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Biomedical subjects

A Pasi

Publications and source records attributed to A Pasi.

At least 37 records · Page 2Linked to original sources

Cerebral beta-endorphin levels in a woman with Prader-Labhart-Willi syndrome.

By means of a specific two-site immunoradiometric assay, we explored the beta-endorphin levels in various brain regions of a patient affected by Prader-Labhart-Willi Syndrome. The rank of the beta-endorphin levels of five cerebral zones (hypothalamus, substantia grisea centralis, pons dorsalis, medulla oblongata dorsalis medialis, thalamus medialis) of the patient was homologous to that of subjects without the syndrome, except for the medulla oblongata dorsalis medialis. In patient with the Prader-Labhart-Willi Syndrome this region had a higher ranking level than in subjects without it. However, a functional meaning cannot be attributed to such difference because the patient of this study did not exhibit neurological disturbances relating to elevated beta-endorphin levels in the medullary region investigated.

Adult↗

Beta-endorphin-like immunoreactivity levels in the hypothalamus, the periaqueductal grey and the pituitary of the DBA mouse: determination by ELISA and relationship to nociception.

The present paper describes the development and application of an enzyme-linked immunosorbent assay (ELISA) for the assessment of beta-endorphin-like immunoreactivity (beta-ELIR) level in the hypothalamus, the periaqueductal grey (PAG) and the pituitary of DBA/2 mice that were subjected to mild social stress (aggressive confrontation). After confrontation these subjects showed elevated tail-flick latencies (TFL) when compared to controls, a finding that indicates stress-induced analgesia (SIA). A positive correlation was found between individual TFLs and beta-ELIR levels in the PAG but not in the hypothalamus and the pituitary. These results suggest that individual baseline PAG beta-ELIR levels may be taken as a predictor of high degrees of stress-induced analgesia.

Agonistic Behavior↗

Social conflict-induced changes in nociception and beta-endorphin-like immunoreactivity in pituitary and discrete brain areas of C57BL/6 and DBA/2 mice.

The present study characterizes the time course of social conflict analgesia and its reversibility by opioid antagonist drugs in the C57BL/6 and DBA/2 inbred strains of mice and examines the relationship between alterations in brain and pituitary levels of beta-endorphin-like immunoreactivity (beta-ELIR) and the antinociception elicited by social stress. Data revealed statistically significant strain differences in regard to beta-ELIR in control animals. The pituitary content of beta-ELIR was higher in DBA/2, while the values in the periaqueductal grey (PAG) and in the amygdala were higher in C57BL/6 mice. No interstrain differences were found in the hypothalamus. Exposure to 50 attack bites resulted in a 6-fold higher analgesia in DBA/2 mice and in a strain-independent fall of beta-ELIR in pituitary (approximately 27%) and PAG (23%). PAG but not pituitary beta-ELIR levels in C57BL/6 mice correlated positively with the increase in tail-flick latency after attack. Mere confrontation with a non-aggressive opponent failed to induce analgesia and was associated in C57BL/6 mice with a significant reduction in the beta-ELIR content of both the pituitary and the PAG. The data are discussed in terms of genotype-dependent sensitivity of the beta-endorphin system to stress and its relation to analgesia.

Aggression↗

Effects of repeated as compared to single aggressive confrontation on nociception and defense behavior in C57BL/6 and DBA/2 mice.

Behavioral reactions (submissive postures, escape, immobility, activity, locomotion) in C57BL/6 and DBA/2 test mice were recorded during single (50 bites) or three repeated (3 X 50 bites, separated by 24 hr) aggressive confrontations, as well as during a nonaggressive confrontation 24 hr after the last aggressive confrontation with opponents of the opposite strain. Nociception (hot plate response latency) was measured 1 min after aggressive or nonaggressive confrontations. During repeated aggressive confrontation, DBA mice reacted with a stable pattern of escape and analgesia, whereas C57 mice failed to develop an analgesic response and changed their behavioral defense strategy during repeated aggressive confrontations (decrease of escape, increase of defensive upright). The conditioned display of submission and of escape behavior during nonaggressive confrontation did not change as a function of earlier repeated aggressive confrontations in DBA mice, while C57 mice showed a significant increase of defensive upright postures and immobility. Conditioned analgesia was not observed after nonaggressive confrontations. The results point toward a dissociation between attack-elicited behavior and antinociception and suggest that encounter-induced analgesia may influence the processing of aversive experience.

Aggression↗

Cerebral distribution of beta-lipotropin and beta-endorphin in infantile progressive spinal muscular atrophy of Werdnig and Hoffman disease.

The regional distribution's profile of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) was determined in the brain of an infant who died from Werdnig-Hoffmann's disease. Regional levels of beta-endorphin-like immunoreactivity (beta-ELIR), resulting from beta-EP and beta-LPH, were generally low in comparison to the homologous levels found in victims dying of other diseases.

Brain Chemistry↗

Characterization of proenkephalin B-derived opioid peptides in the human hypothalamo-neurohypophyseal axis.

Proenkephalin B-derived opioid peptides, such as dynorphin1-17, dynorphin1-8, dynorphin B, alpha-neo-endorphin and beta-neo-endorphin in the human hypothalamo-neurohypophyseal tract were quantitated and characterized by the combined use of various radioimmunoassays, gel filtration, high performance liquid chromatography and enzymatic cleavage. Chromatographic analysis of immuno-reactive peptide levels determined that, in each case, these were comprised almost exclusively of the authentic peptides both in the neurohypophysis and hypothalamus. Concentrations of authentic proenkephalin B-peptides were 100-5000-fold lower in the human as compared to the rat neurohypophysis. However, in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and certain other nuclei of the human hypothalamus concentrations of authentic peptides were found to be in the same range as those in the rat hypothalamus. The ratio of proenkephalin B-peptides in PVN and SON to those of the neurohypophysis in the rat was ca. 1:50. Conversely, in man these ratios were shown to be 80:1 for dynorphin B, 6:1 for alpha-neo-endorphin and 1:1 for all other peptides evaluated. Examination of postmortem degradation of peptides indicated that these lower levels in the neurohypophysis are not due to a higher rate of postmortem breakdown. Since levels of both vasopressin and beta-endorphin were very high, these deficits in proenkephalin B-peptides were selective and do not represent a generalized property of the human pituitary. Experiments involving enzymatic cleavage demonstrated the occurrence of higher molecular weight forms containing the Leu-enkephalin sequence which were not recognized by the antisera employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Cyanide poisoning: forensic toxicology observations in the study of 54 cases of fatal poisoning].

The present study describes various observations made during the examination of 54 cases of lethal cyanide intoxication at the Institute of Forensic Medicine of the University of Zürich during a period of more than 40 years. Data pertain to the scene of death, the medicolegal inspection, the autopsy, the histological examinations, the chemical analyses, the various types of poisoning observed and the diagnostic criteria used. The intoxicated victims were mostly adults who had professional access to various cyanogenic compounds and had ingested them with the intention of committing suicide. Cases of accidental and criminal poisoning were rare. In spite of this fact, and although its frequency has not increased in the last few decades, cyanide poisoning has maintained undiminished importance.

Accidents, Occupational↗

Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms.

Twenty-four distinct areas of human brain were analyzed for the presence of insulin-like growth factor (IGF). As reported for cerebrospinal fluid, only IGF II-like immunoreactivity, but no significant amounts of IGF I-like immunoreactivity, could be found. Upon gel permeation chromatography, two to five distinct size classes were separated on the basis of their immunoreactivity. The smallest component had an apparent molecular mass of 7.5 kDa, identical to the one of purified IGF II from human serum. Radioimmunoassays and a bioassay also gave results indistinguishable from those of serum IGF II. The highest amounts of IGF II-like immunoreactivity occur in the anterior pituitary--namely, 20-25 pmol equivalents/g of wet weight. This is up to 100 times more than in most other brain regions analyzed. The higher molecular mass immunoreactive species were partially characterized. After immunoaffinity purification, the 38- and 26-kDa species are active in a bioassay. Specific IGF-binding protein activity could be shown after purification of the 38- and 26-kDa species on an IGF-affinity column. The 13-kDa species released significant amounts of 7.5-kDa material. The results are interpreted as evidence for the presence of IGF II synthesized locally in human brain. The structure of the larger forms of IGF II-like immunoreactive material as well as the function of IGF II in brain are not yet known.

Brain Chemistry↗

Distribution and characterization of opioid peptides derived from proenkephalin A in human and rat central nervous system.

In various areas of rat and human brain and spinal cord the distributions of opioid peptides derived from the proenkephalin A precursor, the heptapeptide [Met]enkephalin-Arg6-Phe7 (MERF), the octapeptide [Met]enkephalin-Arg6-Gly7-Leu8 (MERGL), and bovine adrenal medulla dodecapeptide (BAM-12P), were determined by a combination of radioimmunoassay, gel filtration, and high-performance liquid chromatography. In the human central nervous system the highest concentrations were seen in the striatum (pallidum greater than caudate nucleus greater than putamen) and in substantia nigra, hypothalamus, and periaqueductal gray. Similarly, in rat brain high levels were found in striatum and hypothalamus. Bovine adrenal medulladocosa peptide (BAM-22P) only occurred in the rat brain, but could not be detected in human brain. No MERF, MERGL, BAM-12P, or BAM-22P could be found in either rat or human pituitary. In contrast to MERF, MERGL and BAM-12P, peptides derived from the proenkephalin B precursor, dynorphin1-8 and dynorphin B, showed high concentrations only in substantia nigra and pallidum, but quite low levels in the other regions of human brain and spinal cord. The present study provides evidence that the proenkephalin A precursor known from adrenal medulla also exists in the rat and human central nervous system. Moreover, the identification of BAM-12P in these tissues indicates that cleavage of the precursor molecule must also involve sites different from those with paired basic amino acids.

Adolescent↗

Characterization and localization of immunoreactive dynorphin, alpha-neo-endorphin, Met-enkephalin and substance P in human spinal cord.

By use of specific antisera, the distributions of immunoreactive dynorphin (ir-DYN), alpha-neo-endorphin (ir-alpha-NEO), Met-enkephalin (ir-MET) and substance P (ir-SP) were evaluated in discrete regions of human spinal cord and spinal ganglia. The relative concentrations of immunoreactive peptides in particular regions were as follows: sacral greater than lumbar greater than cervical greater than thoracic. Concentrations of ir-DYN, ir-alpha-NEO and ir-SP were 2-10-fold, but of ir-MET 1-2-fold, higher in the dorsal as compared to the ventral parts of cervical, lumbar and sacral cord. The concentrations of all peptides (when examined in discrete areas of thoracic cord) were found to be highest in the substantia gelatinosa. All peptides were present in the gray matter but only ir-MET was found in white matter. Gel-permeation chromatography of dorsal sacral spinal cord extracts revealed two major ir-DYN peaks. The smaller molecular weight peak, eluted at the position of synthetic dynorphin1-17. ir-alpha-NEO and ir-SP comigrated exactly with their respective synthetic marker peptides. Substantial amounts of ir-SP and also, as confirmed by high pressure liquid chromatography, ir-MET, were found in the dorsal and ventral roots and spinal ganglia, and very low concentrations of ir-DYN or ir-alpha-NEO were also detected in these tissue. These results suggest that dynorphin and alpha-neo-endorphin, in addition to enkephalins, may be involved in transmission of somatosensory information in the human spinal cord.

Chromatography, Gel↗

Proenkephalin-A-derived peptides are present in human brain.

The opioid peptides [Met] enkephalin-Arg6-Phe7, [Met]-enkephalin-Arg6-Gly7-Leu8, and BAM-12P were identified in various ares of human brain by use of a combination of radioimmunoassay (RIA), gel filtration, and high performance liquid chromatography (HPLC). The highest levels of each peptide were found in striatum, followed by substantia nigra, hypothalamus, and medulla. In all areas, the relative concentrations were [Met] enkephalin-Arg6-Phe7 less than [Met] enkephalin-Arg6-Gly7-Leu8 less than BAM-12P. The apparent existence of BAM-12P suggests that the enzymatic processing of the proenkephalin A precursor in human brain is not restricted to cleavage at sites with two basic amino acids. Our results provide evidence that a precursor similar or identical to that present in the adrenal medulla exists in human brain. It appears that the processing mechanisms are different, as virtually none of the immunoreactivity found in the brain was comprised of the higher molecular weight forms of the peptides seen in the adrenal.

Brain Chemistry↗