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Biomedical subjects

J Gingras

Publications and source records attributed to J Gingras.

11 recordsLinked to original sources

Agrin becomes concentrated at neuroeffector junctions in developing rodent urinary bladder.

The formation of somatic neuromuscular junctions in skeletal muscle is regulated by an extracellular matrix protein called agrin. Here, we have examined the expression and localization of agrin during development of the rodent urinary bladder, as a first step to examining its possible role at autonomic neuroeffector junctions in smooth muscle. We have found that agrin is expressed on the surface of developing smooth muscle cells and in the basement membrane underlying the urothelium. More importantly, agrin is progressively concentrated at parasympathetic varicosities during postnatal development and is present at virtually all junctions in mature muscle. Reverse transcription/polymerase chain reaction analysis has shown that pelvic ganglion neurons that innervate the bladder express LN/z8 agrin, whereas bladder smooth muscle expresses LN/z- agrin. Together, these results demonstrate that nerve and/or muscle agrin becomes localized at cholinergic parasympathetic varicosities in smooth muscle, where it could play a role in the maturation of the neuroeffector junction.

Agrin↗

Expression and localization of agrin during sympathetic synapse formation in vitro.

Agrin is a motoneuron-derived signaling factor that plays a key organizing role in the initial stages of neuromuscular synapse formation. Agrin is expressed in other regions of the developing central and peripheral nervous systems, however, raising the possibility that it also directs the formation of some interneuronal synapses. To address this question, we have examined the expression and localization of agrin during formation of cholinergic, interneuronal synapses in the sympathetic system. In the superior cervical ganglia (SCG) in vivo, we found that agrin is highly expressed, and that it is present at, but is not limited to, synapses. In SCG neuronal cultures that were treated with ciliary neurotrophic factor to induce a uniform cholinergic phenotype, we found that agrin immunostaining colocalized precisely with cholinergic terminals and aggregates of neuronal acetylcholine receptor on the neuronal cell bodies and dendrites. Moreover, we found that alpha-dystroglycan, which is a potential receptor for agrin, is also concentrated at these cholinergic synaptic contacts. Finally, the SCG neurons expressed the C-terminal isoform of agrin that is neural-specific and highly active in synaptogenesis, and also the N-terminal splice isoform that occurs as a type II transmembrane protein. These findings show that agrin is specifically localized at sympathetic synapses in vitro, and are consistent with it playing a role in interneuronal synapse formation.

Agrin↗

Synaptogenesis in the brachial and lumbosacral enlargements of the spinal cord in the postnatal opossum, Monodelphis domestica.

Synaptic proteins were localized in light microscopy on sections of the brachial and lumbosacral enlargements of the spinal cord of postnatal opossums, Monodelphis domestica, to determine whether their expression correlates with the development of major motor pathways and simple motor behaviors. The tissues were fixed, cryoprotected, frozen, cut in 15-micrometer sections, and processed immunohistochemically using antibodies against synaptophysin, synaptotagmin-I, or SNAP-25. Immunolabeling was observed in the presumptive white matter before the presumptive gray matter, suggesting that the proteins are evidenced in growing axons before the onset of synaptogenesis, and it was observed in presumed propriospinal axons before most presumed descending axons of supraspinal origin. In the newborn opossum, the immunolabeling was scant in the gray matter and was limited to the periphery of the ventral horn, and indeed few synapses were seen in electron microscopy in nonexperimental material. Labeling increased in intensity and spread throughout the gray matter until 5-7 weeks, when it was no longer found in the white matter and resembled the adult pattern of labeling. Considering the location and relative intensity of the immunolabeling for the three proteins over time in the two enlargements, synaptogenesis occurs according to three general gradients: rostrocaudal, ventrodorsal, and lateromedial. These gradients match those of spinal cord and limb development, and of the growth of descending axons into the cord. Synaptogenesis is most intense when the spinal sensorimotor reflexes begin to be expressed.

Animals↗

Relations of diabetes intrusiveness and personal control to symptoms of depression among adults with diabetes.

The generalizability of a model linking illness characteristics to psychosocial well-being was tested in a cross-sectional study of 237 adults with type 2 diabetes. It was hypothesized that diabetic complications increase illness intrusiveness, which in turn increases depressive symptomatology either directly or indirectly by reducing personal control over health outcomes. Illness intrusiveness was defined as the result of disruptions of valued activities and interests due to constraints imposed by the illness. An excellent fit of this model to the data was found using structural equation modeling. The model explained 65% of the variance in depressive symptomatology. Assessment of an alternative model excluding personal control suggested that the extent to which diabetes intrudes in life, rather than diabetic complications per se or personal control, is a key factor in relation to depressive symptomatology in individuals with diabetes.

Adult↗

The development of synaptophysin-like immunoreactivity in the lumbosacral enlargement of the spinal cord of the opossum Monodelphis domestica.

The presence of synaptophysin in the lumbosacral enlargement of developing opossums, Monodelphis domestica, was studied immunohistochemically at the light microscopic level. In newborn, synaptophysin-labeling was observed in the presumptive white matter, presumably in growing axons, and was scant in the ventrolateral gray matter. Over the next 3 weeks the labeling filled the gray matter following a general ventrodorsal gradient. Labeling was found in the white matter until the fifth week. Synaptogenesis in the lumbosacral enlargement of the opossum thus occurs mostly postnatally, when many descending axons have already reached that level. It is particularly intense in the ventral horn when the hindlimbs begin to move, and in the dorsal horn when sensorimotor reflexes can be elicited.

Animals↗

The assessment of diabetes-related cognitive and social factors: the Multidimensional Diabetes Questionnaire.

The purpose of this study was to examine the psychometric properties of the recently developed Multidimensional Diabetes Questionnaire (MDQ). The MDQ, which is theoretically linked to a social learning perspective of diabetes, was designed to provide a comprehensive assessment of diabetes-related cognitive and social factors. It includes 41 items grouped into three sections: (1) perceptions related to diabetes and related social support, (2) positive and misguided reinforcing behaviors related to self-care activities, and (3) self-efficacy and outcome expectancies. Confirmatory factor analyses, conducted on a sample of 249 patients with non-insulin-dependent diabetes mellitus, supported the construct validity of the MDQ. Adequate internal consistency and significant demographic, psychological, behavioral, and disease-related correlates were found. The MDQ may prove valuable in understanding individual differences in adjustment to diabetes.

Adult↗

The development of an empirical psychosocial taxonomy for patients with diabetes.

The main purpose of this study was to develop and to cross-validate an empirically derived psychosocial taxonomy of patients with diabetes. In the first study, 101 patients with Type I or Type II diabetes completed the Multidimensional Diabetes Questionnaire. Cluster analysis identified three clusters, labeled adaptive copers, low support-low involvement, and spousal overinvolvement. In the second study, the taxonomy was cross-validated using an independent sample of 132 patients with long-standing Type II diabetes. The results confirmed that the multivariate classification system was unique and highly accurate. External validation, using general psychological as well as diabetes-specific measures, supported the validity and distinctiveness of the patients' profiles. These findings help establish a multiaxial psychosocial taxonomy of diabetes and may have significant implications for the management of patients with diabetes.

Adaptation, Psychological↗

Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats.

This study investigated the effect of delta opioid receptor blockade by naltrindole on the development of physical dependence and tolerance to the antinociceptive and respiratory depressive effects of morphine in rats. Chronic morphine was delivered either by s.c. injection of increasing amounts of morphine over 5 days or by s.c. implantation of morphine pellets. Animals were cotreated with saline or naltrindole. Antinociception and respiratory depression were assessed after administration of a challenge dose of morphine, and withdrawal signs were determined after naloxone challenge. Naltrindole significantly attenuated the development of antinociceptive tolerance after all three chronic treatment regimens. In addition, rats pretreated with naltrindole displayed significantly fewer withdrawal symptoms and less weight loss after a naloxone challenge. In contrast, naltrindole did not prevent the development of tolerance to morphine-induced respiratory depression. These results imply that tolerance to antinociception and physical dependence involves adaptations at interacting mu and delta receptor populations, whereas tolerance to respiratory depression reflects actions of independent mu and delta receptor populations. These findings suggest that delta antagonists may have potential clinical application for decreasing the rapid development of tolerance to opiate-induced analgesia, while allowing for the development of protective tolerance to respiratory depression.

Animals↗

Music therapy following suctioning: four case studies.

This descriptive study evaluates and compares the effectiveness of music, presented both aurally and vibrotactilely, in reducing agitation and physiological instability following a stress-producing intervention (suctioning) in infants with bronchopulmonary dysplasia. Heart rate, oxygen saturation levels, level of arousal, stressful facial expressions, and autonomic indicators were recorded for each of four preterm infants. All infants experienced a reduction in the level of arousal during the taped music intervention when compared with the control condition. Three infants spent an increased amount of time in a quiet alert state and had improved oxygen saturation levels during the vibrotactile intervention. All infants spent more time sleeping during the taped music condition than without music or with the vibrotactile intervention. Results suggest that music is effective in reducing stress-related behaviors for some infants.

Arousal↗

Electrical potential difference and ion transport across nasal epithelium of term neonates: correlation with mode of delivery, transient tachypnea of the newborn, and respiratory rate.

We studied the change in ion transport function by measuring the basal transepithelial potential difference (PD) across the ciliated epithelium of the nose in 85 term neonates during the first 72 hours of life. Differences in PD associated with the mode of delivery or the presence of respiratory disease and differences in the PD response to the superfusion of amiloride (10(-5) mol/L) were assessed. We also studied term neonates with transient tachypnea of the newborn (TTN) and acute respiratory insufficiency. Basal PDs during the first 24 hours of life were higher in neonates delivered by cesarean section without prior labor (-29.7 +/- 2.5 mV) and in those with TTN (-38.5 +/- 6.0 mV) than in neonates born during normal spontaneous vaginal delivery (-23.0 +/- 2.9 mV) or cesarean section with prior labor (-23.7 +/- 0.7 mV) or in those with respiratory insufficiency (-22.4 +/- 2.3 mV). The percentage inhibition of PD by amiloride superfusion (less than 24 hours) was significantly lower in infants with TTN (30.9 +/- 4.9%) and after cesarean section without prior labor (31.8 +/- 2.2%) than in other groups (37.6 +/- 1.6%). By 48 hours, nasal PDs after cesarean section without prior labor and in neonates with TTN had declined; and by 72 hours, values were similar to those in other groups; respiratory rate paralleled the decline in PD. The respiratory rate of neonates with respiratory insufficiency remained high and paralleled the persistence of respiratory distress. Amiloride sensitivity was similar for all groups by 72 hours. These findings indicate (1) that PDs vary with the mode of delivery and support a role for labor in the normal transition of respiratory epithelial ion transport and (2) that TTN is associated with abnormal epithelial ion transport.

Biological Transport↗

Use and abuse of controlled substances by pharmacists and pharmacy students.

The use of controlled substances by samples of pharmacists and pharmacy students in one New England state was surveyed. A questionnaire was sent in November 1984 to a sample of 510 pharmacists randomly selected from the membership list of the state's pharmaceutical association and to a sample of 470 students from the state's pharmacy schools; 76% and 67% of the eligible pharmacists and students responded, respectively. The questionnaire elicited information about the respondents' use of controlled substances for self-treatment and recreation, as well as the instrumental use of stimulants to enhance performance. Almost half of the pharmacists (46%) and two thirds of the students (62%) reported using a controlled substance at some time without a prescription; 19% and 41%, respectively, used one within the past year. Whereas students used the drugs most often for recreation (57% ever, 36% currently), use by pharmacists was more equally divided among self-treatment (29% ever, 13% currently), recreation (29% ever, 9% currently), and instrumental purposes (21% ever). The drugs most often used were marijuana, stimulants (especially cocaine by students), tranquilizers, and opiates. Drug use was generally limited in amount, but 18% of the pharmacists and 35% of the students who ever used a drug either became dependent or were at risk of drug abuse. Current drug use was most strongly associated with age, non-attendance at religious services, student access, year in school, and citizenship. The findings of this study suggest the need for continued development of impaired pharmacist committees and drug abuse prevention programs for pharmacists and pharmacy students.

Adolescent↗