Comparison of gene expression profiles of the jejunum of broilers supplemented with a yeast cell wall-derived mannan oligosaccharide versus bacitractin methylene disalicylate.

1. The addition of yeast cell wall (YCW) mannan fractions or low concentrations of antibiotics to the diet of broilers positively affects gut health by improving intestinal cell morphology and improves feed efficiency and performance; however the exact mechanisms are unclear. Based on these production responses, the objective of this study was to compare the effects of supplementing YCW and bacitracin methylene disalicylate (BMD) in the diet on mRNA levels in the jejunum of 6-week-old broilers. 2. Dietary treatments were a maize-soya control diet and the control diet with the addition of YCW or BMD. Birds (n = 7) from each dietary treatment were randomly selected and killed at d 42. Whole jejunum (with serosa) samples were collected for RNA isolation. Gene expression analysis was performed using the AffymetrixGeneChip Chicken Genome Array (Santa Clara, CA, USA). 3. Supplementation with YCW resulted in 928 genes that were significantly changed (456 down-regulated, 472 up-regulated) and supplementation with BMD resulted in 857 genes that significantly changed (408 down-regulated, 449 up-regulated). In addition, 316 genes were significantly changed by both YCW and BMD (146 down-regulated, 170 up-regulated). 4. BMD increased the expression of genes involved in lipid and carbohydrate metabolism and decreased expression of genes associated with T-helper cell pathways. Gene expression profiles from birds fed on diets containing YCW showed changes on a genomic level that correspond to slower gut cell turnover and therefore increased energy preservation for growth. 5. In conclusion, supplementation with BMD or YCW had similar influences on the number of differentially expressed genes in the jejunum. Biological functions common to both YCW and BMD with positive activation scores included antiviral response and antimicrobial response. Genes that were affected by BMD or YCW classified into both different and common biological functions and pathways related to improved metabolism and health in the jejunum.

Effects of yeast cell wall-derived mannan-oligosaccharides on jejunal gene expression in young broiler chickens.

The use of mannan-oligosaccharides (MOS) as alternatives to antibiotic growth promoters (AGP) has gained in popularity in recent years due to regulatory restrictions of using AGP in food animal production. Benefits of MOS usage include improvement on animal performance, feed efficiency, and gastrointestinal health. The molecular mechanisms of these functions however are not clear. The goal of the current study was to use a transcriptomics approach to investigate the effects of MOS on the intestinal gene expression profile of young broilers and characterize biological gene pathways responsible for the actions of MOS. One hundred and twenty 1-d-old Cobb 500 broiler chicks were randomly divided into 2 groups and were fed either a standard wheat-soybean meal-based (control) diet or the same diet supplemented with 2.2 g/kg of MOS (Bio-Mos, Alltech, Nicholasville, KY) for 3 wk, followed by jejunal gene expression profiling analysis using chicken-specific Affymetrix microarrays. Results indicated that a total of 672 genes were differentially expressed (P < 0.01 and fold change >1.2) in the jejunum by MOS supplementation. Association analysis indicated that differentially expressed genes are involved in diverse biological functions including energy production, cell death, and protein translation. Expression of 77 protein synthesis-related genes was differentially regulated by MOS in the jejunum. Further pathway analysis indicated that 15 genes related to oxidative phosphorylation were upregulated in the jejunum, and expression of genes important in cellular stress response, such as peroxiredoxin 1, superoxide dismutase 1, and thioredoxin, were also increased by MOS. Differential expression of genes associated with cellular immune processes, including lysozyme, lumican, ß 2-microglobin, apolipoprotein A-1, and fibronectin 1, were also observed in MOS-fed broilers. In summary, this study systematically identified biological functions and gene pathways that are important in mediating the biological effects of MOS in broilers.

A comparative transcriptomic study of vitamin E and an algae-based antioxidant as antioxidative agents: investigation of replacing vitamin E with the algae-based antioxidant in broiler diets.

Previous study indicated that inclusion of an algae-based antioxidant as an antioxidative agent [EconomasE, Alltech, Nicholasville, KY; EcoE] significantly reduced the amount of vitamin E (VE) required in broiler diets without compromising performance and meat quality. To assess the mechanisms related to the VE-saving activity of EcoE, as well as other potential functions related to EcoE and VE supplementation, we analyzed gene expression profiles of breast muscle from broilers fed a control diet, the control diet + 50 IU of VE/kg, the control diet + 100 IU of VE/kg, or the control diet + 200 g of EcoE/ton. Evaluation of the serum antioxidant capacity indicated that dietary supplementation of either a high level of VE (50 or 100 IU of VE/kg) or EcoE significantly improved bird antioxidant status. Analysis of gene expression profiles indicated that expression of 542 genes of the breast muscle were altered (P < 0.05, fold change >1.2) by dietary treatments, of which a significant part were commonly regulated by EcoE and VE (especially the control diet + 50 IU of VE/kg). In addition to the process of cellular oxidation, gene ontology analysis indicated the involvement of EcoE and VE on cell morphology, skeletal and muscular system development and function, immune response, and multiple metabolic processes, including lipid, carbohydrate, and drug metabolism. Results of this experiment indicate that the biological roles of high VE, including its activity as an antioxidant, can be greatly mimicked at the transcriptional level by EcoE, and they suggest a relationship of functional redundancy between VE and EcoE in the broiler diets.

Effects of feeding different concentration and forms of zinc on the performance and tissue mineral status of broiler chicks.

1. Two studies were conducted to investigate the effect of feeding different concentration and forms of zinc (Zn) on the performance and tibia Zn status of broiler chicks. 2. In Experiment 1, chicks fed on the control or the diet supplemented with 12?mg of Zn as sulphate had lower feed intake, weight gain and tibia Zn content than other treatment groups. Chicks given 12 and 24 mg of organic Zn in starter and grower phases, respectively, had the same performance and tibia Zn content as those fed 40 mg of Zn as sulphate and the same performance but higher tibia Zn content than those given 12 mg of Zn as organic over the 42 d. 3. In Experiment 2, chicks given 24 mg organic Zn had greater weight gain than chicks fed on the other treatment diets in the starter period. Chicks fed on the control diet had lower tibia Zn content than chicks fed other treatment diets. Chicks given 80 mg Zn as sulphate had higher tibia Zn content than chicks fed the other treatment diets except those given 40 mg of Zn as sulphate. 4. The results from these trials indicate that feeding lower concentration of Zn as organic form may better promote the growth performance of broiler chicks.

Effect of enzyme supplementation and acidification of diets on nutrient digestibility and growth performance of broiler chicks.

Two experiments were conducted to examine the effects of alpha-galactosidase supplementation and acidification of diets on nutrient digestibility and growth performance of broiler chicks. In experiment 1, dietary treatments consisted of feeding a low-energy basal diet (2.74 Mcal of ME/kg) alone, the basal diet supplemented with 1,724 units of alpha-galactosidase per kg, the basal diet supplemented with 2% citric acid, or the basal diet supplemented with both. alpha-Galactosidase significantly increased feed intake, weight gain, AME(n) of the diets, and retention of CP and neutral detergent fiber (NDF) (P < 0.05). Citric acid significantly increased the retention of DM, CP, and NDF, but decreased feed intake and weight gain. The greatest values for DM and NDF retention and for AME(n) were obtained with the combination of alpha-galactosidase plus citric acid. In experiment 2, chicks were fed diets with 2 levels of energy (2.74 or 3.11 Mcal/kg), 2 levels of citric acid (0 or 1.5%), and 2 levels of alpha-galactosidase (0 or 1,724 units/kg) in a 2 x 2 x 2 factorial arrangement of treatments. alpha-Galactosidase significantly increased the reducing sugar concentration in the crop content, whereas citric acid decreased the pH and increased the reducing sugar concentration in the crop content. Citric acid decreased the gain to feed ratio in the absence but not in the presence of alpha-galactosidase. The data from these studies indicate that acidification of diet improves the efficacy of alpha-galactosidase.

Effects of feeding different forms of zinc and copper on the performance and tissue mineral content of chicks.

A study was conducted to investigate the effects of feeding inorganic or organic Zn and Cu on the performance and tissue mineral content of chicks. A corn-soybean meal diet without Cu and Zn supplementation, containing 31 mg of Zn/kg of diet and 6.6 mg of Cu/kg of diet, was used as a basal diet. Organic Zn (a chelated Zn proteinate) and organic Cu (a chelated Cu proteinate) were used as organic sources for comparison with inorganic reagent-grade sulfates. Supplements provided 20 mg/kg of Zn and 8 mg/kg of Cu. A 3x3 factorial arrangement of treatments consisting of feeding the basal diet with 3 supplements (none, sulfate, or organic) of Cu and of Zn was used. Ten groups of 6 one-day-old male broilers were assigned to each of 9 dietary treatments. Tap water and feed were supplied on an ad libitum basis during the 3-wk trial. The Zn and Cu content in the mucosa of the duodenum of the chick was determined. Dietary supplementation of Zn increased (P<0.01) weight gain, feed intake, and G:F of chicks. The G:F for chicks fed both inorganic sources of Zn and Cu was lower (P<0.01) than that for chicks fed only the inorganic source of Zn. Dietary inclusion of Zn increased (P<0.01) tibia and plasma Zn content. The tibia Zn content for chicks fed organic Zn was higher (P<0.01) than that for chicks fed inorganic Zn. Liver Cu content was decreased (P<0.05) by dietary inclusion of Zn. The Zn and Cu contents in the mucosa of chicks fed the organic source were higher (P<0.01) than those of chicks fed the control diet. The feed conversion data suggest that the antagonism between Zn and Cu occurred when the inorganic forms, but not organic forms, of these 2 minerals were included in a chick diet.

Defining osteoblast and adipocyte lineages in the bone marrow.

Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood. With age, the commitment of BMSCs to osteogenesis slows, bone formation decreases, fracture risk rises, and marrow adiposity increases. An unresolved question is whether osteogenesis and adipogenesis are co-regulated in the bone marrow. Osteogenesis and adipogenesis are controlled by specific signaling mechanisms, circulating cytokines, and transcription factors such as Runx2 and Pparγ, respectively. One hypothesis is that adipogenesis is the default pathway if osteogenic stimuli are absent. However, recent work revealed that Runx2 and Osx1-expressing preosteoblasts form lipid droplets under pathological and aging conditions. Histone deacetylase 3 (Hdac3) and other epigenetic regulators suppress lipid storage in preosteoblasts and/or control marrow adiposity. Establishing a better understanding of fat storage in bone marrow cells, as well as the osteoblast-adipocyte relationship within the bone marrow niche is necessary to understand the mechanisms underlying disease- and aging-related marrow fat storage and may lead to the development of new therapeutic targets for "fatty bone" and osteoporosis.

Identification of testicular cancer driver genes by a cross-species comparative oncology approach.

BACKGROUND: Germ cell tumors arise in the testis, ovary, or extragonadal locations and have a wide range of histopathological and clinical presentations. The relative lack of animal models of germ cell tumors has impeded functional assessment of candidate driver genes. Previously, we described the development of testicular germ cell tumors in zebrafish carrying a mutation in bmpr1bb, a BMP family receptor, and demonstrated that human germ cell tumors have defects in BMP signaling. OBJECTIVE: To further credential the zebrafish model for studies of human germ cell tumor, and to elucidate conserved genetic programs underlying the development of germ cell tumor. MATERIALS AND METHODS: We used genetic techniques to ablate the germ cell lineage in developing fish and tested tumors for loss-of-heterozygosity of the wild-type allele of bmpr1bb. We performed comparative gene expression profiling of zebrafish and human germ cell tumors and carried out functional studies of selected genes. RESULTS: Ablation of germ cells completely prevents testis tumor formation in the fish, definitively establishing the germ cell origin of the tumors. Germ cell tumors in bmpr1bb heterozygous mutants retain the wild-type allele, indicating haploinsufficiency of bmpr1bb as the mechanism of tumor formation. Comparison of RNA-Seq and microarray data from human and zebrafish germ cell tumors revealed a unique overlapping signature shared by the zebrafish tumors with human seminomas, yolk sac tumors, and embryonal carcinomas. The most highly conserved gene set in this cross-species analysis included potential driver genes such as JUP, which we show to be essential for germ cell tumor cell growth. CONCLUSION: Our findings highlight the value of cross-species comparative oncology for the identification of candidate human cancer genes.

Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat.

Recent studies have demonstrated nicotinamide (NAM), a soluble B-group vitamin, to be an effective treatment in experimental models of traumatic brain injury (TBI). However, research on this compound has been limited to administration regimens starting shortly after injury. This study was conducted to establish the window of opportunity for NAM administration following controlled cortical impact (CCI) injury to the frontal cortex. Groups of rats were assigned to NAM (50 mg/kg), saline (1 ml/kg), or sham conditions and received contusion injuries or sham procedures. Injections of NAM or saline were administered at 15 min, 4 h, or 8 h post-injury, followed by five boosters at 24 h intervals. Following the last injection, blood was taken for serum NAM analysis. Animals were tested on a variety of tasks to assess somatosensory performance (bilateral tactile adhesive removal and vibrissae-forelimb placement) and cognitive performance (reference and working memory) in the Morris water maze. The results of the serum NAM analysis showed that NAM levels were significantly elevated in treated animals. Behavioral analysis on the tactile removal test showed that all NAM-treated groups facilitated recovery of function compared with saline treatment. On the vibrissae-forelimb placing test all NAM-treated groups also were significantly different from the saline-treated group. However, the acquisition of reference memory was only significantly improved in the 15-min and 4-h groups. In the working memory task both the 15-min and 4-h groups also improved working memory compared with saline treatment. The window of opportunity for NAM treatment is task-dependent and extends to 8 h for the sensorimotor tests but only extends to 4 h post-injury in the cognitive tests. These results suggest that a 50 mg/kg treatment regimen starting at the clinically relevant time point of 4 h may result in attenuated injury severity in the human TBI population.

Effects of organic zinc and phytase supplementation in a maize-soybean meal diet on the performance and tissue zinc content of broiler chicks.

1. The purpose of this study was to investigate the effects of Bioplex Zn (a chelated zinc proteinate) and phytase supplementation in a maize-soybean meal diet on the performance and tissue zinc (Zn) content of broiler chicks. Treatment structure consisted of a 2 x 6 factorial arrangement with two inclusions of phytase (0 or 500 PU/kg) and 6 of Bioplex Zn providing 0, 2, 4, 8, 16 and 32 mg Zn/kg diet. A total of 864 chicks were randomly assigned to each of 12 dietary treatments with 6 replicate cages of 12 chicks. 2. Dietary inclusion of phytase increased feed intake, weight gain, plasma Zn content, tibia Zn content, tibia and ash weight. 3. Dietary supplementation of Bioplex Zn linearly increased feed intake, weight gain, gain to feed ratio, plasma Zn concentration, liver Zn concentration, tibia Zn content, tibia and ash weight. 4. An interactive effect of phytase and Bioplex Zn on feed intake, weight gain, tibia Zn concentration and tibia ash weight was found. 5. One slope, straight broken-line analysis of weight gain regressed on the supplemental Zn level provided as Bioplex Zn indicated that 12 mg/kg supplemental Zn without phytase and 7.4 mg/kg supplemental Zn with phytase were required for the optimal weight gain of chicks.

The lactose carrier of Klebsiella pneumoniae M5a1; the physiology of transport and the nucleotide sequence of the lacY gene.

A comparison has been made between the physiology and amino acid sequence of the lactose carriers of Klebsiella pneumoniae M5a1 and Escherichia coli K-12. The membrane transport of lactose was much weaker in Klebsiella than in E. coli. On the other hand o-nitrophenylgalactoside uptake by Klebsiella was distinctly greater than with E. coli. In spite of the differences in sugar transport between the two organisms, the amino acid sequences of the respective lactose carriers were remarkably similar (60% of the amino acids are identical).

Restricted T cell receptor repertoire for acetylcholine receptor in murine myasthenia gravis.

Immunization of C57BL/6 mice with AChR provokes symptoms similar to those seen in the disease myasthenia gravis. To elucidate the structural requirements for T cell recognition of AChR and to identify TcR features which might provide targets for immunotherapy, a panel of T cell hybridomas was generated after immunization of mice with the immunodominant peptide of the AChR alpha chain. The TcR genes expressed by these hybridomas were sequenced. TcR-V beta 6 was preferentially employed, but other V beta genes were also observed. A conserved acidic residue was present in all CDR3 regions, regardless of the V beta. The TcR-V alpha repertoire was somewhat skewed with three V alpha families accounting for 82% of the sequences. The utilization of multiple T cell receptor V beta genes may contribute to the inability to inhibit EAMG by elimination of V beta 6+ T cells.

Effect of inorganic or organic selenium supplementation on reproductive performance and tissue trace mineral concentrations in gravid first-parity gilts, fetuses, and nursing piglets.

The objective of this experiment was to evaluate 2 supplemental forms of Se on reproductive performance and tissue trace mineral concentration in fetus and first-parity gilts during pregnancy and their progeny. Crossbred gilts (n=100) were selected at 183±2.7 d and 137±10 kg BW and fed a common diet. After 1 mo, 8 gilts were sacrificed to establish baseline liver Se concentration and the remaining 92 gilts allotted to receive Se (0.3 mg/kg diet) as inorganic Se (Na2SeO3) or a Se supplement that contains organoselenium compounds (Sel-Plex; Alltech Inc., Nicholasville, KY). At 267±5.7 d (171±11 kg), gilts were estrus-synchronized and bred. Gilts were then slaughtered at defined time points throughout gestation (d 0, 43, 58, 73, 91, 101, or 108 of gestation; n=6 to 12 gilts/time point). A week before the expected farrowing day, 10 pregnant gilts (5 from each treatment) were moved to farrowing crates and monitored. Two pigs from each litter were randomly selected and euthanized at d 0 (within 2 h after birth; nursing deprived), 7, 14, and 21 from each litter. During the gestation phase, maternal liver, and fetal body and liver were collected for determination of trace mineral concentration by inductively coupled plasma mass spectrometry. Total number of fetus, crown-rump length, and corpora lutea of gilts were recorded as well. During the lactation phase, pigs (without liver and gastrointestinal tract) and associated liver were analyzed for Se concentration. The results demonstrated that the source of Se generally did not affect the maternal reproductive traits and fetal characteristics. Also, the source of Se supplemented to the maternal diet did not, in general, affect Cu, Fe, Mn, or Zn concentrations in the tissues evaluated other than the observation of a greater maternal liver Mn content (P<0.01) in gilts fed Sel-Plex and a greater amount of Fe accumulated in the entire litter (P<0.01) in gilts fed Sel-Plex. However, with regard to Se concentrations, Se in fetal body, fetal liver, and maternal liver were greater (P<0.01) when Sel-Plex was fed. Postnatal pigs from gilts fed Sel-Plex had greater (P<0.05) Se retention in body and liver with similar growth performance during the 21-d period. The results demonstrate Se form differences wherein Sel-Plex is associated with greater Se accumulation in both maternal and fetal tissues.

Evaluation of trace mineral source and preharvest deletion of trace minerals from finishing diets for pigs on growth performance, carcass characteristics, and pork quality.

Weanling crossbred pigs (Sus scrofa; 72 barrows and 72 gilts; BW = 7.4 ± 1.1 kg) were used to evaluate dietary supplemental trace mineral (Cu, Fe, Mn, and Zn) source (inorganic vs. organic) and deletion (0, 2, 4, and 6 wk preharvest) on growth performance, carcass characteristics, and pork quality. Pigs were blocked by BW, ancestry, and sex, and randomly allotted to 24 pens, and fed a diet containing either inorganic or organic trace minerals supplemented at the 1998 NRC requirement estimates for each of 5 BW phases from 7 to 120 kg (equivalent to 14, 14, 42, 28, and 42-d periods, respectively). Two pigs were removed from each pen at the end of Phase IV (BW = 82.6 ± 6.0 kg), and 2 other pigs were removed at the end of Phase V (BW = 128.0 ± 8.3 kg) for collection of various tissues and for determination of carcass characteristics and pork quality. On d 1, 15, and 29 of Phase V, 3 pens within each source of minerals were switched to a common diet without supplemental trace minerals, whereas the remaining 3 pens within each source of minerals were fed diets containing trace minerals throughout the Phase V period. This resulted in 4 groups within each mineral treatment, in which trace mineral supplementation was deleted for 6, 4, 2, or 0 wk of Phase V. Trace mineral source (inorganic vs. organic) did not affect ADG, ADFI, and G:F (773 vs. 778 g/d, 1,680 vs. 1,708 g/d, and 461 vs. 456 g/kg, respectively) during the first 4 phases. During the mineral deletion period, ADG and G:F were not affected by the duration of trace mineral deletion, but ADFI increased when trace minerals were removed from the diet for 6 wk (6 vs. 0 wk, 3,393 vs. 3,163 g/d; P = 0.05). Hot carcass weight, cold carcass weight, carcass shrink, dressing percentage, LM area, 10th rib and midline average backfat, and carcass fat-free lean weight and percentage were not affected (P > 0.10) by the source of mineral or length of mineral deletion, but carcass length tended to decrease (P = 0.09) when time of trace mineral deletion increased. Increasing mineral deletion from 0 to 6 wk tended to reduce linearly (P = 0.08) Hunter a* scores on the day of carcass processing (24 h after slaughter), as well as 2 d after processing, and Hunter b* scores on d 2 and d 6 after processing. Results of this experiment indicate that use of organic trace minerals, rather than inorganic trace minerals, did not influence pig growth performance or carcass characteristics and quality; however, deletion of minerals during the last 6 wk before harvest increased ADFI and affected drip loss, some color scores of the LM, and carcass length.

Effects of spray-dried animal plasma and immunoglobulins on performance of early weaned pigs.

Five experiments were conducted to evaluate the effects of dietary spray-dried porcine plasma (SDPP) and spray-dried bovine plasma (SDBP) and their various molecular weight fractions on performance of pigs weaned at approximately 14 or 21 d of age. In addition, the efficacy of various levels of the immunoglobulin G (IgG)-rich fraction of SDPP and SDBP were evaluated. Experiment 1 evaluated the dietary addition of SDPP and three of its fractions (IgG-rich, albumin-rich, and low molecular weight fractions). Pigs fed SDPP grew faster and consumed more feed than the controls during the first week (P < 0.05). The IgG-rich fraction resulted in improvements in ADG and ADFI that were similar to those of pigs fed SDPP. The albumin-rich fraction had no effect on growth rate, but the low molecular weight fraction decreased feed intake as well as growth rate. Experiments 2 and 3 evaluated SDPP and graded levels of its IgG-rich fraction in pigs weaned at 21 or 14 d, respectively. In Exp. 2, pigs fed SDPP grew faster and consumed more feed than the controls during the first week (P < 0.05). Pig performance was enhanced with the addition of the IgG-rich fraction that provided 80% of the amount of IgG in the SDPP diet. In Exp. 3, there was no response to SDPP during the first week, but a positive growth response to SDPP (P < 0.01) occurred by the end of wk 2 (0 to 14 d). Feeding the IgG-rich fraction increased growth rate compared with controls (P < 0.05). Over the entire experiment, the greatest ADG occurred with the IgG-rich fraction that provided 128% of the amount of IgG provided by SDPP (quadratic; P < 0.05). Two additional experiments assessed feeding SDBP and bovine IgG-rich fractions to early weaned pigs. In Exp. 4, SDPP was superior to SDBP in stimulating growth and feed intake, but this difference did not occur in Exp. 5. In both experiments, the IgG fraction of bovine plasma seemed to be as effective at improving growth as SDPP and more effective than SDBP. The results indicate that both porcine and bovine plasma are beneficial to young pig performance during the first week after weaning and that the IgG fraction of plasma is the component that is responsible for the enhancement in growth rate and feed intake.

Non-referral of psychopathological child firesetters to mental health services.

The present study attempted to determine if those children with significant psychopathology were referred to mental health services after having initially been referred to the fire department. On file at the Portland Fire Department were 30 child firesetters whose parent or guardian had completed the Child Behavior Checklist. The CBCL had not been scored prior to the fire department's treatment referral, or prior to our review of the files. Significant psychopathology, determined after the CBCL had been scored, was not a determinant of future referral for mental health services. Thus, there is a need for fire departments and mental health professionals to work collaboratively to determine the appropriate treatment referral for child firesetters.

An evaluation of residential treatment for sexually aggressive youth.

This longitudinal study investigated the effectiveness of a one and one-half year long residential treatment program for 26 boys aged 11-15 with histories of sexually aggressive behavior. The clients were assessed with self-report and staff-report measures at the beginning and end of treatment and at several time points in between; also, aggressive acts were tabulated during a one-year follow-up period. There was evidence of improved functioning on 10 of the 12 measures. During the follow-up, 27% of the sample committed an aggressive act, and 8% committed a sexually aggressive act. On most of the measures, improvement occurred gradually over the course of treatment, and on some measures most of the improvement occurred late in the placement.

Highly conserved TCR beta chain CDR3 sequences among immunodominant acetylcholine receptor-reactive T cells in murine myasthenia gravis.

In C57BL/6 (B6) mice, the T cell response to acetylcholine receptor from Torpedo californica (TAChR) provides a specific antibody response and symptoms of muscular weakness similar to those displayed in the human disease myasthenia gravis. We had found previously that the B6 T cell response to AChR shows limited clonality, both in terms of the epitopes recognized and in terms of the diversity of the TCR V beta gene segments used. We now report that all TAChR-reactive B6 T cell clones which responded to the dominant antigenic epitope and expressed the dominant TCR V beta 6 gene segment exhibited conservation of amino acid sequence in the VDJ junctional region (CDR3) of the TCR beta chain. The conserved sequence motif contained a glutamic acid residue in the CDR3 of TCR beta. Analysis of TCR beta sequences from antigen-primed lymph node cells (LNC) showed a similar enrichment for sequences having a glutamic acid in CDR3, although the overall appearance of the LNC sequences was somewhat more heterogeneous and consistent with a gradual in vitro selection of the subset of TCR found in the T cell clones. As the first example of TCR sequences in this model of myasthenia gravis, these results begin to provide a context for understanding self-non-self discrimination of AChR. In particular, the unusually conserved CDR3 sequence suggests that the conserved V beta gene utilization seen previously is directly related to recognition of the immunodominant peptide epitope in association with the experimental autoimmune myasthenia gravis-susceptibility determining MHC class II molecule I-Ab.