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Adiponectin receptor 1 (AdipoR1) mediates adiponectin's pleiotropic effects in muscle and liver and plays an important role in the regulation of insulin resistance and diabetes. Here, we demonstrate a pivotal role for microRNA-221 (miR-221) and the RNA-binding protein polypyrimidine tract-binding protein (PTB) in posttranscriptional regulation of AdipoR1 during muscle differentiation and in obesity. RNA-immunoprecipitation and luciferase reporter assays illustrated that both PTB and miR-221 bind AdipoR1-3'UTR and cooperatively inhibit AdipoR1 translation. Depletion of PTB or miR-221 increased, while overexpression of these factors decreased, AdipoR1 protein synthesis in both muscle and liver cells. During myogenesis, downregulation of PTB and miR-221 robustly induced AdipoR1 translation, providing a mechanism for enhanced AdipoR1 protein expression and activation in differentiated muscle cells. In addition, since both PTB and miR-221 are upregulated in liver and muscle of genetic and dietary mouse models of obesity, this novel translational mechanism may be at least partly responsible for the reduction in AdipoR1 protein levels in obesity. These findings highlight the importance of translational control in regulating AdipoR1 protein expression and adiponectin signaling. Given that adiponectin is reduced in obesity, induction of AdipoR1 could potentially enhance adiponectin beneficial effects and ameliorate insulin resistance and diabetes.

Objective: Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiological states., Research Design and Methods: AdipoR1 5'UTR mRNA transcripts, predicted from bioinformatics data, were evaluated in fetal and adult human tissues. Expression and function of the identified transcripts were assessed in cultured human skeletal muscle cells and in muscle biopsies obtained from individuals with normal glucose tolerance (NGT) and type 2 diabetes (n = 49)., Results: Screening of potential AdipoR1 5'UTR splice variants revealed a novel highly abundant muscle transcript (R1T3) in addition to the previously described transcript (R1T1). Unlike R1T1, R1T3 expression was significantly increased during fetal development and myogenesis, paralleled with increased AdipoR1 protein expression. The 5'UTR of R1T3 was found to contain upstream open reading frames that repress translation of downstream coding sequences. Conversely, AdipoR1 3'UTR was associated with enhanced translation efficiency during myoblast-myotube differentiation. A marked reduction in muscle expression of R1T3, R1T1, and R1T3-to-R1T1 ratio was observed in individuals with type 2 diabetes compared with expression levels of NGT subjects, paralleled with decreased expression of the differentiation marker myogenin. Among NGT subjects, R1T3 expression was positively correlated with insulin sensitivity., Conclusions: These results indicate that AdipoR1 receptor expression in human skeletal muscle is subjected to posttranscriptional regulation, including alternative splicing and translational control. These mechanisms play an important role during myogenesis and may be important for whole-body insulin sensitivity.

This study provides clinical and radiographic information and characteristics that may best define the presence of significant lumbar foraminal stenosis and reports on the outcome of surgical intervention. Although anatomy of the lumbar intervertebral foramen (including static and dynamic pathologic compression of the exiting nerve root) has been described, few studies have focused on the clinical and radiographic features of foraminal stenosis requiring surgical intervention. We retrospectively studied 65 patients with lumbar foraminal stenosis for presenting clinical and radiographic features and intraoperative findings. Symptoms included leg and back pain (100%), paresthesias (45%), and subjective weakness (31%). Examination revealed lumbar tenderness (71%), limited lumbar extension (57%), focal motor weakness (48%), and positive tension signs (42%). The L5 nerve root was most often involved (75%). Almost 50% of patients had already undergone spinal decompression surgery. Surgical procedures included laminectomy and foraminotomy (52 patients) and laminotomy and foraminotomy (23 patients). A concomitant arthrodesis was performed in 63 patients. There were 29 excellent, 25 good, 6 fair, and 5 poor results based on a modified outcome scale at 32.5-month follow-up. Findings suggest that foraminal stenosis is a frequent cause of persistent symptoms after surgery, is most common at the lumbosacral junction, is best identified on parasagittal magnetic resonance images or on images reconstructed with computed tomography, and may be static or dynamic in etiology.

A cadaveric study was done to investigate the variability of interfacet distances from C3 to C7, to learn pedicle morphology at C7-T2, and to determine potential dangers of plate-screw osteosynthesis technique of the cervical spine. Twenty-two cadavers were dissected from C2 to C7 to expose the lateral masses and nerve roots. The interfacet distances from the center of the lateral mass to the next lateral mass from C3 to C7 vary widely among different individuals, ranging from 9 mm to 16 (average, 13 mm). A new plate design is necessary to better accommodate the differences in interfacet distances among different patients and different levels. The second part of the study involved 11 dissected cadaveric specimens of the cervicothoracic junction. The pedicle entry point was 1 mm inferior to the midportion of the facet joint for C7, T1, and T2. The medial angulation averaged 34 degrees at C7, 31.8 degrees at T1, and 26.5 degrees at T2. The mediolateral and superoinferior outer pedicle diameters were 6.9 mm and 7.5 mm at C7, 8.5 mm and 9.5 mm at T1, and 7.5 mm and 10.7 mm at T2, respectively. The mediolateral inner diameter averaged 5.18 mm, 6.4 mm, 5.5 mm for C7, T1 and T2, respectively. The pedicle distances (from the entry point to the posterior vertebral body line) measured 9.1 mm, 9.9 mm, and 10.4 mm for respective levels. The margins for error are small when using pedicle screws at these levels. If a pedicle screw must be used at C7, T1, and T2, one must have precise knowledge of the entrance point, diameters, and 25-30 degrees medial direction.(ABSTRACT TRUNCATED AT 250 WORDS)

A mixture of vitamin B12 and normal gastric juice, instilled through an intestinal tube into the ileum, produces haematological remission in patients with tapeworm pernicious anaemia. When a similar mixture is administered by mouth, this effect fails to occur. This observation constitutes evidence in favour of the view that Diphyllobothrium latum, attached to the proximal portion (jejunum) of the intestine, absorbs the vitamin B12 contained in the food, thus preventing vitamin bound to the intrinsic factor of the gastric juice from reaching the receptors in the distal portions of the small intestine of the host. In genuine pernicious anaemia, remission results from the administration of vitamin B12+gastric juice both by mouth and into the ileum.

Two cases are reported in whom primary hypothyroidism preceded thyrotoxic Graves' disease. The hypothesis is advanced that this sequence of events was mediated by spontaneous changes in the patient's autoimmune reactions to thyroid. In particular, it may reflect a spontaneous alteration in the balance between blocking antibodies reactive at or near the TSH receptor or cytotoxic thyroid autoimmune mechanisms on the one hand, and thyroid stimulating autoantibodies on the other.