Showing papers by "Rockefeller University published in 1976"

Human malaria parasites in continuous culture

Abstract: Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). The original parasite material, derived from an infected Aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. The have remained infective to Aotus.

Central control of song in the canary, Serinus canarius

Abstract: We have traced central nervous pathways controlling bird son in the canary using a combination of behavioral and anatomical techniques. Unilateral electrolytic brain lesions were made in adult male canaries whose son had been previously recorded and analysed on a sound spectrograph. After severral days of postoperative recording, the birds were sacrificed and their brains processed histologically for degeneration staining with the Fink-Heimer technique. Although large lesions in the neostriatum and rostral hyperstriatum had no effect on song, severe song deficits followed damage to a discrete large-celled area in the caudal hyperstriatum ventrale (HVc). Degenerating fibers were traced from this region to two other discrete nuclei in the forebrain: one in the parolfactory lobe (area X, a teardrop-shaped small-celled nucleus) and a round large-celled nucleus in the archistriatum (RA). Unilateral lesions of X had no effect on song; lesions of RA, however, caused severe song deficits. Degenerating fibers from RA joined the occipitomesencephalic tract and had widespread ipsilateral projections to the thalamus, nucleus intercollicularis of the midbrain, reticular formation, and medulla. It is of particular interest that direct connections were found onto the cells of the motor nucleus innervating the syrinx, the organ of song production. Unilateral lesions of n. intercollicularis (previously implicated in the control of vocal behavior) had little effect on song. One bilateral lesion of HVc resulted in permanent (9 months) and complete elimination of the audible components of song, although the bird assumed the posture and movements typical of song. Preliminary data suggest that lesions of the left hemisphere result in greater deficits than lesions of the right one. This finding is consistent with earlier reports that the left syrinx controls the majority of song components. Results reported here suggest a localization of vocal control in the canary brain with an overlying left hemispheric dominance.

Correlation of Glucose Regulation and Hemoglobin AIc in Diabetes Mellitus

Abstract: We studied the increased levels of hemoglobins AIa+Ib and AIc in five hospitalized diabetic patients to determine whether changes in diabetic control would cause parallel changes in the levels of these hemoglobins. Before control of diabetes the mean fasting blood sugar for all patients was 343 mg per deciliter (range, 280 to 450), and hemoglobin AIc concentration 9.8 per cent (range, 6.8 to 12.1). During optimal diabetic control the blood sugar concentration was 84 mg per deciliter (range, 70 to 100), and hemoglobin AIc concentration 5.8 per cent (range, 4.2 to 7.6). Hemoglobin AIc concentration appears to reflect the mean blood sugar concentration best over previous weeks to months. The periodic monitoring of hemoglobin AIc levels provides a useful way of documenting the degree of control of glucose metabolism in diabetic patients and provides a means whereby the relation of carbohydrate control to the development of sequelae can be assessed.

Sexual dimorphism in vocal control areas of the songbird brain

Abstract: In canaries and zebra finches, three vocal control areas in the brain are strikingly larger in males than in females. A fourth, area X of the lobus parolfactorius, is well developed in males of both species, less well developed in femal canaries, and absent or not recognizable in femal zebra finches. These size differences correlate well with differences in singing behavior. Males of both species learn song by reference to auditory information, and females do not normally sing. Exogenous testosterone induces singing in female canaries but not in female zebra finches. This is believed to be the first report of such gross sexual dimorphism in a vertebrate brain.

Taste pathways to hypothalamus and amygdala

Abstract: The projections of a third order gustatory relay in the dorsal pons of rats have been traced using tritiated proline autoradiography and antidromic activation of pontine neurons from electrodes in the thalamus and amygdala. Labelled axons collect in the central tegmental tract and ascend to the thalamic taste area in the medial extension of the ventrobasal complex. The majority of the fibers remain ipsilateral, but a few cross in the rostral pons and midbrain. The largest crossing occurs at the level of the thalamic termination. Many fascicles of fibers continue rostrally by passing beneath the thalamic taste area, piercing the medial lemniscus, and spreading out along the dorsomedial corner of the internal capsule (IC). The terminal field at this level caps IC from the subthalamic nucleus down into the far-lateral hypothalamus. Labelled axons grandually penetrate through the internal capsule, and ramify throughout the underlying substantia innominata. This terminal zone extends laterally into the rostral end of the central nucleus of the amygdala, which is densely labelled to its caudal exremity. At the caudal end of the amygdala labelled fibers are visible in one component of the stria terminalis. These fibers can be followed over the dorsal thalamus into a smaller, but equally dense terminal area in the dorsolateral bed nucleus of the stria terminalis. The electrophysiological data demonstrate that pontine gustatory units can be antidromically activated by electrodes located in or near the central nucleus of the amygdala. Since many of the same units can also be driven from the thalamic taste area, at least some of the axons traced autoradiographically probably convey gustatory information to the hypothalamus and amygdala.

Infrared Bounds, Phase Transitions and Continuous Symmetry Breaking

Abstract: We present a new method for rigorously proving the existence of phase transitions. In particular, we prove that phase transitions occur in (φ·φ) 3 2 quantum field theories and classical, isotropic Heisenberg models in 3 or more dimensions. The central element of the proof is that for fixed ferromagnetic nearest neighbor coupling, the absolutely continuous part of the two point function ink space is bounded by 0(k−2). When applicable, our results can be fairly accurate numerically. For example, our lower bounds on the critical temperature in the three dimensional Ising (resp. classical Heisenberg) model agrees with that obtained by high temperature expansions to within 14% (resp. a factor of 9%).

Hormone concentrating cells in vocal control and other areas of the brain of the zebra finch ( Poephila guttata).

Abstract: Using the autoradiographic method in the zebra finch (Poephila guttata), areas of the brain were identified which contain cells which accumulate testosterone or its metabolites after intramuscular injection of tritiated testosterone. Among these areas are the caudal nucleus of the hyperstriatum ventrale, nucleus intercollicularis of the midbrain, and the tracheosyringeal portion of the hypoglossal nucleus of the medulla (nXIIts). These three are known to control or influence androgen dependent song and other vocalizations of passeriform birds, and nXIIts is composed of the motoneurons innervating the vocal (syringeal) muscles. Other areas containing hormone-concentrating cells are the medial preoptic area, nucleus periventricularis magnocellularis of the hypothalamus, dorsal infundibular layers, dorsomedial thalamus, lateral septum, magnocellular nucleus of the anterior neostriatum, periventricular medial neostriatum, nucleus taeniae of the archistriatum, and ventral paleostriatum augmentatum. Accumulation by cells in the preoptic area, hypothalamus, and limbic forebrain is consistent with a general vertebrate pattern of distribution of brain cells which accumulate sex steroids. Some of these same areas may be involved in the control of androgen dependent events such as courtship, copulation, aggression, and feedback regulation of the hypophysis.

Reproductive development in a female songbird: differential stimulation by quality of male song.

Abstract: Female canaries exposed to playback of large repertoires of male songs built nests faster and laid more eggs than did those females exposed to smaller song repertoires: females are attentive to attributes of male song, and their choices have played a role in the evolution of oscine singing behaviors.

Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man

Abstract: This study was undertaken to examine the influence of changes in dietary carbohydrate and protein content on the oxidation of antipyrine and theophylline in man. When the diets of 6 normal volunteers were changed from their usual home diets to low carbohydrate-high protein diets, the plasma half-life of antipyrine decreased from 16.2 hr to 9.5 hr, and the half-life of theophylline decreased from 8.1 hr to 5.2 hr. When the subjects' diets were changed from low carbohydrate-high protein diets to a high carbohydrate-low protein diets, the mean antipyrine half-life increased from 9.5 hr to 15.6 hr and the mean theophylline half-life increased from 5.2 hr to 7.6 hr. These changes in half-lives were accompanied by changes in metabolic clearance rates but not in the apparent volumes of distribution of the drugs tested. Qualitatively similar results were obtained when the subjects were placed on standard diets followed by the standard diets supplemented with carbohydrate or protein. Supplementing the standard diets with carbohydrate caused an increase in drug half-lives, whereas a protein supplement caused a decrease in the drug half-lives. These data demonstrate marked influences of nutritional factors on oxidative biotransformation of drugs in man.

Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro

Abstract: Leishmania donovani, the etiological agent of human visceral leishmaniasis, was grown in hamster peritoneal macrophages in vitro. By electron microscopy, using a lysosomal marker, these parasitic protozoa were seen to multiply within host cell phagolysosomes. The survival mechanism of this intracellular parasite is based apparently upon resistance to macrophage lysosomal enzymic digestion.

Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes.

Abstract: Hemoglobin AIc concentration, fasting blood sugar, response to an oral glucose tolerance test, and skeletal muscle capillary basement membrane thickness were measured in diabetic patients. Hemoglobin AIc concentration correlates with both response to a glucose tolerance test (r = 0.82, p less than 0.001) and fasting blood sugar (r = 0.62, p less than 0.001). The correlation of hemoglobin AIc concentration with glucose tolerance is independent of fasting blood sugar concentration (partial r = 0.61, p less than 0.005), whereas that of hemoglobin AIc with fasting blood sugar probably reflects the relationship between fasting blood sugar levels and glucose tolerance (partial r = 0.22, p less than 0.05). Hemoglobin AIc levels do not correlate with basement membrane thickness ( r = 0.15, p less than 0.05).

Antitrichomonad Action, Mutagenicity, and Reduction of Metronidazole and Other Nitroimidazoles

Abstract: Twelve 4- and 5-nitroimidazole derivatives, including metronidazole and two of its metabolites, tinidazole, dimetridazole, and nimorazole, were tested for antitrichomonad action on Tritrichomonas foetus (KV(1)) and Trichomonas vaginalis (ATCC 30001) for mutagenicity on a nitroreductase-positive (TA 100) and a nitroreductase-deficient (TA 100-FR(1)) strain of Salmonella typhimurium, as well as for the reducibility of the nitro group by T. foetus homogenates. Compounds with activity <1% of that of metronidazole are regarded as inactive. All antitrichomonad compounds induce mutations and can be reduced. S. typhimurium TA 100 gave mutations under both aerobiosis and anaerobiosis; TA 100-FR(1), however, gave mutations only under anaerobiosis. Certain compounds that are reducible, and the nonreducible derivatives, were inactive. Metronidazole and its inactive 4-nitro analogue were reduced in a four-electron process in ferredoxin- or methyl viologen-mediated reactions with the same velocity. The results underscore the role of the reduction of the nitro group in the antitrichomonad and in the mutagenic activity of nitroimidazoles.

Spinal branching of corticospinal axons in the cat

Abstract: The branching patterns of rubrospinal (RS) axons projecting to the cervical spinal cord between C3 and C8 were studied in the cat. RS neurons were identified by their antidromic responses to microstimulation of local axon branches within the cervical gray matter. Twenty-six of 58 RS neurons projecting to the cervical gray matter also sent axon branches to the thoracic spinal cord. Two out of 40 of these RS neurons also sent axon branches to the lumbar spinal cord. Using a collision technique, it was demonstrated that stem axons of rubrospinal neurons commonly sent multiple collaterals to different cervical segments. Neurons projecting to the cervical spinal cord alone were located in the dorsal quadrants of the red nucleus. Those projecting to cervical, as well as to more caudal segments, were intermingled with the former, and in slightly more ventral portions of the red nucleus. The presence of RS neurons projecting to widely separate levels of the spinal cord suggests that individual RS neurons may be capable of ultimately influencing two or more different motoneuron pools.

Left Hypoglossal Dominance in the Control of Canary and White-crowned Sparrow Song

Abstract: The syrinx of songbirds includes two separate sound sources, the internal tympaniform membranes (ITM), which form the medial wall of each bronchus. The performance of each ITM is controlled by the muscles of that syringeal half. In the canarySerinus canarius, hypoglossal fibers reaching the syrinx via the tracheosyringealis branch of the hypoglossus are responsible for sound modulation. The muscles controlling the performance of the left syringeal half are innervated solely by the left tracheosyringealis; those controlling the right syringeal half are innervated only by the right tracheosyringealis. In the canary and white-crowned sparrow (Zonotrichia leucophrys) a great majority of song elements disappears after section of the left tracheosyringealis, yet remains intact after section of the right one. This phenomenon, earlier described in the chaffinch (Nottebohm, 1970, 1971, 1972) and confirmed in the white-throated sparrow (Lemon, 1973), has been called left hypoglossal dominance. Left hypoglossal dominance occurs in canaries with small or large song repertoires. It occurs in chronically deafened canaries that never had access to their own auditory feedback; it also occurs in birds that had the right or left cochlea removed at an early age. To this extent, left hypoglossal dominance seems to emerge in the individual as a motor phenomenon.

The serological classification of Neisseria gonorrhoeae. I. Isolation of the outer membrane complex responsible for serotypic specificity

Abstract: Neisseria gonorrhoeae has been subdivided into several classes of serological distinct groups. The serotyping system is based upon the antigenic specificity of a protein serotype antigen. This protein is the major polypeptide of the outer membrane of the gonococcus and accounts for over 60% of that membrane's total protein. The serotype antigen complex was isolated by mild extraction of intact organisms in 200 mM lithium acetate buffer, pH 6.0 with 10 mM EDTA for 2 h at 45 degrees C. The extract was fractionated on Sepharose 6B and partially purified by precipitation at pH 4.2 by addition of 10% (vol/vol) acetic acid. Each serotype antigen has a unique subunit molecular size as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Preliminary typing of a gonococcal strain may be performed by comparative SDA-PAGE. To date, 16 different serotypes, representing a diverse distribution, have been isolated.

Studies on the mechanism of induction of haem oxygenase by cobalt and other metal ions.

Abstract: Cobalt ions (Co2+) are potent inducers of haem oxygenase in liver and inhibit microsomal drug oxidation probably by depleting microsomal haem and cytochrome P-450. Complexing of Co2+ ions with cysteine or glutathione (GSH) blocked ability of the former to induce haem oxygenase. When hepatic GSH content was depleted by treatment of animals with diethyl maleate, the inducing effect of Co2+ on haem oxygenase was significantly augmented. Other metal ions such as Cr2+, Mn2+, Fe2+, Fe3+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ were also capable of inducing haem oxygenase and depleting microsomal haem and cytochrome P-450. None of these metal ions had a stimulatory effect on hepatic haem oxidation activity in vitro. It is suggested that the inducing action of Co2+ and other metal ions on microsomal haem oxygenase involves either the covalent binding of the metal ions to some cellular component concerned directly with regulating haem oxygenase or non-specific complex-formation by the metal ions, which depletes some regulatory system in liver cells of an essential component involved in controlling synthesis or activity of the enzyme.

New evidence on the location of the saccharide-binding site of concanavalin A.

Abstract: THE biological activities1–4 of the mitogenic lectin concanavalin A (con A) depend on the binding of the protein to receptors on the cell surface, and this binding can be inhibited by specific saccharides related to D-mannose and D-glucose5. Knowledge of the location and nature of the saccharide-binding site of con A would therefore contribute greatly to understanding the molecular basis of its biological activities. Although the complete amino acid sequence6–8 and three-dimensional structure6,9–11 of con A are known, there has been conflicting evidence on the location of the carbohydrate-binding site. Crystallographic studies with saccharides labelled with heavy atoms indicated that it was in a deep cavity in the molecule, more than 20 A from the Mn2+ and Ca2+ ions6,9,12 (Fig. 1). Subsequent magnetic resonance measurements13–15 as well as crystallographic considerations16 suggested that the site was 10–12 A from the metals, and led to the hypothesis that the previously studied saccharides labelled with heavy atoms (for example, o-iodo-phenyl-β-D-glucopyranoside (β-IPG)) were bound by their hydrophobic aglycones, rather than by their saccharide moities9,17.

Black widow spider venom: effect of purified toxin on lipid bilayer membranes

Abstract: A purified toxin (the B5 fraction) from black widow spider venom added to the solution on one side of a lipid bilayer membrane interacts irreversibly with the membrane to produce a continuous, linear rise of membrane conductance with time. Conductances greater than 10(-4) reciprocal ohm per square centimeter can eventually be attained without any loss of membrane stability. Membranes treated with toxin are ideally selective for alkali cations over anions and are substantially permeable to calcium ion. These effects of the toxin result from the formation of permanent channels in the membrane of uniform conductance, 3.6 X 10(-10) reciprocal ohm (in 0.1 molar potassium chloride), that remain open almost all the time. Both the divalent cation permeability and the smaller conductances at low pH of toxin-treated membranes suggest that there is negative charge (possibly from carboxyl groups) associated with the channels. We discuss the possible relation of the action of this toxin on lipid bilayer membranes to its ability to stimulate massive transmitter release at the neuromuscular junction and to produce profound morphological changes on tissue cultured neurons.

Further study on the excitation of pyramidal tract cells by intracortical microstimulation.

Abstract: The effective spread of stimulating current for pyramidal tract (PT) cells and fibers was studied using a method of cancelling the shock artifacts and the following results were obtained: 1. The excitability of PT axon collaterals was as high as that of PT cells. 2. These axon collaterals extended as far as 1.0 mm horizontally from the PT cells. 3. The low threshold area for activation of a given PT cell was as wide as 3–4 mm2 on the surface of the cortex. 4. Intracortical microstimulation (ICMS) delivered to the PT cell layer produced direct (D) and indirect (I) descending volleys in the pyramidal tract, but ICMS to the superficial layer (III) produced only I-waves. 5. These I-waves grew significantly larger after 15–20 msec from the start of the train of stimuli. 6. It is concluded that either surface stimulation, or short train of ICMS is inadequate for delineating fine localization of motor function within the cortex. Longer train (30–40 msec) with high frequency pulses (300–400 cy/sec) can produce muscle contraction with much smaller currents, increasing the accuracy of measuring the localization of motor function.

Serial position functions for letter identification at brief and extended exposure durations

Abstract: The properties of serial position functions for tachistoscopic report were investigated over a wide range of viewing times. Four-letter strings of random consonants were presented in varying display locations relative to the fixation point with the observers’ eye movements monitored to limit them to a single fixation for each display. Salient properties of the serial position curves include an overall central-peripheral gradient, higher performance at the ends than the interior of letter strings regardless of absolute location, and left-right asymmetry in the visual field, all of these being largely independent of viewing time. Errors reflecting loss of positional information are prominent even at extended viewing times, are more nearly symmetrical in the left and right visual fields than other types of errors, and, in contrast to item errors, occur less frequently in letter sequences that have high frequencies in English. Further, transposition errors exhibit a pronounced peripheral-to-central drift, possibly reflecting gradients of positional uncertainty. Such gradients may be implicated in the peripheral-central asymmetry of the lateral interference effects exerted by other letters on a target letter in a nonfoveal location.