Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program.

S6 kinases (S6Ks) are mechanistic target of rapamycin substrates that participate in cell growth control. S6Ks phosphorylate ribosomal protein S6 (rpS6) and additional proteins involved in the translational machinery, although the functional roles of these modifications remain elusive. Here we analyze the S6K-dependent transcriptional and translational regulation of gene expression by comparing whole-genome microarray of total and polysomal mouse liver RNA after feeding. We show that tissue lacking S6Ks 1 and 2 (S6K1 and S6K2), displays a defect in the ribosome biogenesis (RiBi) transcriptional program after feeding. Over 75% of RiBi factors are controlled by S6K, including Nop56, Nop14, Gar1, Rrp9, Rrp15, Rrp12 and Pwp2 nucleolar proteins. Importantly, the reduced activity of RiBi transcriptional promoters in S6K1;S6K2(-/-) cells is also observed in rpS6 knock-in mutants that cannot be phosphorylated. As ribosomal protein synthesis is not affected by these mutations, our data reveal a distinct and specific aspect of RiBi under the control of rpS6 kinase activity, that is, the RiBi transcriptional program.

Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients.

INTRODUCTION: Mutations in the voltage-gated sodium channel SCN1A gene are the main genetic cause of Dravet syndrome (previously called severe myoclonic epilepsy of infancy or SMEI). OBJECTIVE: To characterise in more detail the mutation spectrum associated with Dravet syndrome. METHODS: A large series of 333 patients was screened using both direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Non-coding regions of the gene that are usually not investigated were also screened. RESULTS: SCN1A point mutations were identified in 228 patients, 161 of which had not been previously reported. Missense mutations, either (1) altering a highly conserved amino acid of the protein, (2) transforming this conserved residue into a chemically dissimilar amino acid and/or (3) belonging to ion-transport sequences, were the most common mutation type. MLPA analysis of the 105 patients without point mutation detected a heterozygous microrearrangement of SCN1A in 14 additional patients; 8 were private, partial deletions and six corresponded to whole gene deletions, 0.15-2.9 Mb in size, deleting nearby genes. Finally, mutations in exon 5N and in untranslated regions of the SCN1A gene that were conserved during evolution were excluded in the remaining negative patients. CONCLUSION: These findings widely expand the SCN1A mutation spectrum identified and highlight the importance of screening the coding regions with both direct sequencing and a quantitative method. This mutation spectrum, including whole gene deletions, argues in favour of haploinsufficiency as the main mechanism responsible for Dravet syndrome.

Microbial reduction and precipitation of vanadium by Shewanella oneidensis.

Shewanella oneidensis couples anaerobic oxidation of lactate, formate, and pyruvate to the reduction of vanadium pentoxide (V(V)). The bacterium reduces V(V) (vanadate ion) to V(IV) (vanadyl ion) in an anaerobic atmosphere. The resulting vanadyl ion precipitates as a V(IV)-containing solid.

The accuracy of technetium-99m-labeled red cell scintigraphy in localizing gastrointestinal bleeding.

OBJECTIVE: To evaluate the success of technetium-99m-labeled red blood cell scintigraphy in localizing the site of gastrointestinal bleeding, and to identify the clinical and technical factors that contribute to scan accuracy. METHODS: A retrospective review was conducted of all patients who underwent a tagged red blood cell scan for the evaluation of gastrointestinal bleeding at our institution from 1981 to 1991. RESULTS: Of a total of 153 patients, 90 (59%) had positive scans, whereas, in 63 (41%), they were negative. Of the 90 patients who had positive scans, it was possible to assess scan accuracy in 44 who had corrective surgery or an additional diagnostic procedure which definitively localized the site of bleeding. Of those 44 patients, the correct bleeding site was identified by red blood cell scanning in 33 patients (75%) overall and in all six patients with a left colon bleeding site. In this group of 44 patients, 22 scans were positive within 2 h, and of these the scan was accurate in localizing the bleeding site in 19 of 22 (86%). When the three subjects with upper gastrointestinal bleeding were excluded, the scan was positive in 100% of the remaining 19 patients. CONCLUSION: The technetium-labeled red blood cell scan is a reliable tool for the assessment of unexplained lower gastrointestinal bleeding when the scan is positive within the first 2 h, and an upper gastrointestinal source has already been excluded.

Provider-patient communication and metabolic control.

OBJECTIVE: To determine whether nurses' and NIDDM patients' communication styles during consultations are related to subsequent metabolic control and to examine factors influencing patterns of communication in these consultations. RESEARCH DESIGN AND METHODS: A total of 47 NIDDM patients participated in the study and completed the following procedures: 1) assessment of baseline HbA1, 2) attended 3.5 days of diabetes education, 3) returned in 1 mo for a follow-up consultation with a nurse, and (4) returned in 9-12 wk for a follow-up HbA1 assessment. The communication variables coded from the consultations were the frequency with which nurses produced controlling, informative, and patient-centered utterances and the frequency with which patients sought information, engaged in decision making, and expressed negative affect. RESULTS: The results were as follows: 1) patients experienced poorer metabolic control after interacting with nurses who were more controlling and directive in their communication with patients (r = 0.39, P < 0.01); 2) the nurses' use of patient-centered responses was directly related to the degree to which patients expressed feelings (r = 0.34, P < 0.01) and exhibited decision-making behavior (r = 0.62, P < 0.01); and 3) several of the nurses' and patients' communicative behaviors were related to patient characteristics such as age, sex, education, and baseline HbA1 levels. CONCLUSIONS: The results suggest that providers' attempts to exert considerable control during consultations with NIDDM patients may be counterproductive and contribute to poorer outcomes. The findings also indicate that patient-centered behaviors (e.g., encouraging the patient's involvement, respecting the patient's opinion, and offering support) facilitate the patient's ability to be an active participant in the consultation.

Efficacy of diabetes education: classroom versus individualized instruction.

A pilot study was conducted using the concerns based adoption model (CBAM) developed at the University of Texas-Austin. This model uses two diagnostic dimensions: stages of concern (SC) and levels of use (LU). Movement in these dimensions is an important determinant of self-motivated disease management. It is postulated that this self-motivation is the basis of long-term adherence to the patient's therapeutic regimen and results in the decreased use of medical services. Twenty patients who attended a series of formal diabetes education classes were compared with 20 patients who received individualized instruction. Classroom education was significantly more effective in increasing the SC about diabetes management. However, the increase in LU (technical skills) was not significantly different in either setting. At 2- to 3-month follow-up evaluation, results indicated that retention of skills and motivation are excellent and that SC and LU continued to improve. In summary, this study demonstrated that classroom education is technically equivalent, more cost-effective, and may be more conducive to learning than individualized instruction.

Radioiodine uptake following iodine-131 therapy for Graves' disease: an early indicator of need for retreatment.

Forty-five patients with Graves' disease were studied prospectively to determine if 24-hour I-131 uptake measurements alone or in combination with serum thyroid hormone levels at six weeks would determine the necessity for retreatment of the thyrotoxicosis. All patients with an I-131 uptake greater than 30% at six weeks required retreatment. No patient with an I-131 uptake of less than 15% required retreatment. Patients with uptakes between 15% and 30% were variable. An elevated free thyroxin index at 6 weeks is not helpful to determine which patients will remain thyrotoxic. Patients with a free thyroxin index within the normal range at six weeks can be predicted to be euthyroid by 12 weeks if their 24-hour I-131 uptake is between 15% and 30% and to be hypothyroid if their 24-hour I-131 uptake is below 15%. There was no difference between patient groups treated initially with antithyroid medication and those who were not.

Gallium-67 uptake by a benign adrenocortical adenoma.

A 55-yr-old man presented with an atypical relapsing meningitis and was found to have intense unilateral adrenal uptake by 67Ga imaging. Computed tomography showed a 4-cm right adrenal mass which was hypointense on the T1-weighted images and mildly hyperintense on the T2-weighted images of a magnetic resonance (MR) scan. At surgery, a coincidental benign adrenocortical adenoma was found. Because 67Ga uptake is usually associated with inflammatory or malignant lesions and malignant adrenal lesions are hyperintense on T2-weighted MR images, these findings contributed to diagnostic uncertainty in this patient. Thus, a nonhyperfunctional adrenocortical adenoma may be associated with abnormal 67Ga uptake and atypical MR findings.

Response of local vascular volumes to lower body negative pressure stress.

The present study involved an intravenous injection of radio-active iodinated serum albumin, equilibration of this isotope within the vascular space, and the continuous measurement of isotope activity over selected anatomical areas before, during and following multiple human LBNP tests. Both rate and magnitude of vascular pooling were distinctly different within each of five selected lower body anatomical areas. In the upper body, all areas except the abdomen showed depletions from their resting vascular volumes during LBNP. The presence of uniquely different pooling patterns in the lower body, the apparent stability of abdominal vascular volumes, and a possible decrease in cerebral blood volume during LBNP represent the major findings of this study.