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T cell regulation of B cell activation. Lyt-1+,2-T cells modify the MHC-restricted function of heterogeneous and cloned T suppressor cells.

Previous studies have shown the existence of both heterogeneous Lyt-1-,2+ suppressor (Ts) cells and cloned Lyt-1+,2- Ts cells which, despite the difference in their Lyt phenotypes, functioned in a similar antigen-specific and major histocompatibility complex (MHC)-restricted fashion to suppress the antibody responses generated by cloned helper T (Th) cells and hapten-primed B cells. Our studies were carried out to assess in further detail the genetically restricted cell interactions that mediate this immune response suppression. We show that the activation of both heterogeneous and cloned Ts cells is antigen-specific and MHC-restricted under our experimental conditions. After appropriate activation, the effector function of both cloned Lyt-1+,2-Ts cells and heterogeneous Lyt-1-,2+ Ts cells was also antigen-specific. In contrast, once activated, Ts cells suppressed the responses generated by cloned Th cells and hapten-primed B cells in an MHC-unrestricted fashion. We also showed, however, that a population of unprimed Lyt-1+,2-T cells was able to significantly alter the genetic restriction requirements for Ts cell function. The activity of this population was itself MHC-restricted, and was observed only when the unprimed Lyt-1+,2-T cells shared the MHC restriction specificity of the cloned Th cells functioning in a given response. When these requirements were satisfied, Lyt-1+,2- T cells significantly modified the suppression mediated by both heterogeneous and cloned Ts cells, resulting in suppression that was then MHC restricted in its effector function as well as in its activation requirements. Thus, our findings suggest that the observed MHC restriction in Ts function is the result of a complex interaction involving Ts cells, Th cells, and an additional population of MHC-restricted Lyt-1+,2- T cells. This newly characterized activity of Lyt-1+,2- T cells functionally resembles that of an MHC-restricted contrasuppressor population that selectively blocks a pathway of MHC-unrestricted Ts activity, while leaving intact susceptibility to MHC-restricted Ts effects.

Animals↗

Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones.

We have examined requirements for antigen presentation to a panel of MHC class I-and class II-restricted, influenza virus-specific CTL clones by controlling the form of virus presented on the target cell surface. Both H-2K/D- and I region-restricted CTL recognize target cells exposed to infectious virus, but only the I region-restricted clones efficiently lysed histocompatible target cells pulsed with inactivated virus preparations. The isolated influenza hemagglutinin (HA) polypeptide also could sensitize target cells for recognition by class II-restricted, HA-specific CTL, but not by class I-restricted, HA-specific CTL. Inhibition of nascent viral protein synthesis abrogated the ability of target cells to present viral antigen relevant for class I-restricted CTL recognition. Significantly, presentation for class II-restricted recognition was unaffected in target cells exposed to preparations of either inactivated or infectious virus. This differential sensitivity suggested that these H-2I region-restricted CTL recognized viral polypeptides derived from the exogenously introduced virions, rather than viral polypeptides newly synthesized in the infected cell. In support of this contention, treatment of the target cells with the lysosomotropic agent chloroquine abolished recognition of infected target cells by class II-restricted CTL without diminishing class I-restricted recognition of infected target cells. Furthermore, when the influenza HA gene was introduced into target cells without exogenous HA polypeptide, the target cells that expressed the newly synthesized protein product of the HA gene were recognized only by H-2K/D-restricted CTL. These observations suggest that important differences may exist in requirements for antigen presentation between H-2K/D and H-2I region-restricted CTL. These differences may reflect the nature of the antigenic epitopes recognized by these two CTL subsets.

Animals↗

Regulation of hepatic transthyretin messenger RNA levels during moderate protein and food restriction in rats.

This study was designed to determine whether the decrease in serum transthyretin that occurs during food restriction results from gross energy reduction or from depressed protein or lipid intake and to examine the relationship between serum transthyretin and hepatic transthyretin mRNA during moderate protein or food deficiency. Groups of young rats were allowed free access to either a 18% (control) or a 6% protein diet (protein-restricted), or reduced intakes. The food-restricted groups received 60% of control intake from the control diet, a 40% protein-enriched diet, or a 40% lipid-enriched diet, for 28 d. Serum transthyretin concentrations were lower in all experimental groups on d 7 relative to the control group. Control values were reached only in the protein-restricted group by d 14. The low serum transthyretin levels, which were similar in the food-restricted groups, likely resulted from gross energy restriction. Hepatic transthyretin mRNA levels were determined in the control, protein-restricted and food-restricted groups. They were unchanged relative to controls in the protein-restricted group but declined moderately in the food-restricted group on d 7 and 14, before returning to control values by d 28. Thus, the changes in liver transthyretin mRNA levels could partially explain the changes in serum transthyretin in food-restricted rats.

Animals↗

Protein restriction during pregnancy affects postnatal growth in swine progeny.

Protein deficiency during pregnancy affects fetal development. The critical period, when the fetus is most susceptible to maternal protein deficiency and its effect on neonatal growth, is unknown. Therefore, we studied the effect of a protein-restricted diet during early and late pregnancy and throughout pregnancy on growth of pigs from birth to market weight. Sows were fed a control (13% protein) or protein-restricted (0.5% protein) diet throughout pregnancy or protein-restricted diet from d 1 to 44, then control diet to term or control diet from d 1 to 81, then the protein-restricted diet to term. In Experiment 1, birth weights were measured, and 12 pigs/diet group were weaned at 4 wk and raised to market weight. Feeding the protein-restricted diet throughout pregnancy reduced birth and slaughter weights, whereas the control followed by protein-restricted and protein-restricted followed by control diets reduced only birth weight relative to controls. Indices of carcass lean were reduced in the protein-restricted piglets, with carcass fat not affected. In Experiment 2, control and control-protein-restricted litters were reduced to six piglets and 3/litter cross-fostered to a sow of the other treatment group. After weaning at 4 wk, 4 piglets/group were individually fed to 8 wk. The control and control followed by protein-restricted diet fed piglets had similar weights at birth, but piglets raised by a control-protein-restricted sow tended to weight less at weaning than their littermates raised by a control sow. After weaning, these piglets had greater feed intakes relative to other groups and there were no weight differences by 8 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electroacupuncture stimulation suppresses the increase in alcohol-drinking behavior in restricted rats.

BACKGROUND: Although a number of studies on traditional eastern or Chinese medicine, such as acupuncture, moxibustion, and herbal drugs, have been reported, few reports describe electroacupuncture (EAC) effects on drug- and alcohol-seeking behaviors in animal models. The purpose of the present study was to investigate the effect of EAC on changes in alcohol-drinking behavior in rats challenged with restriction and immobilization stress. MATERIAL AND METHODS: Male Sprague Dawley rats (260-280 g) were tightly hung and immobilized in restriction models for 10 min. These immobilization stresses were performed twice a week for 1 week and for 3 consecutive weeks for the short- and long-restricted stress groups, respectively. EAC was applied for 10 min to the hindlimb point, Tsu-San-Li (ST 36), and the lumbar point, Shen-Shu (BL 23). These points are used to treat mental and psychosomatic disorders and are known clinically to produce a sedation effect. Time-access alcohol-drinking behavior was determined at 24 hr after the termination of EAC. Finally, brain dopamine (DA) levels were assayed in the two groups. A sham-control group underwent only restricted stress without EAC. RESULTS: Time-access alcohol-drinking behavior increased significantly in the long-restricted group compared with the short-restricted group and controls. EAC applied to the ST 36 (Tsu-San-Li) point suppressed the increased alcohol-drinking behavior in restricted rats. However, EAC applied to the Shen-Shu (BL 23) point was not effective, because alcohol-drinking behavior was significantly increased in long-restricted rats compared with short-restricted rats. Striatal DA levels of restricted rats with EAC stimulated at Tsu-San-Li were increased significantly compared with the rats with EAC applied to the Shen-Shu point. CONCLUSION: These findings suggest that EAC applied at ST 36 (Tsu-San-Li) was more effective for reducing the increased alcohol-drinking behavior in restricted rats, and they showed that a point specific in EAC procedure was associated with an increase of striatal DA levels. These findings provide new information for understanding alcohol-drinking behavior and for treating human alcoholics.

Alcohol Drinking↗

Capsid processing requirements for abrogation of Fv1 and Ref1 restriction.

Murine leukemia virus is restricted in mouse cells lines by a host factor known as Fv1 and in human cell lines by Ref1. Genetic evidence indicates that these restriction factors target the virus capsid (CA) protein. Restriction can be overcome by adding virus at a high multiplicity of infection, indicating that the restriction factors can be saturated. Cells preexposed to restricted virus will allow infection by a second virus which would normally be restricted. This phenomenon is known as abrogation; it provides us with a tool with which to study the interaction of virus with restriction factors. We tested the abilities of several Gag processing mutants to abrogate restriction. Our results show that CA must be cleaved from both p12 and nucleocapsid in order for the incoming virion to interact with the restriction factor. Endogenous expression of properly processed CA, however, failed to abrogate restriction. These results suggest that as well as being processed, CA must also be properly assembled in the form of a condensed viral core in order to interact with Fv1 and Ref1. This polymeric structure may contain restriction factor binding sites not present in monomeric CA.

Animals↗

Effect of water restriction on feeding and metabolism in dairy cows.

We investigated how lactating cows are able to cope with a sustained water restriction. In experiment 1, body weight and meal patterns were recorded with ad libitum access to water (baseline) and during 8 days of 25 and 50% restriction of drinking water relative to ad libitum intake. In experiment 2, indirect calorimetry was combined with nitrogen and energy balance and plasma hormone and metabolite measurements to assess the effects of 50% water restriction on digestion and metabolism. In experiment 1, food intake and body weight declined during the first 3 days of water restriction depending on the restriction level and stabilized thereafter at a lower level. The daily food intake reduction with 50% water restriction was entirely due to a reduction of meal size. The size of the first meal on every day was markedly (>50%) reduced with 25 and 50% water restriction. In experiment 2, urea concentrations in milk and blood as well as plasma sodium and hematocrit were increased by 50% water restriction. Energy balance was not affected by 50% water restriction, but nitrogen balance became negative, because, relative to intake, nitrogen excretion via urine and milk was higher. The lower energy intake during 50% water restriction was compensated by a lower milk production, a higher digestibility of organic matter and energy, and, apparently, a more efficient energy use. Through these changes and a preserved water balance, the cows reached a new equilibrium at a lower water turnover level, which enabled them to cope with a sustained drinking water restriction of 50%.

Animals↗

Mortality rate and longevity of food-restricted exercising male rats: a reevaluation.

Food restriction increases the maximal longevity of rats. Male rats do not increase their food intake to compensate for the increase in energy expenditure in response to exercise. However, a decrease in the availability of energy for growth and cell proliferation that induces an increase in maximal longevity in sedentary rats only results in an improvement in average survival, with no extension of maximal life span, when caused by exercise. In a previous study (J.O. Holloszy and K.B. Schechtman. J. Appl. Physiol. 70:1529-1535, 1991), to test the possibility that exercise prevents the extension of life span by food restriction, wheel running and food restriction were combined. The food-restricted runners showed the same increase in maximal life span as food-restricted sedentary rats but had an increased mortality rate during the first one-half of their mortality curve. The purpose of the present study was to determine the pathological cause of this increased early mortality. However, in contrast to our previous results, the food-restricted wheel-running rats in this study showed no increase in early mortality, and their survival curves were virtually identical to those of sedentary animals that were food restricted so as to keep their body weights the same as those of the runners. Thus it is possible that the rats in the previous study had a health problem that had no effect on longevity except when both food restriction and exercise were superimposed on it. Possibly of interest in this regard, the rats in this study did considerably more voluntary running than those in the previous study. It is concluded that 1) moderate caloric restriction combined with exercise does not normally increase the early mortality rate in male rats, 2) exercise does not interfere with the extension of maximal life span by food restriction, and 3) the beneficial effects of food restriction and exercise on survival are not additive or synergistic.

Animals↗

Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size.

Age-related decreases of hormone-sensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormone-sensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) and in the presence of maximally stimulating concentrations of glucagon, ACTH, epinephrine, and fluoride. Activities were calculated per milligram ghost protein or per cell. Restriction of food intake for 3 mo starting at 1 or 12 mo produced fat cells equal in size to those of 5-wk-old animals fed ad lib. In young animals restricted for 1 mo, hormone-stimulated activity expressed as fold increase (stimulated/basal) was not merely maintained as the cells were prevented from enlarging, but was enhanced two to three times over the initial values with all three hormones. With continued restriction epinephrine-sensitive activity remained two times increased. Glucagon and ACTH responses subsequently decreased, but even by 3 mo of restriction, responses to the latter hormones, although declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal- and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an "increase of responsiveness" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormone-responsive adenylate cyclase under conditions of dietary restriction...

Adenylyl Cyclases↗

The effects of acute and life-long food restriction on basal and stress-induced serum corticosterone levels in young and aged rats.

The effects of short term (1-month) and life-long 60% ad libitum food restriction on the adrenocortical response to restraint stress were compared in young and aged Fischer 344 rats. In rats restricted for 1 month (study 1), the adrenocortical response differed as a function of age. In 8-month-old animals, the initial steep rise in corticosterone in response to stress was of similar magnitude in ad libitum and restricted animals. In 23-month-old animals the corticosterone response was severely blunted in restricted animals. In life-long restricted animals (study 2), the corticosterone response to restraint stress was tested at 8, 16, and 24 months of age. The general pattern of response to stress in these animals was similar to that in study 1. The 16- and 24-month-old animals showed the same blunted response to stress found in the 23-month-old animals restricted for only 1 month, suggesting that the severe restriction per se and not life-long food restriction blunted the response to stress in aged animals. The similarity between the response to stress in study 1 and study 2 was evident even though animals were tested in one case before feeding when corticosterone levels were high, and in the other 4-5 h after feeding when corticosterone levels were lower. In study 3 it was found that in food-restricted young rats, the mean corticosterone level over a 24-h period was significantly elevated above that in ad libitum fed young rats. In aged rats, however, except before daily feeding, corticosterone levels of food-restricted rats remained significantly below those of ad libitum fed animals, whose levels were, in turn, significantly elevated compared to those of ad libitum fed young rats. These findings suggest that in aged animals severe food restriction reduces basal corticosterone levels, adrenal responsiveness to stress, and adrenal size and has the potential to protect against the consequences of high corticosterone levels in aging.

Adrenal Cortex↗

Dietary protein restriction stress and adrenocortical function: evidence for transient and long-term induction of enhanced cellular function.

Previous work has demonstrated that 4-week protein restriction of the domestic fowl (Gallus gallus domesticus) increases both adrenocortical cell sensitivity to ACTH and corticosteroidogenic capacity. In the present study we examined the transience (study 1) and the persistence (study 2) of this effect of protein restriction. In study 1, two strains of domestic fowl were used: a slower-growing White Leghorn strain and a faster-growing Cobb broiler strain. Cockerels (2 weeks old) were fed isocaloric diets containing either low (L; 5% or 8%) or control (C; 20%) levels of soy protein for 2 weeks, and then were either switched to the alternate diet (C-L, L-C) or maintained on the initial diet (C-C, L-L) for an additional 2 weeks. Cockerels were killed at 6 weeks of age. In study 2, White Leghorn cockerels (2 weeks old) were fed either diet for 4 weeks and then switched to or maintained on the control diet for an additional 4 weeks (i.e. C vs. restriction followed by repletion). In this study cockerels were killed at 10 weeks of age. In both studies highly enriched populations of adrenocortical cells were isolated from cockerel adrenal glands, and their steroidogenic properties (basal and maximally induced corticosterone and cAMP production; steroidogenic agent ED50 values) were evaluated in 2-h suspension incubations. In study 1, regardless of strain, the greater the length of the restriction period, the greater the magnitude of maximal cellular corticosterone production induced by ACTH; the average value for 4-week restriction (L-L) was 39.5% greater than that for 2-week restriction (L-C, C-L) and 117.5% greater than that for control (C-C). In addition, the value for restriction from 4-6 weeks of age (C-L) was 34% greater than that for restriction from 2-4 weeks of age (L-C), suggesting that the enhancement of maximal ACTH-induced corticosterone production after a 2-week restriction interval might be transient. Although there were no strain differences in the effect of protein restriction on maximal ACTH-induced corticosterone production, there were strain differences in its effect on cellular sensitivity to ACTH, as indicated by the ACTH ED50 values (the lower the ED50 value, the greater tha cellular sensitivity). With the White Leghorn strain, the greater the duration of protein restriction, the greater the adrenocortical cell sensitivity to ACTH; the sensitivity of L-L cells was 3.0 times the sensitivities of L-C and C-L cells and 4.1 times the sensitivity of C-C cells.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

Restriction in complex activities of daily living in MCI: impact on outcome.

OBJECTIVE: To describe the restriction in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess the impact of IADL restriction on the progression to dementia and on MCI reversibility. METHODS: The study sample included 1,517 participants of the PAQUID cohort, visited at 8- and 10-year follow-ups. Subjects classified as having MCI had no dementia but a cognitive deficit according to five neuropsychological tests. Four IADL (telephone, transports, medication, finances) were assessed and considered restricted if at least two of them were not performed at the highest level of performance. Cross-sectional and longitudinal analyses were conducted. RESULTS: A total of 285 subjects were classified as having MCI at baseline, and 15.2% developed dementia within 2 years. MCI subjects were more frequently IADL restricted (34.3%) than controls (5.4%) but less than those with dementia (91.1%). The IADL-restricted MCI subjects were more likely to develop dementia over 2 years (30.7%) than the nonrestricted ones (7.8%). In multivariate analyses, the odds ratio for dementia was 7.4 (CI: 3.3 to 16.5) in the IADL-restricted MCI and 2.8 (CI: 1.3 to 6.0) in the non-IADL-restricted MCI compared with the non-IADL-restricted controls. IADL restriction also lowered the chance of reversibility to normal, observed in 10.7% of the restricted MCI and 34.7% of the nonrestricted MCI. CONCLUSIONS: Inclusion of instrumental activities of daily living restriction in the criteria of mild cognitive impairment improves the prediction of dementia and the stability of this status over time. Conversely, its exclusion results in inappropriate selection of subjects with a low probability of short-term progression to dementia.

Activities of Daily Living↗

A possible thermodynamic approach to the change of rectal temperature of rabbits due to forced restricting conditions.

It was found that the rectal temperature of rabbits restricted by a normal neck stock position dropped about 1.2-1.5 degrees C when the restriction position changed from a normal restriction to a supine restriction position. This temperature change was also reversible. We studied the mechanisms of this phenomenon from a thermodynamic point of view and obtained the following results: 1) The rectal temperature of rabbit restricted in the supine position did not increase after the injection of lipopolysaccharide (LPS). 2) In the supine restricted rabbit, endogenous pyrogen which was induced by the injection of LPS to these rabbits appeared the same as the control. 3) Some pharmaceuticals (urethan, iproniazid, atropin and hexamethonium) did not show any influence on the drop of rectal temperature in either normal or supine restrictions. 4) The rectal temperature of shorn rabbits dropped more than that of normal rabbits in both normal and supine restrictions. 5) When the normal restriction position was changed to the supine and prone restriction positions, the mean surface temperature was also decreased. From these results, it was concluded that rabbit rectal temperature was changed with a change in the restriction position which could change the surface skin area.

Animals↗

Pain among children and adolescents: restrictions in daily living and triggering factors.

OBJECTIVES: Pain among children and adolescents has been identified as an important public health problem. Most studies evaluating recurrent or chronic pain conditions among children have been limited to descriptions of pain intensity and duration. The effects of pain states and their impact on daily living have rarely been studied. The objective of this study was to investigate the impact of perceived pain on the daily lives and activities of children and adolescents. In addition, we sought to delineate self-perceived triggers of pain among children and adolescents. In this study, we (1) document the 3-month prevalence of painful conditions among children and adolescents, (2) delineate their features (location, intensity, frequency, and duration), (3) describe their consequences (restrictions and health care utilization), and (4) elucidate factors that contribute to the occurrence of pain episodes among young subjects. METHODS: The study was conducted in 1 elementary school and 2 secondary schools in the district of Ostholstein, Germany. Children and adolescents, as well as their parents/guardians, were contacted through their school administrators. The teachers distributed an information leaflet, explaining the conduct and aim of the study, to the parents a few days before the official enrollment of the youths in the study. Parents of children in grades 1 to 4 of elementary school were asked to complete the pain questionnaire for their children at home, whereas children from grade 5 upward completed the questionnaire on their own during class, under the supervision of their teachers. The response rate was 80.3%. As previously stated, chronic pain was defined as any prolonged pain that lasted a minimum of 3 months or any pain that recurred throughout a minimal period of 3 months. The children and adolescents were surveyed with the Luebeck Pain-Screening Questionnaire, which was specifically designed for an epidemiologic study of the characteristics and consequences of pain among children and adolescents. The questionnaire evaluates the prevalence of pain in the preceding 3 months. The body area, frequency, intensity, and duration of pain are addressed by the questionnaire. In addition, the questionnaire inquires about the private and public consequences of pain among young subjects. Specifically, the questionnaire aims to delineate the self-perceived factors for the development and maintenance of pain and the impact of these conditions on daily life. RESULTS: Of the 749 children and adolescents, 622 (83%) had experienced pain during the preceding 3 months. A total of 30.8% of the children and adolescents stated that the pain had been present for >6 months. Headache (60.5%), abdominal pain (43.3%), limb pain (33.6%), and back pain (30.2) were the most prevalent pain types among the respondents. Children and adolescents with pain reported that their pain caused the following sequelae: sleep problems (53.6%), inability to pursue hobbies (53.3%), eating problems (51.1%), school absence (48.8%), and inability to meet friends (46.7%). The prevalence of restrictions in daily living attributable to pain increased with age. A total of 50.9% of children and adolescents with pain sought professional help for their conditions, and 51.5% reported the use of pain medications. The prevalence of doctor visits and medication use increased with age. Weather conditions (33%), illness (30.7%), and physical exertion (21.9%) were the most frequent self-perceived triggers for pain noted by the respondents. A total of 30.4% of study participants registered headache as the most bothersome pain, whereas 12.3% cited abdominal pain, 10.7% pain in the extremities, 8.9% back pain, and 3.9% sore throat as being most bothersome. A total of 35.2% of children and adolescents reported pain episodes occurring > or =1 time per week or even more often. Health care utilization because of pain differed among children and adolescents according to the location of pain. Children and adolescents with back pain (56.7%), limb pain (55.0%), and abdominal pain (53.3%) visited a doctor more often than did those with headache (32.5%). In contrast, children and adolescents with headache (59.2%) reported taking medication because of pain more often than did those with back pain (16.4%), limb pain (22.5%), and abdominal pain (38.0%). The prevalence of self-reported medication use and doctor visits because of pain increased significantly with age (chi2 test). The prevalence of self-reported medication use was significantly higher among girls than among boys of the same age, except between the ages of 4 and 9 years (chi2 test). The prevalence of restrictions in daily activities varied among children and adolescents with different pain locations; 51.1% of children and adolescents with abdominal pain and 43.0% with headache but only 19.4% with back pain reported having been absent from school because of pain. The prevalence of restrictions attributable to pain was significantly higher among girls than among boys of the same age, except between the ages of 4 and 9 years (chi2 test). The self-reported triggers for pain varied between girls and boys. Girls stated more often than boys that their pain was triggered by weather conditions (39% vs 25%), illness (eg, common cold or injury) (35.9% vs 23.9%), anger/disputes (20.9% vs 11.9%), family conditions (12.1% vs 5.2%), and sadness (11.9% vs 3.4%). In contrast, boys stated more often than girls that their pain was triggered by physical exertion (28% vs 17.2%). We used a logistic regression model to predict the likelihood of a child paying a visit to the doctor and/or using pain medication. Health care utilization was predicted by increasing age, greater intensity of pain, and longer duration of pain but not by the frequency of pain. We used a logistic regression model to predict restrictions in daily activities. Only the intensity of pain was predictive of the degree of restrictions in daily life attributable to pain; the duration of pain and the frequency of pain episodes had no bearing on the degree to which the daily lives of the children were restricted because of pain. CONCLUSIONS: More than two thirds of the respondents reported restrictions in daily living activities attributable to pain. However, 30 to 40% of children and adolescents with pain reported moderate effects of their pain on school attendance, participation in hobbies, maintenance of social contacts, appetite, and sleep, as well as increased utilization of health services because of their pain. Restrictions in daily activities in general and health care utilization because of pain increased with age. Girls > or =10 years of age reported more restrictions in daily living and used more medications for their pain than did boys of the same age. We found gender-specific differences in self-perceived triggers for pain. Pain intensity was the most robust variable for predicting functional impairment in > or =1 areas of daily life. Increasing age of the child and increasing intensity and duration of pain had effects in predicting health care utilization (visiting a doctor and/or taking medication), whereas restrictions in daily activities were predicted only by the intensity of pain. Our results underscore the relevance of pediatric pain for public health policy. Additional studies are necessary and may enhance our knowledge about pediatric pain, to enable parents, teachers, and health care professionals to assist young people with pain management, allowing the young people to intervene positively in their conditions before they become recurrent or persistent.

Activities of Daily Living↗

Effects of feeding growing cattle high-concentrate diets at a restricted intake on feedlot performance.

Three trials were conducted to compare effects of restricted intake of high-concentrate diets vs ad libitum intake of corn silage diets during the growing phase on feedlot cattle performance. In Trial 1, 120 steers (initial BW, 246 kg) were fed 1) a corn silage-based diet ad libitum, 2) a high-moisture corn-corn silage-based diet with intake restricted to a level 20% less than that of the corn silage diet or 3) a high-moisture corn-based diet with intake restricted to a level 30% less than that of the corn silage diet. Steers fed the 20% restricted corn-corn silage-based diet tended (P = .07) to gain slower than those fed the corn silage or 30% restricted high-concentrate diet. Feed efficiency and diet digestibility were greatest for steers fed the 30% restricted-intake, high-concentrate diet (P less than .01). Performance of steers during the subsequent 118-d finishing period was not affected (P greater than .65) by source of energy during the growing period. In Trial 2, ADG of steers fed the 30% intake-restricted, high-concentrate diet was lower (P less than .01) than that of steers with ad libitum access to corn silage. During the 84-d growing period, steers fed supplemental blood meal had 8.3% greater gains and a 6% greater efficiency of feed use than those fed supplemental soybean meal (P less than .01). Monensin did not affect (P = .82) performance of steers fed 30% restricted-intake diets. During the 76-d finishing period, gains and feed conversion were improved (P less than .01) for steers fed the restricted-intake diet in the growing period compared with those given ad libitum access to corn silage. During the growing period in Trial 3, ADG of steers restricted-fed an all-concentrate diet were slightly greater (P less than .10) than ADG of those given ad libitum access to corn silage. Gains did not differ (P = .37) during the subsequent finishing period when steers were switched to 85 or 100% concentrate diets. We concluded that intake of all concentrate diets can be restricted to achieve gains equal to those of steers given ad libitum access to corn silage-based diets without detrimental effects on finishing performance.

Animal Feed↗

Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions.

Maternal nutrient restriction from early to midgestation can lead to fetal growth retardation, with long-term impacts on offspring growth, physiology, and metabolism. We hypothesized that ewes from flocks managed under markedly different environmental conditions and levels of nutrition might differ in their ability to protect their own fetus from a bout of maternal nutrient restriction. We utilized multiparous ewes of similar breeding, age, and parity from 2 flocks managed as 1) ewes adapted to a nomadic existence and year-long, limited nutrition near Baggs, WY (Baggs ewes), and 2) University of Wyoming ewes with a sedentary lifestyle and continuous provision of more than adequate nutrition (UW ewes). Groups of Baggs ewes and UW ewes were fed 50 (nutrient restricted) or 100% (control fed) of National Research Council recommendations from d 28 to 78 of gestation, then necropsied, and fetal and placental data were obtained. Although there was a marked decrease (P < 0.05) in fetal weight and blood glucose concentrations in nutrient-restricted vs. control fed UW ewes, there was no difference in these fetal measurements between nutrient-restricted and control-fed Baggs ewes. Nutrient-restricted and control-fed UW ewes exhibited predominantly type A placentomes on d 78, but there were fewer (P c0.05) type A and greater (P < 0.05) numbers of type B, C, and D placentomes in nutrient-restricted than control-fed Baggs ewes. Placental efficiency (fetal weight/placentomal weight) was reduced (P = 0.04) in d 78 nutrient-restricted UW ewes when compared with control-fed UW ewes. In contrast, nutrient-restricted and control-fed Baggs ewes exhibited similar placental efficiencies on d 78. This is the first report of different placental responses to a nutritional challenge during pregnancy when ewes were selected under different management systems. These data are consistent with the concept that Baggs ewes or their conceptuses, which were adapted to both harsh environments and limited nutrition, initiated conversion of type A placentomes to other placentomal types when subjected to an early to mid-gestational nutrient restriction, whereas this conversion failed to occur in UW ewes. This early placentomal conversion in the Baggs ewes may function to maintain normal nutrient delivery to their developing fetuses during maternal nutrient restriction.

Animal Husbandry↗

Effects of feed restriction on production performance of replacement pullets.

Two experiments were conducted to evaluate the effects of feed restriction on production performance of egg production pullets. In Experiment 1, two brown-egg strains (A and B) were subjected to full feeding, a restricted duration of feeding program, and a quantitative feed restriction program. Two White Leghorn strains (C and D) were subjected to full feeding and restricted duration of feeding only. For Experiment 2, only strains B and D were used and an additional restricted duration of feeding program was studied. Pullets were maintained on these programs to 20 weeks of age. Production data were collected to 66 and 62 weeks of age for Experiments 1 and 2, respectively. Restricted duration of feeding was found to depress body weight by 2 to 3%, and quantitative feed restriction depressed body weight by 5% with feed intake depressed by the same magnitudes. Feed restriction at these levels had no significant effects on hen-day or hen-housed egg production, egg weight, egg mass, or egg grades. Net egg income over feed cost was significantly improved by feed restriction in Experiment 2. Pullets on quantitative restriction produced the greatest returns. This was due to increased numbers of large eggs and the decrease in rearing feed consumption. Feed restriction had no effect on mortality or sexual maturity. Feed consumption, body weight, egg weight, and economic returns were higher for the heavy strain of pullets. Mortality was highest within the light strains.

Animals↗

Mycobacterium tuberculosis-reactive CD8+ T lymphocytes: the relative contribution of classical versus nonclassical HLA restriction.

Previous studies in mice and humans models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). In humans, CD8+ Mtb-reactive T cells have been described that are HLA-A2-, B52-, as well as CD1-restricted. Recently, we have described Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or C- nor group 1 CD1-restricted. At present, little is known about the relative contribution of each of these restriction specificities to the overall CD8+ response to Mtb. An IFN-gamma enzyme-linked immunospot assay was used to determine the frequency of Mtb-reactive CD8+ T cells directly from PBMC. The effector cell frequency among five healthy purified protein derivative-positive subjects was 1/7,600 +/- 4,300 compared with 1/16,000 +/- 7,000 in six purified protein derivative-negative controls. To determine the frequencies of classically, CD1-, and nonclassically restricted cells, a limiting dilution analysis was performed. In one purified protein derivative-positive subject, 192 clones were generated using Mtb-infected dendritic cells (DC). Clones were assessed for reactivity against control autologous DC, Mtb-infected autologous DC, and HLA-mismatched CD1+ targets (DC), as well as HLA-mismatched CD1- targets (macrophages). Of the 96 Mtb-reactive CD8+ T cell clones, four (4%) were classically restricted and 92 (96%) were nonclassically restricted. CD1-restricted cells were not detected. Of the classically restricted cells, two were HLA-B44 restricted and one was HLA-B14 restricted. These results suggest that while classically restricted CD8+ lymphocytes can be detected, they comprise a relatively small component of the overall CD8+ T cell response to Mtb. Further definition of the nonclassical response may aid development of an effective vaccine against tuberculosis.

Antigen-Presenting Cells↗