Showing papers by "University of Virginia published in 1974"

Cyclic Adenosine Monophosphate and Alteration of Chinese Hamster Ovary Cell Morphology: a Rapid, Sensitive In Vitro Assay for the Enterotoxins of Vibrio cholerae and Escherichia coli

Abstract: The major limitation to our understanding of the clinical importance of enterotoxigenic Escherichia coli in diarrheal illness has been the lack of a simple rapid assay for the enterotoxin produced by certain E. coli. On the basis of the activation of adenylate cyclase by heat-labile enterotoxin of E. coli (LT) and by cholera toxin (CT) in intestinal and other tissues, cultured Chinese hamster ovary (CHO) cells with known morphological responses to dibutyryl cyclic adenosine 5'-monophosphate (AMP) were exposed to these enterotoxins. Crude culture filtrates of LT-producing E. coli and CT stimulated cyclic AMP accumulation and cell elongation in CHO cells. The similarity of time course, concentration dependence, and potentiation by phosphodiesterase inhibitors suggested cyclic AMP mediation of the morphological change. Heat inactivated CT and LT in this system. Choleragenoid inhibited CT; antiserum against CT inhibited both enterotoxin effects. In contrast to culture filtrates of 16 strains of E. coli known to produce LT, culture filtrates from 13 E. coli that do not produce LT did not alter CHO cell morphology. The morphological change is a simple, specific assay for these enterotoxins and detect 3 x 10(-17) mol of CT or a 1:250 dilution of crude culture filtrate of LT-producing E. coli 334.

Release of Adenosine from Ischemic Brain

Abstract: A threefold increase in tissue adenosine levels was produced by ischemia in the dog and the rat brain within 1 minute; adenosine levels increased further with longer periods of ischemia. Inosine and hypoxanthine were also increased by ischemia but to different degrees. The nucleosides and hypoxanthine appeared in cerebrospinal fluid during ischemia in the dog brain, and incubation of adenosine in normal cerebrospinal fluid failed to show the presence of degradative enzymes. Intra-arterially administered adenosine in the dog and the cat produced little or no increase in cerebral blood flow or the diameter of pial arterioles, respectively, when it was given in amounts that reduced arterial blood pressure. However, when it was applied topically to exposed pial arterioles of the cat, adenosine induced dilation that was roughly proportional to the dose used. When U-14C-adenosine was infused into the internal carotid arteries of the dog, no radioactivity was detectable in the cerebrospinal fluid and practically...

Studies on the mechanism of the dopamine-mediated inhibition of prolactin secretion.

Abstract: A study of the in vitro effect of dopamine on the release of newly synthesized prolactin is reported. Pituitary glands of female rats were incubated with 4,5-3H-leucine and the radioactive prolactin present in the pituitary gland and that released into the incubation medium were measured. Incubation with 5 × l 10–7M dopamine caused an 85% decrease in prolactin release. Prior injection of the rats with perphenazine or haloperidol rendered the pituitary gland refractory to the in vitro inhibitory effect of dopamine. Although in vitro perphenazine and haloperidol had little or no effect on release of prolactin, 5 × 10–9M of these drugs directly blocked the in vitro action of dopamine on prolactin release. Phentolamine, an α-blocking agent, was partially able to block the inhibitory effect, of dopamine. Propranolol, however, was not effective. Apomorphine, an agent known to mimic the effects of dopamine, caused a significant decrease in the amount of radioactive and radioimmunoassayable prolactin released int...

Redesigning the future: a systems approach to societal problems

Abstract: Part I is composed of four chapters which respectively discuss dynamic programming, applications, problems with imperfect state information, and computational aspects and suboptimal control. The applications chapter presents the linear-quadratic-Gaussian problem (popular in modern control theory), an inventory control problem (an operations research problem), a portfolio analysis problem (an investment problem), and an optimal stopping problem (motivated by a land investment example). The finite-state material discussed for the partial information case is new in textbook form. The subsections concerned with the notion of adaptivity and various suboptimal controllers (also new in textbook form) combine several interesting and valuable concepts and techniques which are probably unfamiliar to many not directly involved with stochastic control research. Part II is composed of three chapters, each one primarily concerned with one of the following performance indices: discounted cost, undiscounted cost, and average cost. The usual computational methodssuccessive approximation, policy iteration, and linear programming--are presented. The important contraction mapping approach is utilized in the discounted (uniformly bounded) cost case, and interesting new monotone mapping results recently developed by the author are presented which do not require the often restrictive boundedness assumption (further results can be found in [4]). The undiscounted cost chapter evolves from the material (presented in Section 6.4) on unbounded cost. The average cost chapter lucidly presents relatively standard material on the topic. There are four short appendices (mathematical review, on optimization theory, on probability theory, on finite state Markov chains) which represent the level and extent of prerequisite material for the text. The list of references is excellent and of substantial value to the research community. The home problems have been thoughtfully developed and represent a particularly nice theoretical and applications-oriented complement to the text. Although not required for the remainder of the text, ChapterI serves as an introduction to several general notions associated with decisionmaking under uncertainty. In summary, the book is an excellent addition to the stochastic control textbook literature. It represents a more appealing format for relating the stochastic control problem formulations of a variety of disciplines and is much broader in perspective than any of the recent well-known stochastic control texts. Although the author has endeavored to present fundamental concepts under general structural assumptions, many of the special cases considered in the examples provoke additional, structure-dependent results, e.g., the existence of an optimal control linear in the conditional expected state for the LQG problem, the existence of optimal strategies composed of monotone policies for the standard countable-state replacement and inventory control problems. The author references Witsenhausen's 1971 IEEE Proceedings paper, which discussed at length structural properties of optimal controls for standard and nonstandard LQG problems; an additional hallmark article regarding general structural attributes for optimal policies under which the aforementioned monotonicity results can be considered is [5].

Bactericidal activity of aerobic and anaerobic polymorphonuclear neutrophils.

Abstract: Human polymorphonuclear neutrophils (PMN) were made anaerobic by nitrogen washout (oxygen saturation <1%, Eh < −42 mV at pH 7.0), and the ability of the cells to kill bacteria was assayed and compared to the bactericidal activity of aerobic PMN. Anaerobic PMN were able to kill Staphylococcus epidermidis, Enterococcus, viridans streptococci, Pseudomonas aeruginosa, Peptostreptococcus anaerobius, Bacteroides fragilis, Clostridium perfringens, and Peptococcus magnus normally. Organisms that were not killed normally by anaerobic PMN included Staphylococcus aureus (strains Wood 46 and 502a), Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Proteus vulgaris, and Salmonella typhimurium. These findings suggest that mechanisms other than those dependent on hydrogen peroxide may be important in the killing of some bacteria.

The oxidation of metals

Abstract: A detailed review of the principles governing the oxidation of metals is presented. It covers the initial stages of oxidation, oxide film formation, thick film and scale formation and oxide structure.

Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives.

Abstract: Probenecid may elevate the cerebrospinal fluid (CSF) concentration of penicillin G by inhibiting the excretion of organic acids from CSF. We have studied this phenomenon with various penicillin and cephalosporin derivatives. Penicillin concentrations were determined in rabbits under steady-state conditions before and after intravenous probenecid administration. With both low-dose and high-dose probenecid, CSF penicillin levels increased two to three times as did CSF concentration as a percentage of serum level. The same probenecid effect was consistently demonstrated in animals with experimental pneumococcal meningitis. Probenecid likewise increased the CSF concentration of ampicillin, carbenicillin, nafcillin, cephacatrile, and cefazolin. Probenecid may prove useful in certain bacterial infections where high CSF antibiotic levels are necessary.

Surface polaritons in a circularly cylindrical interface: Surface plasmons

Abstract: A theoretical investigation of surface polaritons in the circularly cylindrical geometry is presented. The complete set of Maxwell's equations (retardation effects are not neglected) is solved with the simple dielectric function, $\ensuremath{\epsilon}(\ensuremath{\omega})=1\ensuremath{-}\frac{{\ensuremath{\omega}}_{p}^{2}}{{\ensuremath{\omega}}^{2}}$, where ${\ensuremath{\omega}}_{p}$ is the bulk plasma frequency. The resulting transcendental equation for the eigenfrequencies is solved via numerical methods for three representative values of the cylindricality constant, $\ensuremath{\alpha}=\frac{{\ensuremath{\omega}}_{p}a}{c}$, where $a$ is the cylinder radius and $c$ the velocity of light. In addition to the real nonradiative surface plasmons, various virtual radiative surface plasmons exist with properties depending rather strongly on $\ensuremath{\alpha}$. The results are compared with existing experimental data. Further experiments are proposed in order to reveal the most interesting features of the surface plasma modes.

Outer Membrane Proteins of Escherichia coli III. Evidence that the Major Protein of Escherichia coli O111 Outer Membrane Consists of Four Distinct Polypeptide Species

Abstract: Previous studies have shown that the outer membrane of Escherichia coli O111 gives a single, major, 42,000-dalton protein peak when analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis at neutral pH. Further studies have shown that this peak consists of more than a single polypeptide species, and on alkaline SDS-gel electrophoresis this single peak is resolved into three subcomponents designated as proteins 1, 2, and 3. By chromatography of solubilized, outer membrane protein on diethylaminoethyl-cellulose followed by chromatography on Sephadex G-200 in the presence of SDS, it was possible to separate the 42,000-dalton major protein into four distinct protein fractions. Comparison of cyanogen bromide peptides derived from these fractions indicated that they represented at least four distinct polypeptide species. Two of these proteins migrated as proteins 1 and 2 on alkaline gels. The other two proteins migrated as protein 3 on alkaline gels and cannot be separated by SDS-polyacrylamide gel electrophoresis. In purified form, these major proteins do not contain bound lipopolysaccharide, phospholipid, or phosphate. These proteins may contain a small amount of carbohydrate, as evidenced by the labeling of these proteins by glucosamine, and to a lesser extent by glucose, under conditions where the metabolism of these sugars to amino acids and lipids is blocked. All of the proteins were labeled to the same extent by these sugars. Thus, it was concluded that there are at least four distinct polypeptide species with apparent molecular masses of about 42,000 daltons in the outer membrane of E. coli O111.

Protective Action of Methylprednisolone on the Myocardium during Experimental Myocardial Ischemia in the Cat

Abstract: Cats subjected to coronary artery occlusion were used to study the effect of methylprednisolone on the release of lysosomal acid hydrolases and creatine phosphokinase (CPK) from ischemic myocardial tissue. Plasma CPK activity was increased significantly 2 hours after occlusion and increased eightfold 5 hours after ligation in vehicle-treated cats. Intravenous administration of methylprednisolone (30 mg/kg) 30 minutes before or 60 minutes after occlusion significantly limited the increases in plasma CPK activity to values only slightly greater than those observed in sham-operated cats. Plasma activities of the lysosomal hydrolases, β-glucuronidase and cathepsin D, were comparable in all groups of cats and did not change during the 5-hour observation period. Nevertheless, cathepsin D and β-glucuronidase activities were reduced 41% and 33%, respectively, in the ischemic portion of the myocardium of untreated cats subjected to coronary artery ligation. The CPK activity of the ischemic myocardium was reduced 43% in these cats. Pre- or posttreatment of cats with methylprednisolone prevented the decline in CPK and lysosomal hydrolase activity of ischemic myocardium. These data indicate that lysosomal disruption is a consequence of myocardial ischemia and that pre- or posttreatment with methylprednisolone prevents the leakage of myocardial lysosomal and cellular enzymes. Moreover, the methylprednisolone-induced stabilization of myocardial membranes appears to be related to the ability of glucocorticoid to limit infarct size following myocardial ischemia.

Geographic and temporal development of plagues

Abstract: ALTHOUGH deterministic and stochastic descriptions of localised epidemics abound in the literature of epidemiology and quantitative biology1,2, the geographic spread of epidemics has not been analyzed in such detail. (Although in ref. 2, page 205, Bailey gives equations similar in spirit to my equation (1) they seem to lack physical significance.) Realistic mathematical models of the geotemporal development of plagues could be useful in the study of epizootics (that is, in ecology, wildlife management or veterinary medicine), of social phenomena (such as the spread of drug abuse or fads), and of history. Needless to say, such models should also be applicable to public health questions.

Memory for words recently classified

Abstract: This paper describes research whose goal is to determine the implications of verba] classificatory, judgments for recognition memory and recall. Toward this end, St were required to answer 100 queries of attribution and superordination ds a TWINGE sudden? Is SPINACH ecstatic? Is a CORKSCREW an opener? Is a DUNGEON a scholar? before being tested unexpectedly on their ability to remember either the uppercase “keywords” or the lowercase “descriptors.” Lexical memory did not depend on whether a word had been part of an attributive or a superordinate query. But words from “incongruous” queries almost invariably were more poorly remembered-under conditions of free recall, cued recall, and recognition memory-than words from “congruous” queries. Congruous cues, but not incongruous ones, greatly facilitated recall, with keywords being more effective cues than descriptors. Recognition memory of keywords was uniformly superior to that of descriptors. It is argued that the large and pervasive memorial advantages of congruity arise because a congruous query, unlike an incongruous one, fosters a relational encoding of keyword and descriptor.

Scattering of Visible Radiation by Finite Clouds

Abstract: A theoretical model of the scattering of shortwave radiation is applied to clouds finite in horizontal extent. The resulting irradiance patterns are then compared with calculations for horizontally semi-infinite clouds. This analysis shows, that the irradiance fields are dramatically dependent upon energy passing through the vertical sides of the finite sized clouds. Directional reflectance of individual cubic clouds is shown to be approximately 25% less than for semi-infinite clouds of optical depths ranging from 20 to 80. Directional reflectance from the top of cubic clouds for small solar zenith angle continues to increase at large optical depths (∼70) while the infinite cloud becomes nearly asymptotic at this point. It is shown that for a solar zenith angle of 60°, the directional reflectance for a 2/10 sky cover of cubic clouds is 0.29 while for 2/10 coverage of semi-infinite cloud the directional reflectance is 0.185. Implications of differences between the cubic cloud results and the semi-...

Behavioral, electrophysiological and morphological studies of binocular competition in the development of the geniculo–corticalpathways of cats†

Abstract: Cats were raised with one eye sutured and with a lesion in the retina of the other eye. In these cats the competitive interaction between the pathways that go to the cortex from each eye was tested by studying the behavioral capacities, the electrophysiological responses and the morphological appearance of the geniculo-cortical pathways. Two parts of the visual system in which no binocular competition was possible were defined. One is the segment that receives inputs from the monocular crescent of the visual field, which has been called the monocular segment. The other is the artificial monocular segment created by the limited lesion of the non-deprived retina, and this has been called the critical segment. In the binocular segments of the visual pathways we found, as have others, that: (1) behaviorally, cats do not respond to objects viewed by the deprived eye; (2) cortical cells tend not to respond to stimulation of the deprived eye; and (3) geniculate cells innervated by the deprived eye grow less than the normally innervated cells. However, we found that the deprived eye is more effective in driving neurons in contralateral than in ipsilateral cortex. Within the monocular and the critical segments of the visual pathways we found: (1) that cats orient appropriately to visual stimulation of the deprived eye, (2) that cortical cells respond to visual stimulation of the deprived eye, and (3) that geniculate cells grow more than the deprived cells in the binocular segment of the nucleus. Thus, the deleterious effects of visual deprivation of one eye can, to some extent, be prevented by damage to the other.

Force-generating capacity and contractile protein content of arterial smooth muscle.

Abstract: After correction for extracellular space (40%) determined from electron micrographs, the maximum isometric force developed by strips prepared from the media of the hog carotid artery (2.2 x 106 dyn/cm2) can be extrapolated to give a value of 3.7 x 106 dyn/cm2 for the smooth muscle component of the strip. Three independent estimates of the myosin content of the smooth muscle cells were made based on (a) exhaustive extraction and purification with estimates of preparative losses, (b) the myosin catalyzed ATPase activity of media homogenates, and (c) quantitative densitometry of the peaks containing myosin, actin, and tropomyosin after disk electrophoresis of sodium dodecyl sulfate-treated media homogenates. The results were consistent and gave a myosin content of 5–10 mg/g media, or 8–17 mg/g cell. Method (c) gave myosin:actin:tropomyosin weight ratios of 1:3.2:0.8. Although measured force developed by the smooth muscle cell exceeds that of mammalian striated muscle, the myosin content in smooth muscle is about five times lower. The actin content of smooth muscle is relatively high. The actin and myosin contents are consistent with thick and thin filament ratios observed in electron micrographs of vascular smooth muscle.

Outer Membrane Proteins of Escherichia coli IV. Differences in Outer Membrane Proteins Due To Strain and Cultural Differences

Abstract: When the 42,000-dalton major outer membrane protein of Escherichia coli O111 is examined on alkaline polyacrylamide gels containing sodium dodecyl sulfate, it is resolved into three distinct bands designated as proteins 1, 2, and 3. Band 3 consists of two distinct polypeptides, proteins 3a and 3b. E. coli K-12 does not make any protein 2, but makes proteins similar to 1, 3a, and 3b as indicated by comparison of cyanogen bromide peptide patterns. Several Shigella species and most other strains of E. coli resemble E. coli K-12 in that they lack protein 2, whereas Salmonella typhimurium is more similar to E. coli O111. In addition to these species and strain differences, cultural differences resulted in differences in the outer membrane protein profiles. Under conditions of catabolite repression, the level of protein 2 in E. coli O111 decreased while the level of protein 1 increased. An enterotoxin-producing strain similar to E. coli O111 produced no protein 1 and an elevated level of protein 2 under conditions of low catabolite repression. The levels of proteins 1 and 3 are also different in different phases of the growth curve, with protein 1 being the major species in the exponential-phase cells and protein 3 being the major species in stationary-phase cells. A multiply phage-resistant mutant of E. coli K-12 with no obvious cell wall defects produced no protein 1 or 2, but made increased amounts of protein 3. Thus, the major outer membrane proteins of E. coli and related species may vary considerably without affecting outer membrane integrity.

Protein Kinase and Phosphoproteins of Vesicular Stomatitis Virus

Abstract: Protein kinases of similar but not identical activity were found associated with vesicular stomatitis (VS) virions grown in mouse L cells, primary chicken embryo (CE) cells, and BHK-21 cells, as well as being present in VS virions grown in HeLa and Aedes albopictus cells The virion kinase preferentially phosphorylated the nucleocapsid NS protein in vitro and to a lesser extent the envelope M protein Other virion proteins were phosphorylated in vitro only after drastic detergent treatment Partial evidence that the virion kinase is of cellular origin was obtained by finding reduced enzyme activity in virions released from cells pretreated with actinomycin D and cycloheximide Selective detergent and detergent-salt fractionation of VS virions revealed that the kinase activity was present in the envelope but not the spikes The virion kinase activity in a Triton-salt-solubilized envelope fraction could be separated from M and G proteins and partially purified by phosphocellulose column chromatography Virions released from L, CE, and BHK-21 cells infected in the presence of [32P]orthophosphate were labeled almost exclusively in the NS protein Both soluble and nucleocapsid-associated NS phosphoprotein were present in cytoplasmic extracts of VS viral-infected L cells The origin and function of the NS phosphoprotein remain to be elucidated