Two structural domains of initiation factor eIF-4B are involved in binding to RNA

Translation initiation factor eIF-4B promotes the binding of mRNA to 40 S preinitiation complexes and together with eIF-4A possesses RNA helicase activity. To elucidate structural features involved in its function, a series of internal and C-terminal deletions, as well as point mutations, were constructed in the eIF-4B cDNA. The mutated cDNAs were expressed in transiently transfected COS-1 cells, and mutant forms of the factor were overproduced up to about 25-fold over endogenous eIF-4B levels. Inhibition of dihydrofolate reductase (DHFR) synthesis by high levels of eIF-4B variants was determined in vivo, and the binding of the eIF-4B forms to biotinylated RNA was measured in vitro. The results indicate that the N-terminal region containing the RNA binding motif with its RNP1 and RNP2 consensus elements is sufficient for inhibition of DHFR synthesis. Deletion of the RNP1 sequence abrogates RNA binding, but amino acid substitutions at conserved residues do not always inhibit RNA binding. Deletion of the DRYG domain near the middle of eIF-4B results in inhibition of RNA binding, but not of DHFR synthesis. Up to 164 residues of the C terminus are not required for RNA binding, but removal of 226 or more residues completely inhibits RNA binding, perhaps by the loss of two arginine-rich regions. The results suggest that both the RNA recognition motif and the arginine-rich region are required for stable RNA binding but that both are not necessary for in vivo inhibition of protein synthesis.     

Postoperative evaluation in mandibular prognathism treated by bilateral sagittal split osteotomy

The present study was undertaken to evaluate the postoperative relapse from the period of unwiring to 1 year postoperatively and its correlation to the amount of mandibular setback and change in vertical dimension after mandibular bilateral sagittal split osteotomy. Twenty-seven patients were evaluated cephalometrically by the time preoperatively, 6 weeks, 6 months and 1 year postoperatively. It was found that 1) the average amount of mandibular setback at pogonion point, 6 weeks postoperatively, is 7.6mm backward and 1.9mm downward, 2) the average amount of horizontal relapse at pogonion point, 6 months and 1 year postoperatively, are 1.9mm and 2.3mm respectively. 86% of the horizontal relapse, 1 year postoperatively, occurs in the first 6 months after removal of intermaxillary fixation, 3) the average amount of vertical relapse at pogonion point, 6 months and 1 year postoperatively, are 0.9mm and 1.1mm upward. 82% of the vertical relapse, 1 year postoperatively, occurs in the first 6 months after removal of intermaxillary fixation, 4) the amount of 1 year postoperatively horizontal relapse is significantly correlated both with the amount of horizontal mandibular set back and vertical downward change (r = 0.58, 0.67, p < 0.001), whereas the amount of vertical relapse is with the vertical downward change only, but horizontal setback isn't.     

Dominance--one hundred and fifteen years after Mendel''s paper

Eight conscious chronically instrumented sheep were exposed to 1% inspired carbon monoxide (CO) for 35 min. In all sheep, carboxyhaemoglobin (COHb) levels at the end of the exposure were approximately 65%. Mean arterial blood pressure was unchanged with the exception of 2 sheep in which administration was stopped at 25 min following the sudden onset of hypotension. Oxygen delivery to the brain was sustained throughout the administration of CO due to a significant increase in cerebral blood flow (CBF). There was no evidence of either a metabolic acidosis or of lactate production by the brain suggesting the brain did not become hypoxic during the time-course of this study. Despite the apparent lack of hypoxia, oxygen consumption by the brain fell progressively and the sheep showed behavioural changes which varied from agitation to sedation and narcosis. The mechanism of these changes was therefore probably unrelated to hypoxia, but may have been due to raised intracranial pressure or a direct effect of CO on brain function. It is proposed that the time-course of progressive CO poisoning includes a phase in which CBF is elevated, blood pressure is unchanged and the brain is normoxic despite high COHb levels, but that this situation can rapidly evolve into a phase of haemodynamic collapse and severe hypoxia.     

Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study

Clinical characteristics associated with bacillary angiomatosis and bacillary peliosis (BAP) in patients with human immunodeficiency virus (HIV) infection were evaluated in a case-control study; 42 case-patients and 84 controls were matched by clinical care institution. Case-patients presented with fever (temperature, > 37.8 degrees C; 93%), a median CD4 lymphocyte count of 21/mm3, cutaneous or subcutaneous vascular lesions (55%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Many case-patients experienced long delays between medical evaluation and diagnosis of BAP (median, 4 weeks; range, 1 day to 24 months). Case-patients were more likely than controls to have fever, lymphadenopathy, hepatomegaly, splenomegaly, a low CD4 lymphocyte count, anemia, or an elevated serum level of alkaline phosphatase (AP) (P < .001). In multivariate analysis, a CD4 lymphocyte count of < 200/mm3 (matched odds ratio [OR], 9.9; P < .09), anemia reflected by a hematocrit value of < 0.36 (OR, 19.7; P < .04), and an elevated AP level of > or = 2.6 mukat/L (OR, 23.9; P < .05) remained associated with disease after therapy with zidovudine was controlled for. BAP should be considered an AIDS-defining opportunistic infection and should be included in the differential diagnosis for febrile, HIV-infected patients with cutaneous or osteolytic lesions, lymphadenopathy, abdominal symptoms, anemia, or an elevated serum level of AP.     

The importance of geriatrics to family medicine: a position paper by the Group on Geriatric Education of the Society of Teachers of Family Medicine

The role of geriatrics and geriatricians in family medicine remains unsettled. Despite a rapidly aging population, a tremendous shortage now exists of faculty with interest and expertise in geriatrics. Relatively few family practice residents choose to enter geriatric fellowship programs, and federal funding for such programs has been reduced. Despite accreditation requirements, residency programs are not always able to provide the range of geriatric experiences needed to properly prepare graduates to provide care for the broad range of older patients. Medical students' exposure to geriatrics remains limited. The Group on Geriatric Education of the Society of Teachers of Family Medicine believes that family medicine faculty must recognize and be committed to the notion that geriatrics is integral to family medicine. Both undergraduate and residency training programs should emphasize experience with geriatric patients in multiple settings. In particular, the nursing home should not be the main focus of geriatric training. The small number of certified geriatric faculty will be able to provide leadership, but a broad range of faculty must become involved in teaching geriatrics. Faculty development activities and continuing education programs to foster the necessary expertise will be essential to the accomplishment of this task.     

A simple approach to intracytoplasmic sperm injection

OBJECTIVE: To describe a simple injection apparatus and method for performing intracytoplasmic sperm injection in a clinical IVF program. DESIGN: A prospective clinical trial of intracytoplasmic sperm injection. SETTING: A private office-based fertility program. PATIENTS: Five couples undergoing IVF-ET with intracytoplasmic sperm injection as a treatment for male factor infertility. INTERVENTIONS: Intracytoplasmic sperm injection was performed at room temperature (23.5 to 24.5 degrees C) in a simple zwitterion-buffered medium. MAIN OUTCOME MEASURES: Fertilization rates, cleavage rates, clinical pregnancy rates, implantation rates. RESULTS: Intracytoplasmic sperm injection was performed on 44 fresh oocytes from five patients. Twenty-three oocytes fertilized (52.3%) and 22 zygotes cleaved (95.7%). Three of five patients became pregnant (60%), resulting in the live birth of one normal male infant, one continuing singleton pregnancy, and one continuing twin gestation (46XX, 46XY). The implantation rate was 23.5%. CONCLUSION: Intracytoplasmic sperm injection can be performed successfully in a simple medium at room temperature using commercially available microtools.