ABSTRACT
The strongly immunogenic environment in autoimmune diseases such as lupus may pose a stringent barrier to transplantation. Despite available murine models of lupus, transplant tolerance in this setting has yet to be fully investigated in highly penetrant genetic models of disease. Such studies are of clear clinical importance because lupus is a transplant indication in which transplanted kidneys have a substantially increased risk of rejection including a role for recurrent nephritis. In the fully penetrant B6.SLE123 mouse, we determined that CD4 T follicular helper and germinal center B cells were significantly expanded compared with healthy controls. We traced this expansion to resistance of effector CD4 T and B cells in B6.SLE123 mice to regulation by either CD4 T regulatory cells (CD4Tregs) or CD8 T regulatory cells (CD8Tregs), despite demonstrating normal function by Tregs in this strain. Finally, we determined that B6.SLE123 mice resist anti-CD45RB-mediated tolerance induction to foreign islet allografts, even in the absence of islet autoimmunity. Overall, B6.SLE123 lupus-prone mice are highly resistant to transplant tolerance induction, which provides a new model of failed tolerance in autoimmunity that may elucidate barriers to clinical transplantation in lupus through further cellular and genetic dissection.
Subject(s)
Autoantibodies/immunology , Autoimmunity/immunology , Graft Rejection/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis/etiology , T-Lymphocytes, Regulatory/immunology , Transplantation Tolerance/immunology , Animals , Autoantibodies/blood , Cells, Cultured , Dendritic Cells/immunology , Graft Survival/immunology , Islets of Langerhans Transplantation/immunology , Lupus Erythematosus, Systemic/complications , Lupus Nephritis/pathology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Mice, Inbred NODABSTRACT
We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
Subject(s)
Gene Duplication , Genome, Plant , Populus/genetics , Sequence Analysis, DNA , Arabidopsis/genetics , Chromosome Mapping , Computational Biology , Evolution, Molecular , Expressed Sequence Tags , Gene Expression , Genes, Plant , Oligonucleotide Array Sequence Analysis , Phylogeny , Plant Proteins/chemistry , Plant Proteins/genetics , Polymorphism, Single Nucleotide , Populus/growth & development , Populus/metabolism , Protein Structure, Tertiary , RNA, Plant/analysis , RNA, Untranslated/analysisABSTRACT
Searching MEDLINE, the National Library of Medicine's premier bibliographic database covering the fields of medicine, nursing, dental medicine, the healthcare system, veterinary medicine, and the preclinical sciences, is now available free on the Internet through PubMed. This retrieval system allows users of all skill levels to obtain important medical information. Additionally, through the National Network of Libraries of Medicine (NN/LM) program, a division of NLM, user support in the form of phone, e-mail, and training is available free of charge. Those interested in having a training session for PubMed at their facility may contact the NN/LM to make arrangements.
Subject(s)
Internet , MEDLINE , Computer User Training , Hotlines , Humans , National Library of Medicine (U.S.) , Nurse Practitioners , United StatesABSTRACT
Two examples of boys who experienced unwanted sexual contact with females are presented. The literature regarding this type of abuse is reviewed and supports the finding that such contact is relatively common and may have definite negative consequences for the victim. Conventional interview techniques can frequently fail to uncover these occurrences. Clinical, psychological, and sociocultural factors contribute to difficult eliciting the data. Even when young males attempt to report unwanted sexual contact, caregivers may fail to respond in a manner indicating sensitivity to the trauma. Further research could help to determine the long-term consequences of such experiences in male children and adolescents.
Subject(s)
Child Abuse, Sexual/psychology , Gender Identity , Adolescent , Adult , Chronic Disease , Depressive Disorder/psychology , Female , Follow-Up Studies , Humans , Male , Psychosexual Development , Psychotic Disorders/psychologySubject(s)
Child Development Disorders, Pervasive/psychology , Personality Development , Social Adjustment , Social Desirability , Adolescent , Child , Child Development Disorders, Pervasive/diagnosis , Humans , Peer Group , Psychiatric Status Rating Scales , Social Behavior , Social Environment , Verbal BehaviorABSTRACT
Eleven clinical and behavioral syndromes that can result in self-inflicted injury in childhood and adolescence are reviewed and classified. The causes and remedies of such injuries vary both among and within these 11 classes. Pediatricians should be alert to the possible presence and meaning of self-injury.
Subject(s)
Self Mutilation/etiology , Adolescent , Battered Child Syndrome , Child , Child Behavior , Child Development Disorders, Pervasive/complications , Child, Preschool , Depressive Disorder/complications , Depressive Disorder/diagnosis , Diagnosis, Differential , Exploratory Behavior , Factitious Disorders/diagnosis , Feeding and Eating Disorders/complications , Feeding and Eating Disorders/diagnosis , Humans , Infant , Intellectual Disability/complications , Lesch-Nyhan Syndrome/complications , Personality Disorders/complications , Personality Disorders/diagnosis , Self Mutilation/diagnosis , Stereotyped BehaviorABSTRACT
Traction Intolerance Syndrome is defined as a behavioral and/or emotional reaction related to skeletal traction severe enough to require psychiatric consultation and/or the use of major psychiatric medication for prolonged periods in the absence of pre-existing major psychiatric illness. Patients often attribute these reactions to the predicament of traction. This syndrome was present in five of nine patients between the ages of sixteen and forty-five who underwent traction for more than three weeks admitted to the UCLA Orthopedic Service during calendar year 1975. Moreover, all the patients were between sixteen and twenty-six years of age, and all the patients in that age range developed the syndrome. The multiple contributions to the pathogenesis of these reactions are described, and the interventions of the liaison psychiatrist in intervention at the biological, psychological, family and hospital staff levels are discussed.
