Showing papers by "Johns Hopkins University School of Medicine published in 1982"
TL;DR: Impotence after radical prostatectomy results from injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa, and refinements in surgical technique, especially during ligation of the lateral pedicle and apical dissection, can prevent this complication.
1,401 citations
TL;DR: Together analysis of DNA polymorphisms in the human β-globin gene cluster and in cloned β-genes has revealed the association of specific β-thalassaemia mutations and β-gene polymorphisms with particular flanking polymorphisms.
Abstract: Combined analysis of DNA polymorphisms in the human β-globin gene cluster and in cloned β-genes has revealed the association of specific β-thalassaemia mutations and β-gene polymorphisms with particular flanking polymorphisms. A systematic study of cloned genes identified several new mutations, one of which possibly affects transcription. The strategy used may be applicable to other diseases of single-copy genes.
823 citations
TL;DR: The results of this study suggest that superoxide radicals are involved in the pathogenesis of ischemic mucosal lesions and that the enzyme xanthine oxidase is the source ofsuperoxide radicals in the isChemic small bowel.
703 citations
TL;DR: The expression of specific keratin classes appeared to correlate with different types of epithelial differentiation (simple versus stratified; keratinized versus nonkeratinized).
662 citations
TL;DR: The response of tritium-sensitive sheet film ([3H]Ultrofilm) was characterized under conditions used for the light microscopic localization of neurotransmitter receptors by in vitro autoradiographic techniques and compared favorably with results previously obtained in tissue homogenates by biochemical methods.
522 citations
TL;DR: It is proposed that this molecule contains a region of systematically bent B-DNA, which accounts for the fragment's difficulty in snaking through the pores of a polyacrylamide gel, its ease in diffusing into Sephacryl beads, and its smaller rotational relaxation time.
Abstract: We have investigated the unusual physical properties of a restriction fragment of Leishmania tarentolae kinetoplast DNA. A gel-purified fragment comprising slightly more than half of a minicircle was determined by Maxam-Gilbert sequence determination to be 490 base pairs (bp) in length. This fragment has dramatically anomalous electrophoretic behavior; it has an apparent size of 450 bp on a 1% agarose gel but migrates as 1,380 bp on a 12% polyacrylamide gel. However, in gel filtration on Sephacryl S-500, the fragment elutes with an apparent size of 375 bp. Finally, it behaves anomalously in electric dichroism experiments. Field-free rotational relaxation times from transient electric dichroism studies are highly sensitive to effective molecular dimensions. The rotational relaxation time of the kinetoplast fragment is smaller than that of a 309-bp control fragment from pBR322. Because rigorous control experiments rule out the possibility that this fragment is modified, these anomalous properties must be dictated by the sequence itself. Fragment behavior indicates that it has an unusually compact configuration; we propose that this molecule contains a region of systematically bent B-DNA. This model accounts for the fragment's difficulty in snaking through the pores of a polyacrylamide gel, its ease in diffusing into Sephacryl beads, and its smaller rotational relaxation time. Bending of this molecule may be caused by periodicities in the DNA sequence.
516 citations
TL;DR: The delay in serotonin innervation of the suprachiasmatic nucleus, striatum, and middle cortical layers long after the axons have reached these structures suggests that the formation of serotonin axon terminals is dependent on maturation of other elements in local neuronal circuitry.
461 citations
TL;DR: The development of serotonergic (5-HT) neurons is followed from their initiation of transmitter synthesis until the establishment of an essentially mature morphology, using the new and sensitive technique of 5-HT immunocytochemistry to visualize the precise features of this process.
374 citations
TL;DR: An automated version of the Digit Symbol Substitution Test is described that employs a relatively inexpensive, commercially available microcomputer to present and score the task, and task performance data for individual subjects following doses of pentobarbital are presented.
Abstract: An automated version of the Digit Symbol Substitution Test is described that employs a relatively inexpensive, commercially available microcomputer to present and score the task. Advantages of the automated DSST include: (1) objective scoring of both speed and accuracy of test performance, (2) printed copies of test scores, (3) convenient administration under standardized test conditions, and (4) the capacity for repeated assessment of an individual’s performance over time. Task performance data for individual subjects following doses of pentobarbital are presented; these data illustrate both the stability of task performance under constant conditions and the within-subjects sensitivity of task performance to experimental manipulations.
364 citations
TL;DR: An immunoreactive analogue of erythrocyte spectrin has been purified from brain membranes, and has been visualized by rotary shadowing as an extended, flexible rod.
Abstract: An immunoreactive analogue of erythrocyte spectrin has been purified from brain membranes. This protein co-sediments with and cross-links actin filaments, associates with spectrin-binding sites on erythrocyte membranes, and has been visualized by rotary shadowing as an extended, flexible rod. The brain spectrin comprises 3% of the total membrane protein, and may have a major role in mediating linkage of actin to membranes.
328 citations
TL;DR: The observation that the transcriptionally active ovalbumin gene is preferentially associated with the nuclear matrix may have significant implications for gene expression and the organization of nuclear DNA into supercoiled-loop domains.
TL;DR: The results are consistent with evidence that KA has direct excitatory effects on neurones but suggest that its potent neurotoxic action involves the activation of presynaptic receptors on glutamatergic and aspartergic terminals, thereby releasing Asp and Glu.
Abstract: Kainic acid (KA), a conformationally restricted analogue of glutamic acid, exhibits potent neuroexcitatory1 and neurotoxic properties2. The mechanism of the neurotoxicity of KA, however, seems to be complex and indirect because in many brain areas neuronal vulnerability requires the integrity of excitatory afferents3–6. Nevertheless, neurophysiological studies indicate that the neuroexcitatory effects of KA in the mammalian brain are direct7. We have now examined the effects of KA and other excitatory amino acids on the stimulation of cyclic GMP formation in brain slices incubated in vitro as a method for monitoring their depolarizing effects8. We show in the adult mouse cerebellum that the excitatory amino acid antagonist, D-α-aminoadipate (DAA)9, blocks the stimulation of cyclic GMP produced by N-methyl-D,L-aspartate (NMDLA) but potentiates the effects of KA. Whereas KA causes a significant release of both aspartic (Asp) and glutamic (Glu) acids by a calcium-dependent process, NMDLA is without effect; furthermore, the effects of KA on Glu release are markedly reduced in cerebellum deficient in granule cells. KA also releases Glu and Asp from hippocampal and striatal slices, indicating that this response is not unique to the cerebellum. The results are consistent with evidence that KA has direct excitatory effects on neurones7 but suggest that its potent neurotoxic action involves the activation of presynaptic receptors on glutamatergic and aspartergic terminals, thereby releasing Asp and Glu.
TL;DR: The results of an SEM survey of microwear patterns found on occlusal enamel of chimpanzee molars show that microwear within a single species may vary because of factors that are more to biomechanics than to diet.
Abstract: Recent investigations of dental microwear have shown that such analyses may ultimately provide valuable information about the diets of fossil species. However, no background information about intraspecific variability of microwear patterns has been available until now. This study presents the results of an SEM survey of microwear patterns found on occlusal enamel of chimpanzee molars. Methods of pattern analysis are described. Selected sites on the occlusal surface included shearing, grinding, and puncture-crushing surfaces formed by both phases of the power stroke of mastication. The microwear patterns found in this sample of chimpanzees showed a high degree of regularity. However, certain parameters such as relative pit-to-striation frequencies, feature density, striation length, and pit diameter were significantly affected by facet type and molar position. Sex and age of individuals also influenced some microwear parameters, but due to the small sample size these findings are considered to be preliminary. These results show that microwear within a single species may vary because of factors that are due more to biomechanics than to diet. The study also supplies some metrical estimates of "normal" pattern variability due to functional and morphological influences. These estimates should provide a useful baseline for assessing the significance of microwear pattern differences that may be found between species of differing diets.
TL;DR: High-resolution gamma camera images of mouse erythroid tumors were obtained by use of leukemia cell-specific monoclonal antibodies labeled with bifunctional radioactive metal chelates, allowing targeting of a broad spectrum of radioisotopes, including those that are optimum for agamma for gamma camera imaging or positron tomography.
Abstract: High-resolution gamma camera images of mouse erythroid tumors were obtained by use of leukemia cell-specific monoclonal antibodies labeled with bifunctional radioactive metal chelates. Small tumors (200 to 300 milligrams) were visible without subtraction or enhancement 1 to 5 hours after injection of antibody. Chelate-derivitized monoclonal antibodies permit targeting of a broad spectrum of radioisotopes, including those that are optimum for agamma for gamma camera imaging or positron tomography, as well as those that are tumoricidal.
TL;DR: Sensitivity of herpes simplex virus isolates to acyclovir became reduced in two bone-marrow transplant patients treated for established mucocutaneous infections.
TL;DR: Standard enzyme immunoassay techniques are not sufficiently sensitive for the measurement of some antigens from other viruses, bacteria, and parasites in concentrations that commonly occur in body fluids during the course of infectious diseases.
Abstract: Enzyme immunoassays are attaining increased usage for the direct detection of microbial antigens in body fluids. Advantages of enzyme immunoassays include a high degree of sensitivity resulting from the inherent magnification of the enzyme-substrate reaction and the use of objective end points without the need for radioactivity. Enzyme immunoassays have been developed for the reliable detection of several important microbial antigens in body fluids, including antigens of rotavirus, hepatitis B virus, and Haemophilus influenzae type b. However, standard enzyme immunoassay techniques are not sufficiently sensitive for the measurement of some antigens from other viruses, bacteria, and parasites in concentrations that commonly occur in body fluids during the course of infectious diseases. This review examines some of the limitations of currently available enzyme immunoassay technology and discusses approaches to increasing the sensitivity and specificity of enzyme immunoassay systems. Methods for improving these assay systems include the use of monoclonal antibodies, improved methods of enzyme-immunoreactant conjugation, more sensitive substrate systems, improved methods of antigen-antibody access, and the direct measurement of microbial enzymes. The use of such techniques should lead to the development of efficient enzyme immunoassay systems for the direct detection of a wide range of bacterial, viral, and parasitic infections.
TL;DR: Mouse and human DNA used as in vitro-labeled "high-complexity" probes revealed hybridization between specific herpesvirus DNA fragments on Southern transfers and repetitive sequences present at 10(3) to 10(5) copies per mammalian cell genome.
TL;DR: The many different proteins which modify actin polymerization and actin filament structure can be divided into three functional groups and these actin-binding proteins are thought to regulate actin assembly and the formation of the spectacular variety of actin structures found in non-muscle cells.
TL;DR: Neurotransmitter receptor binding studies indicate that effective antiemetic drugs potently block histamine H 1, muscarinic cholinergic, or dopamine D 2 receptors, and designing individual drugs or combinations that influence these three receptors may provide improved emesis control.
TL;DR: A poor correlation between the neurotoxic and convulsant potencies of these excitatory amino acid analogues is demonstrated and it is suggested that receptor-specific interactions may account for these disparities.
TL;DR: Investigating the effects of specific excitatory amino acid receptor agonists and antagonists on the release of 3H-acetylcholine from slices of the rat corpus striatum finds that excitatories amino acid analogues evoke a tetrodotoxin-sensitive release from rat striatal slices superfused in Mg2+-free medium, NMDA and ibotenate being the most potent and kainate and quisqualate the least potent.
Abstract: Several lines of evidence suggest that striatal cholinergic inter-neurones receive an excitatory input from the cerebral cortex which utilizes an excitatory amino acid, L-glutamate or L-aspartate, as its neurotransmitter. Cortical ablation reduces striatal high-affinity glutamate uptake1,2 and concomitantly decreases acetylcholine turnover3. The destruction of cholinergic, as well as other, neurones of the striatum by the rigid glutamate analogue kainic acid seems to require a functional excitatory amino acid innervation4,5. Furthermore, electron microscopic studies6 suggest the existence of a cortical input to the aspiny dendrites of neurones morphologically similar to the presumed striatal cholinergic interneurones7,8. The recent discovery of preferential antagonists of amino acid-induced excitation in the vertebrate central nervous system has led to the classification of excitatory amino acid receptors into three subtypes: the N-methyl-D-aspartate (NMDA), the quisqnalate-and the kainate-preferring receptors9. We have now attempted to characterize the receptor(s) mediating the excitatory amino acid influence on striatal cholinergic neurones by investigating the effects of specific excitatory amino acid receptor agonists and antagonists on the release of 3H-acetylcholine from slices of the rat corpus striatum. We find that excitatory amino acid analogues evoke a tetrodotoxin-sensitive release of 3H-acetylcholine from rat striatal slices superfused in Mg2+-free medium, NMDA and ibotenate being the most potent and kainate and quisqualate the least potent. This effect is antagonized by Mg2+ and by (−)2-amino-7-phosphonoheptanoate (−APHept) and (±)2-amino-5-phosphonopentanoate (±APPent) but not by glutamic acid diethyl ester (GDEE). These data suggest the involvement of a NMDA-type receptor in the excitatory amino acid influence on striatal acetylcholine release.
TL;DR: Comparisons of the members of the two classes which might straddle the function’s inflection point must be made with extreme caution, because reaction time may be a nonlinear function of log frequency, and because there is relatively little overlap between the frequency ranges of theTwo classes.
TL;DR: Data is presented on the prevalence and severity of illness, sequelae of prematurity, and specific common health problems and their sequelae, and the evidence for consistently greater severity of problems or likelihood of sequelae among poor children is striking.
Abstract: Available evidence regarding the relationship between socioeconomic status and health in childhood has been summarized. Only studies that used income, education, or occupation as measures of socioeconomic status and provided data obtained subsequent to legislation facilitating access to care have been cited. Data are presented on the prevalence and severity of illness (mortality, acute conditions as a group, chronic conditions as a group, and hospitalization), sequelae of prematurity, and specific common health problems and their sequelae. These specific health problems are lead poisoning, vision problems, otitis media and hearing loss, cytomegalic inclusion disease, asthma, psychosocial and psychosomatic problems, and iron deficiency anemia. All of the above (with the possible exception of asthma) are more prevalent among poor children than among nonpoor children. Even more striking is the evidence for consistently greater severity of problems or likelihood of sequelae among poor children. Although causality cannot be inferred from these data, the findings suggest a need for more basic research on the social correlates of disease, on the effect of social progress on disease prevalence and severity, and on the effect of medical care in overcoming the disadvantage associated with low socioeconomic status.
TL;DR: The hypothesis that Tourette syndrome may result form a supersensitivity of dopaminergic receptors is supported by the results of a prospective clinical and biochemical study.
Abstract: A prospective clinical and biochemical study on the effects of treatment with haloperidol has been performed in seven patients with Tourette syndrome. Pretreatment cerebrospinal fluid levels of homovanillic acid (CSF HVA) were significantly reduce in all patients, whereas 5-hydroxyindoleacetic acid was reduced in only two. With haloperidol treatment, symptoms decreased in all cases (21 to 88%) and clinical improvement was associated with an increased level of CSF HVA, often returning to the normal range. Optimal therapeutic response was found with serum levels of haloperidol between 1 and 4 ng/ml; however, disturbing side effects also occurred within this range. These results support the hypothesis that Tourette syndrome may result from a supersensitivity of dopaminergic receptors.
TL;DR: It is concluded that early in the maintenance phase of low-dose venom immunotherapy, the risk of a reaction to a challenge sting is significantly greater for those patients with low levels of venom-specific IgG antibodies.
Abstract: Parameters associated with successful venom immunotherapy in insect allergy were sought by comparison of treatment failures with successes. Half-dose treatment was completely protective in 32 patients (successes) but was only partially effective in eight (failures). The outcome of treatment was not related to the severity of pretreatment sting reactions, to the degree of skin-test sensitivity, to an atopic personal history, or to age or gender. The mean yellow jacket venom-specific IgG antibody level (by the Staph-A solid-phase radioimmunoassay) was significantly less in the failures (3.9 ± 0.6 μg/ml) than in the successes (7.3 ± 1.1 μg/ml) (p
TL;DR: It is believed that dietary protein-induced enterocolitis, previously reported in formula-fed infants, occurs occasionally in the exclusively breast-fed infant as well.
TL;DR: Although prolonged survival was demonstrated in patients without extraprostatic extension only a third of all clinical B2 cases were in this favorable category, it seems unwise to recommend radical prostatectomy as the treatment of choice for all men with clinical stage B2 disease.
TL;DR: The 13C/12C ratios of both the apatite phase and the collagen of 24 fossil animal and human bones are determined, and the results indicate that the 13C-12C ratio of fossil bone Apatite cannot be used for dietary reconstruction.
Abstract: The reconstruction of animals' diets from measurements of stable isotope levels in fossils relies on the fact that the 13C/12C ratio of animal carbon reflects the 13C/12C ratio of dietary carbon1,2. Two phases in fresh bone, collagen and the carbonate occurring in apatite, the predominant bone mineral, have isotopic ratios that are related to the 13C/12C ratio of the diet1. The isotopic ratios of both phases have been used to study the diets of extant animals3,4. Reconstruction of the diets of fossil animals using the isotopic method has been limited to analysis of collagen preserved in bone5–8. It has not been possible to use the 13C/12C ratios of carbon in the inorganic phase of fossil bone for dietary reconstruction because most fossil bones contain significant amounts of calcium carbonate, deposited after the animal's death, that contribute to the CO2 evolved from the bone during acid hydrolysis3,4. However, Sullivan and Krueger9 recently presented data which led them to conclude that the 13C/12C ratio of CO2 extracted by acid hydrolysis from the apatite phase of fossil bone records information about an animal's diet. We have now determined the 13C/12C ratios of both the apatite phase and the collagen of 24 fossil animal and human bones, and our results indicate that the 13C/12C ratio of fossil bone apatite cannot be used for dietary reconstruction.