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Biomedical subjects

S Levine

Publications and source records attributed to S Levine.

At least 37 records · Page 2Linked to original sources

Primary social relationships influence the development of the hypothalamic--pituitary--adrenal axis in the rat.

In the developing rodent, there is a period from about days 4 to 14 when the adrenal response to stress is either minimal or non-existent. This has been designated as the stress hyporesponsive period (SHRP). Numerous experiments have demonstrated that maternal factors are critical for the regulation of the pup's hypothalamic--pituitary--adrenal (HPA) axis and the maintenance of the SHRP. Following 24 h of maternal deprivation, the neonatal rat shows elevated basal levels of corticosterone (CORT) and exhibits a robust CORT and ACTH response to mild stress. Further, c-fos mRNA in the paraventricular nucleus (PVN) is enhanced following stress in deprived pups. At least three aspects of maternal behavior play a role in the regulation of the HPA axis during development. Tactile stimulation appears capable of inhibiting most of the brain-related changes that occur following maternal deprivation. Feeding is essential for maintaining the adrenal-unresponsive and reduces the sensitivity of the adrenal to ACTH. Passive contact suppresses the response to stress. In the adult, corticotropin-releasing hormone (CRH) is the major neuropeptide that controls pituitary ACTH secretion. In the maternally deprived pup, CRH gene transcription is downregulated and arginine vasopressin (AVP) appears to assume the major regulatory hormone that modulates ACTH. These data all indicate that maternal factors are responsible for actively inhibiting the endocrine responses to stress postnatally. Thus, during development, most of the peripheral and central stress-responsive systems are capable of being activated. However, under conditions of normal dam-pup interactions, these responses are mostly suppressed by the dam's behavioral interaction with the pups.

Animals↗

Feeding demand conditions and plasma cortisol in socially-housed squirrel monkey mother-infant dyads.

Previous studies have demonstrated that experimentally altering the accessibility and availability of food can have profound impact on behavior and adrenocortical activity in nonhuman primate species. In this study, groups of mother-infant squirrel monkey dyads were housed in either high demand (HFD: 120% normal daily food intake provided), low demand (LFD: 600% normal daily food intake provided) or variable demand (VFD: alternating two-week blocks of low demand and high demand) conditions for 12 weeks. During the 12-week experimental foraging phase, animals in the HFD group exhibited prolonged and consistent cortisol elevations. The cortisol levels in the VFD group reflected the ambient demand condition, with higher levels exhibited during the high demand phases of the study, and lower values when the low demand condition was in effect. Overall, mothers were more affected by the experimental manipulation than were infants. The experimental condition did not affect the infants' response to a 24-h separation from their mothers. A suppression of cortisol levels, particularly in the HFD group, was observed upon resumption of ad-libitum feeding.

Animals↗

Axonal damage to the left musculocutaneous nerve of the left biceps muscle during laparoscopic surgery.

The probable etiology of axonal damage to the left musculocutaneous nerve (motor branch) of the left biceps branchii during a laparoscopic procedure was the position in which the patient was maintained. As a result of unintentional change in the angle of the arm from 90 to approximately 120 degrees while in steep Trendelenburg position, the arm might have suffered hyperextension, resulting in pressure on and stretching of the brachial plexus nerve. This in turn might be the cause of neurologic damage. We recommend taking steps to prevent such occurrences, such as tying the patient's arms parallel to the body.

Adult↗

Lung volume reduction surgery restores the normal diaphragmatic length-tension relationship in emphysematous rats.

OBJECTIVE: Improved respiratory muscle function is a major effect of a lung volume reduction surgery. We studied length adaptation in rat diaphragmatic muscle in an attempt to elucidate the mechanism by which diaphragmatic function improves after this controversial operation. METHODS: We developed a model of elastase-induced emphysema and bilateral volume reduction through median sternotomy in rats. Five months after emphysema induction, maximum exchangeable lung volume was determined in intubated and anesthetized control animals and animals with emphysema. Costal diaphragmatic length was measured in vivo, and the length at which maximal twitch force is generated was determined on muscle strips in vitro. Also 5 months after elastase administration, another cohort underwent volume reduction or sham sternotomy. Five months after the operation, these animals were similarly studied. RESULTS: Lung volume was increased in emphysematous rats versus control rats (50.9 +/- 1.7 vs 45.4 +/- 1.3 mL, P =.001). Lung volume was decreased in emphysematous animals that had undergone volume reduction versus sham sternotomy (44.7 +/- 0.60 vs 49.4 +/- 1.0 mL, P =.001). In situ diaphragm length (1.99 +/- 0.04 vs 2.24 +/- 0.07 cm, P =.001) and the length at which maximal twitch force is generated (2.25 +/- 0.06 vs 2.48 +/- 0.09 cm, P =.038) were shorter in emphysematous than control animals. After volume reduction, in situ diaphragm length (2.13 +/- 0.06 vs 1.83 +/- 0.02 cm, P <.001) and the length at which maximal twitch force is generated (2.50 +/- 0.08 vs 2.27 +/- 0.06 cm, P =.013) were longer than in animals undergoing sham sternotomy. CONCLUSIONS: In this experimental model of emphysema and lung volume reduction surgery, emphysema shortens the length at which maximal twitch force is generated and shifts the diaphragmatic length-tension curve to lower lengths; volume reduction returns the length at which maximal twitch force is generated toward normal and shifts the diaphragmatic length-tension curve back to longer lengths. This restoration toward normal physiology may enable the improvement in diaphragmatic function seen after lung volume reduction surgery. The mechanism by which these length adaptations occur merits further investigation.

Adaptation, Physiological↗

Developing ergonomic solutions for prevention of musculoskeletal disorder disability.

Numerous models have been proposed to help understand the relationship between personal and work factors that affect participation in work. The authors use a generic version of these models as a framework for identifying gaps between job demands and worker capacities. They describe metrics for assessing factors associated with causing or aggravating musculoskeletal disorders. Two case examples are presented to illustrate the hierarchical assessment of jobs and the evaluation of gaps between job demands and worker capacities. Finally, the authors describe the development of a job database to facilitate future evaluations.

Adult↗

Are urea and creatinine uremic toxins in the rat?

Urea and creatinine are not generally considered to be important uremic toxins despite evidence from dialysis experiments to the contrary, and despite striking elevations of these nitrogenous waste products in uremia. In order to study this problem in acute uremia, we used a new dietary method for prolonging the survival of bilaterally nephrectomized rats. Urea or creatinine were injected on three successive days starting one day after the inception of uremia. Urea or creatinine injections shortened the survival time of acutely uremic rats, and increased the involution of thymus and spleen. The extra urea, but not creatinine, increased the serum osmolality. These data indicate that urea and creatinine are toxic in the acutely uremic rat. Hypertonicity of the serum may contribute to the toxicity of urea. Additional mechanisms of toxicity and additional toxins are not excluded.

Acute Disease↗

Map position and expression of the genes in the 38 region of Drosophila.

With the completion of the Drosophila genome sequence, an important next step is to extract its biological information by systematic functional analysis of genes. We have produced a high-resolution genetic map of cytological region 38 of Drosophila using 41 deficiency stocks that provide a total of 54 breakpoints within the region. Of a total of 45 independent P-element lines that mapped by in situ hybridization to the region, 14 targeted 7 complementation groups within the 38 region. Additional EMS, X-ray, and spontaneous mutations define a total of 17 complementation groups. Because these two pools partially overlap, the completed analysis revealed 21 distinct complementation groups defined by point mutations. Seven additional functions were defined by trans-heterozygous combinations of deficiencies, resulting in a total of 28 distinct functions. We further produced a developmental expression profile for the 760 kb from 38B to 38E. Of 135 transcription units predicted by GENSCAN, 22 have at least partial homology to mobile genetic elements such as transposons and retroviruses and 17 correspond to previously characterized genes. We analyzed the developmental expression pattern of the remaining genes using poly(A)(+) RNA from ovaries, early and late embryos, larvae, males, and females. We discuss the correlation between GENSCAN predictions and experimentally confirmed transcription units, the high number of male-specific transcripts, and the alignment of the genetic and physical maps in cytological region 38.

Animals↗

Cutaneous Acanthamoeba in a patient with AIDS: a case study with a review of new therapy; quiz 386.

GOAL: To describe the presenting signs of an Acanthamoeba infection. OBJECTIVES: Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Discuss the clinical presentation of Acanthamoeba infection. 2. Describe the conditions that make a patient susceptible to Acanthamoeba. 3. Outline treatment options for Acanthamoeba infection. CME: This article has been peer reviewed and approved by Michael Fisher, MD, Professor of Medicine, Albert Einstein College of Medicine. REVIEW DATE: April 2001. This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Albert Einstein College of Medicine and Quadrant HealthCom, Inc. The Albert Einstein College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. Albert Einstein College of Medicine designates this educational activity for a maximum of 1.0 hour in category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity. This activity has been planned and produced in accordance with ACCME Essentials.

AIDS-Related Opportunistic Infections↗

Influence of psychological variables on the activity of the hypothalamic-pituitary-adrenal axis.

Psychobiology is the discipline that attempts to integrate the impact of environmental and psychological variables on biological systems. This paper focuses on the psychobiology of the hypothalamic-pituitary-adrenal (HPA) axis and illustrates several processes that influence the response of the HPA axis. The interaction of the developing rodent or primate with their primary care giver has permanent long-term effects on the HPA axis. Manipulations that alter maternal behavior during critical periods of development permanently modify the HPA axis. The HPA axis can be programmed to be hypo-responsive or hyper-responsive as a function of time and length of maternal separation. In the adult organism, the HPA response to stress is highly dependent on specific psychological factors such as control, predictability, and feedback. In primates, social variables have been shown to diminish or exacerbate the HPA stress response. During the post-natal period of development, the mother appears to actively inhibit the pups' HPA axis. Different aspects of maternal behavior regulate different components of the HPA system.

Animals↗

Maternal deprivation regulates serotonin 1A and 2A receptors in the infant rat.

UNLABELLED: Several studies have demonstrated that 5-HT1A and 5-HT2A receptors are altered in rat brain following chronic stress. While this is true in the adult animal, this may be different in the developing animal, which has a limited corticosterone response to acute challenges between days 3 and 14 of life. METHODS: We investigated the effect of maternal deprivation on 5-HT2A and 5-HT1A receptor mRNA levels in the developing brain. In situ hybridization was used to quantify gene expression in rat pups at three ages: 6, 9, and 12 days old. In each age group, half were maternally deprived for 24 h and half were kept with their mothers. Maternally deprived animals showed elevated ACTH and corticosterone plasma levels when compared to NDEP animals, significantly elevated 5-HT1A mRNA levels in the CA1 hippocampal region and, significantly elevated 5-HT2A mRNA levels in the parietal cortex. No changes were observed in 5-HT1A or 5-HT-transporter mRNA levels in the dorsal raphe. Our results indicate that post-synaptic 5-HT receptors in the developing hippocampus and cortex are sensitive to maternal deprivation. Because hippocampal 5-HT1A gene expressions are known to decrease in the adult animal after chronic glucocorticoid elevation, this data also suggests that other mechanisms, perhaps central, predominate during development.

Adrenocorticotropic Hormone↗

Chronic fatigue syndrome: an examination of the phases.

The present study examined the Fennell Phase Inventory, an instrument designed to measure the phases typically experienced by individuals with chronic fatigue syndrome (CFS). This inventory yields three factor scores of Crisis, Stabilization, and Integration. These factor scores have been employed in a cluster analysis, yielding four clusters that matched the four phases predicted by Fennell: Crisis, Stabilization, Resolution, and Integration. The present study represents a partial replication study of a prior investigation of the Fennell Phase Inventory by Jason et al. (in press), but that earlier study did not have an independent physician examination to diagnose patients with CFS. In the present study, 65 patients diagnosed with chronic fatigue syndrome by a physician were recruited and administered the Fennell Phase Inventory and other measures assessing CFS-related symptoms, disability, and coping. Each of the 65 patients was classified into one of four predefined clusters measuring a Crisis phase, a Stabilization phase, a Resolution phase, and an Integration phase. Relationships were explored between three of these cluster groupings and measures of symptoms, disability, and coping. Results confirmed Fennell's model, revealing significant differences between the three clusters in terms of levels of disability and modes of coping. Results suggest that the Fennell Phase Inventory accurately differentiates phases of adaptation to illness experienced by individuals with CFS.

Adaptation, Psychological↗

Stridor and death in multiple system atrophy.

Patients with multiple system atrophy (MSA) have a mean survival of 8 to 10 years. Nocturnal stridor has been considered a poor prognostic feature. We analyzed demographic, clinical, and polysomnographic data and obtained follow-up information from 42 patients with MSA (30 with follow-up data) seen in a Sleep Disorders Center. Group I consisted of 17 patients with nocturnal stridor, including seven with daytime stridor. Group II consisted of 25 patients without stridor. Analysis of survival curves of 30 patients with follow-up information showed a significantly shorter survival from the sleep evaluation, but not from disease onset, for patients with stridor compared with those without. Nine of 11 patients with stridor died a median of 2 years from presentation and the only two survivors had undergone tracheostomy. Patients with daytime stridor and immobile vocal cords had especially poor prognoses. However, two of four patients with tracheostomies also died, as did six of 19 without stridor. We postulate that central hypoventilation and its complications may have been responsible for many of these other deaths. We conclude that stridor does carry a poor prognosis in patients with MSA but that there are also other causes of death. We recommend consideration of tracheostomy for patients with MSA who have stridor, but also assessment for central hypoventilation and appropriate management if it is present.

Aged↗

Frustrative nonreward and pituitary-adrenal activity in squirrel monkeys.

Little is known about frustration-induced changes in stress physiology in humans and nonhuman primates. Here we assess in two experiments with squirrel monkeys plasma levels of pituitary-adrenal stress hormones in conditions designed to provoke frustrative nonreward. In the first experiment 18 prepubertal monkeys were trained to feed from one of eight sites, and then tested without food at any of the sites. These monkeys responded with significant increases in cortisol and adrenocorticotropic hormone (ACTH). In the second experiment 18 adult monkeys were trained to feed from one of eight sites, and then tested after food was moved to a different foraging site. Nine monkeys found food at the relocated site, discontinued foraging at the previously baited site, and responded with decreases in cortisol. The other nine monkeys failed to find the relocated site, initially increased their visits to the previously baited site, and responded with elevations in cortisol and ACTH. In keeping with comparable findings in rats, our observations indicate that frustrative nonreward elicits ACTH-stimulated secretion of cortisol in primates.

Adrenocorticotropic Hormone↗

Pertussis vaccine and pertussis toxin increase lithium levels in rats: possible role of G-proteins.

A single dose of lithium was injected intravenously or intraperitoneally in rats. Lithium levels in serum and tissues 5 or 24 hours later were elevated when the rats were pretreated with pertussis vaccine (PV). The vaccine was effective whether given locally (subcutaneous) or systemically (intravenous). Tests of heated (inactivated) PV suggested that pertussis toxin might be responsible for the effects of PV. Injection of purified pertussis toxin (PT) confirmed this suggestion. Elevation of serum urea nitrogen suggested that lithium levels were increased because the combination of PV or PT with lithium reduced renal excretory function which could cause retention of lithium. Inasmuch as PV and PT are known to inactivate the inhibitory G-proteins, these data suggest G-protein involvement in the elevation of lithium levels by PV and PT.

Animals↗