Showing papers by "University of Virginia published in 1972"

Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor.

Abstract: Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens. A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values. In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence.

Polarized intracellular particle transport: saltatory movements and cytoplasmic streaming.

Abstract: Publisher Summary This chapter discusses the phenomenon of saltatory movement in relation to Brownian movement. It demonstrates that except for the possibility that channels of low viscosity exist in cells, it is not likely that the motive force giving rise to the movements originates from molecular kinetic processes. The most likely types of models that can account for the details of saltatory movement are those in which the motive force arises from some process outside the particle itself, which is passively moved, or one in which movement arises by an interaction of the particle with some external structure. Such an interaction may involve an ATPase mechanism, or may be electrical in nature. The chapter explores the relation of secretory processes to the particle movements, and discusses the control mechanisms involved in the process. The chapter also highlights that a detailed analysis of movement of granules in Heliozoa indicates that microtubules are necessary for the organized streaming of particles along the axopods and in the interior of the organism. It is necessary, however, to look for saltations of short path length which may escape notice after study of the extended movements of particles in intact organisms.

The glycoprotein of vesicular stomatitis virus is the antigen that gives rise to and reacts with neutralizing antibody

Abstract: The glycoprotein, but no other virion protein, of vesicular stomatitis virus was solubilized by the nonionic detergent Triton X-100 in low ionic strength buffer. The solubilized viral glycoprotein induced the synthesis of antibody that formed a single precipitin line with the glycoprotein and that neutralized the infectivity of the virus. The neutralizing activity of the antibody was efficiently blocked by purified glycoprotein.

Dissociation and Reconstitution of the Transcriptase and Template Activities of Vesicular Stomatitis B and T Virions

Abstract: Transcriptase activity was dissociated from vesicular stomatitis virions by highionic-strength buffer containing Triton X-100. Considerable enzyme activity could be restored by recombining inactive sedimentable and nonsedimentable virion fractions. Reconstituted transcriptase activity was dependent on the presence of all four nucleoside triphosphates and the concentration of heat-labile molecules in both supernatant and pellet fractions. Lower NaCl concentrations removed approximately 46% of virion protein, but did not release transcriptase activity from the pellet fraction, nor could incorporation of (3)H-uridine-5'-triphosphate by complete virions be increased by adding soluble transcriptase. Evidence that the virion nucleocapsid is the transcription template was provided by finding that the pellet contained predominantly virion core nucleoprotein, ribonucleic acid, and homogeneous nucleocapsid coils when viewed by electron microscopy. Removal of envelope G and M proteins by Triton and low-salt buffer without decreasing nucleocapsid polymerase activity indicates that neither G nor M protein is necessary for transcription. Additional data are required to determine whether the minor nucleocapsid proteins L or NSl, or both, which are at least partially solubilized in high-salt buffer, are the transcriptase. Preliminary data suggest that the major N nucleoprotein, which was not solubilized by high-salt buffer, is also required for transcription. Defective T virions contained at least as much transcriptase per weight as did B virions, as determined by restoration with T supernatant fluids of transcription function to B nucleocapsid template. However, the T nucleocapsid would not serve as template for B or T transcriptase, a finding which is interpreted as evidence of T template defectiveness. The presence of defective T nucleocapsids did not interfere with B or T transcriptase function reconstituted with B template.

Killing of Intraleukocytie Staphylococcus aureus by Rifampin: In-Vitro and In-Vivo Studies

Abstract: Many virulent Staphylococcus aureus phagocytized by polymorphonuclear neutrophils (PMN) remain viable. Human PMN were mixed with S. aureus aerobically and anaerobically, and it was observed that many intracellular bacteria survived incubation with high concentrations of nine commonly used antistaphylococcal agents. In marked contrast to this, low concentrations of rifampin completely killed intraleukocytic bacteria. Experiments were then performed to evaluate the efficacy of rifampin in staphylococcal infections in mice. Treatment with penicillin or methicillin of mice that had been given intraperitoneal injections of S. aureus was only minimally effective in reducing mortality (93.1% in untreated mice, 83% in penicillin-treated mice, and 70% in methicillin-treated mice). In contrast to this, treatment with rifampin reduced mortality to 27.1% (P < .0005). In other experiments, rifampin alone prevented the formation of abscesses resulting from subcutaneous inoculation of staphylococci. The mechanism for this marked activity of rifampin in the treatment of experimental staphylococcal infections may be the unique ability of this antibiotic to kill intracellular staphylococci.

Classification of rhabdovirus proteins: a proposal.

Abstract: A simple alphabetical classification is offered as a means to codify the proteins of rhabdoviruses, using vesicular stomatitis virus as the prototype.

Significance of intracortical inhibition in the visual cortex.

Abstract: OF the cells found at each level of the retinotopically organized retino-geniculo-cortical system of the cat, only those found in the cortex can be specifically sensitive to the orientation of a contrast line and its direction of movement1–3. These cells are arranged in vertical arrays (columns)2 according to their type of trigger feature.

Superconductivity and Magnetoresistance in Nb Se 2

Abstract: Electron conduction in single crystals of Nb${\mathrm{Se}}_{2}$ has been measured at 4.2\ifmmode^\circ\else\textdegree\fi{}K in magnetic fields up to 150 kOe. The upper critical field ${H}_{c2}$ has been measured as a function of the angle between the applied field and the layers of the crystal for currents flowing both parallel and perpendicular to the layers. An effective-mass model based on simple considerations of the anisotropy of the crystal has been used to obtain a value for the ratio of effective masses for electron motion parallel and perpendicular to the layers, and the best value obtained is $\frac{{m}_{\ensuremath{\parallel}}}{{m}_{\ensuremath{\perp}}}=0.09\ifmmode\pm\else\textpm\fi{}0.01$. Transverse-magnetoresistance rotation diagrams have been studied and structure due to flux flow and flux pinning has been observed.

Changes in Membrane Properties of Chick Embryonic Hearts during Development

Abstract: The electrophysiological properties of embryonic chick hearts (ventricles) change during development; the largest changes occur between days 2 and 8 Resting potential (E(m)) and peak overshoot potential (+E(max)) increase, respectively, from -35 mv and +11 mv at day 2 to -70 mv and +28 mv at days 12-21 Action potential duration does not change significantly Maximum rate of rise of the action potential (+V(max)) increases from about 20 v/sec at days 2-3 to 150 v/sec at days 18-21; + V(max) of young cells is not greatly increased by applied hyperpolarizing current pulses In resting E(m) vs log [K(+)](o) curves, the slope at high K(+) is lower in young hearts (eg 30 mv/decade) than the 50-60 mv/decade obtained in old hearts, but the extrapolated [K(+)](i) values (125-140 mM) are almost as high Input resistance is much higher in young hearts (13 M ohm at day 2 vs 45 M ohm at days 8-21), suggesting that the membrane resistivity (R(m)) is higher The ratio of permeabilities, P(Na)/P(K), is high (about 02) in young hearts, due to a low P(K), and decreases during ontogeny (to about 005) The low K(+) conductance (g(K)) in young hearts accounts for the greater incidence of hyperpolarizing afterpotentials and pacemaker potentials, the lower sensitivity (with respect to loss of excitability) to elevation of [K(+)](o), and the higher chronaxie Acetylcholine does not increase g(K) of young or old ventricular cells The increase in (Na(+), K(+))-adenosine triphosphatase (ATPase) activity during development tends to compensate for the increase in g(K) +E(max) and + V(max) are dependent on [Na(+)](o) in both young and old hearts However, the Na(+) channels in young hearts (2-4 days) are slow, tetrodotoxin (TTX)-insensitive, and activated-inactivated at lower E(m) In contrast, the Na(+) channels of cells in older hearts (> 8 days) are fast and TTX-sensitive, but they revert back to slow channels when placed in culture

Relationship between two-body interatomic potentials in a lattice model and elastic constants. II

Abstract: General equations for the elastic constants associated with a crystal model in which the energy is given by two-body atom-atom interactions and volume-dependent terms are derived for monatomic solids. It is shown that noncentral interactions which require a choice of initial coordinate system do not necessarily give rise to an energy function which is invariant to homogeneous rotations. For central two-body forces, generalized Cauchy relations are defined. Explicit applications of these equations are given for short-ranged central forces in an hcp lattice and noncentral forces in the fcc lattice.

Calcium Current Channels Induced by Catecholamines in Chick Embryonic Hearts Whose Fast Sodium Channels are Blocked by Tetrodotoxin or Elevated Potassium

Abstract: In isolated ventricles of old (9-19 day) chick embryonic hearts made inexcitable by inactivating the fast sodium channels with either tetrodotoxin (TTX) or elevated external potassium, catecholamines induced slow electrical responses and concomitant contractions within 1-3 minutes. These slow responses had a higher threshold and propagated at a slower velocity than did the normal action potential. They were often graded and quite variable from one region of the heart to another. They were blocked by lanthanum or manganese (1 mM) and showed a dependence on the external calcium level. Strontium and barium could substitute for calcium. The slow channels were not completely inactivated when the external potassium concentration was raised until low membrane potentials of -10 to -25 mv were reached. The catecholamine-induced responses had a shape similar to that of the plateau component of the normal action potential, and cooling affected both in a similar manner. In some cases, slow responses persisted in TTX-blocked hearts even without the addition of exogenous catecholamines. Cyclic 3',5' AMP, dibutyryl cyclic AMP, theophylline, and caffeine partially mimicked the catecholamines, but usually the development of the response to these drugs was much slower. Prostaglandins, ryanodine, and acetylcholine had no effect. The order of effectiveness of the catecholamines was isoproterenol > epinephrine ≥ norepinephrine > dopamine ≥ dopa. Phenylalanine and tyrosine were ineffective. Isoproterenol produced a near-maximal effect at 5 x 10-7M. Propranolol blocked the catecholamine-induced effects. In young (2-5 day) hearts, there was no evidence that catecholamines produced a similar effect, and they did not have a positive inotropic action or an effect on the slow sodium channels. The results suggest that catecholamines quickly increase the density of divalent cation channels available in the sarcolemma of older chick hearts, thereby increasing the inward Ca2- current and influencing contraction.

Microvascular Responses to Alterations in Oxygen Tension

Abstract: The changes in microvascular diameter and perivascular oxygen tension resulting from alterations in suffusion solution Po2 were investigated in a study of the participation of oxygen in the regulation of blood flow. Diffusion gradients for oxygen were altered by changing the Po2 of a solution covering the surface of the hamster cheek pouch. As the solution Po2 was raised from a low of 11 mm Hg, perivascular Po2 of the large arterioles initially decreased to a minimum at approximately 40 mm Hg and then increased progressively as solution Po2 was elevated further. Arterial capillary and tissue Po2 remained relatively constant over a range of solution oxygen tensions between 11 and 40 mm Hg, suggesting that either the precapillary sphincters or the terminal arterioles were active in regulating tissue Po2 as the input of O2 from the solution was increased. The arterioles constricted as solution Po2 was elevated. Average arteriolar diameter decreased by 13% as solution Po2 increased from 11 to 47 mm Hg. A more pronounced constriction of 20% occurred when solution Po2 was increased from 11 to 84 mm Hg. These experiments indicated that the response of large and small arterioles was not mediated by a direct effect of oxygen on the vascular smooth muscle, since decreases in perivascular oxygen tension were coincident with decreases in vascular diameter in these vessels over a range of solution Po2 between 11 and 47 mm Hg. The data did not distinguish between a direct and an indirect effect of oxygen on the vascular smooth muscle of the terminal arterioles and precapillary sphincters. However, the oxygen tensions measured at these sites (18-30 mm Hg) required that the vascular smooth muscle cells respond to altered oxygen tension at levels higher than those which have been demonstrated experimentally.

Factors directing the expression of sympathetic nerve traits in cells of neural crest origin.

Abstract: It has been assumed that the phenotype expressed by a particular cell of neural crest origin is determined by the tissues comprising the final site of that crest cell. To test this premise as it applies to differentiation of sympathetic ganglioblasts, the future site of the primary sympathetic ganglia was ablated from embryonic axial trunks and the remaining tissues including the migrating crest cells were grown on chorioallantoic membranes of host chicks. Despite removal of the ultimate site of the primary sympathetic chains, catecholamine-containing cells, identified by a fluorescent test, differentiated ectopically. These results suggest that tissues along the migratory route rather than the tissues comprising the definitive site direct catecholamine synthesis in crest cells. To test this possibility, segments of neural tubes containing neural crest were grown alone or combined with somites on the chorioallantoic membrane. It was found that sympathoblast differentiation requires the presence of somitic mesoderm. In addition, ablation of the ventral neural tube drastically reduces the quantity of sympathetic nervous tissue formed in the presence of somites. Whether the ventral neural tube affects the crest cells directly or affects the capacity of the somites to influence crest cell differentiation is as yet undetermined. Control experiments indicate that mesoderm from other sources will not substitute for the somites in eliciting differentiation of sympathoblasts. These experiments support the hypothesis that neural crest cells give rise to sympathetic neurons in response to conditions imposed while the cells migrate ventrally.

Nervous control of walking in the crab, Cardisoma guanhumi

Abstract: 1. Discharge patterns in the motoneurons innervating the propodite stretcher and bender muscles and dactylopodite opener and closer muscles of the legs of the land crab, Cardisoma guanhumi, were recorded during sideways walking on a styrofoam wheel (Fig. 1). 2. Rhythmic bursts of activity in these motoneurons can be correlated with leg movements during walking in both leading and trailing legs (Figs. 2, 3A, B, D). Similar patterns of activity can be recorded in animals freely walking on a bench (Fig. 3C). 3. These motor output patterns are quite different from those occurring in the same motoneurons during resistance reflexes. In particular, the shared openerstretcher excitor and the stretcher inhibitor show no preferential phase relationship during walking (Figs. 4, 5). It appears that the normal movements of the propo-dactylopodite (P-D) joint during walking do not give rise to resistance reflexes. 4. Opening and closing movements of the P-D joint, manually imposed during walking, induce resistance reflexes (Figs. 6, 7). Reflexes tend to be stronger, both in terms of number of impulses and impulse frequency, when the imposed movement opposes rather than reinforces ongoing P-D movements. 5. Animals walking sideways on the wheel with the P-D joint clamped rigidly in a stable position show only slight changes in their motor output patterns from those seen during normal walking (Fig. 3E). 6. A model is discussed in which the proprioceptive input resulting from the normal movements of the P-D joint during walking is inhibited centrally and so does not give rise to a resistance reflex. 7. These results clearly indicate that resistance reflexes do not play an important role in coordination of antagonistic muscles during walking. Instead it is likely that their primary function is to compensate for changes in the load applied at a joint as would occur on steep inclines and irregular surfaces.

Impaired delayed hypersensitivity in systemic lupus erythematosus.

Abstract: When identical twin sisters discordant for systemic lupus erythematosus (SLE) were immunized with keyhole limpet hemocyanin (KLH) the affected twin failed to develop delayed hypersensitivity and her lymphocytes failed to proliferate in response to KLH in vitro, unlike her normal sister. Subsequently, recently diagnosed SLE patients were skin tested with common antigens and 12 of 14 did not develop a positive skin reaction, in contrast to most patients with tuberculosis, who showed at least one positive response. There was no difference, however, in the leukocyte response to phytohemagglutinin between the two groups. These findings raised the question of a selective defect in cellular immunity in patients with SLE.

The concept of revolutionary terrorism

Abstract: A recent article by Sartori stresses the importance for comparative politics of the construction of basic concepts which are discriminatory and "classificatory," enabling one to study "one thing at a time and different things at different times" (1970, p. 1040). Sartori emphasizes the need for precise conceptual connotation; only by making the definitional attributes of a concept more exact, rather than by increasing their number to extend the range of the concept, does one retain the possibility of empirically testing the concept. The article concludes that the most needed concepts are on a middle-level of abstraction, combining high explanatory power with precise descriptive content (p. 1052). Although the contemporary importance of the phenomenon of insurgent terrorism in internal war is undeniable, a review of theoretical literature on the subject reveals the absence of a concept of terrorism, defined in accordance with Sartori's requirements.

Gene triplication deduced from the tertiary structure of a muscle calcium binding protein.

Abstract: GENE duplication was first observed cytologically in the bar gene of drosophila1. The idea, extended by Dixon2, has been used to explain the obvious repeats in amino-acid sequence in the immunoglobulins, in bacterial ferredoxins, in haptoglobin α-2 (summarized in ref. 3) and in neurophysin4.

A fine-structural analysis of the fusion of myogenic cells

Abstract: The fusion of myogenic cells has been examined on the fine-structural level in muscle cell cultures of embryonic Japanese Coturnix quail. Cells, selected by light microscopy, were serially sectioned normal to their long axis. In this plane, oblique sections of cell membranes are rare and plasmalemmal profiles are more easily traced between adjacent cells. In seven cases, pairs of cells, apparently fixed in the process of fusion, are joined by a single cytoplasmic bridge. Since obliquely sectioned membranes often suggest cytoplasmic confluence, tilting stage analysis was employed to resolve cell membranes in suspect cases. In contrast to such artifacts of superposition, however, the observed intercommunicating pores are contained within a pair of culs-de-sac formed by the fused membranes of both cells. These blind pouches can be traced back between the cells to the external space. The confluent regions are clearly demarcated and they are not simply areas between vesicular profiles. The results of this analysis suggest that ( a ) at no time is there any loss of integrity of the cellular envelope, and ( b ) fusion is most probably initiated at single sites between pairs of cells, the pore enlarging, leaving first vestiges and eventually no trace of the original intervening membranes.

Distribution of lipids in the wall and cytoplasmic membrane subfractions of the cell envelope of Escherichia coli.

Abstract: Cell wall and membrane subfractions of the cell envelope of Escherichia coli have been isolated by a procedure involving particle electrophoresis and sucrose gradient density centrifugation. The lipid content of each fraction has been investigated. The individual phospholipids of both fractions are quantitatively similar except that the proportion of lysophosphatidylethanolamine is greater in the wall than in the membrane. Fatty acid analysis of the phospholipids of each fraction revealed that the wall phospholipids contain a greater proportion of palmitic acid. Coenzyme Q is almost exclusively localized in the cell membrane.

Efimov's effect: a new pathology of three-particle systems. ii.

Abstract: By studying the eigenvalue spectrum of the Faddeev kernel in a certain singular limit, we give an independent proof of an effect recently deduced by Efimov: When three identical particles interact via short-range pairwise potentials, the number of three-body bound states grows without limit when the pairwise scattering length $a$ becomes large. [The number of bound states is then roughly $(\frac{1}{\ensuremath{\pi}})\mathrm{ln}(\ensuremath{\Lambda}|a|)$, where $\ensuremath{\Lambda}$ is a momentum cutoff]. We extend our proof to the case where only two particles are identical and show that Efimov's effect persists in the special limiting cases with two heavy and one light particle, and with two light and one heavy particle.

Effects of puromycin on the structure of rat intestinal epithelial cells during fat absorption.

Abstract: This report provides information on the morphology of rat intestinal epithelial cells during fat absorption. In addition, the role of protein metabolism in this process has been evaluated by blocking its synthesis with puromycin and studying the fine structure of mucosal cells from rats at various times after fat intubation. The results indicate that SER-derived vesicles, containing fat droplets, migrate from the apical cytoplasm of the absorptive cell and fuse with saccules or vacuoles of the Golgi complex. Arguments are made that the Golgi complex is important in completing chylomicron formation and in providing appropriate enveloping membranes for the chylomicron. Such membranes may be necessary for Golgi vacuoles to fuse with the lateral cell membranes and release chylomicra. Puromycin treatment causes the absorptive cell to accumulate increased quantities of lipid that are devoid of membrane during fat absorption. In addition, puromycin-treated cells contain much less RER and Golgi membranes are strikingly decreased in number. In this paper we discuss the consequences of these abnormalities and suggest that continued protein synthesis by the RER is required in order to generate Golgi membranes. If such membranes are absent the cell's ability to discarge chylomicra is impaired and lipid accumulates.

Adenosine cyclic 3',5'-monophosphate in fetal rat brain cell cultures. I. Effect of catecholamines.

Abstract: The effects of various neurohormones and other chemical agents on intracellular levels of adenosine cyclic 39,59-monophosphate were evaluated in surface cultures of fetal rat brain cells. Treatment of cells with dopamine, prostaglandin F2α ,5-hydroxytryptamine, or KCl was without effect on cyclic AMP levels. Increases were found following exposure to adenosine, prostaglandin E1 , norepinephrine, or isoproterenol. The catecholamines were considerably more effective than the other compounds, causing up to a 100-fold increase in cyclic AMP content. This maximal response was not affected by 1 mM theophylline, was blocked by the beta adrenergic antagonists sotalol and dichloroisoproterenol, and was maximal after 5-15 min of exposure of the cells to the catecholamine. The response to isoproterenol developed during culture; its magnitude increased to a maximum after about 14 days in culture.

The effects of terminal-link fixed-interval and variable-interval schedules on responding under concurrent chained schedules.

Abstract: Previous work using variable-interval schedules in the terminal links of concurrent chained schedules suggested that relative choice proportion in the initial links equalled relative rate of reinforcement in the terminal links. With fixed-interval terminal-link schedules, however, matching was not obtained. The present study held pairs of fixed-interval terminal-link schedules in a constant ratio but varied absolute sizes. Relative choice for the smaller terminal-link fixed-interval schedule was a negatively accelerated, increasing function of absolute size of the fixed-interval pairs. Matching was found only with the fixed-interval pair of 5 and 10 sec. When pairs of variable-interval schedules were arranged so that the harmonic mean of the intervals equalled the fixed-interval parameter values, relative choice functions were like those for fixed-interval schedules.

Rare Gases in Metals

Abstract: Using models for fcc and bee metals developed in an earlier paper, the properties of He interstitial and substitutional defects were studied. The He-metal potentials were obtained by a modification of the Wedepohl method. Interstitial activation energies for helium motion are found in general to be quite low, being of the order of 0.5 eV for fcc materials and 0.25 eV for the bcc cases with the exception of palladium (~ 1.7 eV). Substitutional detrapping is found to require an activation energy of from ~2–5 eV, the higher energies found mostly for the bcc materials.

Pituitary Hormones Affecting Adrenal 5α-Reductase Activity: ACTH, Growth Hormone and Prolactin1

Abstract: Adrenal 5α–reductase activity in cortisone—treated rats is increased 2.5–fold after hypophysectomy. Treatment of hypophysectomized rats with either TSH or FSH plus LH did not affect reductase activity whereas ACTH, prolactin or growth hormone each exerted an inhibitory effect. When ovariectomized rats were treated either with TSH, ACTH, growth hormone or prolactin, only prolactin lowered reductase activity. Ovariectomized rats responded to prolactin at doses as low as 10 μg/lOOg bw. The hormone was also effective in orchiectomized animals. Treatment of ovariectomized rats with prolactin also enhanced the output of corticosterone by adrenal slices in vitro while not affecting the production of total corticosteroids. The data suggest that the stimulation of reductase activity after hypophysectomy results from the withdrawal of prolactin and growth hormone, as well as ACTH. In the gonadectomized rat, however, prolactin is the only effective pituitary hormone. Prolactin apparently stimulates the output of cor...