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Biomedical subjects

S Levine

Publications and source records attributed to S Levine.

At least 91 records · Page 5Linked to original sources

The ontogeny of glucocorticoid negative feedback: influence of maternal deprivation.

Glucocorticoid feedback can be viewed as having two modes of operation: proactive and reactive. "Proactive" feedback maintains basal activity of the hypothalamic-pituitary-adrenal axis, whereas the termination of stress-induced hypothalamic-pituitary-adrenal activity is facilitated by "reactive" feedback. In the present study we studied the ontogeny of both feedback modes and tested the hypothesis that the development of feedback depends on mother-pup interaction. On postnatal day 9 or 12, pups were deprived (DEP) of the dam for 24 h; nondeprived pups of the same age served as controls. The pups were adrenalectomized (ADX) at the end of deprivation and given corticosterone (CORT) replacement by either injection or pellet implants using the following two designs: first at the time of adrenalectomy (ADX) to test the role of CORT in the maintenance of basal ACTH levels, and then 3 h after ADX, to investigate CORT suppression of elevated ACTH levels induced by prior ADX. Regarding proactive feedback, the results showed that injection of CORT at the time of ADX was only partially effective in preventing ACTH elevations, whereas CORT pellets maintained basal levels of ACTH in all ADX pups. The reactive mode of negative feedback in nondeprived pups was resistant to CORT injection, whereas the CORT pellet resulted in a return to basal levels within 60 min. Maternal deprivation did not affect proactive feedback, but caused a more sustained increase in ACTH levels and a failure to return to basal levels 3 h after ADX despite significantly higher levels of circulating CORT in these DEP pups. It is concluded that 1) proactive and reactive modes of negative feedback are operative, provided the pups are maintained on chronic replacement with CORT; 2) DEP impairs the reactive, rather than the proactive, mode of feedback inhibition in the neonate.

Adrenalectomy↗

Petechial hemorrhages in the small intestinal Peyer's patches: a new manifestation of systemic anaphylaxis.

Systemic anaphylaxis in the rat has major manifestations in the small intestine. In August rats, but not in other strains, intestinal anaphylaxis was accompanied by petechial hemorrhages in Peyer's patches. The occurrence of petechiae was not proportional to the intensity of prostration, cyanosis or gut congestion. No hemorrhages were found in other organs. The petechiae occurred in August rats of either sex after sensitization and challenge with any of several antigens and adjuvants and after passive sensitization with antiserum. The number of Peyer's patches with hemorrhage varied from one to all 20 in individual rats. The occurrence of petechiae was not influenced significantly by the route of sensitization or challenge, by the presence or absence of pinworms in the cecum, or by ancillary treatment at time of challenge with normal serum, normal blood, heparin, pertussis vaccine or lipopolysaccharide. The intestinal mast cells of the susceptible August rats were not different from the mast cells of the resistant strains. Furthermore, mast cells did not reside in the lymphoid follicles of Peyer's patches which was the site of the petechial hemorrhages in anaphylactic August rats. Nor did injections of histamine, serotonin or both cause hemorrhages in Peyer's patches.

Anaphylaxis↗

Relationship of job strain and iso-strain to health status in a cohort of women in the United States.

OBJECTIVE: This study examined the relationships of job strain and iso-strain psychosocial work-environment exposures to health status in a cohort of working women in the United States. METHODS: In a cross-sectional survey, 33689 women responded to the Karasek job content and the MOS SF-36 health status questionnaires. The psychosocial work-environment exposures were characterized using the job strain and iso-strain frameworks. Health status was assessed with the following 6 scales: physical functioning, vitality, freedom from pain, mental health, role limitations due to physical health, and role limitations due to emotional health. RESULTS: When compared with active work, high-strain work (high job demands and low job control) was associated with lower vitality, mental health, higher pain, and increased risks of both physical and emotional role limitations. Iso-strain work (high strain and low work-related social support) increased the risks further. Job insecurity was also associated with lower health status. CONCLUSIONS: The analyses supported the hypothesis that the psychosocial work environment is an important determinant of health status among working women. The findings suggest that incorporating social conditions at work into the measurement of psychosocial work-environment exposure improves the identification of high-risk work arrangements.

Adult↗

Duration and peak level as co-factors in hearing loss from exposure to impact noise.

The Equal Energy Hypothesis (EEH) is based on the assumption that hearing loss from a given exposure is proportional to the total energy of the exposure. A corollary of this assumption is the power of the exposure and the duration of the exposure are interchangeable. Studies of impulse and impact noise show that hearing loss does not follow the prediction of the EEH (Ward, 1986; Danielson et al., 1991). Thus, the following experiments were designed to assess the relative importance of the duration and peak level of impact noise in the production of hearing loss. Monaural chinchillas served as subjects. Their quiet thresholds were estimated before and after exposures using the evoked potential recorded from a chronic electrode in the inferior colliculus. The four groups of the "intensity" series were exposed for 7.5 hours to 200 msec impacts at 1 per second at levels of 113, 119, 125, and 131 dB peak equivalent SPL. The three groups of the "duration" series were exposed to the 125 dB impacts for either 1.9, 7.5, or 30 hours. With each dB increase in the "duration" series, there was approximately 1.7 dB of increase in hearing loss. For each dB increase in peak level above 125 dB, there was an average of 6.6 dB increase in hearing loss. The 125 dB exposure is just below the "critical level" where the mode of cochlear damage shifts to mechanical failure. The results are discussed in terms of "critical" level and implication for noise standards.

Animals↗

Postnatal foraging demands alter adrenocortical activity and psychosocial development.

Mother squirrel monkeys stop carrying infants at earlier ages in high-demand (HD) conditions where food is difficult to find relative to low-demand (LD) conditions. To characterize these transitions in psychosocial development, from 10- to 21-weeks postpartum we collected measures of behavior, adrenocortical activity, and social transactions coded for initiator (mother or infant), goal (make-contact or break-contact), and outcome (success or failure). Make-contact attempts were most often initiated by HD infants, but mothers often opposed these attempts and less than 50% were successful. Break-contact attempts were most often initiated by LD infants, but mothers often opposed these attempts and fewer LD than HD infant break-contact attempts were successful. Plasma levels of cortisol were significantly higher in HD than LD mothers, but differences in adrenocortical activity were less consistent in their infants. HD and LD infants also spent similar amounts of time nursing on their mothers and feeding on solid foods. By rescheduling some transitions in development (carry-->self-transport), and not others (nursing-->self-feeding), mothers may have partially protected infants from the immediate impact of an otherwise stressful foraging task.

Analysis of Variance↗

Environmental input and cognitive growth: a study using time-period comparisons.

In this study, we examined the relation of input to cognitive growth in a single population of children. We studied 4 domains: Language, Spatial Operations, Concepts, and Associative Memory. Four groups of children drawn from the same population were tested in October of kindergarten, April of kindergarten, October of first grade, and April of first grade. These time points are 6 months apart, but they span periods that differ in amount of school input children receive. Much greater growth was found over time periods with greater amounts of school input (October to April) than over time periods with less school input (April to October) for Language, Spatial Operations, and Concepts, but not for Associative Memory. These findings suggest that amount of input is causally related to cognitive growth in particular domains.

Analysis of Variance↗

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Humans↗

Out in the real world.

Just weeks into his first foray into the complex world of medical practice, family practitioner Warren L. Conway, MD, offers some advice to this year's crop of senior residents: "Go back to college and get a business degree. You need some business training, and it needs to be from a person who's in the real world."

Curriculum↗

Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease.

BACKGROUND: In patients with severe chronic obstructive pulmonary disease, the diaphragm undergoes physiologic adaptations characterized by an increase in energy expenditure and relative resistance to fatigue. We hypothesized that these physiologic characteristics would be associated with structural adaptations consisting of an increased proportion of less-fatigable slow-twitch muscle fibers and slow isoforms of myofibrillar proteins. METHODS: We obtained biopsy specimens of the diaphragm from 6 patients with severe chronic obstructive pulmonary disease (mean [+/-SE] forced expiratory volume in one second, 33+/-4 percent of the predicted value; residual volume, 259+/-25 percent of the predicted value) and 10 control subjects. The proportions of the various isoforms of myosin heavy chains, myosin light chains, troponin, and tropomyosin were determined by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. We also used immunocytochemical techniques to determine the proportions of the various types of muscle fibers. RESULTS: The diaphragm-biopsy specimens from the patients had higher percentages of slow myosin heavy chain I (64+/-3 vs. 45+/-2 percent, P<0.001), and lower percentages of fast myosin heavy chains IIa (29+/-3 vs. 39+/-2 percent, P=0.01) and IIb (8+/-1 vs. 17+/-1 percent, P<0.001) than the diaphragms of the controls. Similar differences were noted when immunohistochemical techniques were used to compare the percentages of these fiber types in the two groups. In addition, the patients had higher percentages of the slow isoforms of myosin light chains, troponins, and tropomyosin, whereas the controls had higher percentages of the fast isoforms of these proteins. CONCLUSIONS: Severe chronic obstructive pulmonary disease increases the slow-twitch characteristics of the muscle fibers in the diaphragm, an adaptation that increases resistance to fatigue.

Biopsy↗

Characterization of apical and basolateral plasma membrane domains derived from cultured rat cholangiocytes.

Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, are composed of plasma membranes with discrete apical (lumenal) and basolateral domains that contain different channels, transporters, and receptors. In recent work, we developed a long-term, primary culture system of normal rat cholangiocytes (NRC). Our aims here were to prepare and characterize apical and basolateral plasma membrane vesicles from NRC. Using serial isopycnic centrifugation on sucrose gradients, we generated separate apical and basolateral plasma membrane vesicles. We characterized these vesicles by transmission electron microscopy, specific marker enzyme assays, and immunoblotting; we also determined the percentage of sealed vesicles and their intravesicular volume and sidedness using biochemical approaches. Our results showed that vesicles derived from the apical and basolateral plasma membrane domains of NRC were highly purified, predominately sealed, right-side-out vesicles that differed in size and lipid and protein composition. This experimental model represents a novel tool that will be useful for additional functional studies on the channels, transporters, and receptors differentially distributed in the plasma membrane of biliary epithelia.

Animals↗

Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter.

Although bile acid transport by bile duct epithelial cells, or cholangiocytes, has been postulated, the details of this process remain unclear. Thus, we performed transport studies with [3H]taurocholate in confluent polarized monolayers of normal rat cholangiocytes (NRC). We observed unidirectional (i.e., apical to basolateral) Na+-dependent transcellular transport of [3H]taurocholate. Kinetic studies in purified vesicles derived from the apical domain of NRC disclosed saturable Na+-dependent uptake of [3H]taurocholate, with apparent Km and Vmax values of 209+/-45 microM and 1.23+/-0.14 nmol/mg/10 s, respectively. Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na+-dependent taurocholate-cotransporting polypeptide and rat ileal apical Na+-dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT. Northern blot analysis demonstrated that the size of the ASBT transcript was identical in NRC, freshly isolated cholangiocytes, and terminal ileum. In situ RT-PCR on normal rat liver showed that the message for ASBT was present only in cholangiocytes. Immunoblots using a well-characterized antibody for the ASBT demonstrated a 48-kD protein present only in apical membranes. Indirect immunohistochemistry revealed apical localization of ASBT in cholangiocytes in normal rat liver. The data provide direct evidence that conjugated bile acids are taken up at the apical domain of cholangiocytes via the ASBT, and are consistent with the notion that cholangiocyte physiology may be directly influenced by bile acids.

Animals↗

Acute unloading of the work of breathing extends exercise duration in patients with heart failure.

OBJECTIVES: This study investigated whether maximal exercise performance can be improved by acutely decreasing the work of breathing in these patients. BACKGROUND: Exertional dyspnea is a frequent limiting symptom in patients with heart failure. It may result from increased work of breathing. METHODS: Fifteen patients with heart failure and nine age-matched normal subjects underwent two maximal exercise tests. Subjects exercised twice in randomized, single-blind manner using room air (RA) and a 79% helium/21% oxygen mixture (He). Respiratory gas analysis, Borg scale recordings of perceived dyspnea and near infrared spectroscopy of an accessory respiratory muscle were obtained during exercise. RESULTS: In normal subjects there was no significant difference in peak oxygen uptake (Vo2) ([mean +/- SD] RA 38 +/- 8 vs. He 35 +/- 7 ml/kg per min), exercise duration (RA 724 +/- 163 vs. He 762 +/- 123 s) or peak minute ventilation (RA 97 +/- 27 vs. He 97 +/- 28 liters/min, all p = NS). Only three of nine control subjects thought that exercise with the He mixture was subjectively easier. In contrast, patients with heart failure exercised an average of 146 s longer with the He mixture (RA 868 +/- 293 vs. He 1,014 +/- 338, p < 0.01). Peak Vo2 (RA 19 +/- 4 vs. He 18 +/- 5 ml/kg per min) and peak minute ventilation (RA 53 +/- 12 vs. He 53 +/- 15 liters/min) were unchanged (both p = NS). The respiratory quotient at peak exercise was lower with the He mixture (RA 1.05 +/- 0.08 vs. He 0.98 +/- 0.06, p < 0.05). Thirteen of the 15 patients thought that exercise with the He mixture was subjectively easier (p < 0.02 vs. control group). CONCLUSIONS: In patients with heart failure, pulmonary factors, including respiratory muscle work and airflow turbulence, contribute to limiting exercise performance. Therapeutic interventions aimed at attenuating work of breathing may be beneficial.

Adult↗

Chronic congestive heart failure elicits adaptations of endurance exercise in diaphragmatic muscle.

BACKGROUND: During rest and exercise, patients with heart failure hyperventilate; therefore, the diaphragm can be viewed as undergoing constant moderate-intensity exercise. Accordingly, we hypothesized that heart failure elicits adaptations in the diaphragm similar to those elicited by endurance exercise in the limb muscles of normal subjects. METHODS AND RESULTS: Costal diaphragmatic biopsy samples were obtained from 7 normal subjects (age, 36 +/- 20 years) and 10 patients (age, 50 +/- 6 years; left ventricular ejection fraction, 18 +/- 8%) at the time of transplant or left ventricular assist-device placement. We measured the distribution of myosin heavy chain isoforms I, IIa, and IIb by SDS gel electrophoresis. We also measured the activities of the following enzymes: citrate synthase, a marker of oxidative metabolism; beta-hydroxyacyl-CoA dehydrogenase, a marker of lipolytic metabolism; and lactate dehydrogenase, a marker of glycolytic metabolism. In normal subjects, the distribution of myosin heavy chain isoforms I, IIa, and IIb was 43 +/- 2%, 40 +/- 2%, and 17 +/- 1%, respectively. In contrast, in heart failure subjects, the fiber distribution was 55 +/- 2%, 38 +/- 2%, and 7 +/- 2% for types I, IIa, and IIb, respectively. Therefore, in heart failure, myosin heavy chain I is increased (P < .0001) and myosin heavy chain IIb decreased from normal levels (P < .001). Additionally, citrate synthase activity (normal, 0.33 +/- 0.14; heart failure, 0.54 +/- 0.21 mumol.min-1.mg protein-1; P < .05) and beta-hydroxyacyl-CoA dehydrogenase activity (normal, 0.27 +/- 0.04; heart failure, 0.38 +/- 0.02 mumol.min-1.mg protein-1; P < .05) were greater in heart failure patients than in normal subjects, whereas lactate dehydrogenase activity was significantly less in heart failure patients than in normal subjects (normal, 11.6 +/- 4.6; heart failure,: 4.3 +/- 2.2 mumol.min-1.mg protein-1; P < .01). CONCLUSIONS: In the diaphragm in heart failure, there is a shift from fast to slow myosin heavy chain isoforms with an increase in oxidative capacity and a decrease in glycolytic capacity. These diaphragmatic muscle changes are consistent with those elicited by endurance training of the limb muscles in normal subjects.

3-Hydroxyacyl CoA Dehydrogenases↗

Leukemia inhibitory factor induces the 85-kDa cytosolic phospholipase A2 gene expression in cultured human bronchial epithelial cells.

Leukemia inhibitory factor (LIF) has become increasingly recognized as an important regulator of inflammation. This study is designed to determine whether LIF has an effect on arachidonate metabolism in human airway epithelial cells. LIF (100 ng/ml) induced a significantly increased release of prelabeled [3H] arachidonic acid (AA) from the human bronchial epithelial cell line (BEAS 2B cell) as well as from the primary cultures of human bronchial epithelial cells. Exposure of the LIF stimulated BEAS 2B cells to calcium ionophore A23187 (10(-5) M, 15 min) caused a further increase of [3H]AA release. To identify the role of cytosolic phospholipase A2 (cPLA2) in this upregulation of AA release, further experiments were performed to determine the expression of cPLA2 in the BEAS 2B cells. Immunoblot analysis indicated that LIF increased cPLA2 protein expression. Ribonuclease protection assay showed that LIF induced an increase of cPLA2 mRNA levels following 3 h to 24 h treatment. Nuclear run-on experiments suggested that LIF upregulated cPLA2 gene expression through post-translational regulation. These results demonstrate that LIF induces cPLA2 gene expression and modulates arachidonate metabolism in airway epithelial cells.

Arachidonic Acid↗

Psychobiological consequences of social relationships.

Social separations can induce long-lasting increases in cortisol, whereas companionship can result in social buffering. Preliminary evidence from studies of squirrel monkeys suggests that social separation-induced hypersecretion of cortisol is initially driven by hypersecretion of ACTH. From 1-21 days postseparation, however, cortisol remains elevated above pre-separation controls, while ACTH levels are consistently reduced. Hypercortisolism is maintained despite reductions in ACTH, because adrenal responsiveness to ACTH is enhanced. Low circulating ACTH, in turn, is maintained by robust feedback mechanisms that apparently inhibit biosynthesis or release of pituitary ACTH. These findings are consistent with neuroendocrine interactions known or hypothesized to occur during major depressive disorders in humans and raise unique possibilities for comparative research in human and nonhuman primates.

Adrenocorticotropic Hormone↗

Influence of body size on lithium levels in rats.

Lithium chloride was injected into rats by the intraperitoneal or intravenous route. The dose was proportional to body weight, in the conventional manner. Lithium levels in blood serum and organs were determined after 3-24 h. Within a given strain, large rats had higher levels than small rats. The size of the rats, and not their age, was the determining factor. The large rats had more adipose tissue than the small rats. Inasmuch as lithium distributes in body water, the excess fat in large rats reduces its volume of distribution, which may be responsible for raising the lithium levels in aqueous compartments, including serum. Male and female rats of equal body size developed equal lithium levels in serum.

Age Factors↗

Incisionless per vaginal bone anchor cystourethropexy for the treatment of female stress incontinence: experience with the first 50 patients.

PURPOSE: We evaluated the safety and efficacy of a new minimally invasive surgical procedure for the treatment of women with genuine stress urinary incontinence. MATERIALS AND METHODS: A total of 50 women (mean age 51 years) was treated for type I or II stress urinary incontinence. A miniature bone anchor and a staple like bone anchor driver were used for fixation of periurethral tissue to the public bone. RESULTS: The procedure was successfully performed in all patients without intraoperative bleeding. No significant persistent postoperative pain was noted and only 1 patient had urinary tract infection. Concomitant vaginal hysterectomy, cystocele repair or perineoplasty was performed in 33 cases. At 12-month followup 41 patients (82%) are completely continent, 7 patients (14%) reported more than 50% decrease in pad usage and 2 cases are considered surgical failures. Mean operative time was 28 minutes. CONCLUSIONS: Data suggest that our new minimally invasive procedure provides a safe, effective and easy to learn alternative for treatment of women with anatomical stress incontinence.

Adult↗