Showing papers by "Johns Hopkins University published in 1979"

Hippocampus, space, and memory

Abstract: We examine two different descriptions of the behavioral functions of the hippocampal system. One emphasizes spatially organized behaviors, especially those using cognitive maps. The other emphasizes memory, particularly working memory, a short-term memory that requires iexible stimulus-response associations and is highly susceptible to interference. The predictive value of the spatial and memory descriptions were evaluated by testing rats with damage to the hippocampal system in a series of experiments, independently manipulating the spatial and memory characteristics of a behavioral task. No dissociations were found when the spatial characteristics of the stimuli to be remembered were changed; lesions produced a similar deficit in both spatial and nonspatial test procedures, indicating that the hippocampus was similarly involved regardless of the spatial nature of the task. In contrast, a marked dissociation was found when the memory requirements were altered. Rats with lesions were able to perform accurately in tasks that could be solved exclusively on the basis of reference memory. They performed at chance levels and showed no signs of recovery even with extensive postoperative training in tasks that required working memory. In one experiment all the characteristics of the reference memory and working memory procedures were identical except the type of memory required. Consequently, the behavioral dissociation cannot be explained by differences in attention, motivation, response inhibition, or the type of stimuli to be remembered. As a result of these experiments we propose that the hippocampus is selectively involved in behaviors that require working memory, irrespective of the type of material (spatial or nonspatial) that is to be processed by that memory.

Extreme ultraviolet observations from Voyager 1 encounter with Jupiter

Abstract: The global hydrogen Lyman alpha, helium (584 angstroms), and molecular hydrogen band emissions from Saturn are qualitatively similar to those of Jupiter, but the Saturn observations emphasize that the H(2) band excitation mechanism is closely related to the solar flux. Auroras occur near 80 degrees latitude, suggesting Earth-like magnetotail activity, quite different from the dominant Io plasma torus mechanism at Jupiter. No ion emissions have been detected from the magnetosphere of Saturn, but the rings have a hydrogen atmosphere; atomic hydrogen is also present in a torus between 8 and 25 Saturn radii. Nitrogen emission excited by particles has been detected in the Titan dayglow and bright limb scans. Enhancement of the nitrogen emission is observed in the region of interaction between Titan's atmosphere and the corotating plasma in Saturn's plasmasphere. No particle-excited emission has been detected from the dark atmosphere of Titan. The absorption profile of the atmosphere determined by the solar occultation experiment, combined with constraints from the dayglow observations and temperature information, indicate that N(2) is the dominant species. A double layer structure has been detected above Titan's limb. One of the layers may be related to visible layers in the images of Titan.

Implantable, programmable medication infusion system

Abstract: An implantable programmable medication infusion system comprises an implantable portion (2) having a medication reservoir (10) at below body pressure and isolated at its input from the body in which it is implanted by an antechamber (8) the pressure integrity of which is checked before filling the medication reservoir (10). Safety features include a leak detector (35), inlet and outlet valves (14 and 212) used with flow impeding filters (12 and 218), and a maximum allowable pressure in a pulsatile bellows pump (202) all of which prevent undesired infusion of medication. Medication flow from the pulsatile bellows pump (202) is in response to programming commands from a drug programming system (1) and processed in an electronics section (30) which uses the commands to program memory units (320 and 322) and to request pulses of medication. Hardwired limit controls (324 and 326) prevent excessive dosage requests from reaching the pulsatile bellows pump (202). For patient convenience and safety, the memory units (320 and 322) are programmed with running integral limits. A record of medication dispensing can be communicated to a physician by means of a telemetry transmitter (336) which sends signals by telemetry to the communications head (300) which information is displayed on the drug programming unit (3).

The DSFI: A multidimensional measure of sexual functioning

Abstract: The present report summarizes work to date on the Derogatis Sexual Functioning Inventory (DSFI), a multidimensional measure of human sexual functioning. We discuss the rationale for the test as well as the selection of the primary domains of measurement. Reliability coefficients for the various subtests are given, and a review section on validation studies is provided, including a factor analysis, predictive validation, and discriminant function analyses. Prototypic clinical profiles are also provided for several of the major types of sexual dysfunction.

Fitting the Gene Lineage into its Species Lineage, a Parsimony Strategy Illustrated by Cladograms Constructed from Globin Sequences

Abstract: activating regulator mutations Analysis of amino acid sequence data from the alpha and beta hemoglobins and myoglobins suggests that the gene lineages deviate relatively little from established species relationships, and that most contemporary gene pairs in this phylogenetic system may be regarded as orthologous (split at the time of speciation) rather than paralogous (split prior to speciation) It also appears that as the statistical sample of orthologous sequence sites becomes greatly enlarged by tandem alignment of enough different types of protein chains, the parsimony reconstruction based strictly on minimal nucleotide replacement length will itself reveal the correct cladogram for the set of contemporary species [Phylogeny reconstruction; parsimony methods; globin sequences; gene phylogeny; species phylogeny]

Regional cardiac dilatation after acute myocardial infarction: recognition by two-dimensional echocardiography.

Abstract: To assess the early topographic changes after acute transmural myocardial infarction, we studied 28 patients during the first two weeks after infarction by serial two-dimensional echocardiography. Regional end-diastolic segment lengths and wall thicknesses for anterior and posterior left ventricular walls were calculated. Eight patients showed infarct expansion, with disproportionate dilatation and transmural thinning in the infarcted zone, that was significantly different (P less than 0.005) from changes in non-infarcted regions. This regional expansion led to an overall left ventricular dilatation in these eight patients of 25 per cent compared to 5 per cent in the 20 patients without infarct expansion. Although the eight patients with regional expansion did not have significantly higher peak creatine kinase or Killip classification, they had a significantly greater eight-week mortality (four of eight versus none of 20, P less than 0.004). Thus, regional cardiac dilatation may be an early, lethal consequence of transmural infarcts, and appears to be an important mechanism of acute cardiac dilatation after myocardial infarction.

Psychological coping mechanisms and survival time in metastatic breast cancer.

Abstract: Thirty-five women with metastatic breast cancer received a battery of baseline psychological tests; results were correlated with length of survival. Patients who died in less than one year from baseline were categorized as short-term survivors, while patients who lived for one year or longer were assigned to the long-term survivor group. The long-term survivors were more symptomatic overall, with particular elevations on measures of anxiety and alienation, and substantially higher levels of dysphoric mood (eg, depression, guilt) than the short-term survivors. Short-term survivors revealed significantly lower levels of hostility, with higher levels of positive mood. Treating oncologists perceived the long-term survivors to show significantly poorer adjustment to their illnesses than the short-term survivors, and an interviewer's ratings indicated that long-term survivors had significantly poorer attitudes toward their physicians. Measures of clinical status and demographic data revealed few differences between the two groups. (JAMA242:1504-1508, 1979)

Evidence for a cholinergic projection to neocortex from neurons in basal forebrain

Abstract: Unilateral stereotaxic injection of 3.5 nmol of kainic acid into the ventral globus pallidus of rats reduced biochemical cholinergic neuronal markers by 45-50% and virtually eliminated histochemical staining for acetylcholinesterase in neocortex ipsilateral to the lesion. At the lesion site, the large, multipolar neurons that stain densely for acetylcholinesterase were absent when compared with the uninjected side. Kainate was as effective as electrocoagulation for reducing cholinergic markers although it did not affect aminergic projections ascending through the lesioned area. The conclusion that the cholinergic projection originated in neuronal perikarya at the lesion site was supported by the failure of kainate or electrolytic lesions in contiguous regions to produce similar effects. These studies provide strong evidence for a cholinergic projection to neocortex from neurons in the forebrain in the nucleus basalis.

Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain.

Abstract: Cholecystokinin octapeptide-like (CCK-OP-like) immunoreactivity was localized in the rat brain by using the indirect immunofluorescence method. Specificity in immunohistochemical studies was demonstrated by the virtual elimination of staining with either preimmune sera or sera preadsorbed with CCK-OP and by the achievement of similar fluorescent patterns with two different primary anti-CCK-OP sera. CCK-OP-like fluorescence was localized in neuronal cell bodies, fibers, and varicose terminals. The most dense collections of CCK-OP cells occurred in the periaqueductal gray and in the dorsomedial hypothalamus. Substantial numbers of cells and fibers also were present in the medial/dorsal and perirhinal cortex; more limited groups of cells were found in the pyramidal layer of the hippocampus and in the dorsal raphe.

Cellular autofluorescence--is it due to flavins?

Abstract: For many cell types, cellular autofluorescence in the 500-600 nm spectral region can result in a significant background signal for measurements of weakly fluorescent probes. Measurements of fluorescence intensity and spectra of a variety of cell types and assays of neuronal homogenates are presented to demonstrate that this autofluorescence is most likely due to endogenous flavoproteins.

Multiple apparent alpha-noradrenergic receptor binding sites in rat brain: effect of 6-hydroxydopamine.

Abstract: [3H]Clonidine (26.7 Ci/mmole) binds with high affinity to sites on rat brain membranes with properties of alpha -noradrenergic receptors. [3H]Clonidine binding shows a biphasic pattern in kinetic and saturation experiments. Fifty percent of the specific binding of 0.4 nM [3H]clonidine is dissociated rapidly in 2 min by excess norepinephrine or clonidine, and the remaining 50% dissociates at a 10-fold slower rate. When slowly-dissociating [3H]clonidine binding is examined in isolation, saturation curves show a single population of high-affinity sites with a KD of 0.5 nM and B max of 1.3-1.6 pmoles/g tissue in cerebral cortex. Rapidly-dissociating [3H]clonidine binding, estimated from the difference between total binding and high-affinity binding, involves a single population of lower affinity sites with a KD of 3.0 nM and B max of 9-10 pmoles/g cerebral cortex tissue. Alpha agonists are in general more potent at the high affinity [3H]clonidine site, while alpha antagonists are more potent at the low affinity site. α-Methylnorepinephrine is less potent than norepinephrine at the high affinity site, but more potent at the low affinity site. Neither [3H]-clonidine binding site resembles the alpha receptor site labeled by [3H]WB-4101. The distribution of high and low affinity [3H]clonidine binding throughout rat central nervous system is different. High affinity binding levels vary 14 fold between lowest values in corpus striatum and cerebellum, and highest values in cerebral cortex. Low affinity binding varies less regionally, with highest levels in hypothalamus. 6-Hydroxydopamine treatment doubles the number of high affinity [3H]clonidine sites in the cortex, but does not alter the number of low affinity sites. 6-Hydroxydopamine increases high affinity binding much more than low affinity binding throughout the brain. 6-Hydroxydopamine also increases by 50% the number of [3H]WB-4101 and [3H]epinephrine alpha receptor sites in the cerebral cortex. ACKNOWLEDGMENTS We thank Mrs. Lynda Hester for excellent technical assistance, and Pam Morgan and Billie Jean Little for manuscript preparation.

Clinical Pharmacokinetics of Cyclophosphamide

Abstract: Cyclosphosphamide is widely used for cancer chemotherapy and for immunosuppression. The parent compound is inactive in vitro and exerts its biological activities through metabolites generated by hepatic microsomal enzymes. The drug may be administered either parenterally or orally. Systemic availability after oral administration is greater than 75% at the low doses which have been studied. Cyclophosphamide is minimally protein bound but some of its metabolites are more than 60% protein bound.

Endometrial cancer and estrogen use. Report of a large case-control study.

Abstract: Our case-control study of the relation between estrogen use and endometrial cancer involved 451 cases and 888 controls. The overall risk of endometrial carcinoma was sixfold for estrogen users as compared with nonusers; long-term users (greater than five years) had a 15-fold risk. Excess risk was present for both diethylstilberstrol and conjugated estrogens. The risk associated with cyclic use was as great as that for continuous use. Increased risk was associated with estrogen use for all histologic grades of the tumor. The risk of advanced-stage carcinoma was fourfold for estrogen users, but rhe confidence interval was wide, and this question requires further study. Finally, this investigation contradicts the speculation that the association between this cancer and estrogen use can be explained by swifter diagnosis for estrogen users, misclassification of estrogen-related hyperplasia or treatment of early symptoms of the tumor with estrogen.

On the demystification of mental imagery

Abstract: What might a theory of mental imagery look like, and how might one begin formulating such a theory? These are the central questions addressed in the present paper. The first section outlines the general research direction taken here and provides an overview of the empirical foundations of our theory of image representation and processing. Four issues are considered in succession, and the relevant results of experiments are presented and discussed. The second section begins with a discussion of the proper form for a cognitive theory, and the distinction between a theory and a model is developed. Following this, the present theory and computer simulation model are introduced. This theory specifies the nature of the internal representations (data structures) and the processes that operate on them when one generates, inspects, or transforms mental images. In the third, concluding, section we consider three very different kinds of objections to the present research program, one hinging on the possibility of experimental artifacts in the data, and the others turning on metatheoretical commitments about the form of a cognitive theory. Finally, we discuss how one ought best to evaluate theories and models of the sort developed here.

Instantaneous pressure-volume relationship of the canine right ventricle.

Abstract: SUMMARY The instantaneous isovolumic and ejecting pressure-volume relationship of the right ventricle was studied in 11 cross-circulated, isolated canine hearts to characterize the right ventricular contractile state. Accurate measurement of volume was achieved by the use of a water-filled, thin latex balloon in the right ventricle connected to a special volume loading and transducing chamber. Pressure was measured with a miniature pressure transducer mounted within the balloon. Wide variations in loading conditions were achieved by changing the volume of air above the volumetric chamber. The pressure and volume data were collected from multiple beats under a constant contractile state in the same mode of contraction while the left ventricle was vented to air. Linear regression analysis applied to each of the isochronal pressure-volume data sets at 20-msec intervals from the onset of contraction showed a highly linear correlation between the pressure and the volume. Both the slope and the volume intercept of the regression lines changed with time throughout the cardiac cycle. The maximal slope of the regression line (E,,,,) averaged 2.50 ± 0.49 mm Hg/ml (mean ± SD) for ejecting beats and 2.68 ± 0.55 mm Hg/ml for isovolumic beats. Epinephrine infusions of 12.5 fig/min and 25.0 /ig/min increased E^u by 31% and 82%, respectively (P < 0.005). We conclude that: (1) The instantaneous pressure-volume relationships of the right ventricle in the isovolumic and ejecting modes can be regarded as linear, at least within the physiological range; however, these two modes of contraction did not yield an identical relationship. (2) The slope of these pressure-volume relationship curves changes with a change in the contractile state. Ore Res 44: 309-315, 1979 IT IS WELL KNOWN that there are major anatomical and physiological differences between the right and left ventricles. Compared with the left ventricle, the right ventricle has a greater regional variation in wall thickness and a more complex geometric shape. The developed pressure in systole is much smaller, and intraventricular pressure falls considerably while ejection proceeds. Much recent research has been focussed on left ventricular function, yet there is little quantitative information concerning the right ventricle, particularly with respect to the question of how to characterize contractile state and pumping ability. Those indices of contractile state used in characterizing left ventricular function have not been quantified in and shown to be valid for the right ventricle. Since there are major differences between left and right ventricles, we investigated whether right ventricular contractile state could be described in a similar fashion as left ventricular contractile state. In this study we determined the time-varying ratio of instantaneous pressure to volume, which has been shown to be sensitive to changes in left ventricular contractile state and nearly independent of

Candida tropìcalis: a major pathogen in immunocompromised patients.

Abstract: Of 89 consecutive patients undergoing treatment for hematologic malignancies or undergoing allogeneic bone marrow transplantation, 60 were colonized with Candida albicans and 25 with C. tropicalis. However, of the 18 disseminated infections caused by Candida species, 15 infections in 14 patients were caused by C. tropicalis and only three infections in three patients by C. albicans. The setting in which the infection occurred, skin lesions, polyarthralgias, or polymyalgias, and the unexplained deterioration of renal function were features suggestive of the diagnosis. Defervescence occurred in 10 of the 14 treated patients with C. tropicalis infections in 1 to 6 d (mean, 2.5 d) after initiation of therapy, even though all continued to be granulocytopenic. Resolution occurred in eight of the 15 C. tropicalis infections. In one case outcome was indeterminate, four patients died due to the infection, and two died from other causes but with the infection unresolved.

A hypothetical explanation of saccadic oscillations.

Abstract: Eye movements in a patient with saccadic oscillations (ocular flutter) were recorded and analyzed. Findings were related to recent microelectrode studies in the monkey pontine reticular formation which have identified three types of premotor neurons related to saccadic eye movements: burst, tonic, and pause cells. We incorporated these cell types into a hypothetical circuit that generates saccades by rapidly driving the eye to a designated orbital position rather than preprogramming a distance for movement. Physiological measurements suggest that this neural network is unstable and that the burst neurons must be tonically inhibited to prevent saccadic oscillations during periods of fixation. Pause cells, which discharge tonically except during saccades, when they pause, appear to inhibit burst cells and prevent such saccadic oscillations. Analysis of our patient's behavior indicates that many types of saccadic oscillations can be explained and classified by assuming an abnormality of pause cell control over saccadic burst neurons.

Comparison of spontaneous and experimentally induced canine prostatic hyperplasia.

Abstract: Spontaneous prostatic hyperplasia in the beagle appears to progress with age from a glandular to a cystic histological appearance. Prostatic hyperplasia can be induced in young beagles with intact testes by treatment for 4 mo with either dihydrotestosterone or 5 alpha-androstane-3 alpha, 17 beta-diol, alone, or with either of these steroids in combination with 17 beta-estradiol. In contrast, the induction of prostatic hyperplasia in young castrated beagles, in which the gland had been allowed to involute for 1 mo, requires the administration of both 17 beta-estradiol and either 5 alpha-androstane-3 alpha, 17 beta-diol or dihydrotestosterone. Testosterone and 17 beta-estradiol, either singly or in combination, did not produce the hyperplastic condition in intact or castrated beagles. The experimentally induced prostatic hyperplasia is identical in pathology to the glandular hyperplasia that occurs naturally in the aging dog with intact testes. However, cystic hyperplasia was not produced by any of the treatments tested in young animals.

Sampling variability on percutaneous liver biopsy.

Abstract: Sampling variability of liver biopsy was determined in three consecutive biopsy specimens obtained from each of 118 patients immediately prior to autopsy. No sampling variability was found for fatty liver, alcoholic hepatitis, nonspecific hepatitis, fulminant hepatitis, leukemic infiltrate, and venous congestion. Cirrhosis was diagnosed in 80% of cases at the first biopsy but in all cases after three biopsies. Chronic aggressive and chronic persistent hepatitis were diagnosed correctly in two of three cases each at the first biopsy, and in all cases after three biopsies. Metastatic carcinoma was detected in 46% of cases at the first biopsy and in 69% after three biopsies. Granulomas were missed once on the first biopsy, but found on a subsequent biopsy. The amounts of fat and fibrosis in the biopsy specimens often were not representative of the amounts present at autopsy. (Arch Intern Med139:667-669, 1979)

Optic Disc Parameters and Onset of Glaucomatous Field Loss: I. Methods and Progressive Changes in Disc Morphology

Abstract: • Serial stereoscopic fundus photographs taken in known relationship to the onset of glaucomatous visual field loss on 12 eyes were intermixed with those from 206 age- and race-matched controls and analyzed in randomized masked fashion. Progressive changes in the size, shape, or contour of the disc, and a newly described parameter, thickness of the nerve fiber layer as it crosses the disc rim, were readily apparent by the time of onset of glaucomatous field loss in all but two abnormal eyes (one case). In the latter instance, direct comparison of stereophotos indicated progressive pallor of the remaining disc tissue. Serial stereophotographs appear superior to fundus drawings for anticipating glaucomatous field loss.

Adenovirus DNA replication in vitro.

Abstract: A soluble extract from the nuclei of HeLa cells infected with adenovirus 5 (Ad5) carries out the semiconservative replication of exogenously added Ad5 DNA in vitro. Maximal DNA synthesis is observed when DNA-protein complex, isolated from Ad5 virions, is added as template. DNA-protein complex from virions of the closely related virus, adenovirus 2, is also active. In contrast, very little in vitro DNA synthesis is observed when deproteinized Ad5 DNA or DNA from a heterologous source (bacteriophage T7) is added as template. The product of the in vitro reaction consists of long Ad5 DNA strands that are hydrogen-bonded, but not covalently linked, to the input DNA template. During the course of the in vitro reaction, branched molecules with structural features identical to in vivo replication intermediates are formed. These findings support the conclusion that replication in the in vitro system closely resembles adenovirus DNA replication in vivo. The system provides an assay that should be useful for the purification and subsequent characterization of viral and cellular proteins involved in DNA replication.

Neurotransmitter Receptors in Frontal Cortex of Schizophrenics

Abstract: • Frontal cerebral cortex brain samples from schizophrenics and controls have been assayed for binding associated with muscarinic cholinergic, serotonin (5HT), γ-aminobutyric acid (GABA), and β-adrenergic receptors as well as for the activity of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Binding levels of tritium-LSD, presumably associated with postsynaptic 5HT receptors, were reduced 40% to 50% in samples from schizophrenics in three independent studies, whereas no other consistent alteration was observed in levels of binding associated with other receptors or in the activity of GAD. This change in receptor binding levels does not seem to be attributable to postmortem changes, to influences of drugs received by the patients, or to demographic features of the patient populations.

The Team/Fleet Models for Simultaneous Facility and Equipment Siting

Abstract: A number of new location models which utilize the notion of coverage were developed, tested and utilized in a study of the Baltimore City Fire Protection System. These models extend the location decision to include not only specification of the sites of the basic facilities but also the distribution of specialized equipment and/or manpower among those sites. They are seen as more realistic representations of the location decisions which are required in public sector applications.

Myocardial infarction in the conscious dog: three-dimensional mapping of infarct, collateral flow and region at risk.

Abstract: Myocardial infarcts were examined in dogs to determine the spatial distribution of infarction in the region at risk and the relation between infarction and collateral blood flow. Permanent occlusion of the left circumflex (LC) coronary artery at a constant site was made in 27 conscious dogs that were sacrificed 2 days later. The anatomic region at risk was defined by postmortem coronary arteriography as the volume of the occluded LC coronary bed. The masses of the left ventricle (LV), infarct (I) and risk region (R) were calculated from planimetered areas of weighted bread-loaf sections of LV. Infarct size was directly related to the mass of the risk region (I = 0.53 R - 9.87; r = 0.97; p < 0.001). There was no infarction when R was less than about 20 g or 20% of the LV. The infarcts were mainly subendocardial and tapered from base to apex of the LV; 34% of the risk region became infarcted at the base compared with 22% at the apex. In all dogs, a significant rim of noninfarcted myocardium was identified at lateral aspects of the risk region, even at the endocardial surface. Using 9-..mu.. radioactive microspheres, initial postocclusion flow at the marginmore » of the infarct, but well within the risk region, was higher than at the center, and outer flows were higher than inner flows. Postocclusion flow was even higher in the noninfarcted rim within the risk region, but was still significantly less than flow to normal, nonrisk areas. Collateral flows throughout the risk region increased during the first hour after occlusion, and were even higher at 2 days.Epicardially and laterally within the anatomic risk region there is a substantial amount of tissue that does not infarct despite initally reduced blood flow.« less