[On a derivative of 4-hydroxycoumarin and dimethylaminotethanol].
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Biomedical subjects
Publications and source records attributed to C Oliver.
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Carboxy-terminal amidation of biologically active peptides, an important characteristic of more than half of these substances, occurs during the maturation process of peptide precursors. It is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM), an enzyme that is copper-dependent. We show here that alterations of copper stores in cultured cells from different origins (pancreas and hypothalamus) affect the immunoreactivity of thyrotropin-releasing hormone (TRH) and corticotropin-releasing factor (CRF) (two alpha-amidated peptides). This suggests that copper can affect neuropeptide biosynthesis and may play a role in the endocrine or central nervous system function.
In order to elucidate the physiological role of the 41 amino-acid residue corticotropin-releasing factor (41-CRF) on the secretion of ACTH, B-Endorphin and alpha-MSH, plasma levels of these peptides were measured by radioimmunoassay in intact and adrenalectomized rats, two hours after the injection of either 41-CRF antiserum (CRF-AS) or normal rabbit serum for controls. The administration of CRF-AS strikingly lowered the plasma ACTH levels in both intact and adrenalectomized rats. A statistically significant reduction of plasma levels of B-Endorphin was also observed in the same rats. However, the effect of CRF-AS on B-Endorphin release was less pronounced than the effect on ACTH release. No changes in plasma alpha-MSH levels were observed after passive immunization with CRF-AS. We conclude that, in the rat, 41-CRF plays a physiological role in the regulation of ACTH and B-Endorphin secretion, but is not involved in the regulation of alpha-MSH release from the pituitary gland.
Passive immunization of pregnant rats with a specific antiserum to rat GRF (GRF-AS) is followed by a decrease in fetal serum GH on the 19th day of gestation. A significant reduction in serum GH is still observed in older fetuses and newborn rats. Pituitary GH content increases in 19- and 20-day-old fetuses after GRF-AS administration to their mothers. These results suggest that endogenous fetal hypothalamic GRF (or placenta GRF) play a physiological role in the secretion of pituitary GH as early as the 19th day of fetal life and may be responsible for the peak of GH release that occurs in fetuses at the end of gestation.
Rat thyrotropin-releasing hormone prohormone (pro-TRH) is a protein containing five copies of TRH, separated by connecting peptides. We have recently developed radioimmunoassays to synthetic peptides corresponding to prepro-TRH(160-169) and prepro-TRH(178-199). In the present study we have used these assays to investigate the ontogenesis of pro-TRH-derived peptides in the rat pancreas. Reverse-phase HPLC analysis of pancreatic extracts from 2-day-old rats showed the presence of two major immunoreactive peptides exhibiting the same retention time as synthetic prepro-TRH(160-169) and prepro-TRH(178-199), respectively. The concentrations of TRH and pro-TRH cryptic peptides in the rat pancreas rose rapidly after birth, reached a maximum at day 2-4 and decreased gradually afterwards. Streptozotocin treatment of newborn rats induced a marked decrease of TRH (96%), prepro-TRH(160-169) (97%) and prepro-TRH(178-199) content (94%) in pancreatic extracts. These results indicate that the evolution of TRH and pro-TRH-derived peptides follows the same pattern during the postnatal period. Our results also suggest that beta-cells are the only source of pro-TRH-derived peptides in the rat pancreas.
We have compared the release of CRF induced by potassium depolarization, noradrenaline or dopamine as monitored either during superfusion of mediobasal hypothalamus or during incubation of whole hypothalamus. The superfusion device was improved in order to prevent gas leakage and to keep constant pO2 and pCO2 in the superfusion chamber. Basal CRF secretion as well as KCl- and norepinephrine-induced CRF release were comparable in superfusion and incubation experiments. Pharmacological investigations suggest that the stimulatory effect of norepinephrine on CRF release is mediated mainly through alpha 1 and alpha 2 adrenergic receptors, and partially through beta receptors.
The TRH secretory responsiveness of the pancreatic islet cell clusters from newborn rat in organ culture was studied. Basal TRH secretion was stable over a 9-day period. The response to various secretagogues was tested on day 4. TRH secretion was stimulated by high potassium-induced depolarization and also through both cAMP and protein kinase-C dependent pathways. Like insulin, TRH release was stimulated by glucose and arginine and inhibited by somatostatin. These data suggest the existence of a common mechanism for TRH and insulin secretion by the pancreatic beta-cells.
Severe self-injurious behavior (SIB) in people with mental retardation is difficult to treat when dangerously frequent or intense responding rules out functional analysis and interventions that permit free responding. This situation is common when restrictive devices, such as straight arm splints, are used. In this study, the effects of introducing flexion into a straight-arm splint, on SIB, self-restraint, adaptive behavior, and behavioral correlates of affect were examined for three individuals with severe mental retardation. Using single-case design methodology, for two individuals self-injury was reduced to zero, while the overall level of restriction was also significantly reduced. From the observed behavioral correlates of affect, there was no evidence of an increase in negative affect with the introduction of the new splint and the fading procedure, but there was evidence of an increase in positive vocalizations. Engagement in activities and social contact were not affected by the introduction of the new splint. The reasons for a decrease in SIB with a corresponding decrease in restriction in the absence of any manipulation of contingencies for SIB are discussed, with particular reference to stimulus control.
Few studies have examined the relationship between communicative and problem behaviors that are already present in a behavioral repertoire. In this study, a detailed microanalysis of the antecedents and consequences of aggressive and communicative behavior of a 7-year-old boy was conducted. By using both descriptive and experimental methodologies, the data suggested that problem and communicative behavior were maintained on thin concurrent schedules of social negative reinforcement. A molar analysis of the descriptive data showed that the relative amount of time allocated to each behavior was a function of the relative amount of reinforcement that each behavior accrued. The implications of these findings are discussed in terms of conducting descriptive analyses and for enhancing the efficacy of interventions for problem behavior.
Aggression and stereotyped behaviors are not uncommon among people with intellectual disabilities and they are often treated separately as operant behaviors. In this single case study, it is argued that the function of a young woman's aggressive behavior appeared to be that of avoiding or escaping the termination of a chain of complex stereotyped behavior (or "ritual"). She became aggressive only when this chain of stereotyped behavior was terminated and the aggression appeared to extinguish when it no longer led to escape from the termination of the "ritual". It is suggested that this is an example of a complex interaction between two behaviors and that it illustrates the need for very careful analysis of the functions of challenging behavior. Furthermore, it is proposed that the lengthening list of variables already documented as determinants of challenging behavior (provision of attention (verbal and physical), mechanical restraint, sensory or tangible events, escape from demands or from social attention, denials, escape from intrusive medical procedures, escape from task difficulty) be lengthened to include the possibility of escape from (or avoidance of) the interruption of a chain of complex stereotyped behavior or "ritual".
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The beta-endorphin-like-immunoreactivity (beta-ELI) has been evaluated both in plasma and in cerebrospinal fluid (CSF) in 30 patients during trans-sphenoidal surgery. Blood and liquoral samples were collected in five conditions: (1) "reference", (2) "pain", (3) "analgesia", (4) "end", and (5) "24th hour". A significant rise of both plasma and liquoral beta-ELI levels (p less than 0.00001 and p less than 0.08, respectively) when compared to basal ones occurred following the painful stimulation due to the divarication of the nasal mucosa by speculum. A significant decrease (p less than 0.01) was noticed for plasma concentrations at the third sample followed by a new significant increase at the end of the operation, (p less than 0.05 when compared to the third sample and p less than 0.01 when compared to the reference sample). In CSF, beta-ELI levels decreased at the third sample (p less than 0.01 when compared to the painful levels) and at the end of surgery (p less than 0.01, p less than 0.01 and p less than 0.05 vs first, second and third samples, respectively). Twenty-four hours after surgery either plasma and liquoral beta-ELI levels decreased (p less than 0.05). The modifications of the opiatergic system after acute painful stimuli should be, hence, characterized by an early rise followed by a progressive decrease of beta-ELI concentrations. The increase of plasma beta-ELI levels, at the end of surgery, could be due to pituitary manipulation with massive release in the peripheral blood.
Double-label immunofluorescence staining studies in virus-infected subclone 11 of LB cells indicated that almost all of the vesicular stomatitis virus (VSV) glycoprotein (G) was plasma membrane-associated during the logarithmic phase of virus replication. In contrast, treatment with interferon (IFN) resulted in inhibition of VSV-G transport, so that almost all of the G remained associated with the Golgi complex (GC) at comparable times after infection. In both IFN-treated and control cells, G was resistant to treatment with the enzyme endo-beta-N-acetylglucosamine H (endo H) indicating that the bulk of the G had reached the trans compartment of the GC.