Picture-naming interference with good and poor readers. 22 third grade children of high and low reading ability (ns = 11) were tested for their ability to name pictures while trying to ignore words or nonword strings of letters printed inside the pictures. Nonoverlapping sets of pictures and words were used as stimuli to avoid the possibility of sensitizing subjects to the particular words used in the experiment (Neisser, 1976). Both groups experienced more interference from intra-category than extra-category words, indicating that they processed the words automatically. Only the good readers experienced more interference from pseudowords than consonant strings, suggesting that poor readers are less sensitive than good readers to orthographic regularity.


Effects of familiarity of music on vigilant performance. 35 subjects, randomly assigned to five groups in a 2 x 2 + 1 between-subjects design, performed a vigilance task under familiar rock, familiar easy-listening, unfamiliar rock, unfamiliar easy-listening, and no music conditions. Familiar music significantly increased heart rate and percent detections and also mitigated the classical vigilance decrement. Type of music had no significant effect. It was concluded that the psychological chaaracteristics of noise are at least as important as its physical characteristics in determining level of vigilance performance.


Strategies for attention allocation in multiple input, multiple response tasks. 9 tasks involving multiple inputs and multiple responses were administered. The tasks involved monitoring, shadowing, and ignoring, in all combinations, monaural and dichotic meassages. Miss rates were compared to determine the effect of adding additional demands to different tasks. Results suggested that, when a demand was added to a task, attention was allocated away primarily from those demands already receiving the greatest amounts of attention, to accommodate the new demand. When the new demand drew attention toward a channel, those demands already receiving the least amounts of attention gained the largest amounts. There were several exceptions to these trends, suggesting that the total amount of effort available for allocation was apparently an important variable. The implication of the results for research in attention was discussed.


Field dependence and short-term memory.

Field dependence and short-term memory. This study examined the relationship between field dependence and short-term memory. It was predicted that relatively field-independent individuals would perform better on short-term memory tests in which a large amount of interference is assumed to be present than would individuals who are more field-dependent. Subjects' appraisals of their own attentional facility, as well as their thoughts and feelings about the experimental tasks, were also elicited, and were looked at in terms of their relationship to field dependence and short-term memory.


Border locking and the Café Wall illusion. The Café Wall illusion (seen on the tiles of a local café) is a Münsterberg chequerboard figure, but with horizontal parallel lines which may have any luminance separating the rows of displaced squares. These (the 'mortar' lines) display marked wedge distortion which is especially affected by: contrast of the squares ('tiles'); width of the 'mortar' lines, and their luminance which must not be significantly higher than that of the light squares or lower than that of the dark squares for distortion to occur. An experiment is described from which quantitative data have been obtained by varying these parameters. It is suggested that contiguous regions of different luminance (and contiguous colour regions) are normally held in spatial register by locking from common luminance boundaries. The Café Wall illusion is attributed to this border locking producing inappropriate contour shifts from neighbouring regions of contrasting luminance when separated by narrow gaps of neutral luminance. Further implications on the border-locking notion are discussed.


Three-dimensional perception of planar line segments. Two-dimensional line drawings can be perceived as three-dimensional images if they are viewed through a grating of parallel lines placed a short distance above the drawing. The position in space of the images is a function of the angle between the lines in the drawing and those in the viewer grating.


Assessment of depth perception in cats.

Assessment of depth perception in cats. A behavioural method is described for the assessment of depth perception of kittens. Measurement is made of the smallest separation in depth that can be discriminated between two adjacent stimuli under both monocular and binocular viewing conditions. Normal animals can discriminate much smaller separations in depth when using two eyes than with monocular viewing, implying the presence of a cue to depth that is uniquely available with binocular viewing. The test provides a quick and reliable way of screening animals for stereopsis.


Visual-geometric illusions: unisex phenomena. The possibility of sex differences in responses to visual-geometric illusions was investigated with the use of forty-five illusion variants and a sample of 221 observers. No difference in illusion magnitude as a function of sex was found. A second experiment measured illusion decrement and transfer of decrement to other illusion configurations. Again there were no significant differences between male and female observers.


Figure-ground formation by movement: influences and effects. A twelve-letter array was segmented into figure and ground by moving some of its letters. Moved letters were shifted one letter-width left of right, independently of each other, in apparent movement. Since the figure of a display attracts attention, identification of letters of the figure segment should show an advantage over letters of the background segment. Three results are of interest. First, moved letters were identified more accurately and faster than stationary letters when only one or two letters moved. Stationary letters showed the advantage when eight of the twelve letters moved. This result suggests that the segment seen as figure is determined by both rapidly encodable letter movement and by the number of moved letters within the display. Second, segmentation of the visual display acids identification of moved letters in less than 90 ms, or well before the eye can move to the selected letter position. Third, letters in the figure segment which are closer to fixation are more likely to be identified than more eccentric letters.


Identification of familiar and unfamiliar faces from internal and external features: some implications for theories of face recognition. Three experiments are reported in which recognition of faces from whole faces or internal or external features was compared. In the first experiment, where the faces were of famous people, an advantage was found for identification from internal features. In the second experiment involving unfamiliar faces, however, no difference was found in recognition rates when subjects were given the internal or the external features. In a third experiment famous faces were presented and mixed with other famous faces for a recognition test. As in experiment 1, better recognition occurred from internals as compared with external features. It is argued that the internal representation for familiar faces may be qualitatively different from that for face seen just once. In particular some advantage in feature saliency may accrue to the internal or 'expressive' features of familiar faces. The implications of these results are considered in relation to general theories of face perception and recognition.


Salt taste adaptation: the psychophysical effects of adapting solutions and residual stimuli from prior tastings on the taste of sodium chloride. The paper reviews how adaptation to sodium chloride, changing in concentration as a result of various experimental procedures, affects measurements of the sensitivity, intensity, and quality of the salt taste. The development of and evidence for the current model that the salt taste depends on an adaptation level (taste zero) determined by the sodium cation concentration is examined and found to be generally supported, despite great methodological complications. It would seem that lower adaptation levels elicit lower thresholds, higher intensity estimates, and altered quality descriptions with predictable effects on psychophysical measures.


Attentive fields: valid scientific constructs or elusive theoretical entities: a reply to Pressey. Pressey conveys the impression that we misunderstood and misapplied his construct of attentive field. In this rejoinder it is argued that by Pressy's own definition and application of this construct his theory should be able to account for our results.


Interactions between simultaneous contrast and adaptation to gradual change of luminance. Following adaptation to a field of light which was modulated by a rising ramp so that it repetitively grows gradually brighter, a steady test field of light appears to be gradually growing dimmer. In this study, if a small grey spot of constant luminance was centered in the brightening field, it appeared to be growing gradually dimmer by simultaneous contrast. This apparent dimming led to a brightening aftereffect in the spot. It was shown that this spot aftereffect had two independent components: the apparent dimming of the adapting spot produced its own aftereffect (contrast produced an aftereffect) and also the dimming aftereffect in the surround field spatially induced an aftereffect into the spot during the test period (aftereffect produced simultaneous contrast). Thus simultaneous contrast can both precede and follow successive contrast in the visual system.


Salt taste detection: an R-index approach to signal-detection measurements. The R-index approach to the signal-detection P(A) index of sensitivity was used to measure taste sensitivity to NaCl solutions. The R-index is the predicted probability of the correct choice of a signal, for a given signal-noise pair. For flow-wise and sipwise presentation, R-indices did not fluctuate significantly, provided subjects could not see the stimuli yet to be presented, indicating a lack of systematic sensitivity drift. The simultaneous measurement of more than one signal strength with reference to a common noise stimulus was seen to be a viable and sensitive procedure. Comparison of flow-wise and sipwise presentation of stimuli using R-indices, indicated that the former elicited greater subject sensitivity to NaCl taste.


Genetic and environmental factors in orientation anisotropy: a field study in the British Isles. Visual acuity for the detection of gratings at four orientations was measured for groups of ten boys and ten girls aged five to seven years, from the following four populations: Scots in Glasgow, Pakistanis in Glasgow, Gaels in Stornoway (Outer Hebrides) and East Anglians in Littleport (Cambridgeshire fenlands). The Glaswegians, both Scottish and Pakistani, showed the normal pattern of anisotropy, with poorest acuity for oblique orientations; the East Anglians showed no significant anisotropy; while the Gaels were unusual in showing poorest horizontal acuity. A group of fourteen Pakistani children in Stornoway differed slightly from a matched group of Gaels. The group differences bore little relation to the visual environments, and were probably due to genetic or cultural factors. The relatively poor horizontal acuity of the Gaels was not correlated with astigmatism. Sex differences were also found, with the boys showing higher mean acuity and a higher ratio between vertical and oblique acuity.


A test for contrast-polarity selectivity in the tilt aftereffect. The tilt aftereffect (TAE) was studied with adapting and test stimuli consisting of black or white bars (experiment 1), and of luminance edges (experiment 2). Both experiments failed to demonstrate selectivity of the TAE to the polarity of luminance contrast.


The effect of spatial frequency and contrast on visual persistence. The visual persistence of sinusoidal gratings of varying spatial frequency and contrast was measured. It was found that the persistence of low-contrast gratings was longer than that of high-contrast stimuli for all spatial frequencies investigated. At higher contrast levels of 1 and 4 cycles deg-1 gratings, a tendency for persistence to be independent of contrast was observed. For 12 cycles deg-1 gratings, however, persistence continued to decrease with increasing contrast. These results are compared with recently published data on other temporal responses, and are discussed in terms of the different properties of sustained and transient channels.


Decrease in metacontrast masking following adaptation to flicker. Selective adaptation was used to explore the characterisitcs of a metacontrast masking stimulus which contribute to its effectiveness in masking the test stimulus. Subjects adapted for 10 s to a configuration like the masking stimulus that was either continuously on or flickering. Following this they viewed a metacontrast presentation and estimated the brightness of the test stimulus. Prior adaptation to a continuously present stimulus did not appreciably affect metacontrast masking; however, masking was greatly reduced following adaptation to flickering stimuli. These results are consistent with recent models of metacontrast masking based on transient and sustained visual channels.


Pattern and flicker detection examined in terms of the nasal-temporal division of the retina. Contrast thresholds for the detection of flicker and the detection of pattern were measured for nasal and temporal retinae of each eye separately. While confirming that these two types of threholds can differ, depending on the spatial frequency, the results provide no support for hemiretinal or hemispheric asymmetries in the distribution of the putative pattern and movement channels.


Exposure-time and spatial-frequency effects in the tilt illusion. The exposure durations of a vertical test line and a tilted inducing grating were varied and the tilt illusion thus generated was found to change as a function of this variation. Significant direct effects (acute-angle expansion) and indirect effects (acute-angle contraction) were found to occur at times consistent with Andrew's estimate of the time course of inhibition in the visual system when the inducing grating had a spatial frequency of 10 cycles deg-1. However, a 2.71 cycles deg-1 grating gave significant effects at exposure durations of 10 as well as 1000 ms, while in a further experiment a 10.91 cycles deg-1 grating gave significant effects at 1000 ms only. These results seem to suggest that orientation interactions thought to be due to inhibition (direct effect) and disinhibition (indirect effect) may occur within both sustained and transient channels with concomitant differences in time constants.


Angle-matching illusions and perceived line orientation. Spatial illusions which occur in angle-matching tasks were examined in six experiments using two different kinds of display. In experiments 1 and 2 illusory errors generally were in the direction predicted by Lennie's hypothesis which states that angle arms are attracted perceptually towards the oblique axes of space, although the display used in these experiments differed from Lennie's. However, experiment 3 showed that these errors might equally be explained by the addition of interactive effects between angle arms (tilt illusions). Parametric investigation of Lennie's figures (experiments 4 and 5) showed that thelargest angular illusion occurred with the largest angle used (45 degrees) and an intermediate line length (2 deg 7 min). These angular illusions were not explicable by the addition of tilt illusions (experiment 6), suggesting that different judgmental processes may underlie orientation and angle estimation.


Recognition of upright and inverted faces: a correlational study. An investigation of ninety-five university admission candidates failed to replicate the finding by Yin of a negative correlation between the ability to recognise upright and inverted faces. A zero correlation was obtained when unknown faces were both learned and recognised upside down, but when well-known faces were presented normally and upside down for identification, a significant positive correlation appeared. Rock has suggested that inverted faces are difficult to recognise because they overtax a mechanism for correcting disoriented stimuli. This explanation satisfactorily accounts for the data with the proviso that, when inverted faces are to be remembered, the best strategy is not to attempt to correct their orientation, but to learn isolated features of the face. This describes the data more parsimoniously than Yin's face-specific mechanism.


Random-dot stereograms of real objects: observation on stereo faces and moulds. A simple technique for producing random-dot stereograms of real objects is described. It is then shown that stereograms of inside-out faces (moulds) cease to be perceptually reversible only when the presentation is truly cyclopean. Further possible applications of the technique are outlined.


The nonequivalence of abrupt and diffuse illusory contours. A distinction is drawn between diffuse regions of apparent brightness and illusory, but abrupt, brightness gradients. Differences between the two phenomena are sufficient to disqualify conclusions about one based on observations about the other. It is suggested that diffuse contours may be attributable to peripheral mechanisms while sharp contours may be central or cognitive in origin.


Frequency, phase, and colour coding in apparent motion: 2. In an earlier paper, Caelli and Finlay demonstrated that the perception of apparent motion was contingent on critical phase relationships between inducing sources, and their spatio-temporal frequency ranges. In their original stimulus red-green centre-surround sources were used and phase-specific inhibition was found at 60 degrees--90 degreee phase angle differences between the complementarily coloured elements. In this experiment we show that, when centre-surround sources are replaced by vertically-horizontally displaced complementary (or identically coloured) sources, symmetrical phase inhibition effects occur with both motions.


The clinical assessment of the normal and abnormal foot during locomotion. The clinical assessment of the weight-bearing foot during locomotion is normally based on subjective judgement rather than on quantitative measurement. Although anatomical abnormalities are often apparent at examination, the accurate assessment of an abnormality of function is more difficult to assess particularly if the abnormality is only apparent under dynamic loading conditions. The many drawbacks in previous methods proposed for the clinical assessment of gait have led to the development of a novel system which allows an immediate quantitative visualization of the magnitude and point of application of the forces applied to the plantar surface of the foot during locomotion. This paper describes the technique and presents visual data on normal locomotion, on abnormal locomotion and the changes induced into a patient's abnormal gait by corrective surgery.


Locomotion of the hemipelvectomy amputee. A locomotion study was performed on a hemipelvectomy amputee wearing a prosthesis. The experimental arrangement described in this paper, combining joint motion developed during walking, a computer analysis of the force pattern between the foot and ground and plotting of pressure point on the foot print, has enabled detailed investigation with demonstration of several abnormal features in the prosthetic gait of a hemipelvectomy amputee.


Orthoses to fit shoes.

Orthoses to fit shoes. Orthoses which fit inside shoes have, in many cases in the past, been fashioned to the shape of the patient's foot. It is suggested that improved stability and comfort is achieved if, instead, the outside shape of the foot-piece of the orthosis is fashioned to the inside shape of the footwear. A method for achieving this is described.


An assessment of a system to monitor the activity of patients in a rehabilitation programme. The need for an objective quantitative method of monitoring performance in the natural environment for use in a rehabilitation programme is discussed. A system of monitoring the number of steps taken has been developed for an amputee programme as a first attempt towards this goal. Instrumentation consists of an inexpensive foot switch, a storage unit and a retrieval unit. Early clinical experience indicates this system may be of value in the rehabilitation programme by (1) indicating low or unusual activity and alerting clinical staff to identify the cause. (2) Restricting the over-anxious patient when excessive activity is contra-indicated. (3) Identifying poor use of the prosthesis in the home environment. (4) Providing motivation for patients to set personal goals. (5) Acting as a base line for the evaluation of research and development of new techniques.


[Essential hypertension in the child and adolescent. A preliminary study at an interval of more than one year (author's transl)]. One to two years after an initial study establishing normal values for blood pressure in a population of 819 children and adolescents, the outcome in 74 individuals, 39 of whom were considered to be hypertensive and the influence of the observer and methods on the collection of cases of hypertension are evaluated. 58% of the hypertensive individuals remained hypertensive. Overweight appeared to be the essential factor in determining the persistence of hypertension. 74 % of the overweight hypertensive subjects remained hypertensive as against a figure of 42 % of subjects with a normal weight prevent arterial hypertension could be considered by preventing excess weight. The influence of the observer is slight if methods and equipment are identical. Failure to follow the reference methodology increases the number of cases of hypertension artificially. In order to avoid this risk, the practitioner should refer to normographic scales, use the same method and apparatus and repeat measurements yearly or twice a year in order to eliminate observer error.


[Ruptured spleen during bacterial endocarditis. 2 cases (author's transl)]. Splenectomy was performed in two patients amongst a group of 120 suffering from bacterial endocarditis. In the first case, rupture of the spleen followed rupture of a partially thrombosed splenic vein and bacteriological specimens were negative despite the presence of multiple infarcted areas, certain of which were suppurative. In the second case surgery was possible before rupture of the spleen. The latter was the site of numerous abcesses, one of which was in the process of fissuration, and bacteriological specimens were positive. The course in both cases was favourable. Twenty two other cases have been found in the literature with 15 deaths. Whilst the prevalence of such complications remains low, their severity is such that routine surveillance of the kidney should be the rule in infectious endocarditis. The methods of such surveillance are discussed, the mechanism of such complications not being fully elucidated: the respective role of splenic infarction, splenic abcess and immunological factors remains to be determined.


[Differentiation between parathyroid adenoma and hyperplasia. Proof by peroperative Wang floating test (author's transl)]. It is sometimes very difficult during operation to distinguish a normal parathyroid gland from a hyperplasic gland. The Wang test offers a solution, very simply demonstrating a difference in density between two glandular specimens. Normal parathyroid tissue, with its fat-containing cells, floats, in contrast to hypersecreting glands which are poor in lipid elements. This test was performed in 30 patients and led to the recognition of hyperplasia in 2 cases.


[Prenatal diagnosis: results of 1530 amniotic taps and prospective study of 1023 cases (author's transl)]. The results confirmed the fiability and the accuracy of the different acts and technics leading to these diagnosis. A prospective study of the safety of amniocentesis involved more than 1000 subjects. The analysis of the information on the pregnancy, the delivery, the state at birth and after birth of the infant did not show any significant increase of pathologic findings which may be related to immediate or delayed consequences of amniocentesis.


[Oxyphenisatin, a laxative responsible for chronic hepatitis and cirrhosis, still marketed in France (author's transl)]. Six patients suffering from chronic liver disease attributed to oxyphenisatin ingestion are presented. They seem to be the first such cases reported in France. These patients were between 22 and 69 years old, 5 of them were female. Three patients had a chronic active hepatitis (CAH). In these three subjects the onset of the illness was a jaundice ; alanine transaminase (ALAT) exceeded 5 times the upper limit of the normal value ; smooth muscle antibodies were present in 2 patients and antinuclear antibodies in the third. Two other patients had cirrhosis, without chronic active hepatitis ; none presented autoantibodies. The sixth patient suffered from a subacute hepatitis, suggested by the presence of jaundice and ascites, high levels of serum ALAT and a very prolonged prothrombin time ; smooth muscle antibodies were present. In all cases, HBs Ag was absent from serum. Each patient had ingested laxative pills containing oxyphenisatin for 4 to 25 years ; the total amount ingested was comprised between 12.5 and 350 g. The chronic liver diseases reported in this series closely resemble those published in the literature. The lesions observed make it necessary to look for oxyphenisatin ingestion in every patient having CAH or cirrhosis without known etiology. These chronic liver diseases imply the rapid withdrawal of oxyphenisatin from french market, as already enforced in Australia and the United States.


[Pituitary microadenoma of Cushing's disease. Course following transsphenoidal excision. Four cases (author's transl)]. Transsphenoidal microsurgery was performed in four patients with a pituitary microadenoma who presented Cushing's disease. Preoperative features were the following: 1) Clinical and laboratory signs of hypercortisolism 2) No radiological evidence of an adrenal tumor 3) Normal or increased ACTH plasma levels 4) Sellar tomograms suggesting the presence of a pituitary microadenoma in only one case. Postoperative outcome after 3 to 30 months follow-up showed persistence or even improved reactivity of the various pituitary functions and especially the early occurence of corticotropin deficiency in all 4 patients. This isolated deficiency regressed spontaneously after 6 and 12 months (2/4 cases). Twenty-four hour studies of ACTH and cortisol profiles and dexamethasone suppression as well as response to metyrapone confirmed the resumption of physiological corticotropin regulation.


[Triangulation external fixation. Biomechanical justification and indications (author's transl)]. This triangular external fixation apparatus is designed for stabilization of traumatized pelvis or open fractures of the limbs. The proposed assembly demonstrates a higher degree of mechanical stability from the Hoffmann's external fixation apparatus.


Complexes of the arginine-rich histone tetramer (H3)2(H4)2 with negatively supercoiled DNA: electron microscopy and chemical cross-linking. Tetramers of the arginine-rich histones H3 and H4 associate with supercoiled SV40 DNA either singly, giving tetrameric nucleoprotein complexes or in pairs giving octameric complexes, both of which are visualized as beads in the electron microscope. The relative amounts of the two complexes may be revealed by complete cross-linking of the proteins, followed by analysis in SDS-polyacrylamide gels. By electron microscopy of unmodified and of cross-linked complexes, both the tetrameric and the octameric complexes are shown to have a diameter of 8-9 nm and to contain about 145 base pairs (a nucleosome core length) of DNA. The compaction of the DNA in both cases is thus similar to that in the nucleosome, which has a diameter of about 12.5 nm and contains 200 base pairs of DNA.


The effect of tRNA and tryptophanyl adenylate on limited proteolysis of beef pancreas tryptophanyl-tRNA synthetase. Limited proteolysis of tryptophanyl-tRNA synthetase was used to detect changes in the enzyme molecule in the presence of substrates. Trypsinolysis of each of the two identical subunits occurs in succession from the N-terminus as follows: 60 leads to 51 leads to 40 leads to 24 kilodaltons. The transition 51 leads to 40 is hindered in tryptophanyl adenylate.enzyme complex. Yeast tRNATrp accelerates the first steps of hydrolysis and decelerates the transition 40 leads to 24. Once tRNATrp is added to the synthetase.adenylate complex, the protective effect of the adenylate disappears. The same effects are found also in the presence of tRNATrp oxidized with NaI04 and tRNATrp lacking the 3'-terminal adenosine. Oxidized tRNATrp (but not tRNATrp without the 3'-A) accelerates tryptophan-dependent hydrolysis of ATP catalyzed by the enzyme. A scheme is proposed for the interaction of yeast tRNATrp with beef pancreas tryptophanyl-tRNA synthetase involving the association of tRNA with a positively charged site(s) of the enzyme and the changes in the conformation of enzyme manifesting itself in unfolding of the acidic N-terminal fragment of the polypeptide chain and in the exposure of the adenylate.


The polarity of the cauliflower mosaic virus genome. We have demonstrated that the 5' termini of the DNAs of cauliflower mosaic virus (CaMV) isolates CM4-184 and Cabb B-JI have free hydroxyl groups accessible for phosphorylation using polynucleotide kinase. This has enabled us, using the Cabb B-JI isolate, to label and identify the 5' nucleotides. Digestion of 5' terminally labelled DNA with EcoRI restriction endonuclease revealed that only three of the eleven single-stranded EcoRI fragments were labelled, those situated adjacent to the three known gaps in the double-stranded genome. Identification of the labelled fragments indicated the polarity of the genome. Hybridization experiments using RNA transcripts from infected leaves gave results consistent with the polarity data and confirmed the direction of transcription. Transcription on the largest DNA strand (alpha strand) is initiated between map units 0.24 and 0.30 and terminates between map units 0.0 and 0.24.


Unique requirements for template primers of DNA polymerase beta from rat ascites hepatoma AH130 cells. The optimal condition for the rat DNA polymerase beta activity with (rA)n . (dT)12-18 as a template-primer was determined. The activity was remarkably affected by the concentration of the primer, (dT)12-18' and the mixing ratio of (dT)12-18 to (rA)n. DNA polymerase beta requires higher primer concentration (Km = 11.1 microM with respect to 3'-OH of the primer) than DNA polymerase gamma (Km = 0.04 microM) or oncornaviral DNA polymerase (Km = 0.08 microM) and the enzyme represented the maximum activity in the base ratio of 2:1 with (dT)12-18 and (rA)n suggesting the difference in reaction mechanisms of these enzymes. Under the optimized conditions, the specific activity of the near homogeneous preparation of DNA polymerase beta was 1,000,000 units per mg protein.


The mode of inhibitory action by pyridoxal 5-phosphate on DNA polymerase-alpha and -beta. The kinetics of the inhibition of DNA polymerases-alpha and -beta from sea urchin embryos by pyridoxal 5-phosphate were studied. The inhibition of DNA polymerase-alpha activity by pyridoxal 5-phosphate was competitive with activated DNA but noncompetitive with each deoxynucleoside triphosphate. With poly(dC)-oligo(dG)12-18 as a template-primer, however, the inhibition of DNA polymerase-alpha was competitive with dGTP but noncompetitive with the template-primer. These results suggest that DNA polymerase-alpha interacts with activated DNA and poly(dC)-oligo(dG)12-18 in different ways. The inhibition of DNA polymerase-beta by pyridoxal 5-phosphate was competitive with deoxynucleoside triphosphate using activated DNA as a template-primer and noncompetitive with activated DNA. Using poly(rA)-oligo(dT)12-18 as a template-primer, DNA polymerase-beta activity yielded sigmoid curves against both dTTP and the template-primer concentrations and was inhibited by pyridoxal 5-phosphate noncompetitively with respect to both dTTP and the template-primer. These results indicate that the inhibitory mode of DNA polymerase-alpha by pyridoxal 5-phosphate is different from that of DNA polymerase-beta.


Preferential expression of unique sequences adjacent to middle repetitive sequences in mouse cytoplasmic RNA. Total single-copy DNA and single-copy DNA contiguous to middle repetitive sequences were isolated from mouse brain by successive hydroxylapatite column chromatographies. These DNAs, termed repeat-contiguous single-copy DNA, were found to constitute 48% of the total single-copy DNA. The saturation hybridization values of these two DNA probes to nuclear RNA and cytoplasmic RNA containing polyA of mouse brain and liver were measured. The saturation hybridization levels of total single-copy DNA to brain and liver nuclear RNA were 13.5% and 8.8%, respectively, and those of repeat-contiguous single-copy DNA to the same RNA samples were 13.3% and 8.5%, respectively. On the contrary, the saturation hybridization levels of single-copy DNA to cytoplasmic RNA containing polyA of brain and liver were 3.8% and 2.0%, respectively, and those of repeat-contiguous single-copy DNA to the same RNA samples were 5.8% and 4.0%, respectively. Similar results were obtained with total cytoplasmic RNA. These results indicate that about half the steady state nuclear RNA is transcribed from repeat-contiguous single-copy DNA, and that cytoplasmic RNA containing polyA is mainly derived from repeat-contiguous single-copy DNA.


Assembly of an active chromatin structure during replication. MSB cells were pulse labeled with 3H-thymidine and the isolated nuclei digested with either staphylococcal nuclease (to about 40% acid solubility) or DNase I (to 15% acid solubility). The purified, nuclease resistant single-copy DNA was then hybridized to nuclear RNA (nRNA). The results of these experiments show that actively transcribed genes are assembled into nucleosome-like structures within 5-10 nucleosomes of the replication fork and that they also acquire a conformation characteristic of actively transcribed nucleosomes (ie, a DNase I sensitive structure) within 20 nucleosomes of the fork. Assuming DNA sequence specific interactions are required for establishing a DNase I sensitive conformation on active genes during each round of replication, our results indicate that a specific recognition event can occur very rapidly and very specifically in eukaryotic cells. The results are discussed in terms of the possible mechanisms responsible for propagating active, chromosomal conformations from mother cells to daughter cells.


Fluoride ion promoted deprotection and transesterification in nucleotide triesters. Tetrabutylammonium fluoride will remove phenyl, trichloroethyl and cyanoethyl groups from nucleotides. In addition to the desired nucleotide products other results including chain cleavage, phosphofluoridates and cyanoethylated thymidine units may be obtained depending on the conditions used. Fluoride ion has been used to successfully exchange phenyl and trichloroethyl groups for methyl, ethyl and butyl groups in nucleotide triesters. This represents a rapid high yield route to a variety of phosphate esters. The synthesis of a novel nucleotide analogue in which two chains are bridged through their phosphates is described.


Increased binding of ethidium bromide to polynucleotide duplexes containing mismatched bases. The binding of the intercalating dye ethidium bromide to a series of synthetic polynucleotide duplexes containing varying concentrations of mismatched bases has been measured by fluorescence titration. The dye binds more strongly to duplexes with mismatches, the estimated increase in affinity being twenty-fold for the series of molecules poly (I).poly (C,Ax) with x denoting the mole fraction of mismatched A residues in the C strand. The results are consistent with one requirement of the Streisinger model for frameshift mutagenesis, namely that frameshifting agents can function by stablizing mismatched transient intermediates in DNA.


Separation of oligo-RNA by reverse-phase HPLC. A rapid and highly reproducible chromatographic technique has been developed for analysis and purification of complex mixtures of oligoribonucleotides. The method utilizes a column of microparticulate porous silica beads fully derivatized with octadecylsilyl groups. The column is eluted with gradients in acetonitrile/water/ammonium acetate pumped at pressures of 1500-300 psi. Most separations are completed in 5-15 min. with usually better than 1% reproducibility of absolute retention times and about 0.1% reproducibility of relative retention times. A single column accomplishes separations of mononucleosides, mononucleotides, and larger oligomers through at least 20-mers. The absolute detection limit is approximately 1 pmole of base though most of the analytical separations described use approximately 1 nmole. In favorable circumstances it is possible to use the analytical colums to purify approximately 1 mg of an oligonucleotide in a single 10-30 min. elution.


Interaction specificities of a platinum metallointercalation reagent to DNA. The interaction specificity of salmon sperm DNA with 2-hydroxyethanethionlato(2,2',2''-terpyridine)platinum(II),PtTS has been studied. The results of 1H and 13C nuclear magnetic resonance, flow dichroism and circular dichroism studies are found to be consistent with an intercalation mode of binding as has been proposed earlier by lippard and coworkers.


Sub-genomic RNA in Moloney leukemia virus grown in lymphoid-derived cell lines consists primarily of homologous viral RNA. Moloney murine leukemia virus (MoMuLV) grown in 2 lymphoid-derived murine cell lines (JLS-V9 and TB) contained 2 size classes of RNA subunits: 2.8 +/- 0.4 x 10(6) (n = 30) and 1.6 +/- 0.1 x 10(6) (n = 15) daltons. Detectable levels of low molecular weight viral RNA (LMW vRNA) were not present in MoMuLV grown in mouse embryo fibroblasts, nor rat cells, nor was it produced by them when they were infected with MoMuLV containing both species of vRNA. DNA probes complementary to both subunits were synthesized separately using purified reverse transcriptase (R.T.) and calf thymus DNA as primer. Polyadenylated LMW vRNA was selected and, by molecular hybridization was found to be completely homologous with the large RNA subunit. This was confirmed using cDNA probes representing defined regions of the genome. The LMW vRNA therefore contains multiple subsets of the viral RNA, which could correspond to multiple deletion mutants possibly generated by an efficient RNA splicing mechanism. In addition, low levels of non-homologous virus-like RNA were detected in MoMuLV grown in TB (2%) AND NIH/3T3 cells (0.4%).


A new series of RNAs associated with the genome of spleen focus forming virus (SFFV) and poly(A)-containing RNA from SFFV-infected cells. A series of low molecular weight RNAs (4.5 to 5.5S) as well as other 4 to 7S RNAs were dissociated from genomic RNA of spleen focus forming virus (SFFV) by heating. On two dimensional polyacrylamide gel electrophoresis, this series of RNAs gave a series of more than thirty spots. RNase T1 fingerprints of these spots were identical except for differences in 3'-terminal oligonucleotides, which were mainly due to different numbers of uridylic acid residues, larger RNA-molecules containing poly(U)sequences at their 3'-termini. This series of RNAs is also associated with poly(A)-containing nuclear and cytoplasmic RNAs from SFFV-infected cells.


Transcription initiation of Xenopus 5S ribosomal RNA genes in vitro. We have studied initiation of transcription of 5S RNA genes in extracts of Xenopus laevis oocyte nuclei. To aid in this study we developed a general assay for specificity of transcription initiation that does not require accurate termination of transcription. Following in vitro transcription with gamma-32P-labeled nucleoside triphosphages, the RNA is digested with pancreatic RNAase and fingerprinted by two dimensional chromatography. A 5S RNA gene with a variant sequence, in which the G residue at position +1 is replaced by a C, initiates transcription at an A residue one nucleotide preceding the C. Although Xenopus RNA polymerase form III can initiate transcription at many sites on plasmid DNA, all of the transcripts start with purines. The majority of these purines are triphosphorylated. When a repeating unit of Xenopus 5s DNA is inserted into the plasmid, initiations at the vector start sites are suppressed and the major labeled 5' oligonucleotide is derived from 5S RNA.


Rapid quantitation of individual RNA species in a complex population. Many investigations require quantitation of one or more individual RNA species in complex populations. Existing methods are tedious when multiple samples are to be assayed. A method is presented which allows rapid and accurate quantitation of many species of RNA simultaneously. Recombinant plasmids containing cDNA inserts are electrophoresed in agarose and blotted to nitrocellulose. After hybridization with labeled RNA and autoradiography, bands are quantitated by scanning. The results were calibrated by solution hybridization. The approach has been validated through the use of plasmids containing inserts of Drosophila cDNA and RNA of cultured cells.


Structure models for DNA in filamentous viruses with phosphates near the center. DNA structure models deduced from X-ray and physicochemical  data for Pfl, Xf, and fd viruses have two antiparallel chains wound in helices of approximately 15 A pitch with the phosphates near the structure axes and the bases directed outward. The models, which differ for each virus, are used to interpret ultraviolet absorbance and fluorescence data in terms of DNA protein interactions.


A DRB (5,6 dichloro-beta-D-ribofuranosylbenzimidazole)-resistant adenovirus mRNA. 5,6-Dichloro-beta-D ribofuranosyl benzimidazole (DRB) inhibits transcription from the major late adenovirus promoter, located on the r-strand at map position 16.3 on the viral genome. 100-500 nucleotides long RNA chains with capped 5'-termini are transcribed from this promoter in the presence of 70 muM DRB. Synthesis of the mRNA for polypeptide IX which is unspliced and maps on the r-strand between positions 9.7 and 10.9 appears, however, to be DRB-resistant although it is transcribed by polymerase II and capped. Translatable mRNA for polypeptide IX is synthesized in the presence of DRB while the mRNAs for the other viral structural proteins are not synthesized. This differential DRB-inhibition of polymerase II transcription suggests either that short mRNAs may escape inhibition or that unspliced mRNAs are insensitive to the drug.


The existence of DNA sequences homologous to adenovirus 5 DNA in the genome of normal rat cells. Three discrete bands specifically hybridizing to adenovirus 5 DNA were found in the rat liver DNA restricted BY Bam HI endonuclease and fractionated electrophoretically. The hybridization with different regions of the viral genome takes place. Similar bands are present in the DNA from different lines of adenovirus 5 transformed cells, but in these cases high molecular weight DNA fragments containing the integrated viral genomes can also be found.


A thermostable, sequence-specific restriction endonuclease from Bacillus stearothermophilus: BstPI. A restriction endonuclease, BstPI, was purified from a strain of B. stearothermophilus, and its cleavage specificity was determined. The enzyme cleaves at palindromic sites of the general structure: (Formula: see text) where N.N' can be any base pair. It produces phosphorylated 5'-termini which are single stranded over a length of 5 nucleotides. Ends generated by cleavage with BstPI can be rejoined by DNA ligase.


Subnucleosome particles containing high mobility group proteins HMG-E and HMG-G originate from transcriptionally active chromatin. Subnucleosome particles SN2 and SN3 containing short DNA fragments and non-histone proteins of the high mobility group, HMG-G and HMG-E respectively, were purified from the chromatin preparations of mouse L cells partially digested with staphylococcal nuclease. Labeled DNAs prepared from these particles were hybridized to an excess of nuclear RNA. The binding of subnucleosomal DNA was about 3-fold higher comparing to total cellular DNA fragmented to the same size. Special control experiments showed that DNA.protein complexes present in subnucleosomes SN2 and SN3 preexisted in nontreated nuclei. The conclusion has been drawn that non-histone proteins HMG-G and HMG-E are associated with the DNA of transcriptionally active chromatin and are released by nuclease as subnucleosomes.


Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. A dot hybridization method is presented for rapidly determining the relative concentrations of nucleic acids in a mixture, as well as the extent of sequence homology between related RNA or DNA species.


Restriction endonuclease mapping by crossed contact hybridization: the ribosomal RNA genes of Achlya ambisexualis. A rapid, convenient and economical method for the hybridization of electrophoretically resolved RNA to DNA restriction fragments immobilized on nitrocellulose filters is described. DNA was digested, electrophoresed on agarose gels in a wide band and transferred to a nitrocellulose filter. The filter was then placed on the surface of a second gel containing radioactively labeled RNA electrophoresed under denaturing conditions in a similar way. The filter and gel were oriented so that the DNA and RNA bands were perpendicular to one another and the RNA was transferred from the gel through the filter under conditions which promote RNA-DNA hybridization. Following washing, the filter was autoradiographed. RNA-DNA sequence relationships could be conveniently determined from the spots produced at regions of intersection of homologous nucleic acids. The two dimensional array formed in this procedure fascilitates the rapid ordering of DNA restriction fragments. An example of its use for this purpose is presented.


The binding of aminoacyl-tRNA synthetases to triazine dye conjugates. The binding of thirteen aminoacyl-tRNA synthetases to thirty two immobilised procion dyes has been investigated. Most dyes bind one or more enzymes. The amino acid substrates are not normally potent eluants, with the notable exception of tryptophan eluting tryptophanyl-tRNA synthetase from Brown MX-5BR. Phosphate is frequently extremely effective, much more than expected by simple considerations of ionic strength, indicating that many of the dyes are able to mimic the phosphate groups of the phosphodiester backbone of the nucleic acid. Procedures for the purification of methionyl-, tryptophanyl- and tyrosyl-tRNA synthetases are presented and compared to the conventional purifications of these enzymes. The results indicate the general applicability of these dye columns to the purification of most enzymes of of nucleic acid metabolism and the necessity of investigating as many different dyes as possible for any individual enzyme.


Correlation between the presence of tRNA His GUG and the erythropoietic function in foetal sheep liver. Histidyl-tRNAs from foetal and adult sheep liver were compared to their reticulocyte counterparts. The combination of various techniques revealed the existence of two histidyl-tRNA species in reticulocytes, one of which was not retained on acetylated DBAE-cellulose columns and was guanylatable. Three histidyl-tRNA isoacceptors were identified in foetal liver. Two of these species were not adsorbed on acetylated DBAE-cellulose but only one was found to be guanylatable. An identical chromatographic behaviour on RPC-5 columns was observed for guanylated histidyl-tRNAs from both origins. These results suggest the occurrence of a GUG anticodon in these guanine-accepting tRNAs. In foetal liver the amount of guanylatable histidyl-tRNA was estimated to be 7% of the total tRNA population. This observation is in agreement with the erythropoietic function of liver during the foetal life.


Cross-linked informofers.

Cross-linked informofers. The proteins of 30S RNP particles containing pre-mRNA (hnRNA) were cross-linked with bifunctional reagents (dimethyl-suberimidate and dimethyl-3,3'-dithiobispropionimidate). Further treatment with 1 or 2 M NaCl dissociates all RNA from protein. However, a significant part of protein particles--informofers being cross-linked survived high salt treatment. Their sedimentation coefficients were close to those of original particles. No RNA could be detected in the informofers even after labeling the cells with a precursor for a long period of time. Sodium dodecylsulfate or urea dissociated cross-linked informofers into oligomeric polypeptides. They could be dissociated by beta-mercaptoethanol treatment if a reversible cross-linked reagent had been used. The resulting polypeptides were represented by informatin. RNP particles (30S RNP or poly-particles) were reconstituted upon mixing of cross-linked informofers with pre-mRNA and removal of 2 M NaCl.


Chemical modification of N6-(N-threonylcarbonyl) adenosine. Part II. Condensation of the carboxyl group with amines. Carboxyl group of N6-/N-threonylcarbonyl/adenosine was quantitatively modified with amines/aniline, glycine ethyl ester and ethylenediamine/in the presence of a water-soluble carbodiimide, yielding the respective amides. The reaction was carried out in a water solution of pH about 4 at 20 degrees C and was finished within minutes. The structure of the products was confirmed by UV and PMR spectra, and by chemical reactivity. Under conditions applied for modification of T6A, four common nucleosides and internucleotide linkage of UpA were unreactive, while 5'-AMP was transformed to the respective phosphoramides. At pH 4, the rate of 5'-AMP modification was over 100 times lower than the rate of t6A reaction.


Evidences for the function of DNA polymerase-beta in unscheduled DNA synthesis. The activities of DNA polymerase-alpha and -beta isolated from pig spleen were determined at different temperatures and in the presence of different concentrations of inhibitors. The results were compared with parallel estimations of replicative DNA synthesis and UV-induced repair synthesis in spleen cells. In respect to pCMB and aCTP, polymerase-alpha is more sensitive than polymerase-beta and similarly is replication more sensitive than repair. Repair synthesis and the activity of polymerase-beta decreases at temperatures higher than 40 degrees C whereas both replication and the activity of polymerase-alpha are greatly stimulated at elevated temperatures with optima of 45 degrees C (polymerase-alpha) and 41 degrees C (replication). The results favour the hypothesis that polymerase-beta is involved in repair synthesis.


The similarity of DNA sequences remaining bound to scaffold upon nuclease treatment of interphase nuclei and metaphase chromosomes. The fragments of DNA attached to protein skeleton of interphase nuclei or metaphase chromosomes were obtained. Both the method involving restriction endonuclease treatment/1,2/and a novel procedure based on mild staphylococcal nuclease digestion were used. In the latter case, DNA fragments remaining bound to nuclei or chromosomes are not enriched in satellite but only in abundant middle repetitive DNA. The shorter the fragments of attached DNA, the higher the content of middle repetitive DNA in the fraction. It has a slightly higher density in a CsCl gradient comparing to the main DNA. The yield of attached DNA, its distribution in a CsCl density gradient, and its renaturation properties are essentially the same for interphase and metaphase chromosomes. The average size of DNA loops was found to be equal to approximately 60 kb for both metaphase chromosomes and interphase nuclei. The conclusion has been drawn that the bulk of attachment sites of DNP fibrils to axial chromosomal structures remains unchanged during the cell cycle.


[The determination of the left ventrical volume curve without background correction and its validation by direct intercomparison with the ejection fractions as determined by biplane laevocardiography (author's transl)]. Background corrections applied on the left ventricular volume curve determined by the "gated blood pool"--method are based on an estimated rather than on a directly measured background. This imposes an uncertainty on the values determined from the volume curve, especially on the ejection fraction. A method which does not require background correction may be applied if all available measurement and evaluation facilities are utilized fully. High temporal and spatial resolution is of fundamental importance, permitting the exact determination of the time-dependent scintigraphic contour variations of the left ventricle during the mechanical action of the heart. A good criterion of the validity of the volume curves with respect to interfering background radiation is the ejection fraction calculated from these curves. The direct intercomparison of 10 ejection fractions obtained by an expanded "gated blood pool"-method, employing cardiac catheterization, immediately before a biplane laevocardiography demonstrated very good agreement. A small systematic underestimation of the ejection fraction by the nuclear method was observed. This understimulation shows that the influence of the true background is small if other interfering count rate contributions or methodical uncertainties are excluded systematically.


A radiocolloid study of the reticulo-endothelial system in tropical diseases. Radiocolloids were used to study the trapping function of the reticulo-endothelial system in 361 children with infectious or non-infectious tropical diseases. Responses of the system varied not only between different types of diseases but also between individuals suffering from the same type of disease, as illustrated (primarily) by numerous scans of the liver and spleen.


[Experimental investigation with 198Au colloid as to lymph communications between the retrobulbar space and the thyroid gland (author's transl)]. The problem of a direct connection of lymph drainage between the retrobulbar space and the thyroid gland was examined using the lymphotropic radioactive tracer 198Au colloid. Twelve rabbits were examined. Six animals were injected with 50 muCi 198Au colloid into the right thyroid lobe and six animals into the right retrobulbar space. Distribution and total body radioactivity was measured in vivo using a scintillation camera with a computer. After 6 hrs tissue specimens of different organs were measured in a well-counter. The discharge of activity from the thyroid after 6 hrs was significantly higher than that from the retrobulbar space (63% versus 33.5%). This was probably due to a higher vascularisation and to a higher degree of lymph drainage of the thyroid. The lymph drainage of the thyroid gland as well as of the retrobulbar space occurred mainly via the lymphonodi cerv. proff. No significant activity was found in the retrobulbar space after thyroid injection or in the thyroid after retrobulbar injection. It may be concluded from these results that there are no direct lymph connections between the retrobulbar space and the thyroid gland. However, indirect communications via the deep cervical lymph nodes cannot be excluded in the event of reverse lymph flow.


Relationship of molecular structure to the in vivo-distribution of carbon-11-labeled compounds. V. Carbon-11-labeled N-alkyl-p-iodobenzenesulfonamides. Carbon 11-labeled HCN was collected in methanol containing carrier NaCN following bombardment of 99% N2-1% H2 with 22 MeV protons. Ten new N-alkyl-p-iodobenzenesulfonamides were synthesized and labeled with 11C in radiochemical yields averaging 27% by condensation of p-iodobenzenesulfonyl chloride with the 11C-labeled aliphatic amine obtained by reduction of the intermediate 11C-labeled aliphatic nitrile prepared from Na 11CN and the corresponding alkyl bromide. They were chemically characterized and for nine of them the relationship between their molecular structure and their in vivo-distribution in rats was studied. As the length of the alkyl chain was increased from 2 to 8 carbon atoms, the early concentration of activity in most viscera decreased and the urinary excretion increased. Within this range, chains containing an even number of carbon atoms showed greater early tissue concentration of activity than did chains containing an odd number of carbon atoms. For alkyl chains containing greater than 8 carbon atoms the concentration of activity in some tissues increased and urinary excretion decreased. A possible explanation for the results is offered which postulates that early tissue concentration of activity is related to both total lipophilicity of the sulfonamide as well as to the presence of tissue sulfonamide binding sites whose preferred conformation results in hindred binding of sulfonamides with odd-numbered aliphatic chains to a greater extent than with even-numbered aliphatic chains.


Studies of gallium accumulation in inflammatory lesions. IV. Kinetics of accumulation and role of polymorphonuclear leukocytes in the distribution of gallium in experimental inflammatory exudates. The kinetics of 67Ga accumulation in experimental inflammatory exudates were studied. In six rabbits with S. aureus induced abscesses, serial samples of exudate and blood were obtained at 1, 2, 4, 24 and 48 hrs after intravenous injection of 67Ga. The accumulation of 67Ga in the inflammatory exudate was slow with an accumulation half-time of 5.5 hrs. The concentration of 67Ga in the abscesses approached that of blood 48 hrs after injection. Analysis of the distribution of 67Ga in the inflammatory exudate revealed that the portion of 67Ga in the cellular fraction (1,600 xg pellet) correlated best with the number of non-viable polymorphonuclear leukocytes (PMN) (r = 0.81). Its correlation with total number of PMN and bacteria was r = 0.69 and r = 0.35, respectively. Autoradiographic studies confirmed that the majority of 67Ga in the cellular fraction of the exudate was associated with non-viable PMN's.


A simplified method for the determination of intestinal calcium absorption. The double-isotope technique for the estimation of intestinal calcium absorption was simplified by using the scintillation liquid Insta-Gel. The urine was mixed with Insta-Gel without any previous preparation. A suitable constitution of the sample was ascertained by preliminary experiments (1 ml urine + 10 ml Insta-Gel); the stability of the samples, the correctness of 45Ca (counting separately as well as mixed with 47Ca) and the linearity of the counting rates of 45Ca obtained in a range of doses over four orders was proved. In 43 subjects aged 20 to 65 years and without any disturbance of calcium metabolism or intestinal function, the average normal value of fractional calcium absorption was 45.9 +/- 1.6% (SEM).


Enzymatic hydrolysis of leucylaminoantipyrine in various tissues and subcellular fractions of rat liver and kidney. Enzymatic hydrolysis of L-leucylaminoantipyrine occurs in homogenates of kidney, small intestine, liver, lung, brain, spleen, heart and blood plasma. The activity of the drug hydrolyzing enzyme was found in all tested subcellular fractions of liver and kidney. In contrast to L-leucylaminoantipyrine, neither its stereoisomer D-nor 4-L-(N,N-dimethylleucylamino)-antipyrine undergoes enzymatic hydrolysis in any tissue tested. The results suggest, that in vivo L-leucylaminoantipyrine could be very rapidly hydrolyzed to 4-aminoantipyrine.


Effects of p-bromo-methamphetamine (V-111) on conditioned avoidance behavior in rats with lesioned raphe nuclei. Effect of treatment with p-bromo-methamphetamine (V-111), the serotonin depleting drug, on two way avoidance conditioning (CAR) was studied in raphe lesioned male Wistar rats. Both sham lesioned and raphe lesioned animals treated with V-111 showed increased avoidance acquisition and increased number of inter-trial responses. Lesions of the raphe nuclei increased by itself the number of avoidance responses, the treatment with V-111 however produced further facilitation of avoidance acquisition. These results are discussed in terms of the role oserotonergic system in the processes of learning and retention of CAR, and direct action of V-111 on serotonergic system of the brain is suggested.


Synthesis and biological activity of pyrazo-[3,4-b]-pyridine derivatives. Part I. 3 (3'-Morpholino-2'-hydroxypropoxy)--7--9 as well as 3 (3'-morpholino-2'-hydroxypropyloamino) 14 -- 16 derivatives of 1-methyl and 1-phenyl pyrazo-[3,4-b]-pyridines were prepared and screened for expected circulatory activity. Compounds 7, 11--14, 20 mg/kg, produced hypotension in cats; Compounds 7 and 14, 50--80 mg/kg, had antiarrhytmic action in BaCl2 -- induced arrhytmic in the rabbit.


Some remarks of penicillin and desacetylcephalosporin synthesis by mixed anhydrides method. The possibilities of 6-APA and 7-ADCA acylation by means of mixed anhydrides from ethyl chloroformate and cyclic carboxylic acids were investigated. The complexity of acylation course was observed, which depends upon kind of aminoderivative and structure of starting acid, respectively. In the case of mixed anhydrides formed from acid derivatives of which vicinal carbon atoms of ethylene bond built on into appropriate cyclic system were connected with methyl and carboxylic group (-C)CH3=C(COOH(-), it was found, that the main reaction products were: the suitable ureids and ethoxypenicillin or ethoxydesacetylcephalosporin. After treatment of 6-APA or 7-ADCA with different esters of chloroformic acid the corresponding alkoxy-, aralkoxy- or aryloxyderivatives were obtained. The MIC estamination showed, that only penicillin derivatives may be considered as interesting microbicides.


Lack of habituation of pain evoked potentials after naloxone. Pain evoked potentials (EPs) were recorded in nucleus caudatus (NC) of rabbits after electric stimulation of the dental pulp. After 50--60 noxious stimuli the decrease in amplitude of evoked potentials occured. Naloxone, 1 mg/kg, temporarily abolished this effect and even after 350 noxious stimuli the habituation was not observed. On the other hand, naloxone did not affect the diminution of monosynaptic transcallosal potentials (TC--EP) evoked by repeated stimulation. It may be suggested that the habituation of EPs elicited by pain stimulation is due to endorphin release.


Effect of papaverine and atropine on pharmacokinetics of paracetamol administered orally. The effect of intramuscular injection of atropine and papaverine on the pharmacokinetics of a single oral dose of paracetamol in healthy men was investigated. The open two-compartment model was applied and the calculations were performed using a program for the Hewlett-Packard 9830 B system. An increase of the extent of bioavailability of paracetamol was observed after the atropine administration, however the absorption of the drug was delayed. The administration of papaverine did not change the AUC and Cmax, but tmax was significantly longer.


[Biomedical materials and products].

[Biomedical materials and products]. The authors present propositions of definitions and repartition of biomedical materials and products. After a historical review particular groups of biomedical materials were discussed, with special regard to implants.


Radiation sterilization of cellulose dressing materials. The results of investigations in the field of application of 60 Co gamma-irradiation for sterilization of cellulose dressing materials have been presented on the ground of our own experiments. The investigations were carried out for the model objects which are contents of all dressing materials, nowadays used in medical practice: cotton gauze, viscose-cotton gauze, cotton wool and cotton-viscose wool. In the present report there have been discussed the results of the test estimation of sterilized materials immediately after irradiation and during long storage as well (3-5 years after irradiation). The estimation was carried out according to the requirements of Pharmacopoeia. Moreover, the choice of parameters of sterilization process from the view-point of microbiological experiments and estimation of initial contamination degree of irradiated materials have been discussed.


[Implantation of prostheses in the treatment of deformations following mastectomy]. The selection of proper incision is an important problem when removing immense tumors of mammas with immediate or delayed implantation of silicone prosthesis. Transversal incision facilitates - from the technological point of view - the removal of mammary gland. The same goal may be obtained applying incision in submammary furrow. The operation of this type may be done in selected cases of mammary cancers.


Risk factors in hypertension and ischaemic heart disease. Among the identified precursors of cardiovascular disease hypertension acts as a major risk factor. Hyperlipidaemia, hyperglycaemia and cigarette smoking are the other major factors that increase the risk of symptomatic cardiovascular disease (CVD). Other factors influence (obesity, stress, hyperuricaemia, etc.) but are not independent risk factors. More definitive information on the efficacy of multifactorial intervention is needed.


Hypertension, renal function and gout.

Hypertension, renal function and gout. Hypertension was found in 18% of 65 patients with untreated gout, a lower prevalence than that previously reported. The clinical characteristics and renal function of these patients were compared with those of age matched groups of both normotensive gouty subjects and normouricaemic patients. The hypertensive patients had significantly greater body weights than their controls and also had a lower glomerular filtration rate. Other aspects of renal function were not significantly different between the three groups. The association of hypertension with gout and impaired renal function is complicated by many possible contributory factors and a simple cause and effect relationship is unlikely.


Uricosuric therapy and urate solubility in blood and urine. In most patients with primary gout hyperuricaemia results from a renal defect in tubular uric acid secretion. An increased endogenous purine biosynthesis is observed in only 2% of all patients with gout. Secondary hyperuricaemai results either from an increased breakdown of endogenous nucleic acids as in polycythaemia or from a decreased renal excretion of uric acid due to drug treatment, renal insufficiency or metabolic disturbances. Hyperuricaemia may be defined either in statistical terms from epidemiological studies of normal and gouty populations or from physicochemical properties of urate. Monosodium urate and uric acid are soluble in water to the extent of 6.32 mmol/l and 0.39 mmol/l respectively. In human plasma saturation of monosodium urate occurs at a concentration of about 0.42 mmol/l. The solubility of uric acid and urate in urine is more complicated as it is affected by changes in pH and salt concentration. Uricosuric drugs decrease serum uric acid concentration by enhancing the renal excretion of uric acid. Effects and side effects of uricosuric therapy are discussed.


Renal handling of urate: application to the action of tienilic acid. The renal handling of urate is complex, involving its filtration by glomeruli, partial tubular reabsorption, tubular secretion and also the reabsorption of a portion of the secreted urate. Studies employing tienilic acid, both acutely and chronically, have suggested that this compound exerts its uricosuric action and decreases the plasma urate by inhibiting renal urate reabsorption. The magnitude of the natriuretic and uricosuric actions of tienilic acid are correlated with the concentration of drug in the urine. Crystal equilibration studies have suggested that tienilic acid should not predispose to crystalluria with either uric acid or monosodium urate.


Tienilic acid: pharmacokinetics, salicylate interaction and creatinine secretion studies. Tienilic acid is a diuretic-uricosuric compound whose natriuretic site of action is in the cortical diluting segment of the distal nephron. Oral doses of 250 mg given to normal human volunteers provided peak blood levels of 10--11 micrograms/ml at 3--4 hours after administration. Approximately 40% of the dose was recovered in 24 hours, 30% as the parent compound and 10% as the alcohol and diacid metabolites. A 650 mg dose of acetylsalicylic acid significantly decreased the uricosuric effect of tienilic acid by inhibiting uric acid secretion. Urine pH fell significantly with tienilic acid administration. Tienilic acid inhibited salicylate excretion by either competition for tubular secretion or by increasing passive, pH dependent reabsorption. In normal subjects given a creatinine load, tienilic acid did not inhibit creatinine secretion.


The use of tienilic acid in nephrotic syndrome: a clinical study. The diuretic and uricosuric activities of tienilic acid 250--50 mg daily over a minimum six week period have been studied in seven patients with the nephrotic syndrome secondary to glomerulonephritis proven by renal biopsy. Tienilic acid failed to control oedema in one patient who had to be withdrawn. In the six other patients a hypouricaemic effect with increased urate clearance was noted. No consistent effects were noted with respect to the serum cholesterol and triglyceride concentrations. No side effects were observed. It is concluded that in nephrotic patients tienilic acid behaves as a mild diuretic with consistent hypouricaemic and uricosuric effects.


Tienilic acid in hypertension with hyperuricaemia. The biochemical and haematological changes seen with tienilic acid in comparison with other diuretics are discussed. Tienilic acid has a profound uricosuric effect which is maintained after 24 weeks of treatment. In the short term serum uric acid was usually lower on tienilic alone than on bendrofluazide and allopurinol.


Antihypertensive and renal effects of tienilic acid. Tienilic acid, a diuretic agent effective at the cortical diluting segment of the distal tubule, has been found to have equivalent antihypertensive action in a dose of 250 mg twice daily to hydrochlorothiazide in a dose of 50 mg twice daily. Tienilic acid reduced arterial pressure without diminishing renal plasma flow or endogenous creatinine clearance; moreover, it did so whilst achieving hypouricaemia through a uricosuric effect. Hypokalaemia was observed but corrected by supplemental potassium. A transient but reversible, slight elevation in serum creatinine concentration and significant hypertriglyceridaemia were also observed. In conclusion, tienilic acid seems to be a novel diuretic, well-suited for the patient with hypertension, particularly if there is coincidental gout or coexisting hyperuricaemia.


The effect of thiazide diuretics on coronary risk factors. Benzothiadiazine diuretics (thiazides) were introduced twenty years ago (Hollander and Wilkins, 1957), and remain the most commonly used type of antihypertensive drug. Their long term use alone provides smooth control of blood pressure in mild to moderate hypertensives (Beevers, Hamilton and Harpur, 1971), and they are also valuable as adjuvant therapy with other antihypertensive drugs. Whilst thiazides are virtually free of any clinical side effects, they do cause many biochemical changes, the significance of which is uncertain. Many of these biochemical abnormalities are possible risk factors for the development of coronary heart disease (C.H.D.), or other serious conditions. The magnitude and importance of these changes are discussed in this review.


[Value of lymphoblastic transformation test for diagnosis and treatment of microbial asthmas in adults (author's transl)]. A lymphoblastic transformation test (LTT) done on 9 germs in 30 patients (270 tests) with bacterial asthma was found positive 117 times out of 170 (43.3%) while the same study done on a control group of 100 non microbial asthma was generally negative (5% of positive responses). Positive LTT confirmed, in 59.2% of cases, the cutaneous tests. In the other cases, discrepancies can be found in both ways: positive LTT and negative cutaneous tests (16.9%) or the reverse (23.9%). The significance of disagreeing results is discussed. Specific desensitizations done only with the bacteria producing agreeing positive reactions, gave interesting though inconstant results.


[Non suppurative acute "bacterial" pneumonia in alcoholics. Study of 54 cases (author's transl)]. Pneumonia in alcoholics are frequent and often severe. A retrospective study, including two groups of patients, 25 in internal medicine and 29 in intensive care, was undertaken to define the main clinical, prognostic and therapeutical characters of these pneumonias. Death rate was very high in patients admitted to intensive care units (60%) but nil in patients in internal medicine. The principal elements of the prognosis were the existence of a neutropenia at the beginning, the condition of denutrition of the patient, failure to recognize the responsible germ because of an antibiotic treatment given blindly, and the delay of the treatment. The pneumococcus was the most frequently encountered germ (77%). After discussing the mechanisms of the quantitative and qualitative involvement of the neutrophilic leukocytes, the authors stated the measures which would lower the death rate and stressed the value of transtracheal puncture enabling an early bacteriological diagnosis.


[Levamisole-induced immunitary responses in patients operated from bronchogenic carcinoma (author's transl)]. The authors studied the immunitary responses to Levamisole in a group of patients recently operated for bronchogenic carcinoma. The results were compared with those obtained from two other groups, i.e. one of patients recently operated of bronchogenic carcinoma but not treated with Levamisole and another one of patients recently operated for a non-neoplastic disease and also not treated with Levamisole. All subjects underwent a similar investigation of the cell-mediated and the humoral immunity parameters at the beginning of the study and after 30 days. The comparison of the results showed a depression of the cell-mediated immunity in the patients operated for bronchogenic carcinoma. This depression subsided more promptly in patients submitted to Levamisole therapy. This effect was achieved particularly through a better blastogenic responsiveness to the PHA and an enhanced Rosettes E forming. The use of Levamisole in the pre- and post-operative period is thought to be beneficial in order to avoid distant recurrences. This effect is obtained by a stimulation of host defense mechanisms.


[Bronchial cytology of "occult" lung cancers (author's transl)]. Having underlined the value of bronchial cytology for the early diagnosis of lung cancers, the authors report 7 observations concerning a particular clinical form: the "occult" lung cancer with a malignant cytological precession more or less in advance in relation with the radiological or fibroscopical data. Malignant cells can be found in sputum from 9 months to 8 years beforehand. All histological types can be seen but no cancer of the anaplasic type with small cells was identified either in this series or in the literature. The authors insist also on the difficulty in localizing these cancers in situ at a very early stage. They set apart the insufficiencies of the X-ray results in several observations and the limits of other investigating techniques (bronchography, scintigraphy, echotomography, ...). These tumours seem to have a mild evolutivity.


[Nieman-Pick disease revealed by a pulmonary miliary tuberculosis (author's transl)]. A diagnosis of Niemann-Pick disease was made in a 26 years old man with chronic pulmonary miliary tuberculosis and splenomegaly. It was confirmed by the drop of sphingomyelinase level in leucocytes and fibroblasts of the skin. The authors showed the presence of foamy cells with sphingomyelin in the spleen and bone marrow. They underlined the value of dosing sphingomyelinase in leucocytes for diagnosis purposes. They also observed blue histocytes in the spleen and bone marrow, next to the foamy cells which are not specific of Niemann-Pick disease and can be found in numerous other affections. This pure visceral form with delayed development without neurological involvement, corresponds to the phenotype B of Crocker.


[Alveolar proteinosis and acute leucosis. One observation (author's transl)]. The authors observed a pulmonary alvelolar proteinosis in an 11 years old child with acute leucosis. They underlined the exceptional character of this association in a child, while it is known in the adult and almost always with a bad prognosis. A dysimmunity context linked to a hematological disease and/or its treatment, is favoured among the pathogenic hypotheses.


[Tumours or mediastinal pseudo-tumours of Castleman? One observation (author's transl)]. Through a routine examination a Castleman tumour of left hilary topography was discovered in a 30 years old man. No recurrence followed exeresis. With regard to this case, the authors underlined the infrequency of these tumours with no preferential mediastinal topography and its occurrence at any age. Diagnosis is often reached after surgery by histological analysis of the tumour which enabled the distinction in two types according to Flendrig: type I plasmocytic with inflammatory signs; type II hyalino-vascular without any inflammatory signs. Surgery usually advised is not without any drawbacks because of the vascularization of the tumour and its adherence to neighbouring organs. But Castleman tumours still set nosological problems and the debate remains opened on the question of a nodal origin or a true neo-formation.


Purification and properties of guinea pig antithrombin III. Guinea pig antithrombin III has been purified from plasma by sequential heparin-Sepharose affinity chromatography, DE-52 cellulose chromatography, isoelectric focussing, and Sephadex G-100 gel filtration chromatography. The final product was homogeneous as judged by sodium dodecyl sulfate disc gel electrophoresis. Purification was 202-fold with a yield of 41%. Antiproteinase activity of antithrombin III was determined by progressive inactivation of thrombin coagulant and amidolytic activity. Heparin cofactor activity was demonstrated by immediate inactivation of thrombin by antithrombin III in the presence of minute quantities of heparin. It also could be demonstrated that thrombin inactivation by antithrombin III occurs by formation of a bimolecular complex whose rate of formation is markedly enhanced by minute quantities of heparin.


The synthesis of 125I-2-iodohistamine for radioimmunoassay. Recently radioactively labeled iodohistamines have been claimed to have superior shelf-life to the iodophenols more commonly used in radioimmunoassay of small molecules. This claim is based largely on theoretical considerations; no systematic study has appeared. We found that iodination of histamine on a macroscale proceeds rapidly at pH 7-8.4 to yield principally 2-iodohistamine. With a large excess of iodine, substantial diiodination can be achieved. In 0.5 N sodium hydroxide solution, triiodination produces 1,2,5-triiodohistamine; the N-I bond, however, is somewhat labile. 125I-2,5-Diiodohistamine is also somewhat unstable, having a first order decomposition rate of 1.6 X 10(-3) day-1 (t1/2, 182 days), while 125I-2-iodohistamine shows a barely perceptible change in 60 days (7.5 X 10(-5) day-1). The assignment of the first iodine introduced to C-2 is based on a comparison of the NMR spectra of monoiodohistamine and histamine. Iodination with carrier-free iodine-125 using the Hunter-Greenwood procedure (chloramine-T) produces a 76% yield of mono- and a 19% yield of diiodo product which are easily isolable by a single TLC using silica gel in the solvent system, ethanol:ethyl ether:water, 5:5:2.


Zone precipitation chromatography: its use in the isolation of different collagen types. Zone Precipitation Chromatography is a useful technique for the initial isolation of the different collagen types in their native configuration. Small quantities of collagen mixtures can be rapidly separated into different collagen types with a relatively high degree of purity, based upon stained protein patterns on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) slab gels. In the commonly used bulk salt preparative method for isolating the different collagens, 50 mg of starting material was needed. Three days were required to complete the procedure. The stained protein patterns on SDS-PAGE slab gels showed about 25% contamination with the bulk purified Type III fraction and 20% contamination with the bulk purified type AB collagen. With Zone Precipitation Chromatography 5 mg of starting material was used and in less than 4 hours the mixture was separated with Types III and AB fractions showing less than 10% contamination from other collagen types. The technique is patterned after the Zone Precipitation method reported by Porath seventeen years ago and utilizes a step-wise sodium chloride gradient to precipitate and redissolve the collagens, eluting from the interbead spaces of a molecular sieve column.


An insert for the reorienting gradient rotor for virus extraction from infected plants. A device made of nylon and which is inserted in the bowl of the reorienting gradient rotor is described. This insert acts as a container for holding infected plant tissues for the purpose of separating virus by centrifugal force from intact and fresh plants, from frozen and thawed plants and from plant tissue disintegrated by mechanical means. The extracted fluid represents 80 to 90% of that present in the untreated plant tissue. Electron micrographs taken of concentrates of the viruses prepared by the centrifugation extraction procedure indicate that extraneous materials are reduced to a low level.


Limulus amebocyte lysate - a means to monitor inactivation of lipopolysaccharide. A properly selected Limulus Amebocyte Lysate (LAL) has been demonstrated to have a good correlation with the in vivo United States Pharmacopeial pyrogen test when testing lipopolysaccharide (LPS) inactivated with ethylene oxide, 60 Co irradiation, and dry-heat treatments. Thus, LAL may be used to determine degradation or depyrogenation kinetics of LPS. A criteria for acceptance of an LAL lot for correlation with the USP pyrogen test is described.


Initiation of maternal behavior in the rat: possible involvement of limbic norepinephrine. The dorsal norepinephrine (NE) fiber system was manipulated in pregnant female rats. Brainstem lesions of the dorsal bundle, depleting NE in cortex and hippocampus, resulted in deficits in maternal-behavior onset in primiparous rats. Similarly, fornix-bundle transections, depleting only hippocampal NE, were associated with an absence of pup care. Hypothalamic NE levels, as well as dopamine and serotonin concentrations in cortex, hippocampus and hypothalamus, were not significantly affected by these manipulations. The data are discussed in terms of behavioral specificity, possible hormonal involvement and interactions with diencephalic mechanisms controlling the onset of maternal behavior in the female rat.


Morphine reduces social cohesion in rats. The effect of low (1 mg/kg) doses of morphine on maintenance of physical proximity were evaluated in paired rats observed in a 4 square foot test arena. Morphine reliably reduced proximity maintenance time, and this was apparently not due to sedation, since the effect was unmodified by doses of amphetamine which substantially increased motor activity. The effects of naloxone were inconsistent on this measure of social motivation. In general, the results are consistent with the theoretical proposition that a brain neurochemical change which might lead to social attraction is the activation of endogenous opioid systems. When opiate activity is exogenously sustained, animals exhibit a subnormal tendency to be gregarious.


The effect of phenobarbital dose upon a variety of drinking related response measures. Amount of water ingested, total laps, duration of drinking, amount per lap, laps per minute, and running velocity were investigated as a function of phenobarbital dosage (0 to 60 mg/kg). Twenty-three and a half (23 1/2) hour water deprived females rats served in the experiment. Amount of water ingested, total laps, and duration of drinking all responded similarly to phenobarbital all rose and subsequently fell as a function of phenobarbital dose on the day of drug treatment, rose as a linear function of dose a day later, and had no significant relation with dose 2 days after drug administration. These measures significantly intercorrelate with each other on the day of drug treatment and the day thereafter though not 2 days thereafter. Running velocity largely declines as a function of drug dosage on the day of treatment but is unaffected by the drug thereafter. The other measures show no definite trend. However these measures, running velocity and amount/lap and laps/minute, intercorrelate significantly with each other on the day of treatment and not thereafter. The first group of response measures and the latter group do not consistently correlate with each other. It was concluded that there are two identifiable classes of variables: one motor, which is largely a decremental function of dose, the other uncharacterized, initially rising, then falling as a function of phenobarbital dose on the day of drug treatment.


The effects of fenfluramine on schedule-induced drinking in rats. The lever pressing of rats was maintained by a fixed-interval 60 sec schedule of food reinforcement. Water bottles were available during sessions and high levels of schedule-induced drinking developed. Both fenfluramine (0.5, 1.0, 2.0, 4.0, 8.0 mg/kg) and d-amphetamine (0.25, 0.5, 1.0, 2.0 mg/kg) produced dose related decreases in this drinking with d-amphetamine approximately four times as potent as fenfluramine. d-Amphetamine produced large increases in overall rates of lever pressing and greatly decreased the duration of postreinforcement pauses. Fenfluramine exerted similar actions but at all doses studied these effects were much less than the effects of d-amphetamine on these measures.


Stimulus-response relationships in a quickly learned escape from shock: effects of morphine. The relationship between stimulus intensity and analgesic effectiveness of morphine was investigated by means of an operant technique. Various doses of morphine were tested in rats trained to press a bar to escape from shocks of varying intensity. Under control conditions a good linear relationship between the log of the stimulus intensity and the log of the speed to press the lever was found. Morphine showed inhibitory effects upon this escape behavior, which were greater at any given dose with greater intensity of the shock. These effects were dose related, that is, the slopes of the shock-response lines decreased by increasing the dose. The data obtained do not appear to be a consequence of a general depressant effect of the drug upon behavior and are in line with several experimental observations showing that in animals, as well as in humans, the magnitude of the analgesic effect of morphine tends to increase as pain severity increases.


Effects of sodium pentabarbital on matching behavior in the pigeon. Nine pigeons in a matching-to-sample task with 5 alternative stimuli were exposed to 4 dose levels of sodium pentobarbital. Each drug session alternated with a control session, and 6 determinations were made at each dose level. Dose-response curves were obtained, and drug effects are described for position-specific and stimulus-specific behaviors. These results suggest that the drug effect is to weaken control by the sample stimulus and shift control to properties of the comparison stimuli.


Differential experience following developmental lead exposure: effects on brain and behavior. Long Evans hooded rat pups were exposed to lead (Pb) via the maternal milk supply from Postnatal Day 1 (PN 1) to PN 25. Mothers were fed diets containing either 4% Pb CO3 (High Pb), 0.4% Pb CO3 (Low Pb) or 2.2% Na2 CO3 (Controls) throughout this period. Pups were weaned at PN 30 and littermates randomly assigned to either an Enriched or Isolated environment for a period of 30 days. Increases in activity levels and decreases in passive avoidance latencies were observed in Pb exposed animals. However, there were minimal effects due to Pb on symmetrical maze performance. Experience in the enriched environment had no effect on open field activity levels but resulted in a marked reduction in symmetrical maze errors. While enrichment had no effect on passive avoidance performance in High Pb animals, it was capable of raising latencies in Low Pb animals to Control values. Thus, the therapeutic value of environmental enrichment in Pb exposed animals depends on both the task employed and the severity of the pre-enrichment brain damage. From both brain regional analysis and behavioral testing results, it appeared that the hippocampus was a major site of Pb action. From comparison of blood Pb levels of our animals and those reported in children, it became apparent that the rat may have a greater tolerance for Pb, and as such, caution must be used in making direct comparisons between the two species in terms of blood Pb levels.


Simultaneous assay for L-tryptophan, serotonin, 5-hydroxyindoleacetic acid, norepinephrine and dopamine in brain. A routine simultaneous assay for the title compounds is described, which uses a cation-exchange resin for separations, and standard fluorometric methods for analyses. Practicability of the ion-exchange chromatography is enhanced by means of a novel apparatus, and the procedure has the flexibility to permit extension to other endogenous compounds using published techniques.


Naloxone antagonism of electrical stimulation induced tail erection in mice. Tail erection was induced by focal electrical stimulation of the mesencephalic central gray through chronically implanted electrodes in mice. The response was current intensity dependent. Pretreatment with naloxone (5 mg/kg IP), a specific narcotic antagonist, abolished tail erection produced by low electrical current. In contrast, the tail response elicited by higher current was only partially blocked by naloxone. The results suggest that electrical stimulation induces tail erection by releasing an endogenous opioid peptide from the mesencephalic central gray.


A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs. Adult male Sprague-Dawley rats were placed in an apparatus consisting of 2 distinctive interconnected chambers. Choice preferences developed and stabilized over three 30 min exposures. Central injection of morphine or an enkephalin analogue in conjunction with placement upon the nonpreferred side caused a preference shift which was not evident in control subjects. Classical conditioning of opiate effects to distinctive environments may offer a novel means of assessing the hedonic effects of these compounds.


Perinatal naloxone: when does naloxone affect hyperalgesia? Pregnant mice were treated with naloxone via subcutaneous implants, from about 5 days prior to parturition. At birth entire litters were cross-fostered so that groups of offspring were exposed to naloxone treated mothers; before birth, after birth to weaning, from about 5 days prior to birth to weaning, or not exposed to naloxone. When tested on a hot-plate at 50 days of age, females either prenatally treated or treated pre- and postnatally showed hyperalgesia to heat. For males, this effect was not evident. This sex difference may have been induced by the cross-fostering procedure.


Effects of clozapine and chlorpromazine upon operant response measures in rats. Rats responded under a FR20 schedule of water reinforcement by paw-pressing a silent, isometric, force-sensing manipulandum. Two seven-animal groups differed in terms of the force requirement for reinforcer delivery, i.e., a low-force condition (4-g requirement for reinforcer delivery) or a high-force condition (32-g requirement for reinforcer delivery). Oral dose ranges of chlorpromazine (1.0, 3.0, 9.0 mg/kg) and clozapine (2.5, 5.0, 10.0 mg/kg) were evaluated for their effects on intensitive measures of response (i.e., peak force and duration), in addition to the conventional rate measure. Peak force, duration, and rate of response were recorded with a laboratory computer system. Conjoint examination of these three dependent variables revealed that clozapine, a new anti-psychotic agent which produces virtially no extrapyramidal side effects in man, affected FR responding in the same way as did chlorpromazine. More specifically, response rate and peak force declined as a function of dose for each drug. Duration of response tended to be increased at the highest dose for both clozapine and chlorpromazine, but this effect was limited primarily to the high-force condition.


Dopamine and macromolecule synthesis in rat hippocampus. In hippocampus slices both dopamine and apomorphine lead to an increased incorporation of (3H)-fucose into total proteins, whereas the incorporation of (14C)-leucine was unchanged or decreased, respectively. Noradrenaline did not alter the incorporation of both precursors, whereas haloperidol partially reduced the dopamine induced increase in incorporation of fucose. Thus, an induction process of the observed macromolecular changes involving dopaminoceptive structures of hippocampus can be assumed.


Effects of a novel experience on rat brain chromatin. In this study adult Fischer, inbred rats experienced (1) training to avoid footshock (2) unavoidable footshock or (3) no training or footshock. Each animal was sacrificed at one of several time points (1-60 hours) following experience. Brain chromatin was extracted and used as template for RNA synthesis in vitro. Both groups which received the novel experience demonstrated greater template activity than the unshocked, untrained groups. This effect was brief. The two groups which received the experience did not differ from each other. These results suggest that a brief, novel experience can temporarily alter the transcriptional activity of brain chromatin.


Effects of gamma-acetylenic GABA and gamma-vinyl GABA on metrazol-activated, and kindled seizures. Pretreatment of adult male Sprague-Dawley rats with a single dose of gamma-vinyl GABA (GVG) (1200 mg/kg, IP) or gamma-acetylenic GABA (GAG) (100 mg/kg, IP) did not affect the threshold of metrazol-activated generalized seizures, but increased their duration to the point of status epilepticus. In rats with epilepsy kindled by amygdaloid stimulation, a single dose of GVG (800 mg/kg, IP) and five subsequent daily administrations of GAG (80 mg/kg, IP) tended to reduce the motor manifestations of seizures leaving unaffected their electrographic pattern. The effects of GVG and GAG are attributed in part to decreased arousal. Practical implications of these findings are discussed.


Facilitation of self-stimulation behavior following intracerebral microinjections of opioids into the ventral tegmental area. The intracerebral microinjection technique was used to localize sites in the brain where morphine facilitated the self-stimulation rate at hypothalamic electrode sites. Bilateral injections of morphine (2 x 1 microgram) into the ventral tegmental area and substantia nigra produced the strongest enhancement at the shortest latencies. At these sites, bilateral injections of 200 ng of morphine also produced a significant enhancement whereas a dose of 50 ng was below threshold for the rate increasing effect. The enhancement by morphine was effectively antagonized by naloxone (5 mg/kg). When injected bilaterally into the same area, D-Ala2-Met5-enkephalinamide (2 x 1 microgram) also induced a strong enhancement of self-stimulation lasting for 70 minutes. A possible dopaminergic substrate for the opiate induced behavioral stimulation is discussed.


2-Deoxy-D-glucose analgesia: influences of opiate and non-opiate factors. Acute administration of 2-deoxy-D-glucose (2-DG), an antimetabolic glucose analogue induces a powerful analgesia which adapts following repeated administration. 2-DG analgesia displays significant cross-tolerance with morphine, and like morphine analgesia, is potentiated in hypophysectomized rats. The present study examined further the role of opiates in 2-DG analgesia by examining whether the opiate antagonist, naloxone, would affect 2-DG analgesia, and whether ineffective doses of 2-DG and morphine would interact in a synergistic fashion to induce analgesia. Nociceptive thresholds were measured by the flinch-jump test. Naloxone doses of 1, 5, 10 and 20 mg/kg were all ineffective in reducing significantly 2-DG (600 mg/kg) induced pain threshold elevations. Naloxone failed to attenuate 2-DG (350 mg/kg) analgesia whether administered before or after the 2-DG injection. On the other hand, simultaneous administration of sub-analgesic doses of 2-DG (200 mg/kg) and morphine (2.5 mg/kg) summated to produce significant analgesia. This, 2-DG analgesia is similar to opiates in its tolerant and summative actions, yet dissimilar in that naloxone is ineffective in reversing its effects.