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To elucidate the mechanisms underlying relapse from chemotherapy in multiple myeloma, we performed a longitudinal study of 33 patients entered into Total Therapy protocols investigating them using gene expression profiling, high-resolution copy number arrays, and whole-exome sequencing. The study illustrates the mechanistic importance of acquired mutations in known myeloma driver genes and the critical nature of biallelic inactivation events affecting tumor suppressor genes, especially TP53, the end result being resistance to apoptosis and increased proliferation rates, which drive relapse by Darwinian-type clonal evolution. The number of copy number aberration changes and biallelic inactivation of tumor suppressor genes was increased in GEP70 high risk, consistent with genomic instability being a key feature of high risk. In conclusion, the study highlights the impact of acquired genetic events, which enhance the evolutionary fitness level of myeloma-propagating cells to survive multiagent chemotherapy and to result in relapse., (© 2016 by The American Society of Hematology.)

We examine the relationships that internalization, need thwarting (NT), and drive for muscularity (DFM), along with their interactions, had with weightlifting, muscle dissatisfaction (MD), and muscle-related-worry (MRW). A sample of 552 men (MAge=20.5 years, SD=3.1) completed the Psychological Need Thwarting Scale, the Internalization subscale of the male version of the Sociocultural Attitudes Towards Appearance Questionnaire, the Drive for Muscularity Scale-Attitudes subscale, the Male Body Attitudes Scale-Muscularity subscale, the Body Change Inventory-Worry subscale, and an inventory assessing weightlifting behavior. DFM significantly predicted weightlifting, MRW, and MD. Internalization significantly predicted weightlifting and MRW. NT significantly predicted weightlifting and MD, and its relationship with MRW approached significance. The interaction terms did not predict weightlifting or MRW. The NT/DFM and NT/Internalization interaction terms predicted MD. These results highlight the role of NT in predicting appearance variables in men., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We examined if there were both direct and indirect relationships (via the drive for muscularity) between the perceived pressure to be muscular and internalization of the mesomorphic ideal, and if autonomy moderates these relationships in physically active men. A sample of 330 men, who were undergraduate students studying sport, completed the Behavioral Regulation in Exercise Questionnaire-2, the Mesomorphic Ideal Internalization subscale of the revised male version Sociocultural Attitudes Toward Appearance Questionnaire, the Perceived Sociocultural Pressure Scale-Modified, and the Drive for Muscularity Scale Attitudes subscale. Perceived pressure predicted internalization directly, and indirectly through the drive for muscularity. The direct relationship between pressure and internalization was weaker under higher levels of autonomy. The indirect path, via drive for muscularity, was stronger under higher levels of autonomy. These results provide insights into why men vary in the degree to which they internalize pressure to develop a mesomorphic ideal, supporting further examination of autonomy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to review some of the basic principles of extracellular electrical stimulation used in spinal cord stimulation therapy for intractable pain., Materials and Methods: Spinal cord stimulation has been used therapeutically for more than 40 years. We present the basic principles of extracellular stimulation on which the therapy is based, describe electrode operation and current configurations, and explain the implications of these technological advances for the clinical application of spinal cord stimulation., Results: Computational studies of coupled electric field and neuron models have significantly advanced our understanding of the therapeutic effects of neurostimulation. Neurostimulation is intended to obtain maximal selectivity of desired neural elements while avoiding those resulting in side-effects. Preferential stimulation of the dorsal columns is achieved with a narrow spacing between electrodes using bipolar or tripolar electrode configurations. Stimulus parameters such as amplitude and pulse width may be used to selectively control which neuronal elements are excited during stimulation., Conclusions: A better understanding of the interaction between electric fields and the targeted neural elements may guide the selection of stimulation parameters in contemporary neurostimulators and lead to continuing advances in engineering solutions for therapeutic spinal cord stimulation., (© 2014 International Neuromodulation Society.)

Aim: The aim of this anatomical study was to define the intraosseous vascular territory of the facial artery. The clinical issue is whether ipsilateral facial artery anastomosis will guarantee blood supply to the ipsi- and contralateral mandibular symphyses and maxillae in allotransplantation., Material and Methods: Of 10 human cadaveric heads, the left facial artery was injected with a positive contrast agent. The maxillae and mandibular symphyses were investigated with cone-beam computed tomography (CBCT)., Results: Each ipsilateral maxilla and mandibular bone segment showed contrast medium in the intraosseous vessels. In 50% of cases, this was also the case on the contralateral side of the maxilla and anterior mandible., Conclusions: The maxillae and the mandibular symphyses receive ipsilateral blood supply from the facial artery and, in 50% of cases, also from the contralateral facial artery. Internal maxillary artery anastomosis is not required for a vascularized maxillary bone flap. Additionally, involvement of the submental artery is not needed for a mandibular symphyseal bone flap., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Antibodies (IgG and IgM) recognizing a 240 kD antigen of the cat fetal brain were found in sera of healthy people and in sera (IgG) obtained at uncomplicated delivery from the umbilical cord of the newborn infant. The method applied was immunoblotting. Using the same method, the 240 kD antigen could not be detected in the adult brain or other fetal tissues. It seems that the antigen is specific for the fetal brain. The role of the antigen and the origin of generation and significance of function of the antibodies in the circulation are the objects of our further studies.

Our studies provide evidence for the presence of cyclin D1 in an early G1 cycle-specific DNA binding complex Yi1. Previously we identified several complexes including Yi and E2F that at different times during G0 to S transition bind to three distinct DNA sequences (MT1, MT2, MT3) located in the mouse thymidine kinase upstream promoter. These various complexes contain DNA binding proteins (Sp1, E2F, p110, p60), cyclins A and E, cyclin-dependent kinase 2 (cdk2), and retinoblastoma-related proteins (pRB, p107). Here we report that Yi1 is different from the E2F complexes. Yi1 contains cyclin D1/cdk2 kinase as shown by using specific antibodies to cyclins, cdks and the Yi1 DNA-binding protein in gel retardation, western blotting, and immunoprecipitation assays. Yi1 binding is specific to a consensus sequence different from that of E2F.

We have investigated the glycosaminoglycan composition of normal human liver, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma. Uronic acid increased about 4 fold in the benign and reactive lesions, and greater than 7 fold in the carcinoma. Whereas in focal nodular hyperplasia and adenoma dermatan sulfate was the predominant glycosaminoglycan, in hepatocellular carcinoma chondroitin sulfate was the predominant species; it increased 24 fold over normal liver and 3-5 fold over all the other tissues. HPLC analysis of chondroitinase ABC or AC digests showed a 58 fold increase in Delta-Di-OS disaccharides in hepatocellular carcinoma, indicating significant undersulfation of chondroitin sulfate. Surprisingly, the normal-appearing liver surrounding the carcinoma showed glycosaminoglycan changes similar to adenoma and nodular hyperplasia. These results thus indicate that specific glycosaminoglycan changes occur in hepatocellular carcinoma, and suggest for the first time that proteoglycan metabolism is also altered in the non-cirrhotic, hepatic parenchyma adjacent to liver carcinoma.

Cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5HIAA), homovanillic acid, and tryptophan were measured in 33 depressed, 36 alcoholic, and 32 neurological control female patients selected by strict operational criteria and investigated under controlled circumstances. Plasma total tryptophan was also measured in blood samples taken simultaneously with lumbar punctures. A multivariate regression analysis was done to discover the effect of age, height, and body weight on these four biochemical measures. Only CSF 5HIAA was significantly dependent on the nonspecific patient variables: height, but neither age nor weight, accounted for more than 10% of the variance of 5HIAA. The same analysis was carried out in all three separate patient groups: the relationship between height and CSF 5HIAA was present throughout, and only 2 of 12 correlations proved to be non-homogeneous. To demonstrate the significantly of these clinical parameters a multivariate analysis of covariance was done to eliminate their effect on the four biochemical variables. As a result significant differences emerged in CSF 5HIAA and total plasma tryptophan for some of the patient groups which were not demonstrable without this correction.

During hypoglycemia induced by an infusion of porcine insulin, impaired suppression of endogenous insulin secretion as measured by C-peptide was demonstrated in 11 of 12 patients with insulinoma. During hypoglycemia (plasma glucose less than or equal to 40 mg/dl) the mean C-peptide immunoreactivity (CPR) of normal subjects was less than or equal to 1.2 ng/ml, whereas 11 of 12 insulinoma patients had a mean CPR of larger than or equal to 1.9 ng/ml. One patient showed normal CPR suppression by these criteria but may have shown impaired CPR suppression for glucose less than or equal to 30 mg/dl. Impaired CPR suppression during insulin-induced hypoglycemia may prove to be a useful test for insulinoma.