Object-based attention requires monocular visual pathways.

Mechanisms of object-based attention (OBA) are commonly associated with the cerebral cortex. However, less is known about the involvement of subcortical visual pathways in these processes. Knowledge of the neural mechanisms subserving OBA can provide insight into the evolutionary trajectory of attentional selection. In the current study, the classic double-rectangle cueing task was implemented using a stereoscope in order to differentiate between the involvement of lower (monocular) and higher (binocular) visual pathways in OBA processes. We found that monocular visual pathways are involved in two main aspects of OBA: exogenous orienting towards a cued object (Experiment 1; N =33) and attentional deployment within a cued object (Experiment 2; N =23); this is evident by the presence of OBA only when both the cue and target were presented to the same eye. Thus, these results indicate that monocular (mostly subcortical) visual regions are not simply passing information to higher cortical areas but have a functional computational role in OBA. These findings emphasize the importance of lower regions in attentional processes and, more specifically, in OBA.

A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice.

OBJECTIVE: A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose tissue and gene expression, comparing differentially expressed genes in diet-induced obese mice with mice maintained on a chow diet. RESEARCH DESIGN AND METHODS: We used a microarray approach to determine whether there are sexual dimorphisms in gene expression in age-matched male, female or ovariectomized female (OVX) C57/BL6 mice maintained on a high-fat (HF) diet. We then compared expression of validated genes between the sexes on a chow diet. RESULTS: After exposure to a high fat diet for 12 weeks, females gained less weight than males. The microarray analyses indicate in intra-abdominal/gonadal adipose tissue in females 1642 genes differ by at least twofold between the depots, whereas 706 genes differ in subcutaneous/inguinal adipose tissue when compared with males. Only 138 genes are commonly regulated in both sexes and adipose tissue depots. Inflammatory genes (cytokine-cytokine receptor interactions and acute-phase protein synthesis) are upregulated in males when compared with females, and there is a partial reversal after OVX, where OVX adipose tissue gene expression is more 'male-like'. This pattern is not observed in mice maintained on chow. Histology of male gonadal white adipose tissue (GWAT) shows more crown-like structures than females, indicative of inflammation and adipose tissue remodeling. In addition, genes related to insulin signaling and lipid synthesis are higher in females than males, regardless of dietary exposure. CONCLUSIONS: These data suggest that male and female adipose tissue differ between the sexes regardless of diet. Moreover, HF diet exposure elicits a much greater inflammatory response in males when compared with females. This data set underscores the importance of analyzing depot-, sex- and steroid-dependent regulation of adipose tissue distribution and function.

Freeze-fracture and electrophysiological studies of newly developed acetylcholine receptors in Xenopus embryonic muscle cells.

The development of acetylcholine receptors on Xenopus embryonic muscle cells both in culture and in situ was studied using electrophysiology and freeze-fracture electron microscopy. Acetylcholine sensitivity first appeared at developmental stage 20 and gradually increased up to about stage 31. Freeze-fracture of muscle cells that were nonsensitive to acetylcholine revealed diffusely distributed small P-face intramembraneous particles. When cells acquired sensitivity to acetylcholine, a different group of diffusely distributed large P-face particles began to appear. This group of particles was analyzed by subtracting the size distribution found on nonsensitive cells from that found on sensitive cells. We call this group of particles difference particles. The sizes of difference particles were large (peak diameter 11 nm). The density of difference particles gradually increased with development. The density of small particles (less than 9 nm) did not change with development. At later stages (32-36) aggregates of large particles appeared, which probably represent acetylcholine receptor clusters. The size distribution of difference particles was close to that of the aggregated particles, suggesting that at least part of difference particles represent diffusely distributed acetylcholine receptors. Difference particles exist mostly in solitary form (occasionally double), indicating that an acetylcholine receptor can be functional in solitary form. This result also shows that diffuse acetylcholine receptors that have previously been observed with 125I-alpha-bungarotoxin autoradiography do indeed exist in solitary forms not as microaggregates.

Identification of genes potentially involved in rupture of human atherosclerotic plaques.

Although rupture of an atherosclerotic plaque is the major cause of acute vascular occlusion, the exact molecular mechanisms underlying this process are still poorly understood. In this study, we used suppression subtractive hybridization to make an inventory of genes that are differentially expressed in whole-mount human stable and ruptured plaques. Two libraries were generated, one containing 3000 clones upregulated and one containing 2000 clones downregulated in ruptured plaques. Macroarray analysis of 500 randomly chosen clones showed differential expression of 45 clones. Among the 25 clones that showed at least a 2-fold difference in expression was the gene of perilipin, upregulated in ruptured plaques, and the genes coding for fibronectin and immunoglobulin lambda chain, which were downregulated in ruptured plaques. Reverse transcriptase-polymerase chain reaction analysis on 10 individual ruptured and 10 individual stable plaques showed a striking consistency of expression for the clones SSH6, present in 8 ruptured and 2 stable plaques, and perilipin, expressed in 8 ruptured plaques and completely absent in stable plaques. Localization studies of both perilipin mRNA and protein revealed expression in cells surrounding the cholesterol clefts and in foam cells of ruptured atherosclerotic plaques. No expression was observed in nondiseased artery, and only a few cells in the shoulder region of stable plaques tested positive for perilipin. In conclusion, this study shows that it is possible to identify genes that are differentially expressed in whole-mount stable or ruptured atherosclerotic plaques. This approach may yield several potential regulators of plaque destabilization.

Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia.

To investigate whether interleukin 6 (IL-6) might be a potential mediator of the depleted fat reserves observed in malignancy-associated cachexia, we measured lipoprotein lipase (LPL) activity in adipose tissue of mice after administration of IL-6 or tumor necrosis factor and in cultured adipocytes after addition of these cytokines. Injection of IL-6 i.p. reduced adipose tissue LPL activity by 53% within 4.5 to 5.5 h. Injection of tumor necrosis factor elevated serum IL-6 levels and reduced adipose tissue LPL activity by 70%. Both human and murine IL-6 reduced heparin-releasable LPL activity in 3T3-L1 adipocytes in a dose-dependent manner; half-maximal inhibition of LPL activity was achieved with 5000 hybridoma growth factor units/ml. Thus, IL-6 reduces adipose LPL activity and may contribute to the loss of body fat stores associated with some cases of cancer cachexia. Since tumor necrosis factor increases circulating IL-6, some of its effects may be mediated or potentiated by IL-6.

BRL 49653 blocks the lipolytic actions of tumor necrosis factor-alpha: a potential new insulin-sensitizing mechanism for thiazolidinediones.

Thiazolidinediones (TZDs) such as BRL 49653 are a class of antidiabetic agents that are agonists for the peroxisome proliferator-activated nuclear receptor (PPAR-gamma2). In vivo, TZDs reduce circulating levels of free fatty acids (FFAs) and ameliorate insulin resistance in individuals with obesity and NIDDM. Adipocyte production of TNF-alpha is proposed to play a role in the development of insulin resistance, and because BRL 49653 has been shown to antagonize some of the effects of TNF-alpha, we examined the effects of TNF-alpha and BRL 49653 on adipocyte lipolysis. After a 24-h incubation of TNF-alpha (10 ng/ml) with 3T3-L1 adipocytes, glycerol release increased by approximately 7-fold, and FFA release increased by approximately 44-fold. BRL 49653 (10 pmol/l) reduced TNF-alpha-induced glycerol release by approximately 50% (P < 0.001) and FFA release by approximately 90% (P < 0.001). BRL 49653 also reduced glycerol release by approximately 50% in adipocytes pretreated for 24 h with TNF-alpha. Prolonged treatment (5 days) with either BRL 49653 or another PPAR-gamma2 agonist, 15-d delta-12,14-prostaglandin J2 (15-d deltaPGJ2), blocked TNF-alpha-induced glycerol release by approximately 100%. Catecholamine (isoproterenol)-stimulated lipolysis was unaffected by BRL 49653 and 15-d deltaPGJ2. BRL 49653 partially blocked the TNF-alpha-mediated reduction in protein levels of hormone-sensitive lipase and perilipin A, two proteins involved in adipocyte lipolysis. These data suggest a novel pathway that may contribute to the ability of the TZDs to reduce serum FFA and increase insulin sensitivity.

The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes.

HIV protease inhibitors (HPIs) are potent antiretroviral agents clinically used in the management of HIV infection. Recently, HPI therapy has been linked to the development of a metabolic syndrome in which adipocyte insulin resistance appears to play a major role. In this study, we assessed the effect of nelfinavir on glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. An 18-h exposure to nelfinavir resulted in an impaired insulin-stimulated glucose uptake and activation of basal lipolysis. Impaired insulin stimulation of glucose up take occurred at nelfinavir concentrations >10 micromol/l (EC(50) = 20 micromol/l) and could be attributed to impaired GLUT4 translocation. Basal glycerol and free fatty acid (FFA) release were significantly enhanced with as low as 5 micromol/l nelfinavir, displaying fivefold stimulation of FFA release at 10 micromol/l. Yet, the antilipolytic action of insulin was preserved at this concentration. Potential underlying mechanisms for these metabolic effects included both impaired insulin stimulation of protein kinase B Ser 473 phosphorylation with preserved insulin receptor substrate tyrosine phosphorylation and decreased expression of the lipolysis regulator perilipin. Troglitazone pre- and cotreatment with nelfinavir partly protected the cells from the increase in basal lipolysis, but it had no effect on the impairment in insulin-stimulated glucose uptake induced by this HPI. This study demonstrates that nelfinavir induces insulin resistance and activates basal lipolysis in differentiated 3T3-L1 adipocytes, providing potential cellular mechanisms that may contribute to altered adipocyte metabolism in treated HIV patients.

A retrospective analysis of medical or surgical therapy in young patients with diverticulitis.

BACKGROUND: Acute diverticulitis is increasingly being recognized in younger patients, but its management remains controversial. AIM: To compare long-term outcomes of young patients treated with surgery vs. medical therapy for their first episode of diverticulitis. METHODS: A retrospective chart analysis at a university and an affiliated community hospital between 1991 and 2002 revealed 149 patients < or = 40 years of age with confirmed diverticulitis. Forty-nine patients (38 males, 11 females) were contacted at least 1 year after their first episode of diverticulitis. Outcomes were compared based on initial therapy--antibiotics or surgical resection. The groups were compared by outcomes, gender, age, white blood cell count, temperature and diet. RESULTS: Three (15%) of 20 surgical patients (mean follow-up 6.89 years), and 16 (55%) of 29 medical patients had a recurrence of diverticulitis (mean follow-up 5.72 years; P = 0.01). The treatment groups did not differ in age, white blood cell count, or temperature. CONCLUSIONS: (i) Surgical treatment is effective initial therapy but disease may recur in a minority of patients; (ii) medical treatment is less effective initial therapy, with recurrence in half of the patients; (iii) initial presentation is not a strong predictor of disease recurrence.

Depressed 5-hydroxyindole levels associated with hyperactive and aggressive behavior. Relationship to drug response.

Monitoring of 5-hydroxyindole (5-HI) levels in blood in hyperactive institutionalized mentally retarded patients before and after drug therapy revealed depression of 5-HI levels in 83% of hyperactive patients. In these patients with low serotonin levels, elevation of 5-HI levels in blood into the normal range by administration of a variety of psychoactive agents was associated with the disappearance of the hyperkinetic syndrome. Patients who remained hyperactive continued to have low 5-HI levels. Return of hyperactivity upon withdrawal of meidication in patients who were previously well controlled was associated with a fall in 5-HI levels. Adverse responses were seen in these patients when they were treated with medications usually tending to lower 5-HI levels in blood. Medications used in the treatment of hyperactivity may be classified as to whether they usually elevate, lower, or have no significant effect on 5-HI levels in blood.

The short- and long-term effects of tumor necrosis factor-alpha and BRL 49653 on peroxisome proliferator-activated receptor (PPAR)gamma2 gene expression and other adipocyte genes.

Expression of tumor necrosis factor-alpha(TNFalpha) in adipocytes has been reported to correlate with insulin resistance associated with obesity. The thiazolidinediones such as BRL 49653 have been reported to improve insulin sensitivity in obese animals and humans. Although its exact mechanism of action is not known, BRL 49653 has been shown to antagonize some of the inhibitory actions of TNFalpha. BRL 49653 binds and activates the peroxisome proliferator-activated receptor (PPARgamma2), an important nuclear transcription factor in adipocyte differentiation; however, its regulation of PPARgamma2 in differentiated adipocytes is unknown. In this paper, we find that BRL 49653 blocked the ability of TNFalpha to down-regulate the expression and transcription of several adipocyte genes, but BRL 49653 did not prevent TNFalpha from down-regulating PPARgamma2. Moreover, BRL 49653 alone initially decreased the expression of PPARgamma2 mRNA and protein greatly. After 24 h of treatment in 3T3-L1 adipocytes, BRL 49653 down-regulated PPARgamma2 by greater than 90% and potentiated the decrease of PPARgamma2 mRNA by TNFalpha at this time. These unexpected results prompted us to repeat the experiments for a longer time to determine whether BRL 49653 would continue to down-regulate PPARgamma2. With prolonged BRL 49653 treatment, PPARgamma2 mRNA expression was not decreased as greatly, and the protein levels were decreased 20-30% below control at 72 h compared to 90% at 24 h. Although BRL 49653 continued to prevent the inhibitory effects of TNFgamma on perilipin and aP2 mRNA, by 72 h, BRL 49653 was not as potent an inhibitor of TNFalpha's down-regulation of perilipin protein. Since PPARgamma2 protein was more abundant at this time, these results suggest that the level of PPARgamma2 protein is not the sole factor that regulates the transcriptional control by BRL 49653.

Stimulation of collagen synthesis by the anabolic steroid stanozolol.

There is evidence that anabolic steroids, which are derived from testosterone and have markedly less androgenic activity, promote tissue growth and enhance tissue repair; however, the mechanisms involved in their anabolic activities remain unclear. In this report, we measured the effect of the anabolic steroid stanozolol on cell replication and collagen synthesis in cultures of adult human dermal fibroblasts. Stanozolol (0.625-5 microg per ml) had no effect on fibroblast replication and cell viability (p = 0.764) but enhanced collagen synthesis (p < 0.01) in a dose-dependent manner (r = 0.907). Stanozolol also increased (by 2-fold) the mRNA levels of alpha1 (I) and alpha1 (III) procollagen and, to a similar extent, upregulated transforming growth factor-beta1 (TGF-beta1) mRNA and peptide levels (p < 0.001). There was no stimulation of collagen synthesis by testosterone. The stimulatory effects of stanozolol on collagen synthesis were blocked by a TGF-beta1 anti-sense oligonucleotide, by antibodies to TGF-beta, and in dermal fibroblast cultures derived from TGF-beta1 knockout mice. We conclude that collagen synthesis is increased by the anabolic steroid stanozolol and that, for the most part, this effect is due to TGF-beta1. These findings point to a novel mechanism of action of anabolic steroids.

Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid.

The purpose of this study was to determine whether human adipocytes from different depots of obese subjects produce interleukin-6 (IL-6) and whether IL-6 release is regulated by glucocorticoids. Fragments of omental and abdominal sc adipose tissue released immunodetectable IL-6 into the medium during acute incubations. Omental adipose tissue released 2-3 times more IL-6 than did sc adipose tissue. Isolated adipocytes prepared from these tissues also released IL-6 (omental > sc), but this accounted for only 10% of the total tissue release. Culture of adipose tissue fragments for 7 days with the glucocorticoid dexamethasone markedly suppressed IL-6 production. These data show for the first time that substantial quantities of IL-6 (up to 75 ng/mL) accumulate in the medium during incubations of both adipocytes and adipose tissue. Although little is known about the effects of IL-6 on adipose tissue, one action is a down-regulation of adipose tissue lipoprotein lipase. The regulated production of this multifunctional cytokine may modulate regional adipose tissue metabolism and may contribute to the recently reported correlation between serum IL-6 and the level of obesity.

Psychological measures of eating behavior and the accuracy of 3 common dietary assessment methods in healthy postmenopausal women.

BACKGROUND: Factors affecting the accuracy of reported energy intake (rEI) need to be identified. OBJECTIVE: Our objective was to investigate the association of psychological measures of eating behavior with the accuracy of rEI assessed by 7-d weighed intakes, a 24-h recall, and a food-frequency questionnaire. DESIGN: Subjects were 26 restrained eaters aged 60.3 +/- 0.6 y (mean +/- SEM) and weighing 63.8 +/- 1.7 kg and 34 unrestrained eaters aged 59.4 +/- 0.6 y and weighing 64.0 kg. rEI was assessed by using 3 dietary assessment methods and total energy expenditure (TEE) was determined by using doubly labeled water. Calculated EI (cEI) was determined as TEE corrected for the estimated change in body energy. Subjects completed the Eating Inventory. RESULTS: rEI values were significantly lower than TEE values for all 3 dietary assessment methods (P < 0.05); there was no significant relation between rEI and TEE by any method. There was no significant difference in 100 x rEI:TEE between restrained and unrestrained eaters by any of the dietary assessment methods. When combined data from the 3 methods were used, 100 x rEI:cEI was not significantly different from 100% in unrestrained eaters (99 +/- 6.8%) but was lower in restrained eaters (89.1 +/- 5.3%; P < 0.05). There was a positive relation between hunger and 100 x rEI:TEE (P < 0.05). CONCLUSIONS: Low hunger is associated with undereating relative to normal eating during measurement of dietary intake; high dietary restraint may be associated with a reduction in reporting of consumed foods. Dietary hunger and restraint assessed with use of the Eating Inventory may help to identify subjects likely to underreport dietary intake.

Adverse impact of interstitial pulmonary fibrosis on prognosis in polymyositis and dermatomyositis.

Interstitial pulmonary fibrosis occurs in approximately 9% of patients with PM/DM, yet its effect on the course of PM/DM has been scarcely noted. In this report, two patients with PM/DM and IPF were presented to highlight the fact that pulmonary disease can overshadow the primary muscle disorder and progress despite therapy with corticosteroids and nonsteroidal immunosuppression. Our patients were added to previously reported cases and an overview of PM/DM and IPF was presented. Sixty-seven patients with the diagnosis of PM/DM and IPF, with a mean age of 60 +/- 18 years, were identified. Pulmonary complaints were present in 64 cases. Fever was present in 18, arthritis or arthralgias in 11, and Raynaud's phenomenon in 9. Forty percent died after followup of 31 +/- 32 months. This mortality was significantly higher (P less than .05) than that in 745 historical controls with PM/DM without IPF. Progressive IPF was the immediate cause of death in 58% of those who died. A subgroup of 29 patients who had histologic documentation of both myositis and IPF had a mortality of 62% after 22 +/- 25 months. In this latter group, six patients had RP; five of these died. Patients who were not treated with corticosteroids also appeared to fare worse but, given the small number of patients involved, definite conclusions cannot be drawn. We conclude that patients with PM/DM can be adversely affected by the presence of IPF and that this negative impact may be exaggerated by RP and perhaps by lack of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The new obesity genes.

Individual susceptibility to obesity is recognized to be influenced significantly by genetic inheritance. Recently, candidate obesity genes have been identified that may contribute to the inheritance of body fat mass and the partitioning of fat between central and peripheral fat depots. In studies of animal models of obesity, the genetic basis for obesity in the obese (Ob/Ob) mouse, the Fat mouse, and the Yellow (Vvy) mouse has been identified. Further research is needed to determine whether abnormalities in these genes contribute to human obesity as well. In studies of humans, sequence variation in at least six genes has been linked to increased body fatness and/or susceptibility to obesity. In addition, five other encoding genes have been linked to a disproportionate storage of fat in the abdominal region. These genes identified in studies of humans are currently thought to be modifying or background genes, each separately conferring a modest increase in susceptibility to fatness. Further research is needed to identify additional candidate genes that confer susceptibility to obesity and to determine the relative importance of each one in a range of human populations with distinct environments.

Effects of a 6-week hypocaloric diet on changes in body composition, hunger, and subsequent weight regain in healthy young and older adults.

Recent studies have suggested a short-term impairment in the regulation of food intake in older adults, but further studies are needed to determine if a longer-term impairment exists and to identify underlying causes. Changes in body weight and composition were measured over a 6-week underfeeding study and a 6-month follow-up period in healthy young (n = 23) and older (OLD, n = 18) men and women. The young adults were either normal weight (YNW, n = 12) or overweight (YOW, n = 11). Energy intakes during underfeeding were 896 +/- 18 (SEM) kcal less than weight-maintenance energy requirements determined prior to underfeeding. In addition, changes in perceived hunger during underfeeding were monitored in a subgroup (n = 19). OLD and YOW subjects lost significantly more weight during underfeeding than did YNW subjects (p = .025 and .000, respectively), and they did not gain back significant weight in the 6-month follow-up. In addition, OLD subjects reported a significantly lower frequency of hunger during underfeeding (p = .05). There was no significant difference among groups in the relationship between weight lost and fat-free mass lost. Healthy OLD adults have an impaired ability to regulate food intake over at least 6 months following underfeeding compared with YNW adults, and a reduction in their perceived frequency of hunger may be a contributing factor.

Blood glucose and hormonal responses to small and large meals in healthy young and older women.

Blood glucose regulation in the fasting and fed states has important implications for health. In addition, the ability to maintain normal blood glucose homeostasis may be an important determinant of an individual's capacity to regulate food intake. We tested the hypothesis that aging is associated with an impairment in the ability to maintain normal blood glucose homeostasis following the consumption of large meals but not small ones, a factor that could help to explain age-related impairments in the control of food intake and energy regulation. The subjects were eight healthy younger women (25 +/- 2 years, SD) and eight healthy older women (72 +/- 2 years) with normal body weight and glucose tolerance. Following a 36-h period when diet and physical activity were controlled, subjects consumed test meals containing 0, 1046, 2092, and 4184 kJ (simulating extended fasting, and consumption of a snack, a small meal, and a moderately large meal), with 35% of energy from fat, 48% from carbohydrate, and 17% from protein. Each subject consumed each of the test meals on a separate occasion. Serial blood samples were collected at baseline and during 5 h after consumption of the meals. Measurements were made of circulating glucose, insulin, glucagon, free fatty acids, and triglycerides. There was no significant difference between young and older women in their hormone and metabolite responses to fasting and consumption of the 1046-kJ meal. However, following consumption of 2092 and 4148 kJ, older individuals showed exaggerated responses and a delayed return to premeal values for glucose (p = .023), insulin (p = .010), triglycerides (p = .023), and the ratio of insulin to glucagon (p = .026). In conclusion, these results suggest an impairment in the hormonal and metabolite responses to large meals in older women.

Effects of age on energy expenditure and substrate oxidation during experimental overfeeding in healthy men.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of overfeeding on changes in energy expenditure, substrate oxidation, and energy deposition between young men (age 23.7 +/- 1.1 [SEM] years) and older men (age 70.0 +/- 7.0) of normal body weight who were leading unrestricted lives. Changes in total energy expenditure, resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient (RQ), and body energy content were determined in response to overeating by 4.09 +/- 0.07 Megajoule (MJ)/day for 21 days in 16 healthy subjects consuming a typical diet. After excluding data from one young subject with unusual results and adjusting for individual differences in excess energy intake, there was a tendency towards a smaller increase in REE in older men compared to the young men (p = .07) which was accounted for by their lower fat-free mass (p = .016). There was also a significantly smaller increase in resting energy expenditure averaged over fasting and fed states (i.e, REE + TEF) with overfeeding in older men than in young men (p < .01). Combined, these smaller increases in energy expenditure with overfeeding in the older subjects averaged an estimated 365 kilojoule (kJ)/day (8.9% of the excess energy intake) (p < .02). There were also significant effects of age on fasting RQ (p < .001) and the change in RQ with overfeeding (p < .001), but no significant increase in energy expenditure for physical activity and thermoregulation with overfeeding in either age-group. These results are consistent with the suggestion that older individuals experience both a reduction in the ability to increase energy expenditure, and an alteration in the pattern of substrate utilization, in response to overfeeding. These changes may promote cumulative increases in body energy during normal cycles of positive energy balance unless compensated for by adaptive variations in energy intake.

Metabolic, psychological, and health correlates of dietary restraint in healthy postmenopausal women.

BACKGROUND: Dietary restraint, a term used to describe the intentional control of food intake to prevent weight gain or promote weight loss, is commonly practiced by older adults, but little is known about its effects on physiology and metabolism. METHODS: We therefore compared a wide range of parameters between groups of healthy non-obese postmenopausal women classified psychometrically as unrestrained eaters (body mass index [BMI] 23.8 +/- 0.6 [SEM] kg/m(2), n = 28) or restrained eaters (BMI 24.5 +/- 0.5, n = 39). Measurements were made of reported micronutrient intakes, cardiopulmonary function, hematology, body temperature, skin thickness, bone mass, and immune function; in addition, self-perceived health, mood, and some dimensions of eating behavior were assessed by questionnaire. RESULTS: Macronutrient and micronutrient intakes were not significantly different between restrained and unrestrained eaters reporting energy intake to within 30% of predicted total energy expenditure. Restrained eaters had significantly lower hemoglobin (12.9 +/- 0.1 [SEM] vs 13.2 +/- 0.1 g/dl; p <.05), but values were within the normal range in both groups. In addition, restrained eaters scored significantly higher on the Eating Attitudes Test (p <.01) and drive-for-thinness (p <.001) and maturity fears (p <.05) subscores of the Eating Disorders Inventory, but values were again within the normal range. No other parameter differed significantly between groups. CONCLUSIONS: In this normal-weight population, restrained eating was not associated with detrimental effects in a wide range of physiological, metabolic, and health characteristics. Further work is needed to determine the relevance of these results to the general population.

Functional properties of newly inserted acetylcholine receptors in embryonic Xenopus muscle cells.

Single-channel properties of nicotinic acetylcholine receptors in Xenopus embryonic muscles were investigated by the patch clamp technique. Dissociated muscle cells were prepared from embryos in early stages of development (stages 18-19) before innervation takes place, and were cultured without neurons for 4-6 days. Despite the absence of innervation in their history, the cells displayed two classes of acetylcholine receptors, one characterized by a small channel conductance (32 pS), and the other by a large conductance (48 pS) (13 degrees C; agonist, suberyldicholine). The small conductance events had longer mean open times than the large conductance events. Both types of channels had reversal potentials near -15 mV. Hyperpolarization prolonged the open times of both channels; an e-fold change was produced by a 70-80 mV polarization. In order to characterize channel properties of newly inserted receptors, existing receptors were inactivated by alpha-bungarotoxin, and recordings were made over the next 4-8 h. These new receptors already exhibited the two classes of characteristics, which were similar to those of old acetylcholine receptors. These results suggest that innervation is not a prerequisite for expression of the two classes of acetylcholine receptors, and indicate that receptors become functionally mature soon after insertion into the plasma membrane. These results of 'metabolically' new receptors are in sharp contrast with the data of Leonard et al. (Soc. Neurosci. Abstr., 9 (1983) 1180), who reported that 'ontogenetically' new acetylcholine receptors had much longer open times than old receptors.