ABSTRACT
Fragile X syndrome is caused by the loss of expression of the fragile X mental retardation protein (FMRP). As a RNA binding protein, FMRP functions in translational regulation, localization, and stability of its neuronal target transcripts. The Drosophila homologue, dFMR1, is well conserved in sequence and function with respect to human FMRP. Although dFMR1 is known to express two main isoforms, the mechanism behind production of the second, more slowly migrating isoform has remained elusive. Furthermore, it remains unknown whether the two isoforms may also contribute differentially to dFMR1 function. We have found that this second dFMR1 isoform is generated through an alternative translational start site in the dfmr1 5'UTR. This 5'UTR coding sequence is well conserved in the melanogaster group. Translation of the predominant, smaller form of dFMR1 (dFMR1-S(N)) begins at a canonical start codon (ATG), whereas translation of the minor, larger form (dFMR1-L(N)) begins upstream at a non-canonical start codon (CTG). To assess the contribution of the N-terminal extension toward dFMR1 activity, we generated transgenic flies that exclusively express either dFMR1-S(N) or dFMR1-L(N). Expression analyses throughout development revealed that dFMR1-S(N) is required for normal dFMR1-L(N) expression levels in adult brains. In situ expression analyses showed that either dFMR1-S(N) or dFMR1-L(N) is individually sufficient for proper dFMR1 localization in the nervous system. Functional studies demonstrated that both dFMR1-S(N) and dFMR1-L(N) can function independently to rescue dfmr1 null defects in synaptogenesis and axon guidance. Thus, dfmr1 encodes two functional isoforms with respect to expression and activity throughout neuronal development.
Subject(s)
Codon, Initiator/genetics , Drosophila Proteins/genetics , Drosophila melanogaster/growth & development , Drosophila melanogaster/genetics , Fragile X Mental Retardation Protein/genetics , Animals , Drosophila Proteins/biosynthesis , Drosophila Proteins/physiology , Fragile X Mental Retardation Protein/biosynthesis , Fragile X Mental Retardation Protein/physiology , Gene Expression Regulation/genetics , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , Protein Isoforms/physiologyABSTRACT
Change, challenge, and commitment motivate staff at the University of Miami/Jackson Memorial Medical Center in Miami, Florida, to prepare its health care system for the 21st century. Doctors, nurses, environmental workers, pharmacists, cashiers, nursing assistants, laboratory technologists, and many others are participating on a variety of teams to bring about the changes needed for our delivery system to be competitive.
Subject(s)
Academic Medical Centers/organization & administration , Hospital Restructuring/organization & administration , Patient Care Team/organization & administration , Patient-Centered Care/organization & administration , Economic Competition , Humans , Organizational Culture , Organizational Innovation , Program EvaluationABSTRACT
AIDS is being recognized with ever-increasing frequency in children. This article includes a discussion of the common radiographic manifestations of AIDS as well as some rarely encountered problems. It is hoped that with heightened awareness of this spectrum of radiographic findings, radiologists may contribute to a prompt diagnosis of AIDS so that appropriate short-term therapy and counseling may be instituted.
Subject(s)
Acquired Immunodeficiency Syndrome/diagnosis , Brain Diseases/diagnosis , Gastrointestinal Diseases/diagnosis , Humans , Infant , Lung Diseases/diagnosis , Mediastinal Diseases/diagnosis , Pneumonia, Pneumocystis/diagnosis , Sarcoma, Kaposi/diagnosisABSTRACT
The diagnosis of renal cell carcinoma was established by computed tomography-guided aspiration in two small solid lesions occurring in end-stage kidneys. This represents a safe means of providing more specific information about the various lesions that specific information about the various lesions that frequently develop in chronic hemodialysis patients: complex cysts, adenoma, and renal cell carcinoma. The proposed conservative approach of simple observation of these lesions may be altered if a precise diagnosis is obtained. Computed tomography is considered the most reliable imaging modality for evaluation and guided aspiration.
Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Adult , Biopsy, Needle/methods , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/pathology , Female , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Kidney Neoplasms/complications , Kidney Neoplasms/pathology , Middle Aged , Renal Dialysis , Tomography, X-Ray ComputedABSTRACT
A retrospective analysis of the plain abdominal films of 53 "body packer" drug smugglers was performed to ascertain the importance of radiographic studies in the diagnosis and management of these patients. Eighty-nine percent had studies diagnostic for foreign body ingestion. Multiple, well-defined, homogeneous oval or oblong densities, especially if surrounded by a crescent of air (double-condom sign), are key findings. If these densities were found in the proximal ascending colon or upper gastrointestinal tract, the diagnosis was almost assured. Six percent of patients exhibited complications suggested on serial radiographs, proving the necessity for follow-up studies until complete expulsion or removal of the foreign body. Radiologic evaluation is essential in the diagnosis and management of the cocaine smuggler.
