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Biomedical subjects

A Goldstein

Publications and source records attributed to A Goldstein.

At least 163 records · Page 9Linked to original sources

Pro-dynorphin peptides are found in the same neurons throughout rat brain: immunocytochemical study.

It is known that the opioid peptide dynorphin A has a broad distribution throughout the neuraxis. Recent biochemical studies have extended the sequence of dynorphin A by 15 amino acids to include another [Leu]enkephalin-containing peptide known as dynorphin B. These sequence data have been validated by the elucidation of the structure of the hypothalamic mRNA coding for alpha- and beta-neo-endorphin, dynorphin A, and dynorphin B. Using specific antisera directed against each of the three opioid peptides, we have studied their cellular distribution in rat brain. Their distribution patterns are extremely similar, if not identical. Furthermore, all three peptide immunoreactivities can be localized to the same cells in five nuclear groups throughout the brainstem--the supraoptic nucleus, the paraventricular nucleus, a group of cells in the lateral hypothalamic area, the nucleus parabrachialis, and the nucleus tractus solitarius. The sequence of a common precursor for dynorphin A, B, and alpha- and beta-neo-endorphin was deduced from hypothalamic mRNA. The ability to localize all three peptides together within cells in widely placed nuclei strongly supports the use of the same biosynthetic precursor for the neo-endorphin and dynorphin peptides in other parts of the central nervous system as well.

Animals↗

Particle image-resolution test object.

A blur definition and measurement technique for high-subject-contrast image resolution is proposed. A new test object utilizing the blur principle has been developed and feasibility tested. In developing this new test object, tests of various sizes and concentrations of small plastic particles in a gelatin base were performed. Optimum particle sizes and concentrations were selected for the popular clinical transducer frequencies. Test images were obtained with static and real-time transducers of various focal properties. In all cases the proposed test object clearly indicated the zone (focal zone) of optimum high-subject-contrast image resolution. The advantages of the proposed blur definition and measurement technique of high-subject-contrast image resolution include: test object simplicity, ease of performing and interpreting the measurement, usefulness for all types of real-time scanners, and the need for only one scan for both axial and lateral resolution information at all image depths.

Equipment and Supplies↗

Regional distribution of dynorphin and neo-endorphin peptides in rat brain, spinal cord, and pituitary.

Five products of the dynorphin gene--alpha-neo-endorphin, beta-neo-endorphin, dynorphin A, dynorphin A-(1-8), and dynorphin B--were measured in various regions of rat brain and in rat spinal cord and pituitary. Specific antisera were used, supplemented by gel permeation analysis and high performance liquid chromatography, confirming the presence of dynorphin-32, dynorphin A, and dynorphin B in rat brain. In whole brain, alpha-neo-endorphin, dynorphin A-(1-8), and dynorphin B are present in much greater amounts than beta-neo-endorphin or dynorphin A. Although a general parallelism was found in the distribution of the five peptides, there were also noteworthy exceptions, suggesting that differential processing may occur.

Animals↗

[Analysis of infectious sequelae of 1000 neurosurgical operations. Effects of prophylactic antibiotherapy].

Postoperative infections: cellulitis at the site of skin incision and/or meningitis, were reported in 5.1 p. cent of 1 000 cases treated by neurosurgery in Pr R. Houdart's department between december 1980 and march 1982. Statistically significant factors predisposing to infection were: emergency surgery, opening of the sinus, presence of a foreign body, and operation lasting more than 5 hours. The age of the patient, diabetes, or previous corticoid therapy did not significantly alter the risk of infection. Prophylactic antibiotic therapy had been administered to 37 p. cent of patients, but this had not affected the incidence of general infection, a statistically significant effect being observed only after operations lasting for more than 5 hours. The risk of infection was high after craniotomies and major after external ventricular shunts (valves). For the latter type of operation it was not possible to determine factors favorable for infection: neither duration of surgery, nor age of patient, nor absence of antibiotic therapy. The risk of postoperative infection was low (less than 1 p. cent) in the absence of factors favorable for its development, but its frequency increased considerably in patients presenting one or more other intercurrent infections. It is therefore possible to recognize surgical and general factors influencing infection, but prophylactic antibiotic therapy has only a weak effect on morbidity modification.

Anti-Bacterial Agents↗

[Lung injury after use of respiratory revival materials sterilized with ethylene oxide].

One of the most used method of medical appliances sterilization uses ethylene oxide. At high concentration, this very reactive product, causes caustic burns of skin and mucous membranes. In one case of acute pulmonary oedema, levels of ethylene oxide in the endotracheal catheter were discovered. This led us to review the toxicological data on this substance. It should be emphasized that the sterilization and the desorption according to simple and precise rules should prevent such acute accidents.

Adult↗

Effects of eight-hour naloxone infusions on human subjects.

Twelve normal male volunteers received saline control, low-dose naloxone, and high-dose naloxone infusions during three weekly sessions. The sessions were 16 hr long: 1 hr for predrug assessments, 8 hr during which either naloxone or saline was infused in a double-blind procedure, and a 7-hr postdrug observation period. The 8-hr infusions of naloxone had no effect on experimental ischemic arm pain. In addition, the ischemic arm pain procedure did not significantly increase either plasma levels of cortisol or immunoreactive beta-endorphin, suggesting that the procedure was not stressful. The high-dose naloxone infusion resulted in a slightly aversive mood state and prevented the normal circadian decrease in cortisol levels. Both doses of naloxone increased systolic blood pressure and prevented the normal diurnal increase in temperature. The 8-hr infusions of naloxone did not result in changes in pain, mood, or physiological indices beyond what was present within a few hours after starting the infusion.

Adult↗

Comparison of the distribution of dynorphin systems and enkephalin systems in brain.

A study of the anatomical distribution of the endogenous opioid dynorphin in rat brain showed that the peptide is localized in a widespread system with multiple cell groups and projections. This network is revealed by the use of multiple antiserums against dynorphin and can be distinguished from the system containing methionine-enkephalin and leucine-enkephalin, which is mapped by the use of antiserums against the enkephalins and biosynthetically related peptides in the adrenal. It thus appears that the brain contains at least three separate opioid neuronal networks: an enkephalin family with components similar to those found in the adrenal, a beta-endorphin family, and a dynorphin family.

Animals↗

Dynorphin and vasopressin: common localization in magnocellular neurons.

The opioid peptide dynorphin is widely distributed in neuronal tissue of rats. By immunocytochemical methods, it was shown previously that dynorphin-like immunoreactivity is present in the posterior pituitary and the cells of the hypothalamic neurosecretory magnocellular nuclei which also are responsible for the synthesis of oxytocin, vasopressin, and their neurophysins. By using an affinity-purified antiserum to the non-enkephalin part of the dynorphin molecule it has now been demonstrated that dynorphin and vasopressin occur in the same hypothalamic cells of rats, whereas dynorphin and oxytocin occur in separate cells. Homozygous Brattleboro rats (deficient in vasopressin) have magnocellular neurons that contain dynorphin separate from oxytocin. Thus dynorphin and vasopressin, although they occur in the same cells, appear to be under separate genetic control and presumably arise from different precursors.

Animals↗

Dynorphin is a specific endogenous ligand of the kappa opioid receptor.

In the guinea pig ileum myenteric plexus--longitudinal muscle preparation, dynorphin-(1--13) and the prototypical kappa agonist ethylketocyclazocine had equally poor sensitivity to naloxone antagonism and showed selective cross protection in receptor inactivation experiments with the alkylating antagonist beta-chlornaltrexamine. In binding assays with membranes from guinea pig brain, ethylketocyclazocine and dynorphin-(1--13) amide were more potent in displacing tritium-labeled ethylketocyclazocine than in displacing typical mu and delta opioid receptor ligands. In the two preparations studied, the dynorphin receptor appears to be the same as the kappa opioid receptor.

Analgesics, Opioid↗

A specific radioimmunoassay for the opioid peptide dynorphin B in neural tissues.

Dynorphin-32 was recently isolated from porcine pituitary and shown to consist of dynorphin A (the originally isolated dynorphin heptadecapeptide) at the amino terminus, followed by Lys-Arg (a putative signal for proteolytic cleavage) and then a tridecapeptide, dynorphin B, at the carboxyl terminus. Dynorphin B, like dynorphin A, contains leucine enkephalin. The present report describes and validates a radioimmunoassay for dynorphin B using an antiserum, "13S", that does not crossreact with other known opioid peptides. Immunoreactive dynorphin B was estimated in rat and porcine neural tissues and found to be 2-3 fold higher than reported values for dynorphin A. Distribution based on tissue concentration was similar to that of dynorphin A, with very high concentrations in neurointermediate pituitary. Small quantities of antiserum "13S" are available to investigators upon request.

Animals↗

Prediction of long-term outcome for heroin addicts admitted to a methadone maintenance program.

Ten pre-treatment and nine during-treatment variables were correlated to outcome 5 years after admission to a methadone program for 171 subjects who were in treatment for at least 6 months. The pre-treatment variables were employment, education, criminal involvement, opiate and non-opiate drug abuse, periods of abstinence, age, sex, and ethnic group. During-treatment variables were employment, arrests or incarcerations, opiate and non-opiate drug abuse, living with an addict, marital status, and months of methadone treatment. Three measures of 'successful' outcome were defined. In general, subjects with more involvement with criminal justice before treatment, heavy alcohol use before or during treatment, continued daily heroin use or living with an addict during treatment, or minority ethnicity were more likely to have a poor outcome. However, the correlation coefficients for even the most significant correlations were weak; the highest was r = 0.26. We conclude that none of these 19 variables provide a basis for a priori judgment about whether or not a patient applying for admission to a methadone program is likely to have a favorable long-term outcome.

Female↗

A dynorphin-like opioid in the central nervous system of an amphibian.

We have provided evidence for the existence of a biologically active opioid in toad (Bufo marinus) brain that is immunoreactive with antiserum raised against dynorphin (1-13). Compared with porcine dynorphin, this opioid is similar in apparent molecular weight on the basis of gel permeation chromatography and is more hydrophobic on the basis of high-performance liquid chromatography. After purification, its opioid biological activity was demonstrated on the guinea pig ileum myenteric plexus-longitudinal muscle preparation. It was found to be less potent, and to have a similar sensitivity to antagonism by naloxone, in comparison with porcine dynorphin. Because it is immunoreactive with antiserum specific for porcine dynorphin, it probably has considerable sequence homology. Generally, the tissue distribution of immunoreactive dynorphin in the toad is similar to that in the rat, with highest concentrations in the neurointermediate lobe of the pituitary. However, the anterior lobe of the toad pituitary contains considerably lower concentrations than are found in the rat anterior lobe. There appear to be three size classes of immunoreactive dynorphin in toad neural tissue, each with apparent molecular weight below 12,000, similar to the size classes of immunoreactive dynorphin found in pig and rat. However, in toad spinal cord (and possibly in brain) there is immunoreactive dynorphin of greater apparent molecular weight, which has not been reported in mammalian tissue. The contribution of each molecular size to the total immunoreactivity varies from tissue to tissue and is different from that observed in the rat.

Animals↗

Localization of immunoreactive dynorphin in neurons cultured from spinal cord and dorsal root ganglia.

Antisera specific for dynorphin were used to study the cellular distribution of opioid peptides in spinal cord and dorsal root ganglion neurons in dissociated cell culture. Radioimmunoassay of 4-wk-old cultures yielded levels of dynorphin immunoreactivity similar to those in adult rodent spinal cord. Immunohistochemistry showed staining confined to the perinuclear region of neuronal cell bodies. In contrast, enkephalin immunoreactivity was found in extensive neurite fields as well as in neuronal perikarya. Opioid peptide immunoreactivity was observed in approximately equal to 5% of the spinal cord neurons either with dynorphin or enkephalin antiserum. No substantial increase in the number of reactive cells was observed when the two sera were applied simultaneously. These results suggest that the perinuclear region of opioid spinal cord neurons in culture contains peptide with an amino acid sequence similar to that of the midportion of dynorphin, whereas the neurites appear to contain smaller peptides related to NH2-terminal fragments of dynorphin. By using simple morphological criteria, spinal sensory neurons can be identified in these cell cultures and in cultures prepared from dorsal root ganglia without spinal cord. Approximately 1-2% of these ganglion cells showed intense immunostaining with an affinity-purified dynorphin antiserum. An additional few percent of the sensory neurons showed less intense opioid immunoreactivity. This result extends the observations of opioid peptides one step further along the pathway that processes sensory information.

Animals↗