, a DNA virus, may have some implication for the pathology of the acquired immunodeficiency syndrome and related diseases.
Immunoregulatory Lymphokines of T Hybridomas from AIDS Patients: Constitutive and Inducible Suppressor Factors
Authors: Laurence Jeffrey , Mayer Lloyd
Published: October 2006

Supernatants derived from peripheral blood mononuclear cell cultures of certain patients with the acquired immunodeficiency syndrome (AIDS) or its prodromes have the capacity to block T cell-dependent immune reactivity in vitro. T cells derived from a patient positive for antibody to the lymphadenopathy associated virus (LAV), and elaborating high titers of these soluble suppressor factors, were fused to a mutagenized clone of the human T lymphoblastoid cell line KE37. Molecules capable of profoundly depressing T cell-dependent polyclonal antibody production and DNA synthetic responses, either directly or after incubation with normal adherent cells, were isolated from stable hybrid clones.
Human Insulin from Recombinant DNA Technology
Authors: Johnson Irving S.
Published: October 2006

Human insulin produced by recombinant DNA technology is the first commercial health care product derived from this technology. Work on this product was initiated before there were federal guidelines for large-scale recombinant DNA work or commercial development of recombinant DNA products. The steps taken to facilitate acceptance of large-scale work and proof of the identity and safety of such a product are described. While basic studies in recombinant DNA technology will continue to have a profound impact on research in the life sciences, commercial applications may well be controlled by economic conditions and the availability of investment capital.
Fibronectin Binds to Some Bacteria But Does Not Promote Their Uptake by Phagocytic Cells
Authors: Van de Water L. , Destree A. T. , Hynes R. O.
Published: October 2006

The involvement of plasma fibronectin in phagocytosis of bacteria was investigated by testing the binding of fibronectin to several species of bacteria and by evaluating the ability of fibronectin to promote binding and endocytosis of two species of these bacteria by phagocytic cells. Fibronectin binds non-covalently to Gram-positive and Gram-negative bacteria and to yeast but did not appear to be necessary or sufficient for uptake of
Staphylococcus aureus
and
Salmonella typhimurium
by several different phagocytic cell types.
Clustered Third-Base Substitutions Among Wild Strains of
Escherichia coli
Authors: Milkman Roger , Crawford Irving P.
Published: October 2006

Nucleotide sequences of translated regions of the
trp
operon in 12 wild strains of
Escherichia coli
reveal striking uniformity among eight strains (suggesting recent common ancestry and supporting the importance of periodic selection in natural populations) and clustered substitutions in four strains (implicating events affecting runs of nucleotides).
Expression of the Major Neurofilament Subunit in Chicken Erythrocytes
Authors: Granger Bruce L. , Lazarides Elias
Published: October 2006

The 70,000-dalton core polypeptide of neurofilaments, thought to exist only in neurons, has been detected in chicken erythrocytes, where it coexists with vimentin and synemin as a component of the intermediate filament network. It is present in the circulating erythroid cells of embryos and young chickens but is nearly absent from the erythroid cells of adults. These findings are inconsistent with current models of intermediate filament expression, but provide another example of unexpected similarities between the nervous and hemopoietic systems.
Expression of Naphthalene Oxidation Genes in
Escherichia coli
Results in the Biosynthesis of Indigo
Authors: Ensley Burt D. , Ratzkin Barry J. , Osslund Timothy D. , Simon Mary J. , Wackett Lawrence P. , Gibson David T.
Published: October 2006

A fragment of plasmid NAH7 from
Pseudomonas putida
PpG7 has been cloned and expressed in
Escherichia coli
HB101. Growth of the recombinant
Escherichia coli
in nutrient medium results in the formation of indigo. The production of this dye is increased in the presence of tryptophan or indole. Several bacteria that oxidize aromatic hydrocarbons to
cis
-dihydrodiols also oxidize indole to indigo. The results suggest that indigo formation is due to the combined activities of tryptophanase and naphthalene dioxygenase.
Surface Molecules Identify Groups of Growing Axons
Authors: McKay R. D. G. , Hockfield S. , Johansen J. , Thompson I. , Frederiksen K.
Published: October 2006

Studies on vertebrate and invertebrate species have established that, during development, axons have the ability to choose particular paths over others. The chemical basis of this pathfinding is not clear but biochemical differences between neurons have long been postulated to account for the specificity of neuronal connections. Such subtle molecular differences between different cells in a single tissue are difficult to study with standard biochemical techniques but hybridoma technology has offered a potential solution to this type of problem. This technique has made possible the production of monoclonal antibodies for identifying and characterizing a family of glycoproteins which are expressed on the surface of specific axon bundles during the development of the leech nervous system. The results show that groups of growing axons do indeed carry chemically distinct surface molecules.
Human Physiology at Extreme Altitudes on Mount Everest
Authors: West John B.
Published: October 2006

Extreme altitude presents an enormous physiological challenge to the human body because of severe oxygen deprivation. The American Medical Research Expedition to Everest was specifically designed to study man under these conditions, and successfully obtained physiological data above 8000 meters, including a few measurements on the summit itself. The results show that man can tolerate the extreme hypoxia only by an enormous increase in ventilation, which results in an alveolar partial pressure of carbon dioxide of 7.5 torr on the summit and an arterial
p
H of over 7.7. Even so, the arterial partial pressure of oxygen is apparently less than 30 torr, and maximum oxygen uptake is about 1 liter per minute. Additional measurements of ventilation, blood physiology, and metabolic and psychometric changes clarified how man responds to this hostile environment.
Insulin: Carrier Potential for Enzyme and Drug Therapy
Authors: Poznansky Mark J. , Singh Rajkumari , Singh Bhagirath , Fantus George
Published: October 2006

Several carrier systems and targeting agents have been considered as means of delivering enzymes and drugs to specific tissues or cells. In this report insulin is shown to be effective in delivering enzyme-albumin conjugates to cells and tissues rich in insulin receptors. The complex is transported into cells by a process that resembles receptor-mediated endocytosis and can be identified in a lysosomal fraction. The enzyme-albumin-insulin complex retains its enzymatic activity and its ability to bind antibodies to insulin. It also has a hypoglycemic effect; however, plasma glucose concentrations can be maintained by glucose administration.
Organ-Specific Adhesion of Metastatic Tumor Cells in Vitro
Authors: Netland Peter A. , Zetter Bruce R.
Published: October 2006

Binding of tumor cells to cryostat sections of host organs was studied. B16-F10 melanoma cells and reticulum cell sarcoma cells demonstrated an organ specificity in their binding in vitro that reflected the organ specificity of their metastatic distribution 25 days after intravenous injection. These results provide evidence for specific binding of tumor cells to the tissues that they selectively colonize in vivo.
A Model Study of Fecapentaenes: Mutagens of Bacterial Origin with Alkylating Properties
Authors: Gupta Indranil , Suzuki Kunio , Bruce W. Robert , Krepinsky Jiri J. , Yates Peter
Published: October 2006

Fecapentaene-14 and -12 are directly acting mutagens that do not require metabolic activation. Their unusual structure suggests a possible mechanism of action. A carbocation that is formed by the addition of an electrophilic species (such as a proton) to the enol ether is most probably the reactive species. A series of model enol ethers with conjugated systems of various lengths was prepared, and a correlation between mutagenicity and increasing reactivity of derived carbocations was found. The glycerol moiety does not play a crucial role in the overall reactivity of the fecapentaenes.
Estrogen-Dependent Leydig Cell Protein Recognized by Monoclonal Antibody to MCF-7 Cell Line
Authors: Ciocca Daniel R. , Dufau Maria L.
Published: October 2006

A protein (27,000 molecular weight) was previously found in rat Leydig cells after treatment with estradiol (E
2
) and human chorionic gonadotropin (hCG) in vitro. The effect of hCG occurred through increased E
2
production. This hormone-regulated rat testicular protein was compared to an estrogen-regulated protein of similar physical characteristics isolated from a human mammary cancer cell line (MCF-7) and present in normal human estrogen target organs. The Leydig cells from rat and human tissue showed specific immunofluorescence and immunoperoxidase staining in the cytoplasm upon incubation with a monoclonal antibody (C11) to the estrogen-regulated protein from MCF-7 cells. Leydig cells after exposure to E
2
or hCG showed the highest fluorescence intensity; this intensity was reduced by treatment with Tamoxifen. No reaction was associated with other testicular cells. The estrogen-regulated protein from human cell lines is therefore immunologically similar to that from the rat Leydig cell. The monoclonal antibody should be useful for further characterization of the Leydig cell protein.
Shiga-Like Toxin-Converting Phages from
Escherichia coli
Strains That Cause Hemorrhagic Colitis or Infantile Diarrhea
Authors: O'Brien Alison D. , Newland John W. , Miller Steven F. , Holmes Randall K. , Smith H. Williams , Formal Samuel B.
Published: October 2006

Escherichia coli
K-12 acquired the ability to produce a high titer of Shiga-like toxin after lysogenization by either of two different bacteriophages isolated from a highly toxinogenic
Escherichia coli
O157:H7 strain that causes hemorrhagic colitis. One of these phages and another Shiga-like toxin-converting phage from an
Escherichia coli
O26 isolate associated with infantile diarrhea were closely related in terms of morphology, virion polypeptides, DNA restriction fragments, lysogenic immunity, and heat stability, although a difference in host range was noted. These phages are currently the best-characterized representatives from a broader family of Shiga-like toxin-converting phages.
Bovine × Mouse Hybridomas That Secrete Bovine Immunoglobulin G
1
Authors: Srikumaran S. , Guidry A. J. , Goldsby R. A.
Published: October 2006

The interspecific fusion of normal bovine lymphocytes with a nonsecreting mouse hybridoma produced stable cell lines secreting bovine immunoglobulins. One of these lines has continued to secrete immunoglobulin G
1
(5 to 10 micrograms per milliliter) for over 16 months. The bovine × mouse hybrid cells can be expected to provide bovine monoclonal immunoglobulins for sequencing studies and for use as serological standards as well as to provide messenger RNA for cloning bovine immunoglobulin genes.
Atypical Pulmonary Thrombosis Caused by a Toxic Cyanobacterial Peptide
Authors: Slatkin D. N. , Stoner R. D. , Adams W. H. , Kycia J. H. , Siegelman H. W.
Published: October 2006

Parenteral injection into mice of a toxic pentapeptide isolated from the cyanobacterium
Microcystis aeruginosa
induced thrombocytopenia, pulmonary thrombi, and hepatic congestion. The lethality of the toxin was unaffected by several anticoagulants. The acute liver damage that follows injection of the toxin has been attributed to direct action on liver cells but may be due to hypoxemia, heart failure, and shock.
Coronary Artery Spasm Induced in Atherosclerotic Miniature Swine
Authors: Shimokawa Hiroaki , Tomoike Hitonobu , Nabeyama Shozo , Yamamoto Hideo , Araki Haruo , Nakamura Motoomi , Ishii Yutaka , Tanaka Kenzo
Published: October 2006

Angiographically demonstrable coronary artery spasm could be provoked repeatedly by giving intracoronary or intravenous injections of histamine to miniature swine with experimentally induced atherosclerotic lesions of the coronary artery. The spasm induced in this way subsided either spontaneously or after the administration of nitroglycerin and was prevented by a calcium antagonist or an agent that blocks histamine H
1
receptors. This model, which suggests that atherosclerotic changes may be one of the primary factors in the occurrence of coronary artery spasm, should facilitate studies on the pathogenesis of this condition.
Differential Expression of the Translocated and the Untranslocated c-
myc
Oncogene in Burkitt Lymphoma
Authors: ar-Rushdi Abbas , Nishikura Kazuko , Erikson Jan , Watt Rosemary , Rovera Giovanni , Croce Carlo M.
Published: October 2006

Burkitt lymphoma cells carrying either a rearranged or unrearranged c-
myc
oncogene were examined with the use of probes from the 5′ exon and for the second and third exon of the oncogene. The results indicate that the normal c-
myc
gene on chromosome 8 and the 5′ noncoding and 3′ coding segments of the c-
myc
oncogene separated by the chromosomal translocation are under different transcriptional control in the lymphoma cells. Burkitt lymphoma cells carrying a translocated but unrearranged c-
myc
oncogene express normal c-
myc
transcripts. In contrast, lymphoma cells carrying a c-
myc
gene rearranged head to head with the immunoglobulin constant μ region gene express c-
myc
transcripts lacking the normal untranslated leader.
Inhibition of Cholesterol Crystal Formation by Apolipoproteins in Supersaturated Model Bile
Authors: Kibe Akihiro , Holzbach R. Thomas , LaRusso Nicholas F. , Mao Simon J. T.
Published: October 2006

Apolipoproteins A-1 and A-2 were purified from human plasma. At concentrations present in human bile these proteins prolonged the nucleation time of cholesterol monohydrate crystals when added to model systems of supersaturated bile. In contrast, apolipoprotein C-3 and other serum proteins did not have this effect. Also, when human gallbladder bile was fractionated by gel filtration chromatography, apolipoproteins A-1 and A-2 were among the proteins present in a fraction of bile enriched in potent inhibitors of cholesterol crystal nucleation. These findings suggest that apolipoproteins A-1 and A-2 in supersaturated human gallbladder bile could inhibit the rate of formation of solid cholesterol crystals and thus help to prevent spontaneous cholesterol gallstone formation in humans.
Potassium Activation Associated with Intraneuronal Free Calcium
Authors: Eckert Roger , Tillotson Douglas
Published: October 2006

Relations between calcium entry and activation of a calcium-dependent outward current during depolarization were examined under voltage clamp in dorid giant neurons injected with the calcium-sensitive photoprotein aequorin. Activation kinetics and amplitude of the slow calcium-dependent component were both found to be related to the rate and extent of free calcium accumulation and to the electromotive force acting on potassium ions, independent of the calcium activation kinetics. This indicates that the activation of the calcium-dependent outward current is more closely related to the transient intracellular accumulation of free calcium ions than to the movement of calcium through the plasma membrane during depolarization.
Saccharin-Induced Sister Chromatid Exchanges in Chinese Hamster and Human Cells
Authors: Wolff Sheldon , Rodin Brita
Published: October 2006

Since the induction of sister chromatid exchanges in cultured cells has been shown to be the most sensitive mammalian system to detect the effects of mutagenic carcinogens, Chinese hamster ovary cells and human lymphocytes were exposed to the sodium saccharin found to induce bladder cancer in rats. Both that saccharin and a highly purified extract of it increased the yield of sister chromatid exchanges in both types of cells. The results, which were repeatable and statistically highly significant, indicated that the weak carcinogen, saccharin, is also mutagenic in the sense that it induces cytogenetic changes.
Regeneration of Symmetrical Hindlimbs in Larval Salamanders
Authors: Stocum David L.
Published: October 2006

The complete circle rule of the polar coordinate model of pattern regulation was tested for regenerating hindlimbs of
Ambystoma
larvae. The hindlimbs were made symmetrical in the circumference of either the thigh or the shank, and their ability to regenerate from both levels was observed. Thighs composed of two anterior halves failed to regenerate, whereas thighs composed of two posterior halves often regenerated distally complete, correspondingly symmetrical limbs; shanks composed of either two anterior or two posterior halves regenerated distally complete, correspondingly symmetrical limbs. These results are in contrast to what is predicted by the complete circle rule and suggest a modification of this rule.
The Development and Regulation of New Medications
Authors: Lasagna Louis
Published: October 2006

The unmet needs of many patients make the successful search for new and better drugs an urgent goal. Increasing regulatory demands have generated delays in the availability of new drugs and concerns about the long-term profitability of the innovative pharmaceutical industry. A rational and flexible approach to drug regulation could ease some of the most worrisome constraints without jeopardizing the public welfare. Changes in our national drug regulatory policy and in the performance of the Food and Drug Administration will serve our society better than drastic legislative mandates intended either to emasculate the FDA or to grant the agency broad new powers.
Cross-Contamination of Cells in Culture
Authors: Nelson-Rees W. A. , Daniels D. W. , Flandermeyer R. R.
Published: October 2006

Lists are presented of references to all known publications describing cell properties that serve to characterize (i) known strains of HeLa and purported human cell lines indicted as HeLa contaminants, (ii) strains of human cell lines contaminated with human but non-HeLa cells, and (iii) strains of cells contaminated by cells from one or more other species. Frequencies of cell cross-contaminations are cited and references are presented to relatively simple techniques that could serve to detect such contamination.
Dopamine Receptor Binding Is Increased in Diabetic Rats
Authors: Lozovsky David , Saller Charles F. , Kopin Irwin J.
Published: October 2006

The binding of [
3
H]spiperone, a dopamine receptor ligand, to striatal membranes was increased 30 to 35 percent in rats made diabetic with alloxan or streptozotocin. Binding of [
3
H]spiperone was normal in rats made diabetic with alloxan but treated with insulin. Thus the number of dopamine receptors and central dopaminergic transmission may be altered in diabetes.
Cloned Mycoplasma Ribosomal RNA Genes for the Detection of Mycoplasma Contamination in Tissue Cultures
Authors: Göbel Ulf B. , Stanbridge Eric J.
Published: October 2006

A cloned fragment of the mycoplasma ribosomal RNA operon was used as a molecular probe for the detection of mycoplasmas in cell cultures. According to the conditions of hybridization, the probe can detect prokaryotes in general or mycoplasmas specifically.
The Hydrophobic Effect and the Organization of Living Matter
Authors: Tanford Charles
Published: October 2006

Biological organization may be viewed as consisting of two stages: biosynthesis and assembly. The assembly process is largely under thermodynamic control; that is, as a first approximation it represents a search by each structural molecule for its state of lowest chemical potential. The hydrophobic effect is a unique organizing force, based on repulsion by the solvent instead of attractive forces at the site of organization. It is responsible for assembly of membranes of cells and intracellular compartments, and the absence of strong attractive forces makes the membranes fluid and deformable. The spontaneous folding of proteins, however, involves directed polar bonds, leading to more rigid structures. Intercellular organization probably involves polar bonds between cell surface proteins.
Potentiation of Opiate Analgesia and Apparent Reversal of Morphine Tolerance by Proglumide
Authors: Watkins L. R. , Kinscheck I, B. , Mayer D. J.
Published: October 2006

Exogenous cholecystokinin selectively antagonizes opiate analgesia, which suggests that endogenous cholecystokinin may act physiologically as an opiate antagonist and may play a role in opiate tolerance. The use of the selective cholecystokinin antagonist proglumide provided a test of these hypotheses in rats that were either inexperienced with or tolerant to opiates. Proglumide potentiated analgesia produced by morphine and endogenous opiates and seemed to reverse tolerance. These results suggest that endogenous cholecystokinin systems oppose the action of opiates.
Allylamine Derivatives: New Class of Synthetic Antifungal Agents Inhibiting Fungal Squalene Epoxidase
Authors: Petranyi Gabor , Ryder Neil S. , Stütz Anton
Published: October 2006

A new class of synthetic antifungal agents, the allylamines, has been developed by modification of naftifine, a topical antimycotic. SF 86-327, the most effective of these compounds so far, is highly active in vitro against a wide range of fungi and exceeds clinical standards in the oral and topical treatment of guinea pig dermatophytoses. SF 86-327 is a powerful specific inhibitor of fungal squalene epoxidase, a key enzyme in sterol biosynthesis.