Showing papers by "University of Maryland, Baltimore published in 1972"

Biological properties of Norwalk agent of acute infectious nonbacterial gastroenteritis.

Abstract: SummaryAcute infectious nonbacterial gastroenteritis was induced in adult volunteers through three serial passages by oral administration of bacteria-free stool filtrates. This suggested that a replicating agent of subbacterial size was responsible for the observed disease. The biophysical properties of the agent, as assayed in volunteers, were consistent with those of a small virus, most closely related to the parvovirus group among known animal viruses. The agent appeared to have a diameter less than 66 nm and likely less than 36 nm. It appeared to lack a lipid containing envelope and was acid stable. It was stable to heating at 60° for 30 min. The agent appeared to be relatively host specific for man and conferred at least short-term immunity. Because of the high frequency of disease induced in unselected volunteers, widespread natural immunity to this agent may be absent or perhaps incomplete. Preliminary evidence suggested that the Norwalk agent replicated in an in vitro system, human fetal intestina...

Immunity in Shigellosis. II. Protection Induced by Oral Live Vaccine or Primary Infection

Abstract: Two attenuated strains of Shigella flexneri 2a, a Shigella-E. coli hybrid, and a streptomycin-dependent mutant, were safely given to adult male volunteers. When vaccinated individuals ingested virulent S. flexneri 2a, clinical disease and fecal excretion of virulent organisms occurred with less frequency than in unvaccinated volunteers. The level of immunity resembled that seen after recovery from active infection. These studies have given some indication that bacillary dysentery may be controlled by an oral live vaccine, and field trials designed to quantitate induced immunity are planned for the near future.

The Effect of Aggregation on Prediction in the Autoregressive Model

Abstract: The article shows that if the original variable follows a pth order autoregressive system then the non-overlapping moving sum follows a pth order autoregression with at most a pth order moving-average of an independent sequence regardless of the length of the summation. From such an aggregate model we derive the optimal predictor of the aggregate variable and show that it performs remarkably well compared to the optimal disaggregate predictor. The article contains both theoretical and numerical analysis.

Inactivation of the sodium current in Myxicola giant axons. Evidence for coupling to the activation process.

Abstract: Experiments were conducted on Myxicola giant axons to determine if the sodium activation and inactivation processes are coupled or independent. The main experimental approach was to examine the effects of changing test pulses on steady-state inactivation curves. Arguments were presented to show that in the presence of a residual uncompensated series resistance the interpretation of the results depends critically on the manner of conducting the experiment. Analytical and numerical calculations were presented to show that as long as test pulses are confined to an approximately linear negative conductance region of the sodium current-voltage characteristic, unambiguous interpretations can be made. When examined in the manner of Hodgkin and Huxley, inactivation in Myxicola is quantitatively similar to that described by the h variable in squid axons. However, when test pulses were increased along the linear negative region of the sodium current-voltage characteristic, steady-state inactivation curves translate to the right along the voltage axis. The shift in the inactivation curve is a linear function of the ratio of the sodium, conductance of the test pulses, showing a 5.8 mv shift for a twofold increase in conductance. An independent line of evidence indicated that the early rate of development of inactivation is a function of the rise of the sodium conductance.

Morphology and morphogenesis of Sindbis virus as seen with freeze-etching techniques.

Abstract: Freeze-etch electron microscope studies of the morphogenesis and morphology of Sindbis virus confirmed results obtained by other workers employing thin-sectioning techniques. The 68-nm virion was found to have a nucleocapsid 36 nm in diameter surrounded by a double-layered, unit membrane. The membranous envelope is acquired as the capsid buds through the plasma membrane of the infected cell. The freeze-etch technique also provided the following new information. (i) At any one time, budding occurs in patches rather than evenly over the cell surface. (ii) The nucleocapsid is composed of capsomers 7 nm in diameter. (iii) The capsid interacts strongly with the membrane, both prior to budding and after maturation. (iv) The 7- to 10-nm particles characteristic of the internal faces of plasma membranes, which presumably represent host membrane proteins, are present in early stages of budding but disappear as morphogenesis progresses. (v) Fusion of the cell membrane at the base of the budding virion is a two-step process; the inner leaflet fuses into a sphere before the outer one. (vi) The outer surface of the viral envelope is covered with 4-nm subunits with a center-to-center spacing of 6 nm.

Initial dentin formation in human deciduous teeth. An electron microscope study.

Abstract: Dentin matrix formation is initiated as far as 11 μ deep in the prospective dental pulp. From this area, growth of the preodontoblast processes occurs toward the ameloblast. Process elongation is followed successively by 3 stages of dentin matrix formation: 1) fibril formation, 2) matrix maturation and 3) matrix calcification. These stages occur concurrently with differentiation of the odontoblasts. The bases of the odontoblast processes and distal surfaces of their cell bodies extrude cytoplasmic buds into the surrounding matrix. These function as initial sites of calcification.

Immunity in Shigellosis. I. Response of Man to Attenuated Strains of Shigella

Abstract: Four attenuated strains of Shigella flexneri 2a have been tested for stability and safety as vaccines in man. One strain, a Shigella-Escherichia coli hybrid, was virulent for man in doses of 108 cells, while a mutant strain reverted to virulence when 1010 cells were administered orally. Two vaccine strains, a Shigella mutantE. coli hybrid and a streptomycin-dependent mutant, were safely given to adult males in doses of 5-10 X 1010 cells. Pretreatment with sodium bicarbonate was essential for the assurance of intestinal transit of viable vaccine organisms, and less than one-third of those vaccinated developed rises in humoral antibody. Streptomycin-independent revertants could be recovered only rarely in vivo when the streptomicin-dependent mutant was used, and one revertant found was avirulent. These studies have outlined the important biologic requirements of potential live oral shigella vaccines. Strains must not penetrate the intestinal mucosa and must be stable without reverting to virulence at levels of dosage used.

Microsomal lipid peroxidation: morphological characterization.

Abstract: Lipid peroxidation of liver and kidney microsomes induces a highly characteristic sequence of morphological changes typified by detachment of ribosomes and formation of large aggregates of vesicles bound together by dense amorphous material and myelin figure-like debris. The trilaminar structure of the membrane is, however, retained even after complete peroxidation, though its spacing may be increased. The aggregates resemble lysosomal lipofuscin pigment as well as the membranous aggregates of endoplasmic reticulum seen in the liver after carbon tetrachloride poisoning.

Lack of enhanced oxygen consumption by polymorphonuclear leukocytes on phagocytosis of virulent Salmonella typhi.

Abstract: Human polymorphonuclear leukocytes exhibit an enhanced rate of oxygen consumption during phagocytosis of relatively avirulent strains of Salmonella typhi or Staphylococcus aureus However, phagocytosis of a virulent strain of Salmonella typhi is not associated with augmented oxygen consumption The ability of a bacterial strain to alter the postphagocytic rate of oxygen consumption of polymorphonuclear leukocytes may be related to its in vivo virulence

An Endogenous Mediator of Depression of Amino Acids and Trace Metals in Serum during Typhoid Fever

Abstract: : Concentrations of most amino acids and of zinc in serum were depressed during periods of incubation and illness in 11 volunteers who developed symptoms after an oral dose of 100,000 virulent Salmonella typhosa. When a 1.0-ml sample of sterile serum from volunteers who were ill with typhoid fever was injected into normal rats, it stimulated a prompt and significant depression of the concentration of zinc in the rats' sera and a flux of amino acids into their livers. These observations support the hypothesis than an endogenous factor (similar to endogenous pyrogen released by polymorphonuclear leukocytes) was present in the blood during typhoid fever and served as a mediator for the observed depression in zinc and amino acids in serum. The magnitude and pattern of infection-related depression in individual amino acids in serum may be, in part, a function of the amount of endogenous mediator released and of the rates of utilization of amino acids by tissues.

Inhibition of Sindbis Virus Release by Media of Low Ionic Strength: an Electron Microscope Study

Abstract: Release of Sindbis virus from infected cells is inhibited by lowering the ionic strength of the medium. To determine the nature of the inhibited step, we examined, by electron microscopy, both freeze-etched and thin-sectioned preparations which had been fixed with either glutaraldehyde or formaldehyde. Inhibitory medium had two different effects on Sindbis virus release: virus budding was partially inhibited, and those virions which did mature were precipitated on the surface of the cell. Freeze-etched, inhibited cells showed very few viral buds. After shift to normal medium, the number of budding virions increased dramatically, far exceeding the quantity found in normal controls. Thus, low ionic strength medium clearly inhibited an early stage of virus maturation. The results were the same regardless of the fixative. Thin sections of glutaraldehyde-fixed, inhibited cells contained large extracellular aggregates of mature virus which were not present in similar, formaldehyde-fixed preparations. Fixation of radioactively-labeled, inhibited cultures revealed that approximately half of the virus that could be released from inhibited cells by raising the ionic strength of the medium could also be released by formaldehyde, but not by glutaraldehyde. This fraction probably represents mature virus attached to the cell surface by the ionic conditions.

Inhibition of a discrete bacterial DNA polymerase by 6-(p-hydroxyphenylazo)-uracil and 6-(p-hydroxyphenylazo-)-isocytosine.

Abstract: 6-(p-HYDROXYPHENYLAZO)-URACIL (HPUra) specifically inhibits the semi-conservative replication of DNA in Gram-positive bacteria1–3. We have reported that HPUra inhibits ATP-dependent polymerization of deoxyribonucleotides in vitro in toluene-treated B. subtilis4. Further studies of the effect of HPUra and its amino analogue, HPIsocytosine (6-(p-hydroxyphenylazo)-2-amino, 4-keto pyrimidine), in toluene-treated B. subtilis have provided considerable information on the mechanism of arylazopyrimidine action. First, HPUra and HPIsocytosine do not inhibit DNA synthesis unless they first are reduced to their colourless, hydrazo forms (refs. 4 and 5 and Mackenzie, Wright and Brown, unpublished results). Second, the inhibitory action of reduced HPUra and that of reduced HPIsocytosine are completely antagonized, respectively, by dGTP and dATP5. Third, drug-resistant mutants have been isolated which catalyse drug-resistant DNA synthesis following their permeabilization with toluene. These observations suggest that reduced HPUra and HPIsocytosine inhibit DNA replication by interfering competitively with the enzymatic polymerization of specific purine deoxyribonucleotides. We examined, therefore, cell free preparations of B. subtilis in an effort to identify a discrete DNA polymerase as the site of drug action. We report here experiments with crude and partially fractionated extracts of DNA polymerase I-deficient mutants which indicate the existence of at least one drug sensitive polymerase. Bazill and Gross6 have independently isolated chromatographically discrete HPUra-sensitive polymerases from extracts of B. subtilis.

Ultrastructure and chromatin disaggregation of human sperm head with thioglycolate treatment.

Abstract: The active interest in determining the ultraThe washed sperm samples were then treated with structural organization of ejaculated human sperm alkaline thioglycolate (18) . A 0 .8 M concentration of nucleus by the normal thin-sectioning technique alkaline thioglycolate was prepared by raising the has led to a state of understanding that is still pH to 9 with I N NaOH. This reagent was mixed incomplete. The findings obtained by this method 1 :1 or 1 :2 with the sperm solution . The reaction show that the nuclei of intact human sperm heads period ranged from 1 to 5 min and was followed by

Morphology and Physical Properties of Staphylococcus Bacteriophage P11-M15

Abstract: The Group B Staphylococcus phage P11-M15 is shown to be 51% protein and 49% deoxyribonucleic acid (DNA). The intact virion has a molecular weight of 66.7 x 10(6) daltons. The purified viral DNA has a molecular weight of 32.7 x 10(6) daltons. The intact virion is shown to be composed of a polyhedral head which is attached at one of its vertices to a flexible tail having helical symmetry. The tail structure is terminated by a complex baseplate which has sixfold symmetry. The virion contains a single molecule of double-stranded DNA which has no apparent single-strand nicks or single-stranded terminal redundancies.

Inhibition of Bacterial DNA Replication by 6-(p-Hydroxyphenylazo)-uracil

Abstract: THE semi-conservative replication of DNA of Gram-positive bacteria is specifically inhibited by 6-(p-hydroxyphenyIazo)-uracil (HPUra; obtained from ICI) in an apparently novel mechanism1–4. We have attempted to characterize the HPUra-sensitive site in replication using in vitro preparations of drug-sensitive bacteria. In particulate and soluble preparations of sensitive bacteria, however, HPUra at high concentration does not significantly inhibit polymerization of deoxyribonucleotides2,4. Since these systems may not accurately represent the process of DNA replication as it occurs in vivo, we have examined the effect of HPUra on a more suitable, toluene-treated preparation of Bacillus subtilis described by Matsushita et al.5. In this preparation, DNA replication is ATP-dependent, utilizes deoxyribonucleotides to give biologically active DNA, semi-conservatively and sequentially in the proper gene order. HPUra can inhibit DNA replication by this system. We describe here the characteristics of HPUra inhibition and the conditions necessary for it to occur.

Nutritional Studies of Rickettsia quintana: Nature of the Hematin Requirement

Abstract: Rickettsia quintana grew in a liquid medium consisting of a brain-heart infusion base supplemented with starch and hematin. The growth requirement for hematin could not be substituted by compounds of known catalytic activity for H(2)O(2), viz., catalase, potassium pyruvate, or charcoal, or by the reducing compounds sodium sulfite and sodium thioglycollate. R. quintana was catalase-negative, but no H(2)O(2) production could be demonstrated by the catalase-aminotriazole technique. A minimum inoculum giving 10(5) cells/ml was required to initiate growth. The generation time at 33 C was 10 hr. The temperature range for growth was 28 to 37 C. Growth was enhanced when succinate or glutamate was added as energy source.

Child Behavior During Sequential Dental Visits

Abstract: A statistically significant relationship was observed between the behavior of 86 children (3 to 7 years old) who underwent an oral examination on their initial dental visit and their mothers’ scores on the Taylor Manifest Anxiety Scale and a short preoperative questionnaire. This relationship was not found for the second and third visits when restorative procedures were performed.

Catecholamines and memory: Enhanced verbal learning during L-dopa administration.

Abstract: Verbal learning was measured during the administration of l-DOPA in large oral doses to depressed patients. Longer-term memory on two different tasks improved during treatment, while short-term memory (immediate recall) was unaffected. In contrast, the catecholamine synthesis inhibitor α-methyl-p-tyrosine did not alter either memory process.

An electron microscopic study of intimal cushions in intracranial arteries of the cat.

Abstract: Subendothelial protuberances associated with the tunica intima have been described by light microscopy at branching sites of arteries in various animal species. These structures are termed intimal cushions or intimal pads. Some investigators regard them as being pathologic, preceding the appearance of atherosclerosis in the vessel wall. This fine structural study was done because of the possible role of intimal cushions in the regulation of cerebral blood flow at branching sites of intracranial arteries. The internal elastic lamina is split at the margins of a cushion to enclose irregularly arranged bundles of smooth muscle cells and collagenous fibrils. These smooth muscle cells are generally arranged at a right angle to smooth muscle cells in the underlying media. The outermost layer of the internal elastic lamina forms a boundary between the body of the cushion and the media; however, areas of discontinuity cause this border to be poorly defined in some instances. Perivascular autonomic nerves do not extend into either media or intimal cushions. Intercellular contacts between smooth muscle cells are observed within cushions as well as in the media, suggesting that cushions may be contractile and capable of modifying cerebral blood flow.

Effects of Alcohol on the Neuron

Abstract: It should be made clear at once that the nature of the ensuing discussion is deliberately limited. Consideration of the effects of alcohols on cerebral neurons (or stated another way, cerebral effects of alcohols at the cellular and subcellular levels) necessitates taking a quite specific point of view. The latter is based on certain assumptions, some of which can be stated, as well as on the setting up of arbitrary limits or boundaries with regard to both data and theory (or, depending on the degree of libidinal investment, with regard to both fact and fancy). The limits are particularly obvious if the concept of “behavior” is involved; this is certainly the primary interest of psychiatrists and psychologists dealing with the use of alcohol consumed either occasionally or chronically. For present purposes, i.e., in the neurophysiologic or neurobiologic frame of reference, behavior is also a central issue, but in more than the usual sense. The neurophysiologist, in other words, hopes, in time, to understand the effects of alcohol on the total organism (alone and in its relationships to others), but focuses his investigative efforts on least suborders of behaviors: 1. Effects of alcohols on the integrated activity of the nervous system 2. Effects of alcohols on behavior of specific of the central nervous system 3. Effects of alcohols on behavior of the neuron (the functional unit of the nervous system) and its junctions with other neurons.

Changes during maturation and metamorphosis in the synaptic organization of the tadpole retina inner plexiform layer.

Abstract: ELECTROPHYSIOLOGICAL studies have shown that there is considerable variation in the degree of processing of visual information carried out by the retinas of different species, apparently correlated with anatomical difference between species. In amphibian and avian retinas with complex receptive fields there seem to be more conventional (amacrine cell) synapses than in mammalian retinas with simple organization. Moreover, the greater density of serial-conventional synapses, in which a presynaptic amacrine process is also postsynaptic to another amacrine process, is particularly striking in complex retinas. The density of ribbon (bipolar cell) synapses remains fairly constant from species to species1. The fact that tadpoles apparently make little use of visual cues, whereas adult frogs depend on them for survival, suggests that electrophysiological and anatomical retinal reorganization occurs during metamorphosis. There is some evidence for this2,3. Here I report changes in retinal synaptic organization found in Rana pipiens both during maturation and metamorphosis and as a result of a hormone pellet implantation.