Sample records for t1 radiculopathy electrodiagnostic

  1. T1 Radiculopathy: Electrodiagnostic Evaluation

    PubMed Central

    Radecki, Jeffrey; Zimmer, Zachary R.

    2008-01-01

    Electromyography (EMG) studies are useful in the anatomical localization of nerve injuries and, in most cases, isolating lesions to a single nerve root level. Their utility is important in identifying specific nerve-root-level injuries where surgical or interventional procedures may be warranted. In this case report, an individual presented with right upper extremity radicular symptoms consistent with a clinical diagnosis of cervical radiculopathy. EMG studies revealed that the lesion could be more specifically isolated to the T1 nerve root and, furthermore, provided evidence that the abductor pollicis brevis receives predominantly T1 innervation. PMID:19083061

  2. The prognostic value of electrodiagnostic testing in patients with sciatica receiving physical therapy.

    PubMed

    Savage, Nathan J; Fritz, Julie M; Kircher, John C; Thackeray, Anne

    2015-03-01

    To investigate the prognostic value of electrodiagnostic testing in patients with sciatica receiving physical therapy. Electrodiagnostic testing was performed on 38 patients with sciatica participating in a randomized trial comparing different physical therapy interventions. Patients were grouped and analyzed according to the presence or absence of radiculopathy based on electrodiagnostic testing. Longitudinal data analysis was conducted using multilevel growth modeling with ten waves of data collected from baseline through the treatment and post-treatment periods up to 6 months. The primary outcome measure was changes in low back pain-related disability assessed using the Roland and Morris disability questionnaire (RMDQ). Patients with radiculopathy (n = 19) had statistically significant and clinically meaningful improvements in RMDQ scores at every post-treatment follow-up occasion regardless of treatment received. The final multilevel growth model revealed improvements in RMDQ scores in patients with radiculopathy at the 6-week (-8.1, 95 % CI -12.6 to -2.6; P = 0.006) and 6-month (-4.1, 95 % CI -7.4 to -0.7; P = 0.020) follow-up occasions compared to patients without radiculopathy. Treatment group was not a significant predictive factor at any follow-up occasion. An interaction between electrodiagnostic status and time revealed faster weekly improvements in RMDQ scores in patients with radiculopathy at the 6-week (-0.72, 95 % CI -1.4 to -0.04; P = 0.040) through the 16-week (-0.30, 95 % CI, -0.57 to -0.04; P = 0.028) follow-up occasions compared to patients without radiculopathy. The presence of lumbosacral radiculopathy identified with electrodiagnostic testing is a favorable prognostic factor for recovery in low back pain-related disability regardless of physical therapy treatment received.

  3. Clinical findings and electrodiagnostic testing in 108 consecutive cases of lumbosacral radiculopathy due to herniated disc.

    PubMed

    Mondelli, M; Aretini, A; Arrigucci, U; Ginanneschi, F; Greco, G; Sicurelli, F

    2013-10-01

    This prospective study aim to examine whether clinical findings and electrodiagnostic testing (EDX) in patients with lumbosacral monoradiculopathy due to herniated disc (HD) differ as a function of root involvement level (L5 vs. S1) and HD zone (paramedian vs. intraforaminal). All patients with L4, L5 or S1 monoradiculopathy were prospectively enrolled at four electromyography (EMG) labs over a 2-year period. The diagnosis was based on a congruence between patient history and MRI evidence of HD. We compared the sensitivities of clinical findings and EDX with respect to both root involvement level and HD zone. Multivariate logistic regression was performed in order to verify the association between abnormal EMG, clinical, and neuroradiological findings. One hundred and eight patients (mean age 47.7 years, 55% men) were consecutively enrolled. Sensory loss in the painful dermatome was the most frequent finding at physical examination (56% of cases). EMG was abnormal in at least one muscle supplied by femoral and sciatic nerves in 45 cases (42%). Inclusion of paraspinal muscles increased sensitivity to only 49% and that of proximal muscles was useless. Motor and sensory neurography was seldom abnormal. The most frequent motor neurographic abnormalities were a delay of F-wave minimum latency and decrease in the compound muscle action potential amplitude from extensor digitorum brevis and abductor hallucis in L5 and S1 radiculopathies, respectively. Sensory neurography was usually normal, the amplitude of sensory nerve action potential was seldom reduced when HD injured dorsal root ganglion or postganglionic root fibres. Multivariate logistic regression analysis showed that EMG abnormalities could be predicted by myotomal muscular weakness, abnormal deep reflexes, and paraesthesiae. The only clinical and electrophysiological differences with respect to root involvement level concerned deep reflexes and motor neurography of deep peroneal and tibial nerves. Only some EDX

  4. The relationship between history and physical examination findings and the outcome of electrodiagnostic testing in patients with sciatica referred to physical therapy.

    PubMed

    Savage, Nathan J; Fritz, Julie M; Thackeray, Anne

    2014-07-01

    Cross-sectional diagnostic accuracy study. To investigate the relationship between history and physical examination findings and the outcome of electrodiagnostic testing in patients with sciatica referred to physical therapy. Electrodiagnostic testing is routinely used to evaluate patients with sciatica. Recent evidence suggests that the presence of radiculopathy identified with electrodiagnostic testing may predict better functional outcomes in these patients. While some patient history and physical examination findings have been shown to predict the presence of disc herniation or neurological insult, little is known about their relationship to the results of electrodiagnostic testing. Electrodiagnostic testing was performed on 38 patients with sciatica who participated in a randomized trial that compared different physical therapy interventions. The diagnostic gold standard was the presence or absence of radiculopathy, based on the results of the needle electromyographic examination. Diagnostic sensitivity and specificity values were calculated, along with corresponding likelihood ratios, for select patient history and physical examination variables. No significant relationship was found between select patient history and physical examination findings, analyzed individually or in combination, and the outcome of electrodiagnostic testing. Diagnostic sensitivity values ranged from 0.03 (95% confidence interval [CI]: 0.00, 0.24) to a high of 0.95 (95% CI: 0.72, 0.99), and specificity values ranged from 0.10 (95% CI: 0.02, 0.34) to a high of 0.95 (95% CI: 0.72, 0.99). Positive likelihood ratios ranged from 0.15 (95% CI: 0.01, 2.87) to a high of 2.33 (95% CI: 0.71, 7.70), and negative likelihood ratios ranged from 2.00 (95% CI: 0.35, 11.48) to a low of 0.50 (95% CI: 0.03, 8.10). In this investigation, the relationship between patient history and physical examination findings and the outcome of electrodiagnostic testing among patients with sciatica was not found to be

  5. Lateral Pectoral Nerve Injury Mimicking Cervical Radiculopathy.

    PubMed

    Aktas, Ilknur; Palamar, Deniz; Akgun, Kenan

    2015-07-01

    The lateral pectoral nerve (LPN) is commonly injured along with the brachial plexus, but its isolated lesions are rare. Here, we present a case of an isolated LPN lesion confused with cervical radiculopathy. A 41-year-old man was admitted to our clinic because of weakness in his right arm. Previous magnetic resonance imaging (MRI) examination revealed right posterolateral protrusion at the C6-7 level. At the initial assessment, atrophy of the right pectoralis major muscle was evident, and mild weakness of the right shoulder adductor, internal rotator, and flexor muscles was observed. Therefore, electrodiagnostic evaluation was performed, and a diagnosis of isolated LPN injury was made. Nerve injury was thought to have been caused by weightlifting exercises and traction injury. Lateral pectoral nerve injury can mimic cervical radiculopathy, and MRI examination alone may lead to misdiagnosis. Repeated physical examinations during the evaluation and treatment phase will identify the muscle atrophy that occurs 1 or more months after the injury.

  6. Physical examination, magnetic resonance image, and electrodiagnostic study in patients with lumbosacral disc herniation or spinal stenosis.

    PubMed

    Lee, Jung Hwan; Lee, Sang-Ho

    2012-10-01

    To compare the clinical implications of electro-diagnostic study with those of magnetic resonance imaging in patients with lumbosacral intervertebral herniated disc or spinal stenosis. Retrospective study of clinical data. Patients with lumbosacral intervertebral herniated disc or spinal stenosis, diagnosed by clinical assessment and magnetic resonance imaging (MRI), were selected. A total of 753 patients (437 with lumbosacral intervertebral herniated disc and 316 with spinal stenosis) were included in the study. Clinical data for electrodiagnostic study (EDX)and MRI were compared and the sensitivity and specificity of these studies were evaluated. Among all subjects, 267 had radiculopathy on EDX (EDX (+)) and 486 no radiculopathy (EDX(-)). Furthermore, 391 had root compression on MRI (MRI (+)) and 362 no root compression on MRI (MRI (-)). Patients with radioculopathy on EDX (+) showed a significantly higher visual analogue scale score for radiating pain and a higher Oswestry Disability Index than those with negative findings by EDX (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and there was a trend toward higher Oswestry Disability Index in the spinal stenosis subgroup. Although patients with radioculopathy on root compression on MRI (+) also had a higher visual analogue scale for radiating pain than patients with negative findings by MRI (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, no significant difference was seen in the Oswestry Disability Index. EDX revealed a significant correlation with muscle weakness in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and trends toward muscle weakness in the spinal stenosis subgroup, whereas there was no such significant correlation for MRI findings in any group. Electrodiagnostic study had a higher specificity in terms of physical examination data than MRI, in spite of its lower sensitivity

  7. The prevalence of tarsal tunnel syndrome in patients with lumbosacral radiculopathy.

    PubMed

    Zheng, Chaojun; Zhu, Yu; Jiang, Jianyuan; Ma, Xiaosheng; Lu, Feizhou; Jin, Xiang; Weber, Robert

    2016-03-01

    Tarsal tunnel syndrome (TTS) is a painful foot condition. Lumbosacral radiculopathy (LR) may also present with symptoms occurring in TTS. However, no studies have been reported to determine the possible coexistence of these two conditions. The aim of our study was to identify the prevalence of TTS in patients with confirmed LR and to analyze the clinical and electrodiagnostic features of patients with both TTS and LR. Medial and lateral plantar nerve mixed studies, peroneal motor studies and deep peroneal sensory studies were performed in 81 normal subjects and 561 patients with LR. The Tinel's test and other provocative tests were performed in the LR patient group, and the clinical symptoms of TTS were also analyzed. The frequency of TTS was investigated in all radiculopathy group patients with different nerve root lesions. Concomitant TTS was found in 27 (4.8%) patients with LR. Abnormal results of sensory/mixed conduction tests were observed in 25/27 (92.6%) patients, and 11/27 (40.7%) patients had abnormal results of motor conduction tests. Positivity for the Tinel's test and special provocative tests was found in 15/27 (55.6%) and 17/27 (63.0%) patients, respectively. Overall, 9/27 (33.3%) patients had typical symptoms, and suspicious clinical symptoms were found in the other 14/27 (51.9%) patients. The frequency of coexisting TTS was not statistically different among the single-level L4, L5 or S1 radiculopathy, or between the single-level and multi-level radiculopathies (P > 0.05). The findings suggest that the prevalence of TTS is significant in patients with LR. Thus, more caution should be paid when diagnosing and managing patients with LR due to the possible existence of TTS, as their management strategies are quite different.

  8. Nonoperative Management of Cervical Radiculopathy.

    PubMed

    Childress, Marc A; Becker, Blair A

    2016-05-01

    Cervical radiculopathy describes pain in one or both of the upper extremities, often in the setting of neck pain, secondary to compression or irritation of nerve roots in the cervical spine. It can be accompanied by motor, sensory, or reflex deficits and is most prevalent in persons 50 to 54 years of age. Cervical radiculopathy most often stems from degenerative disease in the cervical spine. The most common examination findings are painful neck movements and muscle spasm. Diminished deep tendon reflexes, particularly of the triceps, are the most common neurologic finding. The Spurling test, shoulder abduction test, and upper limb tension test can be used to confirm the diagnosis. Imaging is not required unless there is a history of trauma, persistent symptoms, or red flags for malignancy, myelopathy, or abscess. Electrodiagnostic testing is not needed if the diagnosis is clear, but has clinical utility when peripheral neuropathy of the upper extremity is a likely alternate diagnosis. Patients should be reassured that most cases will resolve regardless of the type of treatment. Nonoperative treatment includes physical therapy involving strengthening, stretching, and potentially traction, as well as nonsteroidal anti-inflammatory drugs, muscle relaxants, and massage. Epidural steroid injections may be helpful but have higher risks of serious complications. In patients with red flag symptoms or persistent symptoms after four to six weeks of treatment, magnetic resonance imaging can identify pathology amenable to epidural steroid injections or surgery.

  9. Radiculopathy in neuromyelitis optica. How does anti-AQP4 Ab involve PNS?

    PubMed

    Kim, Seungyeon; Park, Joonghyun; Kwon, Bum Sun; Park, Jin-Woo; Lee, Ho Jun; Choi, Jin-Ho; Nam, Kiyeun

    2017-11-01

    Until recently, the peripheral nervous system (PNS) had been known to be spared in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, some studies of late have reported PNS damage in demyelination diseases of the central nervous system (CNS) such as MS and NMOSD. Although multiple studies have reported characteristics reminiscent of peripheral neuropathy in MS, there have been limited reports in NMOSD. To investigate the incidence and pathology of peripheral neuropathy in NMOSD, we reviewed articles describing such cases including our own case. We performed a search of all clinical studies of peripheral neuropathy in NMOSD published up to December 17, 2016. We put no restrictions on language or year of publication in our search. The following keywords were searched: radiculopathy, peripheral nervous system diseases, neuromyelitis optica, neuromyelitis optica septrum disorder, aquaporin 4, electrodiagnosis, neural conduction and electromyography. We review ten cases (nine published reports and our own case study) of peripheral neuropathy in NMOSD. Each case could be confirmed as radiculopathy by electrodiagnostic (EDX) testing. Presently, there are two disparate viewpoints on peripheral neuropathy in NMOSD. In the first, aquaporin 4, which exists in the transitional zone of the CNS-PNS at the root level, may be the target of radiculitis in NMOSD. In the second, there may be some other unknown antibody to an axoglial antigen or something else that may play an active role in PNS damage. In our survey of ten case studies, the EDX results confirmed mixed axonal loss as well as demyelination type radiculopathy, which lends support to the first viewpoint. Pathophysiology of PNS damage in NMOSD might be due to radiculopathy. Although it seems to be rare, radiculopathy may actually be underestimated, and correspondingly underreported, due to its overlap with symptoms of myelitis. Therefore, further evaluation is needed to establish the

  10. Postfixed brachial plexus radiculopathy due to thoracic disc herniation in a collegiate wrestler: a case report.

    PubMed

    Kuzma, Scott A; Doberstein, Scott T; Rushlow, David R

    2013-01-01

    To present the unique case of a collegiate wrestler with C7 neurologic symptoms due to T1-T2 disc herniation. A 23-year-old male collegiate wrestler injured his neck in a wrestling tournament match and experienced pain, weakness, and numbness in his left upper extremity. He completed that match and 1 additional match that day with mild symptoms. Evaluation by a certified athletic trainer 6 days postinjury showed radiculopathy in the C7 distribution of his left upper extremity. He was evaluated further by the team physician, a primary care physician, and a neurosurgeon. Cervical spine injury, stinger/burner, peripheral nerve injury, spinal cord injury, thoracic outlet syndrome, brachial plexus radiculopathy. The patient initially underwent nonoperative management with ice, heat, massage, electrical stimulation, shortwave diathermy, and nonsteroidal anti-inflammatory drugs without symptom resolution. Cervical spine radiographs were negative for bony pathologic conditions. Magnetic resonance imaging showed evidence of T1-T2 disc herniation. The patient underwent surgery to resolve the symptoms and enable him to participate for the remainder of the wrestling season. Whereas brachial plexus radiculopathy commonly is seen in collision sports, a postfixed brachial plexus in which the T2 nerve root has substantial contribution to the innervation of the upper extremity is a rare anatomic variation with which many health care providers are unfamiliar. The injury sustained by the wrestler appeared to be C7 radiculopathy due to a brachial plexus traction injury. However, it ultimately was diagnosed as radiculopathy due to a T1-T2 thoracic intervertebral disc herniation causing impingement of a postfixed brachial plexus and required surgical intervention. Athletic trainers and physicians need to be aware of the anatomic variations of the brachial plexus when evaluating and caring for patients with suspected brachial plexus radiculopathies.

  11. Restless legs syndrome mimicking S1 radiculopathy.

    PubMed

    Zambelis, Th; Wolgamuth, B R; Papoutsi, S N; Economou, N T

    2016-01-01

    Α case of a chronic idiopathic form of a severe type of Restless Legs Syndrome (RLS), which developed during pregnancy and persisted after this, misdiagnosed for 34 years as radiculopathy S1, is reported. In spite of the thorough clinical and laboratory investigation, in addition to constant changes of the therapeutic approach, the diagnosis of S1 radiculopathy could not be confirmed, resulting in a chronic clinical course; the latter was characterized by relapses and remissions not attributed or linked in any way to the treatment (various types of). In fact, it was due to a routine workup in a sleep clinic, where the patient was referred because of a coincident chronic insomnia (Restless Legs Syndrome is a known and important cause of insomnia/chronic insomnia), which resulted in a proper diagnosis and treatment of this case. With the use of Restless Legs Syndrome appropriate treatment (Pramipexole 0.18 mg taken at bedtime, a dopaminergic agent and Level A recommended drug for Restless Legs Syndrome) an excellent response and immediate elimination of symptoms was achieved. Restless Legs Syndrome may present with a variety of symptoms (with the most prominent shortly being reported with the acronym URGE: Urge to move the legs usually associated with unpleasant leg sensations, Rest induces symptoms, Getting active brings relief, Evening and night deteriorate symptoms); given the fact that Restless Legs Syndrome presents with a great variety and heterogeneity of symptoms (mostly pain, dysesthesia and paresthesia), which may occur in several other diseases (the so called "RLS mimics"), proper diagnosis of Restless Legs Syndrome usually fails. Restless Legs Syndrome misinterpreted as S1 radiculopathy, to the best of our knowledge, has not been reported yet in the literature. Here, case history, clinical course and common RLS mimics are presented. Different forms of Restless Legs Syndrome manifestations, which are commonly -as in this case- misinterpreted due to their

  12. Three-tesla magnetic resonance neurography of the brachial plexus in cervical radiculopathy.

    PubMed

    Yoshida, Takeshi; Sueyoshi, Takeshi; Suwazono, Shugo; Suehara, Masahito

    2015-09-01

    There have been no reports of the use of 3-Tesla magnetic resonance neurography (3T MRN) to characterize cervical radiculopathy. In particular, there are no reports of MRN of brachial plexus involvement in patients with cervical radiculopathy. We reviewed retrospectively 12 consecutive patients with cervical radiculopathy who underwent 3T MRN. The median age was 54.5 years. Eleven of 12 patients were men. The distribution of nerve-root signal abnormality was correlated with intervertebral foraminal stenosis and the presence of muscles that exhibited weakness and/or signs of denervation on electromyography. MRN abnormalities were found to extend into the distal part of the brachial plexus in 10 patients. This study demonstrates that MRN is potentially useful for diagnosis in patients with suspected cervical radiculopathy. Moreover, the finding of brachial plexus involvement on MRN may indicate a possible pathophysiological relationship between cervical radiculopathy and brachial plexopathy. © 2014 Wiley Periodicals, Inc.

  13. [Usefulness of curved coronal MPR imaging for the diagnosis of cervical radiculopathy].

    PubMed

    Inukai, Chikage; Inukai, Takashi; Matsuo, Naoki; Shimizu, Ikuo; Goto, Hisaharu; Takagi, Teruhide; Takayasu, Masakazu

    2010-03-01

    In surgical treatment of cervical radiculopathy, localization of the responsible lesions by various imaging modalities is essential. Among them, MRI is non-invasive and plays a primary role in the assessment of spinal radicular symptoms. However, demonstration of nerve root compression is sometimes difficult by the conventional methods of MRI, such as T1 weighted (T1W) and T2 weighted (T2W) sagittal or axial images. We have applied a new technique of curved coronal multiplanar reconstruction (MPR) imaging for the diagnosis of cervical radiculopathy. Ten patients (4 male, 6 female) with ages between 31 and 79 year-old, who had clinical diagnosis of cervical radiculopathy, were included in this study. Seven patients underwent anterior key-hole foraminotomy to decompress the nerve root with successful results. All the patients had 3D MRI studies, such as true fast imaging with steady-state precession (FISP), 3DT2W sampling perfection with application optimized contrasts using different fillip angle evolution (SPACE), and 3D multi-echo data image combination (MEDIC) imagings in addition to the routine MRI (1.5 T Avanto, Siemens, Germany) with a phased array coil. The curved coronal MPR images were produced from these MRI data using a workstation. The nerve root compression was diagnosed by curved coronal MPR images in all the patients. The compression sites were compatible with those of the operative findings in 7 patients, who underwent surgical treatment. The MEDIC imagings were the most demonstrable to visualize the nerve root, while the 3D-space imagings were the next. The curved coronal MPR imaging is useful for the diagnosis of accurate localization of the compressing lesions in patients with cervical radiculopathy.

  14. Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile virus infection.

    PubMed

    Al-Shekhlee, Amer; Katirji, Bashar

    2004-03-01

    West Nile virus (WNV) infection is a potentially fatal disease, with meningoencephalitis being its most common neurological manifestation. Guillain-Barré syndrome (GBS) has also been described, but acute paralytic poliomyelitis has only recently been recognized. We report the clinical and electrodiagnostic findings of five patients with WNV infection, who presented with acute paralytic poliomyelitis. Three patients manifested focal asymmetrical weakness, and two had rapid ascending quadriplegia mimicking GBS. Electrodiagnostic studies during the acute illness showed normal sensory nerve action potentials, compound motor action potentials of normal or reduced amplitude, and no slowing of nerve conduction velocities. Depending on the timing of the examination, fibrillation potentials were widespread, including in those with focal weakness. Cervical magnetic resonance imaging in one patient showed abnormal T2-weighted signals in the spinal cord gray matter. On follow-up, signs of clinical improvement were seen in one patient, whereas two remained quadriplegic and ventilator-dependent 5 months after the onset. This report highlights the value of the electrodiagnostic studies in the diagnosis and prognosis of focal or generalized weakness due to acute paralytic poliomyelitis associated with WNV infection.

  15. Frequency of Radiculopathy in Patients With Carpal Tunnel Syndrome and Paracervical Pain.

    PubMed

    Garcia-Santibanez, Rocio; Scelsa, Stephen N

    2016-06-01

    Patients with carpal tunnel syndrome (CTS) and paracervical pain (PCP) are often incorrectly diagnosed with cervical radiculopathy. The objective of the study is to determine how frequently such patients have electrophysiologic evidence of radiculopathy. We reviewed charts of patients with clinical features of CTS and at least 1 median nerve conduction parameter showing slowing across the wrist. Patients were divided into those with and without PCP. Radiculopathy was defined electrophysiologically. We assessed group differences in the frequency of radiculopathy and how radiculopathy frequency varied with median nerve entrapment severity. Of 108 patients meeting criteria, 56 had PCP and 52 did not. Eight of 56 patients with PCP and 4 of 52 without pain had cervical radiculopathy (P = 0.36). There was no difference in the frequency of radiculopathy related to the severity of median nerve entrapment (P = 0.64). In patients with CTS, PCP is not associated with cervical radiculopathy. Cervical radiculopathy is not more frequent in more severe CTS.

  16. Contraction induced h reflexes in the diagnosis of cervical radiculopathy.

    PubMed

    Bodofsky, Elliot B; Campellone, Joseph V; Cohen, Stephen J; Caten, Holly N; Schindelheim, Adam M

    2015-06-01

    To determine whether Contraction Induced H Reflexes (CIHR) can accurately detect cervical radiculopathy. Comparison of CIHR results with Needle Electromyography at academic outpatient Electromyography/Nerve Conduction laboratories. Participants were all patients over 18 with a needle electromyography diagnosis of cervical radiculopathy. Patients were tested for CIHR in at least two upper extremity muscles in electromyographically proven myotomes bilaterally. Patients were requested to perform a moderate contraction while stimulus was applied proximally (elbow or Erb's point). Outcome measures included H Reflex onset latency and side-to-side latency differences. These were compared against previously established normal values. Overall, 10 of 15 patients who met criteria for cervical radiculopathy showed CIHR abnormalities (sensitivity = 67%; 95% confidence interval, 43-91). Counting each side and level separately, CIHR identified 16/27 radiculopathies (sensitivity = 59.2%; 95% confidence interval, 40.6-77.8). Contraction Induced H Reflexes identified 1 possible radiculopathy not seen on electromyography (specificity = 98%; 95% confidence interval, 95-100). Contraction induced H Reflexes have a sensitivity and specificity for cervical radiculopathy similar to the resting Gastroc-Soleus H Reflex.

  17. Clinical value of transforaminal epidural steroid injection in lumbar radiculopathy.

    PubMed

    Leung, S M; Chau, W W; Law, S W; Fung, K Y

    2015-10-01

    To identify the diagnostic, therapeutic, and prognostic values of transforaminal epidural steroid injection as interventional rehabilitation for lumbar radiculopathy. Regional hospital, Hong Kong. A total of 232 Chinese patients with lumbar radiculopathy attributed to disc herniation or spinal stenosis received transforaminal epidural steroid injection between 1 January 2007 and 31 December 2011. Transforaminal epidural steroid injection. Patients' immediate response, response duration, proportion of patients requiring surgery, and risk factors affecting the responses to transforaminal epidural steroid injection for lumbar radiculopathy. Of the 232 patients, 218 (94.0%) had a single level of radiculopathy and 14 (6.0%) had multiple levels. L5 was the most commonly affected level. The immediate response rate to transforaminal epidural steroid injection was 80.2% in 186 patients with clinically diagnosed lumbar radiculopathy and magnetic resonance imaging of the lumbar spine suggesting nerve root compression. Of patients with single-level radiculopathy and multiple-level radiculopathy, 175 (80.3%) and 11 (78.6%) expressed an immediate response to transforaminal epidural steroid injection, respectively. The analgesic effect lasted for 1 to <3 weeks in 35 (15.1%) patients, for 3 to 12 weeks in 37 (15.9%) patients, and for more than 12 weeks in 92 (39.7%) patients. Of the 232 patients, 106 (45.7%) were offered surgery, with 65 (61.3%) undergoing operation, and with 42 (64.6%) requiring spinal fusion in addition to decompression surgery. Symptom chronicity was associated with poor immediate response to transforaminal epidural steroid injection, but not with duration of pain reduction. Poor response to transforaminal epidural steroid injection was not associated with a preceding industrial injury. The immediate response to transforaminal epidural steroid injection was approximately 80%. Transforaminal epidural steroid injection is a useful diagnostic, prognostic, and

  18. The comparison of multiple F-wave variable studies and magnetic resonance imaging examinations in the assessment of cervical radiculopathy.

    PubMed

    Lin, Chu-Hsu; Tsai, Yuan-Hsiung; Chang, Chia-Hao; Chen, Chien-Min; Hsu, Hung-Chih; Wu, Chun-Yen; Hong, Chang-Zern

    2013-09-01

    The aims of this study were to investigate the correlation of the findings of multiple median and ulnar F-wave variables and magnetic resonance imaging examinations in the prediction of cervical radiculopathy. The data of 68 patients who underwent both nerve conduction studies of the upper extremities and cervical spine magnetic resonance imaging within 3 mos of the nerve conduction studies were retrospectively reviewed and reinterpreted. The associations between multiple median and ulnar F-wave variables (including persistence, chronodispersion, and minimal, maximal, and mean latencies) and magnetic resonance imaging evidence of lower cervical spondylotic radiculopathy (i.e., C7, C8, and T1 radiculopathy) were investigated. Patients with lower cervical radiculopathy exhibited reduced right median F-wave persistence (P = 0.011), increased right ulnar F-wave chronodispersion (P = 0.041), and a trend toward increased left ulnar F-wave chronodispersion (P = 0.059); however, there were no other consistent significant differences in the F-wave variables between patients with and patients without magnetic resonance imaging evidence of lower cervical radiculopathy. In comparison with normal reference values established previously, the sensitivity and positive predictive value of F-wave variable abnormalities for predicting lower cervical radiculopathy were low. There was a low correlation between F-wave studies and magnetic resonance imaging examinations. The diagnostic utility of multiple F-wave variables in the prediction of cervical radiculopathy was not supported by this study.

  19. AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine.

    PubMed

    Maselli, R A; Bakshi, N

    2000-07-01

    Early diagnosis of botulism is essential for effective treatment. Electrophysiologic testing can be of major help to establish a prompt diagnosis, but the classic electrodiagnostic features of botulism are often elusive. Decrement or increment of compound muscle action potential (CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent. Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit potentials in affected muscles are found more frequently but they are less specific. In general, the electrophysiologic findings taken together suggest involvement of the motor nerve terminal, which should raise the possibility of botulism. The case reported here illustrates a common clinical presentation of botulism. This study emphasizes realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the electrophysiologic data. Copyright 2000 American Association of Electrodiagnostic Medicine.

  20. [Study on the area of pain and numbness in cases with lumbosacral radiculopathy].

    PubMed

    Kuraishi, Keita; Hanakita, Junya; Takahashi, Toshiyuki; Minami, Manabu; Watanabe, Mizuki; Uesaka, Toshio; Honda, Fumiaki

    2012-10-01

    In the clinical diagnosis of lumbosacral radicular symptoms, dermatome maps are commonly used, by which the segmental location of the affected nerve can be determined. However, the diagnosis is often difficult because the pattern of sensory disturbance does not necessarily match the patterns of classical dermatomes, and there are many dermatome maps made by different methods. The author examined the area of pain and numbness in cases of lumbosacral radiculopathy. Clinical features of pain and numbness in consecutive seventy three cases of lumbosacral radiculopathy were investigated (L3: n=13, L4-S1: n=20). Patients of L3 radiculopathy showed symptoms at the upper buttock and ventral surface of the thighs, knees and upper ventral surface of the legs. Patients of L4 radiculopathy showed symptoms at the ventro-lateral surfaces of the thigh and leg. The distinctive region, defined as the region having 100% superimposition, of L4 radiculopathy was the lateral part of the shin. Patients of L5 radiculopathy showed symptoms at the lateral surfaces of the thigh and leg. The distinctive region was the upper buttock. Patients of S1 radiculopathy showed symptoms at the lower buttock, dorso-lateral part of the leg and lateral part of the foot. The distinctive region was the lateral part of the calf. It was found that the regions of pain and numbness formed a continuous band-like zone from thigh to leg in 8% of L3, 45% of L4 and L5, and 35% of S1 radiculopathy. Using a visual analogue scale, the degree of leg pain was more severe than low back pain in 68% of the patients, but in 5% of patients, low back pain was more severe.

  1. Clinical analysis of cervical radiculopathy causing deltoid paralysis.

    PubMed

    Chang, Han; Park, Jong-Beom; Hwang, Jin-Yeun; Song, Kyung-Jin

    2003-10-01

    In general, deltoid paralysis develops in patients with cervical disc herniation (CDH) or cervical spondylotic radiculopathy (CSR) at the level of C4/5, resulting in compression of the C5 nerve root. Therefore, little attention has been paid to CDH or CSR at other levels as the possible cause of deltoid paralysis. In addition, the surgical outcomes for deltoid paralysis have not been fully described. Fourteen patients with single-level CDH or CSR, who had undergone anterior cervical decompression and fusion for deltoid paralysis, were included in this study. The severity of deltoid paralysis was classified into five grades according to manual motor power test, and the severity of radiculopathy was recorded on a visual analog scale (zero to ten points). The degree of improvement in both the severity of deltoid paralysis and radiculopathy following surgery was evaluated. Of 14 patients, one had C3/4 CDH, four had C4/5 CDH, three had C4/5 CSR, one had C5/6 CDH, and five had C5/6 CSR. Both deltoid paralysis and radiculopathy improved significantly with surgery (2.57+/-0.51 grades vs 4.14+/-0.66, P=0.001, and 7.64+/-1.65 points vs 3.21+/-0.58, P=0.001, respectively). In conclusion, the current study demonstrates that deltoid paralysis can develop due to CDH or CSR not only C4/5, but also at the levels of C3/4 and C5/6, and that surgical decompression significantly improves the degree of deltoid paralysis due to cervical radiculopathy.

  2. [Radiculopathy in patients with Heerfordt's syndrome: two case presentations and review of the literature].

    PubMed

    Fukuhara, Kousuke; Fukuhara, Aika; Tsugawa, Jun; Oma, Shinji; Tsuboi, Yoshio

    2013-08-01

    As a subtype of the clinical presentations associated with sarcoidosis, the combination of uveitis, parotid gland swelling, and facial nerve palsy is known as Heerfordt's syndrome. This syndrome is an extremely rare disorder that has been estimated to affect only 4.1-5.6% of patients with sarcoidosis. We present 2 cases of Heerfordt's syndrome associated with radiculopathy in the trunk. The 2 patients experienced unilateral or bilateral radiculopathy in the trunk and in the trigeminal nerve area associated with Heerfordt's syndrome. Radiculopathy is also a rare manifestation in patients with neurosarcoidosis. A literature review revealed that only 51 cases of radiculopathy associated with sarcoidosis have been documented. A diagnosis of Heerfordt's syndrome was observed in 7 out of these 51 cases. Together with our 2 cases, 9 out of 53 patients with radiculopathy associated with sarcoidosis have been diagnosed as having Heerfordt's syndrome (estimated frequency, 16.9%). In conclusion, radiculopathy is a common neurological manifestation in patients with Heerfordt's syndrome. On the basis of our experience, we suggest that physicians consider the possibility of Heerfordt's syndrome in cases of radiculopathy with unknown cause.

  3. Distinct degree of radiculopathy at different levels of peripheral nerve injury

    PubMed Central

    2012-01-01

    Background Lumbar radiculopathy is a common clinical problem, characterized by dorsal root ganglion (DRG) injury and neural hyperactivity causing intense pain. However, the mechanisms involved in DRG injury have not been fully elucidated. Furthermore, little is known about the degree of radiculopathy at the various levels of nerve injury. The purpose of this study is to compare the degree of radiculopathy injury at the DRG and radiculopathy injury proximal or distal to the DRG. Results The lumbar radiculopathy rat model was created by ligating the L5 nerve root 2 mm proximal to the DRG or 2 mm distal to the DRG with 6.0 silk. We examined the degree of the radiculopathy using different points of mechanical sensitivity, immunohistochemistry and in vivo patch-clamp recordings, 7 days after surgery. The rats injured distal to the DRG were more sensitive than those rats injured proximal to the DRG in the behavioral study. The number of activated microglia in laminas I–II of the L5 segmental level was significantly increased in rats injured distal to the DRG when compared with rats injured proximal to the DRG. The amplitudes and frequencies of EPSC in the rats injured distal to the DRG were higher than those injured proximal to the DRG. The results indicated that there is a different degree of radiculopathy at the distal level of nerve injury. Conclusions Our study examined the degree of radiculopathy at different levels of nerve injury. Severe radiculopathy occurred in rats injured distal to the DRG when compared with rats injured proximal to the DRG. This finding helps to correctly diagnose a radiculopathy. PMID:22537715

  4. Restless Leg Syndrome and Sleep Quality in Lumbar Radiculopathy Patients

    PubMed Central

    Terzi, Murat; Akpinar, Kursad; Paksoy, Kemal; Cebeci, Ibrahim; Iyigun, Omer

    2014-01-01

    Background. To investigate the frequency of restless leg syndrome (RLS), sleep quality impairment, depression, fatigue, and sleep behavior disorder and to determine the effects of surgery on these parameters in radiculopathy patients resistant to conservative treatment. Methods. The present study included 66 lumbar radiculopathy patients, who were resistant to conservative treatment and had indication of surgery. Five different questionnaires were performed to assess depression (the Beck Depression Inventory (BDI)), sleep quality (the Pittsburgh Sleep Quality Index (PSQI)), fatigue (the Fatigue Severity Scale (FSS)), and presence of RLS and rapid eye movement sleep behavior disorder (RBD). The same questionnaires were also performed on a control group (n = 61). Results. Of the radiculopathy patients, 68.1% had RLS and 92.4% had fatigue. Of the controls, 16.4% had RLS and 59% had fatigue. RBD was present in 8 (12.1%) patients and 3 (4.9%) controls. The PSQI revealed that sleep quality was impaired in 46 (69.7%) patients and 35 (57.4%) controls (P > 0.05). The number of individuals having substantial depression according to the BDI was significantly higher in the patients than in the controls. Conclusions. There was a significant increase in the frequency of RLS, which was significantly decreased in the postoperative period in the radiculopathy patients. PMID:25110396

  5. Accuracy of physical examination for chronic lumbar radiculopathy

    PubMed Central

    2013-01-01

    Background Clinical examination of patients with chronic lumbar radiculopathy aims to clarify whether there is nerve root impingement. The aims of this study were to investigate the association between findings at clinical examination and nerve root impingement, to evaluate the accuracy of clinical index tests in a specialised care setting, and to see whether imaging clarifies the cause of chronic radicular pain. Methods A total of 116 patients referred with symptoms of lumbar radiculopathy lasting more than 12 weeks and at least one positive index test were included. The tests were the straight leg raising test, and tests for motor muscle strength, dermatome sensory loss, and reflex impairment. Magnetic resonance imaging (n = 109) or computer tomography (n = 7) were imaging reference standards. Images were analysed at the level of single nerve root(s), and nerve root impingement was classified as present or absent. Sensitivities, specificities, and positive and negative likelihood ratios (LR) for detection of nerve root impingement were calculated for each individual index test. An overall clinical evaluation, concluding on the level and side of the radiculopathy, was performed. Results The prevalence of disc herniation was 77.8%. The diagnostic accuracy of individual index tests was low with no tests reaching positive LR >4.0 or negative LR <0.4. The overall clinical evaluation was slightly more accurate, with a positive LR of 6.28 (95% CI 1.06–37.21) for L4, 1.74 (95% CI 1.04–2.93) for L5, and 1.29 (95% CI 0.97–1.72) for S1 nerve root impingement. An overall clinical evaluation, concluding on the level and side of the radiculopathy was also performed, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) calculation for diagnostic accuracy of this evaluation was performed. Conclusions The accuracy of individual clinical index tests used to predict imaging findings of nerve root impingement in patients with chronic lumbar

  6. The impact of extended electrodiagnostic studies in Ulnar Neuropathy at the elbow

    PubMed Central

    Todnem, Kari; Michler, Ralf Peter; Wader, Tony Eugen; Engstrøm, Morten; Sand, Trond

    2009-01-01

    Background This study aimed to explore the value of extended motor nerve conduction studies in patients with ulnar nerve entrapment at the elbow (UNE) in order to find the most sensitive and least time-consuming method. We wanted to evaluate the utility of examining both the sensory branch from the fifth finger and the dorsal branch of the ulnar nerve. Further we intended to study the clinical symptoms and findings, and a possible correlation between the neurophysiological findings and pain. Methods The study was prospective, and 127 UNE patients who were selected consecutively from the list of patients, had a clinical and electrodiagnostic examination. Data from the most symptomatic arm were analysed and compared to the department's reference limits. Student's t - test, chi-square tests and multiple regression models were used. Two-side p-values < 0.05 were considered as significant. Results Ulnar paresthesias (96%) were more common than pain (60%). Reduced ulnar sensitivity (86%) and muscle strength (48%) were the most common clinical findings. Adding a third stimulation site in the elbow mid-sulcus for motor conduction velocity (MCV) to abductor digiti minimi (ADM) increased the electrodiagnostic sensitivity from 80% to 96%. Additional recording of ulnar MCV to the first dorsal interosseus muscle (FDI) increased the sensitivity from 96% to 98%. The ulnar fifth finger and dorsal branch sensory studies were abnormal in 39% and 30% of patients, respectively. Abnormal electromyography in FDI was found in 49% of the patients. Patients with and without pain had generally similar conduction velocity parameter means. Conclusion We recommend three stimulation sites at the elbow for MCV to ADM. Recording from FDI is not routinely indicated. Sensory studies and electromyography do not contribute much to the sensitivity of the electrodiagnostic evaluation, but they are useful to document axonal degeneration. Most conduction parameters are unrelated to the presence of pain

  7. Electrical impedance myography in the diagnosis of radiculopathy.

    PubMed

    Spieker, Andrew J; Narayanaswami, Pushpa; Fleming, Laura; Keel, John C; Muzin, Stefan C; Rutkove, Seward B

    2013-11-01

    We sought to determine whether electrical impedance myography (EIM) could serve as a diagnostic procedure for evaluation of radiculopathy. Twenty-seven patients with clinically and radiologically diagnosed cervical or lumbosacral radiculopathy who met a "gold standard" definition underwent EIM and standard needle electromyography (EMG) of multiple upper or lower extremity muscles. EIM reactance values revealed consistent reductions in the radiculopathy-affected myotomal muscles as compared with those on the unaffected side; the degree of asymmetry was associated strongly with the degree of EMG abnormality (P < 0.001). EIM had a sensitivity of 64.5% and a specificity of 77.0%; in comparison, EMG had a sensitivity of 79.7% but a specificity of 69.7%. These findings support the potential for EIM to serve as a new non-invasive tool to assist in diagnosis of radiculopathy; however, further refinement of the technique is needed for this specific application. Copyright © 2013 Wiley Periodicals, Inc.

  8. Electrodiagnostic findings in a patient with Waardenburg syndrome.

    PubMed

    Ahmed, Aiesha; Simmons, Zachary

    2009-09-01

    Waardenburg syndrome is associated with a variety of clinical features, which may include polyneuropathy. We describe a patient with Waardenburg syndrome type 2 and provide detailed electrodiagnostic findings, thus complementing the biopsy data and brief descriptions of nerve conduction studies found in the literature.

  9. Reduced laser-evoked potential habituation detects abnormal central pain processing in painful radiculopathy patients.

    PubMed

    Hüllemann, P; von der Brelie, C; Manthey, G; Düsterhöft, J; Helmers, A K; Synowitz, M; Baron, R

    2017-05-01

    Repetitive painful laser stimuli lead to physiological laser-evoked potential (LEP) habituation, measurable by a decrement of the N2/P2 amplitude. The time course of LEP-habituation is reduced in the capsaicin model for peripheral and central sensitization and in patients with migraine and fibromyalgia. In the present investigation, we aimed to assess the time course of LEP-habituation in a neuropathic pain syndrome, i.e. painful radiculopathy. At the side of radiating pain, four blocks of 25 painful laser stimuli each were applied to the ventral thigh at the L3 dermatome in 27 patients with painful radiculopathy. Inclusion criteria were (1) at least one neurological finding of radiculopathy, (2) low back pain with radiation into the foot and (3) a positive one-sided compression of the L5 and/or S1 root in the MRI. The time course of LEP-habituation was compared to 20 healthy height and age matched controls. Signs of peripheral (heat hyperalgesia) and central sensitization (dynamic mechanical allodynia and hyperalgesia) at the affected L5 or S1 dermatome were assessed with quantitative sensory testing. Painful radiculopathy patients showed decreased LEP-habituation compared to controls. Patients with signs of central sensitization showed a more prominent LEP-habituation decrease within the radiculopathy patient group. Laser-evoked potential habituation is reduced in painful radiculopathy patients, which indicates an abnormal central pain processing. Central sensitization seems to be a major contributor to abnormal LEP habituation. The LEP habituation paradigm might be useful as a clinical tool to assess central pain processing alterations in nociceptive and neuropathic pain conditions. Abnormal central pain processing in neuropathic pain conditions may be revealed with the laser-evoked potential habituation paradigm. In painful radiculopathy patients, LEP-habituation is reduced compared to healthy controls. © 2017 European Pain Federation - EFIC®.

  10. Treatment of painful radiculopathies with capsaicin 8% cutaneous patch.

    PubMed

    Baron, R; Treede, R D; Birklein, F; Cegla, T; Freynhagen, R; Heskamp, M L; Kern, K U; Maier, C; Rolke, R; Seddigh, S; Sommer, C; Ständer, S; Maihöfner, C

    2017-08-01

    The treatment of neuropathic pain due to low-back (lumbosacral) radiculopathies, a common source of neuropathic pain, is challenging and often requires a multimodal therapeutic approach. The capsaicin 8% patch is the first topical analgesic licensed for peripheral neuropathic pain. To evaluate this treatment, a subset of patients with painful radiculopathy (lumbar and cervical, including ventral and dorsal rami) enrolled into the multicenter, non-interventional QUEPP study (Qutenza 2 - safety and effectiveness in peripheral neuropathic pain) was analyzed. Of the 1044 study participants, 50 were diagnosed with painful radiculopathy as only peripheral neuropathic pain syndrome and were eligible for evaluation. Patients received a single treatment (visit 1) with follow-up visits 2-5 at weeks 1-2, 4, 8 and 12. Parameters assessed at all visits included pain intensity, neuropathy symptoms and side effects. Quality of life (SF-12) and painDETECT 1 questionnaires were completed at baseline and final visit. Data was analyzed by patch application site and duration of pain. Topical treatment led to a significant decrease of pain intensity between weeks 1/2 and week 12 versus baseline at the application sites representing dermatomes of ventral (N = 26) and dorsal rami (N = 13) of spinal nerves. A significant decline (p ≤ .001) of numeric pain rating scale scores was observed between weeks 1/2 following patch application and the end of observation (week 12) in the overall radiculopathy group (N = 50), and the groups with either 3 months to 2 years (N = 14) or >2 years (N = 23) duration of pain. Pain relief of at least 30% was observed in 50.0%, 71.4% and 39.1% of patients in the respective groups. Four patients experienced in total seven adverse drug reactions (application site pain or pruritus). Effective neuropathic pain relief was observed after patch application within the innervation territories of both dorsal and ventral branches of the spinal

  11. Abnormal flexor carpi radialis H-reflex as a specific indicator of C7 as compared with C6 radiculopathy.

    PubMed

    Zheng, Chaojun; Zhu, Yu; Lv, Feizhou; Ma, Xiaosheng; Xia, Xinlei; Wang, Lixun; Jin, Xiang; Weber, Robert; Jiang, Jianyuan; Anuvat, Kevin

    2014-12-01

    The H-reflex of the flexor carpi radialis (FCR H-reflex) has not been commonly used for the diagnosis of cervical radiculopathy when compared with the routinely tested soleus H-reflex. Although both S1 and S2 roots innervate the soleus, the H-reflex is selectively related to S1 nerve root function clinically. Flexor carpi radialis is also innervated by two nerve roots which are C6 and C7. Although they are among the most common roots involved in cervical radiculopathy, few studies reported if the attenuation of the FCR H-reflex is caused by lesions affecting C7 or C6 nerve roots, or both. We aimed to identify whether an abnormal FCR H-reflex was attributed to the C7 or C6 nerve root lesion, or both. The sensitivities of needle electromyography, FCR H-reflex, and provocative tests in unilateral C7 or C6 radiculopathy were also compared in this study. A concentric needle electrode recorded bilateral FCR H-reflexes in 41 normal subjects (control group), 51 patients with C7 radiculopathy, and 54 patients with C6 radiculopathy. Clinical, radiological, and surgical approaches identified the precise single cervical nerve root involved in all patient groups. The H-reflex and M-wave latencies were measured and compared bilaterally. Abnormal FCR H-reflex was defined as the absence of the H-reflex or a side-to-side difference over 1.5 milliseconds which was based on the normal side-to-side difference of the H-reflex latency of 16.9 milliseconds (SD = 1.7 milliseconds) from the control group. We also determined standard median and ulnar conduction and needle electromyography. The provocative tests included bilateral determination of the Shoulder Abduction and Spurling's tests in all radiculopathy group patients. Abnormal FCR H-reflexes were recorded in 45 (88.2%) of C7 radiculopathy group patients, and 2 (3.7%) of C6 radiculopathy group patients (P < 0.05). Needle electromyography was abnormal in 41 (80.4%) of C7 radiculopathy patients and 43 (79.6%) of C6 radiculopathy

  12. Value of physical tests in diagnosing cervical radiculopathy: a systematic review.

    PubMed

    Thoomes, Erik J; van Geest, Sarita; van der Windt, Danielle A; Falla, Deborah; Verhagen, Arianne P; Koes, Bart W; Thoomes-de Graaf, Marloes; Kuijper, Barbara; Scholten-Peeters, Wendy G M; Vleggeert-Lankamp, Carmen L

    2018-01-01

    In clinical practice, the diagnosis of cervical radiculopathy is based on information from the patient's history, physical examination, and diagnostic imaging. Various physical tests may be performed, but their diagnostic accuracy is unknown. This study aimed to summarize and update the evidence on diagnostic performance of tests carried out during a physical examination for the diagnosis of cervical radiculopathy. A review of the accuracy of diagnostic tests was carried out. The study sample comprised diagnostic studies comparing results of tests performed during a physical examination in diagnosing cervical radiculopathy with a reference standard of imaging or surgical findings. Sensitivity, specificity, likelihood ratios are presented, together with pooled results for sensitivity and specificity. A literature search up to March 2016 was performed in CENTRAL, PubMed (MEDLINE), Embase, CINAHL, Web of Science, and Google Scholar. The methodological quality of studies was assessed using the QUADAS-2. Five diagnostic accuracy studies were identified. Only Spurling's test was evaluated in more than one study, showing high specificity ranging from 0.89 to 1.00 (95% confidence interval [CI]: 0.59-1.00); sensitivity varied from 0.38 to 0.97 (95% CI: 0.21-0.99). No studies were found that assessed the diagnostic accuracy of widely used neurological tests such as key muscle strength, tendon reflexes, and sensory impairments. There is limited evidence for accuracy of physical examination tests for the diagnosis of cervical radiculopathy. When consistent with patient history, clinicians may use a combination of Spurling's, axial traction, and an Arm Squeeze test to increase the likelihood of a cervical radiculopathy, whereas a combined results of four negative neurodynamics tests and an Arm Squeeze test could be used to rule out the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Neck pain with radiculopathy.

    PubMed

    Bhagawati, Dimpu; Gwilym, Stephen

    2015-12-23

    Non-specific neck pain has a postural or mechanical basis and affects about two-thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but may become chronic in about 10% of people. Whiplash injuries follow sudden acceleration-deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident, although this varies between countries. We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of surgical treatments for neck pain with radiculopathy? What are the effects of injection treatments for neck pain with radiculopathy? What are the effects of drug treatments for neck pain with radiculopathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 368 studies. After deduplication and removal of conference abstracts, 226 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 142 studies and the further review of 41 full publications. Of the 41 full articles evaluated, four systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for three PICO combinations. In this systematic overview, we categorised the efficacy for three interventions based on information about the effectiveness and safety of drug treatments, injection treatments, and surgical treatments.

  14. Clinical and electrodiagnostic characteristics of nitrous oxide-induced neuropathy in Taiwan.

    PubMed

    Li, Han-Tao; Chu, Chun-Che; Chang, Kuo-Hsuan; Liao, Ming-Feng; Chang, Hong-Shiu; Kuo, Hung-Chou; Lyu, Rong-Kuo

    2016-10-01

    Nitrous oxide-induced neuropathy is toxic neuropathy occasionally encountered in Taiwanese neurological clinics. Only several case reports described their electrodiagnostic features. We used a case-control design to investigate the detailed electrodiagnostic characteristics and possible factors relating to severe nerve injury. We retrospectively reviewed 33 patients with nitrous oxide-induced neuropathy over a 10-year period and reported their demographic data, spinal cord MRI, laboratory examinations and nerve conduction studies. 56 healthy controls' nerve conduction studies were collected for comparison analysis. We noted significant motor and sensory amplitudes reduction, conduction velocities slowing, and latencies prolongation in most tested nerves compared to the controls. Similar nerve conduction study characteristics with prominent lower limbs' motor and sensory amplitudes reduction was observed in patient groups with or without abnormal vitamin B12 and/or homocysteine levels. Among those with lower limbs' motor or sensory amplitudes reduction <20% of the lower limit of normal, higher homocysteine levels were detected. Severe impairments of the lower limbs' sensory and motor amplitudes were frequently noted in patients with nitrous oxide exposure. Nitrous oxide exposure itself is an important factor for the development of neuropathy. Our study contributes to the understanding of electrodiagnostic features underlying the nitrous oxide-induced neuropathy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Cervical radiculopathy: epidemiology, etiology, diagnosis, and treatment.

    PubMed

    Woods, Barrett I; Hilibrand, Alan S

    2015-06-01

    Cervical radiculopathy is a relatively common neurological disorder resulting from nerve root dysfunction, which is often due to mechanical compression; however, inflammatory cytokines released from damaged intervertebral disks can also result in symptoms. Cervical radiculopathy can often be diagnosed with a thorough history and physical examination, but an magnetic resonance imaging or computed tomographic myelogram should be used to confirm the diagnosis. Because of the ubiquity of degenerative changes found on these imaging modalities, the patient's symptoms must correlate with pathology for a successful diagnosis. In the absence of myelopathy or significant muscle weakness all patients should be treated conservatively for at least 6 weeks. Conservative treatments consist of immobilization, anti-inflammatory medications, physical therapy, cervical traction, and epidural steroid injections. Cervical radiculopathy typically is self-limiting with 75%-90% of patients achieving symptomatic improvement with nonoperative care. For patients who are persistently symptomatic despite conservative treatment, or those who have a significant functional deficit surgical treatment is appropriate. Surgical options include anterior cervical decompression and fusion, cervical disk arthroplasty, and posterior foraminotomy. Patient selection is critical to optimize outcome.

  16. Electrodiagnostic medicine skills competency in physical medicine and rehabilitation residents: a method for development and assessment.

    PubMed

    Brown, David; Cuccurullo, Sara; Lee, Joseph; Petagna, Ann; Strax, Thomas

    2008-08-01

    This project sought to create an educational module including evaluation methodology to instruct physical medicine and rehabilitation (PM&R) residents in electrodiagnostic evaluation of patients with neuromuscular problems, and to verify acquired competencies in those electrodiagnostic skills through objective evaluation methodology. Sixteen residents were trained by board-certified neuromuscular and electrodiagnostic medicine physicians through technical training, lectures, and review of self-assessment examination (SAE) concepts from the American Academy of Physical Medicine & Rehabilitation syllabus provided in the Archives of Physical Medicine and Rehabilitation. After delivery of the educational module, knowledge acquisition and skill attainment were measured in (1) clinical skill in diagnostic procedures via a procedure checklist, (2) diagnosis and ability to design a patient-care management plan via chart simulated recall (CSR) exams, (3) physician/patient interaction via patient surveys, (4) physician/staff interaction via 360-degree global ratings, and (5) ability to write a comprehensive patient-care report and to document a patient-care management plan in accordance with Medicare guidelines via written patient reports. Assessment tools developed for this program address the basic competencies outlined by the Accreditation Council for Graduate Medical Education (ACGME). To test the success of the standardized educational module, data were collected on an ongoing basis. Objective measures compared resident SAE scores in electrodiagnostics (EDX) before and after institution of the comprehensive EDX competency module in a PM&R residency program. Fifteen of 16 residents (94%) successfully demonstrated proficiency in every segment of the evaluation element of the educational module by the end of their PGY-4 electrodiagnostic rotation. The resident who did not initially pass underwent remedial coursework and passed on the second attempt. Furthermore, the

  17. Is There an Association Between Lumbosacral Radiculopathy and Painful Gluteal Trigger Points?: A Cross-sectional Study.

    PubMed

    Adelmanesh, Farhad; Jalali, Ali; Jazayeri Shooshtari, Seyed Mostafa; Raissi, Gholam Reza; Ketabchi, Seyed Mehdi; Shir, Yoram

    2015-10-01

    The objective of this study was to compare the prevalence of gluteal trigger point in patients with lumbosacral radiculopathy with that in healthy volunteers. In a cross-sectional, multistage sampling method, patients with clinical, electromyographic, and magnetic resonance imaging findings consistent with lumbosacral radiculopathy were examined for the presence of gluteal trigger point. Age- and sex-matched clusters of healthy volunteers were selected as the control group. The primary outcome of the study was the presence or absence of gluteal trigger point in the gluteal region of the patients and the control group. Of 441 screened patients, 271 met all the inclusion criteria for lumbosacral radiculopathy and were included in the study. Gluteal trigger point was identified in 207 (76.4%) of the 271 patients with radiculopathy, compared with 3 (1.9%) of 152 healthy volunteers (P < 0.001). The location of gluteal trigger point matched the side of painful radiculopathy in 74.6% of patients with a unilateral radicular pain. There was a significant correlation between the side of the gluteal trigger point and the side of patients' radicular pain (P < 0.001). Although rare in the healthy volunteers, most of the patients with lumbosacral radiculopathy had gluteal trigger point, located at the painful side. Further studies are required to test the hypothesis that specific gluteal trigger point therapy could be beneficial in these patients.

  18. Thoracic Radiculopathy following Spinal Cord Stimulator Implantation Treated with Corticosteroids.

    PubMed

    Ghosh, Ritam; Holland, Ryan; Mammis, Antonios

    2017-04-01

    Spinal cord stimulation has been used since 1967 to manage chronic neuropathic pain. Although effective, the literature describes the complication rate to be as high as 35%. One rare complication following spinal cord stimulator (SCS) implantation is the development of radicular pain. We present a case series of 2 patients implanted with SCSs who developed thoracic radiculopathy following implantation that resolved with corticosteroids. Although this complication was previously thought to require surgical intervention, this case series describes the use of corticosteroids to resolve postimplantation thoracic radiculopathy. Two patients were studied in this case series who received permanent thoracic implantation of a paddle lead SCS. Several days later, both developed back pain radiating toward the umbilicus in a dermatomal pattern consistent with thoracic radiculopathy. Corticosteroids were administered to relieve this pain. One received 6 mg dexamethasone intravenously every 6 hours followed by an oral dexamethasone taper for 1 week. The other was treated with an oral methylprednisolone taper for 2 weeks. Upon follow-up, both patients no longer complained of the thoracic radiculopathy and were satisfied with the pain relief the stimulators provided. In conclusion, postsurgical radicular pain is a rare but troubling complication of SCS implantation. In order to avoid further surgical complications or the need to explant a device that provides satisfactory paresthesia coverage, pharmacologic management is desirable. This case series has demonstrated that the use of corticosteroids can effectively resolve postimplantation thoracic radicular pain in a specific subgroup of patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Significance of perianular enhancement associated with anular tears on magnetic resonance imagings in diagnosis of radiculopathy.

    PubMed

    Byun, Woo Mok; Ahn, Sang Ho; Ahn, Myun-Whan

    2008-10-15

    Retrospective analysis of magnetic resonance imaging (MRI) and clinical findings about chemical radiculitis-associated anular tear in patients with radiculopathy. To investigate MRI findings of the chemical radiculitis caused by anular tears and to determine whether chemical radiculitis detected by MRI is the cause of radiculopathy. Many studies document that irritation of adjacent nerve roots by a chemical mediator of inflammation from the nucleus pulposus may result in radiculopathy. Computed tomography (CT) discography may be the best examination for diagnosing discogenic chemical radiculitis but is too invasive. A reliable imaging method for replacing invasive provocative CT discography and diagnosing chemical radiculitis is required. The study population consisted of 12 patients with pain referred to leg(s) with or without low back pain who underwent lumbar spine MRI. All cases of our study demonstrated perianular enhancement caused by chemical radiculitis associated with anular tears. Patterns and locations of perianular enhancement adjacent to anular tears on MRI were assessed. MRI findings were compared with clinical symptoms and/or provocative transforaminal epidural injection (n = 6). For documentation of the relationship between perianular enhancement and radiculopathy, provocative CT discography was performed in 2 cases. Perianular enhancement associated with anular tears revealed thick linear patterns (2.5-7 mm thickness) along margins of anular tears on contrast enhanced axial T1-weighted images with fat suppression. Locations of perianular enhancement adjacent to anular tears were at foraminal (n = 6) and extraforaminal portions (n = 6). CT discography showed a leak of contrast from anular tear to the perianular regions. Pain reproduction at contrast leak level during discography showed concordant pain. There was an apparent correlation between perianular enhancement on MRI and clinical symptoms or provocative epidural nerve root injection in all

  20. Lumbar disc herniation with contralateral radiculopathy: do we neglect the epidural fat?

    PubMed

    Yang, Jun-Song; Zhang, Dong-Jie; Hao, Ding-Jun

    2015-01-01

    Lumbar disc herniation (LDH) is the most common cause of radiculopathy, whose pathological entity underlying nerve root compression is usually on the same side as the symptoms. However, LDH causing contralateral radiculopathy are sometimes encountered by pain physicians. There have been tremendous developments in the treatment options for LDH; the situation of LDH causing contralateral radiculopathy is indeed a dilemma for some pain physicians. We will report a case of a patient with a L4-5 disc herniation whose left herniated disc caused radiculopathy on the right side. After a percutaneous lumbar endoscopic discectomy via the side ipsilateral to the symptomatic side, this case obtained a significant symptom remission. The migrated epidural fat is discussed as a cause of associated contralateral neurological deficit. Only via a surgical approach ipsilateral to the herniated side, could there be a clinical improvement postoperatively.

  1. Cervical Stenosis, Myelopathy and Radiculopathy

    MedlinePlus

    ... and rarely changes in bowel or bladder control. Cervical radiculopathy will manifest itself as pain traveling from the neck into a specific region ... physician feels that this is related to your cervical spine. If you have persistent pain, numbness or weakness in one of your arms ...

  2. Cervical interlaminar epidural steroid injection for unilateral cervical radiculopathy: comparison of midline and paramedian approaches for efficacy.

    PubMed

    Yoon, Ji Young; Kwon, Jong Won; Yoon, Young Cheol; Lee, Jongseok

    2015-01-01

    The objective of this study was to compare the clinical outcomes of the cervical interlaminar epidural steroid injection (CIESI) for unilateral radiculopathy by the midline or paramedian approaches and to determine the prognostic factors of CIESI. We retrospectively analyzed 182 patients who underwent CIESI from January 2009 to December 2012. Inclusion criteria were no previous spinal steroid injection, presence of a cross-sectional image, and presence of follow-up records. Exclusion criteria were patients with bilateral cervical radiculopathy and/or dominant cervical axial pain, combined peripheral neuropathy, and previous cervical spine surgery. Short-term clinical outcomes were evaluated at the first follow-up after CIESI. We compared the clinical outcomes between the midline and paramedian approaches. Possible prognostic factors for the outcome, such as age, gender, duration of radiculopathy, and cause of radiculopathy were also analyzed. Cervical interlaminar epidural steroid injections were effective in 124 of 182 patients (68.1%) at the first follow-up. There was no significant difference in the clinical outcomes of CIESI, between midline (69.6%) and paramedian (63.7%) approaches (p = 0.723). Cause of radiculopathy was the only significant factor affecting the efficacy of CIESI. Patients with disc herniation had significantly better results than patients with neural foraminal stenosis (82.9% vs. 56.0%) (p < 0.001). There is no significant difference in treatment efficacy between the midline and paramedian approaches in CIESI, for unilateral radiculopathy. The cause of the radiculopathy is significantly associated with the treatment efficacy; patients with disc herniation experience better pain relief than those with neural foraminal stenosis.

  3. Preoperative pain neuroscience education for lumbar radiculopathy: a multicenter randomized controlled trial with 1-year follow-up.

    PubMed

    Louw, Adriaan; Diener, Ina; Landers, Merrill R; Puentedura, Emilio J

    2014-08-15

    Multicenter, randomized, controlled trial on preoperative pain neuroscience education (NE) for lumbar radiculopathy. To determine if the addition of NE to usual preoperative education would result in superior outcomes with regard to pain, function, surgical experience, and health care utilization postsurgery. One in 4 patients after lumbar surgery (LS) for radiculopathy experience persistent pain and disability, which is nonresponsive to perioperative treatments. NE focusing on the neurophysiology of pain has been shown to decrease pain and disability in populations with chronic low back pain. Eligible patients scheduled for LS for radiculopathy were randomized to receive either preoperative usual care (UC) or a combination of UC plus 1 session of NE delivered by a physical therapist (verbal one-on-one format) and a NE booklet. Sixty-seven patients completed the following outcomes prior to LS (baseline), and 1, 3, 6, and 12 months after LS: low back pain (numeric rating scale), leg pain (numeric rating scale), function (Oswestry Disability Index), various beliefs and experiences related to LS (10-item survey with Likert scale responses), and postoperative utilization of health care (utilization of health care questionnaire). At 1-year follow-up, there were no statistical differences between the experimental and control groups with regard to primary outcome measure of low back pain (P = 0.183), leg pain (P = 0.075), and function (P = 0.365). In a majority of the categories regarding surgical experience, the NE group scored significantly better: better prepared for LS (P = 0.001); preoperative session preparing them for LS (P < 0.001) and LS meeting their expectations (P = 0.021). Health care utilization post-LS also favored the NE group (P = 0.007) resulting in 45% less health care expenditure compared with the control group in the 1-year follow-up period. NE resulted in significant behavior change. Despite a similar pain and functional trajectory during the 1-year

  4. Cervical Interlaminar Epidural Steroid Injection for Unilateral Cervical Radiculopathy: Comparison of Midline and Paramedian Approaches for Efficacy

    PubMed Central

    Yoon, Ji Young; Yoon, Young Cheol; Lee, Jongseok

    2015-01-01

    Objective The objective of this study was to compare the clinical outcomes of the cervical interlaminar epidural steroid injection (CIESI) for unilateral radiculopathy by the midline or paramedian approaches and to determine the prognostic factors of CIESI. Materials and Methods We retrospectively analyzed 182 patients who underwent CIESI from January 2009 to December 2012. Inclusion criteria were no previous spinal steroid injection, presence of a cross-sectional image, and presence of follow-up records. Exclusion criteria were patients with bilateral cervical radiculopathy and/or dominant cervical axial pain, combined peripheral neuropathy, and previous cervical spine surgery. Short-term clinical outcomes were evaluated at the first follow-up after CIESI. We compared the clinical outcomes between the midline and paramedian approaches. Possible prognostic factors for the outcome, such as age, gender, duration of radiculopathy, and cause of radiculopathy were also analyzed. Results Cervical interlaminar epidural steroid injections were effective in 124 of 182 patients (68.1%) at the first follow-up. There was no significant difference in the clinical outcomes of CIESI, between midline (69.6%) and paramedian (63.7%) approaches (p = 0.723). Cause of radiculopathy was the only significant factor affecting the efficacy of CIESI. Patients with disc herniation had significantly better results than patients with neural foraminal stenosis (82.9% vs. 56.0%) (p < 0.001). Conclusion There is no significant difference in treatment efficacy between the midline and paramedian approaches in CIESI, for unilateral radiculopathy. The cause of the radiculopathy is significantly associated with the treatment efficacy; patients with disc herniation experience better pain relief than those with neural foraminal stenosis. PMID:25995690

  5. Assessing fear-avoidance beliefs in patients with cervical radiculopathy.

    PubMed

    Dedering, Asa; Börjesson, Tina

    2013-12-01

    The study sought to evaluate validity and reliability of the Fear Avoidance Beliefs Questionnaire and the Tampa Scale for Kinesiophobia in patients with cervical radiculopathy. A test-retest design was used to test stability over time in 46 patients with cervical radiculopathy. Differences between patients and healthy subjects were also evaluated comparing the patients with 41 physically active and healthy subjects. The patients answered the Fear Avoidance Beliefs Questionnaire and the Tampa Scale for Kinesiophobia twice. To test for differences between the patients and the healthy subjects, the latter answered the same questionnaires once. Questionnaires about activity, personal factors and health were also used. The test-retest reliability assessed with weighted kappa was 0.68 for the Fear Avoidance Beliefs Questionnaire and 0.45 for the Tampa Scale for Kinesiophobia. Only six of the 11 single items of the Fear Avoidance Beliefs Questionnaire and none of the single items of the Tampa Scale of Kinesiophobia showed kappa coefficients exceeding 0.60 (good reliability). Patients with cervical radiculopathy rated significantly worse on the Fear Avoidance Beliefs Questionnaire and the Tampa Scale for Kinesiophobia than the healthy subjects did. The Fear Avoidance Beliefs Questionnaire may be recommended for test-retest evaluations because 'good' reliability was found. The Tampa Scale for Kinesiophobia had only 'moderate' test-retest reliability, and this should be considered when using this scale in test-retest evaluations. Both questionnaires can discriminate between patients with cervical radiculopathy and healthy subjects. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Sensory Symptom Profiles and Co-Morbidities in Painful Radiculopathy

    PubMed Central

    Gockel, Ulrich; Brosz, Mathias; Freynhagen, Rainer; Tölle, Thomas R.; Baron, Ralf

    2011-01-01

    Painful radiculopathies (RAD) and classical neuropathic pain syndromes (painful diabetic polyneuropathy, postherpetic neuralgia) show differences how the patients express their sensory perceptions. Furthermore, several clinical trials with neuropathic pain medications failed in painful radiculopathy. Epidemiological and clinical data of 2094 patients with painful radiculopathy were collected within a cross sectional survey (painDETECT) to describe demographic data and co-morbidities and to detect characteristic sensory abnormalities in patients with RAD and compare them with other neuropathic pain syndromes. Common co-morbidities in neuropathic pain (depression, sleep disturbance, anxiety) do not differ considerably between the three conditions. Compared to other neuropathic pain syndromes touch-evoked allodynia and thermal hyperalgesia are relatively uncommon in RAD. One distinct sensory symptom pattern (sensory profile), i.e., severe painful attacks and pressure induced pain in combination with mild spontaneous pain, mild mechanical allodynia and thermal hyperalgesia, was found to be characteristic for RAD. Despite similarities in sensory symptoms there are two important differences between RAD and other neuropathic pain disorders: (1) The paucity of mechanical allodynia and thermal hyperalgesia might be explained by the fact that the site of the nerve lesion in RAD is often located proximal to the dorsal root ganglion. (2) The distinct sensory profile found in RAD might be explained by compression-induced ectopic discharges from a dorsal root and not necessarily by nerve damage. These differences in pathogenesis might explain why medications effective in DPN and PHN failed to demonstrate efficacy in RAD. PMID:21573064

  7. Cost of common low back pain and lumbar radiculopathy in rheumatologic consultation in Lomé.

    PubMed

    Fianyo, Eyram; Oniankitan, Owonayo; Tagbor Komi, C; Kakpovi, Kodjo; Houzou, Prénam; Koffi-Tessio Viwalé, E S; Mijiyawa, Moustafa

    2017-03-01

    The cost of low back pain was the subject of few studies in black Africa. To assess the cost of common low back pain and lumbar radiculopathy in Lomé. A six months study was realised in the rheumatologic department of CHU Sylvanus Olympio. 103 consecutive patients suffering from a common low back pain or lumbar radiculopathy were included. To assess direct, indirect and non-financial costs they were questioned about their expense during the year. Financial cost of common low back pain and lumbar radiculopathy amounted to 107.2 $ US (extremes: 5.8 and 726.1 $ US). This amount, quadruple of guaranteed minimum wage, felled under two headings: direct cost (56.3 $ US; 53% of total sum), indirect cost (50.3 $ US; 47% of total sum). Non-financial cost were: disruption in daily activities (94%), impact in emotional and sexual life (59%), impact on the family's budget (69%), abandon of family's projects (58%) or of leisure (42%). In black Africa top priority is given to the fight against infectious diseases those cause an important mortality. But common low back pain and lumbar radiculopathy, those have social and economic impact, should be given more attention.

  8. The short term effects of preoperative neuroscience education for lumbar radiculopathy: A case series

    PubMed Central

    Louw, Adriaan; Diener, Ina

    2015-01-01

    Background Recently a preoperative pain neuroscience education (NE) program was developed for lumbar surgery (LS) for radiculopathy as a means to decrease postoperative pain and disability. This study attempts to determine the short term effects, if any, of providing NE before surgery on patient outcomes. Methods A case series of 10 patients (female = 7) received preoperative one-on-one educational session by a physical therapist on the neuroscience of pain, accompanied by an evidence-based booklet, prior to LS for radiculopathy. Post-intervention data was gathered immediately after NE, as well as 1, 3 and 6 months following LS. Primary outcome measures were Pain Catastrophization Scale (PCS), forward flexion, straight leg raise (SLR) and beliefs regarding LS. Results Immediately following NE for LS for radiculopathy, all patients had lower PCS scores, with 5 patients exceeding the MDC score of 9.1 and 8 of the patients had PCS change scores exceeding the MDC by the 1, 3 and 6 month follow ups. Physical changes showed that fingertip-to-floor test in 6 patients had changes in beyond the MDC of 4.5 cm and 6 patients had changes in SLR beyond the MDC of 5.7°. The main finding, however, indicated a positive and more realistic shift in expectations regarding pain after the impending LS by all patients. Conclusions The results of the case series suggest that immediately after NE, patients scheduled for LS for radiculopathy had meaningful detectable changes in pain catastrophizing, fingertip-to-floor test, passive SLR and positive shifts in their beliefs about LS. PMID:26056626

  9. Diagnosis and Treatment of C4 Radiculopathy.

    PubMed

    Ross, Donald A; Ross, Miner N

    2016-12-01

    Clinical case series. This study sought to clarify symptoms, diagnostic criteria, and treatment of C4 radiculopathy, and the role of diagnostic C4 root block in this entity. Although well understood cervical dermatomal/myotomal syndromes have been described for symptoms originating from impingement on the C2, C3, C5, C6, C7, and C8 roots, less has been written about the syndrome(s) associated with the C4 root. The senior author reviewed surgical records and describes his personal experience with the diagnosis and treatment of C4 radiculopathy. A total of 712 procedures for cervical radiculopathy without myelopathy were reviewed. Among that cohort, 13 procedures involved the C4 root only and five procedures involved two level procedures including the C4 root. Patients described pain as involving the axial cervical region, paraspinal muscles, trapezius muscle, and interscapular region. No patient described pain over the anterior chest wall or radiating distal to the shoulder, one described pain over the medial clavicle. All patients who were offered surgery had a positive response to a diagnostic C4 transforaminal single nerve root block. Thirteen patients underwent posterior foraminotomy (five at two levels) and five patients underwent an anterior discectomy and fusion at C3-4. Mean Oswestry Disability Index score significantly declined; preoperative score 24.3 (range 14-29), postoperative score 9.7 (range 2-18; P = 0.003) at ≥3 months. Mean Short Form-36v2 score significantly increased; preoperative score 34.2 (range 20-40.2), postoperative score 73.7 (range 40.5-88.3, P = 0.001) at ≥3 months. C4 root symptoms overlap those of the C3 and C5 roots and are very similar to facet mediated pain. Asymptomatic C4 foraminal stenosis may be a common imaging finding, it can be difficult to diagnose C4 radiculopathy clinically. Diagnostic C4 root block can make an accurate diagnosis and lead to successful surgical outcomes. 4.

  10. Treatment of cervical radiculopathy: A review of the evolution and economics.

    PubMed

    Ament, Jared D; Karnati, Tejas; Kulubya, Edwin; Kim, Kee D; Johnson, J Patrick

    2018-01-01

    The surgical treatment of cervical radiculopathy has centered around anterior cervical discectomy and fusion (ACDF). Alternatively, the posterior cervical laminoforaminotomy/microdiscectomy (PCF/PCM), which results in comparable outcomes and is more cost-effective, has been underutilized. Here, we compared the direct/indirect costs, reoperation rates, and outcome for ACDF and PCF vs. PCM using PubMed, Medline, and Embase databases. There were no significant differences between the re-operative rates of PCF/PCM (2% to 9.8%) versus ACDF (2% to 8%). Direct costs of ACDF were also significantly higher; the 1-year cost-utility analysis demonstrated that ACDF had $131,951/QALY while PCM had $79,856/QALY. PCF/PCM for radiculopathy are safe and more cost-effective vs. ACDF, and have similar clinical outcomes.

  11. Operative treatment of new onset radiculopathy secondary to combat injury.

    PubMed

    Wagner, Scott C; Van Blarcum, Gregory S; Kang, Daniel G; Lehman, Ronald A

    2015-02-01

    We set out to describe combat-related spine trauma over a 10-year period, and thereby determine the frequency of new onset radiculopathy secondary to injuries sustained in support of combat operations. We performed a retrospective analysis of a surgical database at three military institutions. Patients undergoing spine surgery following a combat-related injury in Afghanistan or Iraq between July 2003 and July 2013 were evaluated. We identified 105 patients with combat-related (Operations Enduring and Iraqi Freedom) spine trauma requiring operative intervention. Of these, 15 (14.3%) patients had radiculopathy as their primary complaint after injury. All patients were diagnosed with herniated nucleus pulposus. The average age was 39 years, with 80% injured in Iraq and 20% in Afghanistan. The most common mechanism of injury was mounted improvised explosive device (33%). The cervical spine was most commonly involved (53%), followed by lumbar spine (40%). Average time from injury to surgery was 23.4 months; 53% of patients had continued symptoms following surgery, and two patients had at least one revision surgery. Two patients were medically retired because of their symptoms. This study is the only of its kind evaluating the operative treatment of traumatic radiculopathy following combat-related trauma. We identified a relatively high rate of radiculopathy in these patients. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  12. Comparison between effectiveness of Mechanical and Manual Traction combined with mobilization and exercise therapy in Patients with Cervical Radiculopathy.

    PubMed

    Bukhari, Syed Rehan Iftikhar; Shakil-Ur-Rehman, Syed; Ahmad, Shakeel; Naeem, Aamer

    2016-01-01

    Cervical radiculopathy is a common neuro-musculo-skeletal disorder causing pain and disability. Traction is part of the evidence based manual physical therapy management due to its mechanical nature, type of traction and parameters related to its applicability and are still to be explored more through research. Our objective was to determine the Effects of Mechanical versus Manual Traction in Manual Physical Therapy combined with segmental mobilization and exercise therapy in the physical therapy management of Patients with Cervical Radiculopathy. This randomized control trial was conducted at department of physical therapy and rehabilitation, Rathore Hospital Faisalabad, from February to July 2015. Inclusion criteria were both male and female patients with evident symptoms of cervical spine radiculopathy and age ranged between 20-70 years. The exclusion criteria were Patients with history of trauma, neck pain without radiculopathy, aged less than 20 and more than 70. A total of 72 patients with cervical radiculopathy were screened out as per the inclusion criteria, 42 patients were randomly selected and placed into two groups by toss and trial method, and only 36 patients completed the study, while 6 dropped out. The mechanical traction was applied in group A and manual traction in group B along with common intervention of segmental mobilization and exercise therapy in both groups for 6 weeks. The patient's outcomes were assessed by self reported NPRS and NDI at the baseline and after completion of 06 weeks exercise program at 3 days per week. The data was analyzed through SPSS version-21, and paired T test was applied at 95% level significance to determine the statistical deference between two groups. Clinically the group of patients treated with mechanical traction managed pain (mean pre 6.26, mean post 1.43), and disability (mean pre 24.43 and mean post 7.26) more effectively as compared with the group of patients treated with manual traction (Pain mean pre 6

  13. Evaluation of electromagnetic fields in the treatment of pain in patients with lumbar radiculopathy or the whiplash syndrome.

    PubMed

    Thuile, Ch; Walzl, M

    2002-01-01

    Back pain and the whiplash syndrome are very common diseases involving tremendous costs and extensive medical effort. A quick and effective reduction of symptoms, especially pain, is required. In two prospective randomized studies, patients with either lumbar radiculopathy in the segments L5/S1 or the whiplash syndrome were investigated. Inclusion criteria were as follows: either clinically verified painful lumbar radiculopathy in the segments L5/S1 and a Laségue's sign of 30 degrees (or more), or typical signs of the whiplash syndrome such as painful restriction of rotation and flexion/extension. Exclusion criteria were prolapsed intervertebral discs, systemic neurological diseases, epilepsy, and pregnancy. A total of 100 patients with lumbar radiculopathy and 92 with the whiplash syndrome were selected and entered in the study following a 1:1 ratio. Both groups (magnetic field treatment and controls) received standard medication consisting of diclofenac and tizanidine, while the magnetic field was only applied in group 1, twice a day, for a period of two weeks. In patients suffering from radiculopathy, the average time until pain relief and painless walking was 8.2 +/- 0.5 days in the magnetic field group, and 11.7 +/- 0.5 days in controls p < 0.04). In patients with the whiplash syndrome, pain was measured on a ten-point scale. Pain in the head was on average 4.6 before and 2.1 after treatment in those receiving magnetic field treatment, and 4.2/3.5 in controls. Neck pain was on average 6.3/1.9 as opposed to 5.3/4.6, and pain in the shoulder/arm was 2.4/0.8 as opposed to 2.8/2.2 (p < 0.03 for all regions). Hence, magnetic fields appear to have a considerable and statistically significant potential for reducing pain in cases of lumbar radiculopathy and the whiplash syndrome.

  14. Transforaminal endoscopic treatment of lumbar radiculopathy after instrumented lumbar spine fusion.

    PubMed

    Telfeian, Albert E; Jasper, Gabriele P; Francisco, Gina M

    2015-01-01

    Transforaminal endoscopic discectomy and foraminotomy is a well-described minimally invasive technique for surgically treating lumbar radiculopathy caused by a herniated disc and foraminal narrowing. To describe the technique and feasibility of transforaminal foraminoplasty for the treatment of lumbar radiculopathy in patients who have already undergone instrumented spinal fusion. Retrospective study. Hospital and ambulatory surgery center After Institutional Review Board approval, charts from 18 consecutive patients with lumbar radiculopathy and instrumented spinal fusions who underwent endoscopic procedures between 2008 and 2013 were reviewed. The average pain relief one year postoperatively was reported to be 67.0%, good results as defined by MacNab. The average preoperative VAS score was 9.14, indicated in our questionnaire as severe and constant pain. The average one year postoperative VAS score was 3.00, indicated in our questionnaire as mild and intermittent pain. This is a retrospective study and only offers one year follow-up data for patients with instrumented fusions who have undergone endoscopic spine surgery. Transforaminal endoscopic discectomy and foraminotomy could be used as a safe, yet, minimally invasive and innovative technique for the treatment of lumbar radiculopathy in the setting of previous instrumented lumbar fusion. IRB approval: Meridian Health: IRB Study # 201206071J

  15. Reoperation Rates After Anterior Cervical Discectomy and Fusion for Cervical Spondylotic Radiculopathy and Myelopathy: A National Population-based Study.

    PubMed

    Park, Moon Soo; Ju, Young-Su; Moon, Seong-Hwan; Kim, Tae-Hwan; Oh, Jae Keun; Makhni, Melvin C; Riew, K Daniel

    2016-10-15

    National population-based cohort study. To compare the reoperation rates between cervical spondylotic radiculopathy and myelopathy in a national population of patients. There is an inherently low incidence of reoperation after surgery for cervical degenerative disease. Therefore, it is difficult to sufficiently power studies to detect differences between reoperation rates of different cervical diagnoses. National population-based databases provide large, longitudinally followed cohorts that may help overcome this challenge. We used the Korean Health Insurance Review and Assessment Service national database to select our study population. We included patients with the diagnosis of cervical spondylotic radiculopathy or myelopathy who underwent anterior cervical discectomy and fusion from January 2009 to June 2014. We separated patients into two groups based on diagnosis codes: cervical spondylotic radiculopathy or cervical spondylotic myelopathy. Age, sex, presence of diabetes, osteoporosis, associated comorbidities, number of operated cervical disc levels, and hospital types were considered potential confounding factors. The overall reoperation rate was 2.45%. The reoperation rate was significantly higher in patients with cervical spondylotic myelopathy than in patients with cervical radiculopathy (myelopathy: P = 0.0293, hazard ratio = 1.433, 95% confidence interval 1.037-1.981). Male sex, presence of diabetes or associated comorbidities, and hospital type were noted to be risk factors for reoperation. The reoperation rate after anterior cervical discectomy and fusion was higher for cervical spondylotic myelopathy than for cervical spondylotic radiculopathy in a national population of patients. 3.

  16. Laser-evoked potentials in painful radiculopathy.

    PubMed

    Hüllemann, P; von der Brelie, C; Manthey, G; Düsterhöft, J; Helmers, A K; Synowitz, M; Gierthmühlen, J; Baron, R

    2017-11-01

    The aims of this exploratory study were (1) to develop a standardized objective electrophysiological technique with laser-evoked potentials to assess dorsal root damage quantitatively and (2) to correlate these LEP measures with clinical parameters and sensory abnormalities (QST) in the affected dermatome. Thirty-eight patients with painful radiculopathy and 20 healthy subjects were investigated with LEP recorded from the affected dermatome and control areas as well as with quantitative sensory testing. Questionnaires evaluating severity and functionality were applied. On average, LEP amplitudes and latencies from the affected dermatomes did not differ from the contralateral control side. In patients with left L5 radiculopathy (more severely affected) the N2 latency was longer and the amplitudes reduced. The N2P2 amplitude correlated with pinprick evoked sensations in QST. The N2 latency from the affected dermatome correlates with pain intensity, chronicity, clinical severity and with a decrease of physical function. An increase in N2-latency indicates a more pronounced nerve root damage, which is associated with a decrease of function and an increase of severity and pain. LEP amplitudes are associated with the functional status of the nociceptive system and may distinguish between degeneration of neuronal systems and central sensitization processes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  17. Prospective medium-term results of multimodal pain management in patients with lumbar radiculopathy

    PubMed Central

    Benditz, A.; Madl, M.; Loher, M.; Grifka, J.; Boluki, D.; Linhardt, O.

    2016-01-01

    Lumbar radiculopathy is one of the most common diseases of modern civilisation. Multimodal pain management (MPM) represents a central approach to avoiding surgery. Only few medium-term results have been published in the literature so far. This study compared subjective and objective as well as anamnestic and clinical parameters of 60 patients who had undergone inpatient MPM because of lumbar radiculopathy before and 1 year ±2 weeks after treatment. The majority of patients were very satisfied (35%) or satisfied (52%) with the treatment outcome. Merely 8 patients commented neutrally and none negatively. The finger-floor distance had decreased significantly (p < 0.01), and 30 patients (50%) had shown improved mobility of the spine after therapy. The need for painkillers had also been significantly reduced after 1 year. The arithmetical average of pain on a visual analogue scale was 7.21 before treatment, which had significantly decreased to 3.58 at follow-up (p < 0.01). MPM is an effective approach for treating lumbar radiculopathy by mechanical nerve root irritation. Therefore, in the absence of an absolute indication for surgery or an absolute contradiction for MPM, patients should first be treated with this minimally invasive therapy. PMID:27305956

  18. Divergent sensory phenotypes in nonspecific arm pain: comparisons with cervical radiculopathy.

    PubMed

    Moloney, Niamh; Hall, Toby; Doody, Catherine

    2015-02-01

    To investigate whether distinct sensory phenotypes were identifiable in individuals with nonspecific arm pain (NSAP) and whether these differed from those in people with cervical radiculopathy. A secondary question considered whether the frequency of features of neuropathic pain, kinesiophobia, high pain ratings, hyperalgesia, and allodynia differed according to subgroups of sensory phenotypes. Cross-sectional study. Higher education institution. Forty office workers with NSAP, 17 people with cervical radiculopathy, and 40 age- and sex-matched healthy controls (N=97). Not applicable. Participants were assessed using quantitative sensory testing (QST) comprising thermal and vibration detection thresholds and thermal and pressure pain thresholds; clinical examination; and relevant questionnaires. Sensory phenotypes were identified for each individual in the patient groups using z-score transformation of the QST data. Individuals with NSAP and cervical radiculopathy present with a spectrum of sensory abnormalities; a dominant sensory phenotype was not identifiable in individuals with NSAP. No distinct pattern between clinical features and questionnaire results across sensory phenotypes was identified in either group. When considering sensory phenotypes, neither individuals with NSAP nor individuals with cervical radiculopathy should be considered homogeneous. Therefore, people with either condition may warrant different intervention approaches according to their individual sensory phenotype. Issues relating to the clinical identification of sensory hypersensitivity and the validity of QST are highlighted. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. Similar outcome despite slight clinical differences between lumbar radiculopathy induced by lateral versus medial disc herniations in patients without previous foraminal stenosis: a prospective cohort study with 1-year follow-up.

    PubMed

    Mérot, Oriane A; Maugars, Yves M; Berthelot, Jean-Marie M

    2014-08-01

    lying or standing), but slight significant differences (t test<0.05) were observed for other items: the 28 patients with lateral herniations were 8 years older (53.4 ±15.8 vs. 45.2±12.6), their herniations involved discs from upper levels of the lumbar spine (above L4-L5: 7/28 vs. 3/31), motor weakness was more frequent (25% vs. 3%), SLR was less restricted (65.0°±24.5° vs. 51.1°±25.7°), DN4 score of neuropathic pain was higher (4.4±2.1 vs. 3.2±1.8), anxiety level was higher (10.3±4.1 vs. 7.9±3.2), length of hospital stay was longer (5.7±2.4 days vs. 4.5±1.4 days), and physician's prognosis of a good outcome was poorer (6.6±2.2 vs. 8.0±1.6). However, at the end of follow-up (12.2±3.3 months), outcome was similar: 37% (vs. 41% for medial herniations) had transiently relapsed, 66% felt finally improved (vs. 63%), and walking capacity was nearly identical despite the fact that only 18% had to be operated (vs. 32% of those with medial herniations). Despite differences in clinical presentation, the outcome of radiculopathy induced by the more lateral lumbar disc herniations was not worse than the outcome of patients with only medial disc herniations. Previous claims of poorer outcome in foraminal herniations might be explained by the inclusion of patients with associated foraminal stenosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Can axial pain be helpful to determine surgical level in the multilevel cervical radiculopathy?

    PubMed

    Suh, Bo-Kyung; You, Ki Han; Park, Moon Soo

    2017-01-01

    Spine surgeons are required to differentiate symptomatic cervical disc herniation with asymptomatic radiographic herniation. Although the dermatomal sensory dysfunction of upper extremity is the most important clue, axial pain including cervicogenic headache and parascapular pain may be helpful to find surgical target level. However, there is no review article about the axial pain originated from cervical spondylotic radiculopathy and relieved by surgical decompression. The purpose is to review the literatures about the axial pain, which can be utilized in determining target level to be decompressed in the patients with cervical radiculopathy at multiple levels. Cervicogenic headaches of suboccipital headaches, retro-orbital pain, retro-auricular pain, or temporal pain may be associated with C2, C3, and C4 radiculopathies. The pain around scapula may be associated with C5, C6, C7, and C8 radiculopathies. However, there is insufficient evidence to make recommendations for the use in clinical practice because they did not evaluate sensitivity and specificity.

  1. Arthroplasty for cervical spondylotic myelopathy: similar results to patients with only radiculopathy at 3 years' follow-up.

    PubMed

    Fay, Li-Yu; Huang, Wen-Cheng; Wu, Jau-Ching; Chang, Hsuan-Kan; Tsai, Tzu-Yun; Ko, Chin-Chu; Tu, Tsung-Hsi; Wu, Ching-Lan; Cheng, Henrich

    2014-09-01

    Cervical arthroplasty has been accepted as a viable option for surgical management of cervical spondylosis or degenerative disc disease (DDD). The best candidates for cervical arthroplasty are young patients who have radiculopathy caused by herniated disc with competent facet joints. However, it remains uncertain whether arthroplasty is equally effective for patients who have cervical myelopathy caused by DDD. The aim of this study was to compare the outcomes of arthroplasty for patients with cervical spondylotic myelopathy (CSM) and patients with radiculopathy without CSM. A total of 151 consecutive cases involving patients with CSM or radiculopathy caused by DDD and who underwent one- or two-level cervical arthroplasty were included in this study. Clinical outcome evaluations and radiographic studies were reviewed. Clinical outcome measurements included the Visual Analog Scale (VAS) of neck and arm pain, Japanese Orthopaedic Association (JOA) scores, and the Neck Disability Index (NDI) in every patient. For patients with CSM, Nurick scores were recorded for evaluation of cervical myelopathy. Radiographic studies included lateral dynamic radiographs and CT for detection of the formation of heterotopic ossification . Of the 151 consecutive patients with cervical DDD, 125 (82.8%; 72 patients in the myelopathy group and 53 in the radiculopathy group) had at least 24 months of clinical and radiographic follow-up. The mean duration of follow-up in these patients was 36.4 months (range 24-56 months). There was no difference in sex distribution between the 2 groups. However, the mean age of the patients in the myelopathy group was approximately 6 years greater than that of the radiculopathy group (53.1 vs 47.2 years, p < 0.001). The mean operation time, mean estimated blood loss, and the percentage of patients prescribed perioperative analgesic agents were similar in both groups (p = 0.754, 0.652, and 0.113, respectively). There were significant improvements in VAS neck

  2. Cervical Radiculopathy due to Cervical Degenerative Diseases : Anatomy, Diagnosis and Treatment

    PubMed Central

    Kim, Kyoung-Tae

    2010-01-01

    A cervical radiculopathy is the most common symptom of cervical degenerative disease and its natural course is generally favorable. With a precise diagnosis using appropriate tools, the majority of patients will respond well to conservative treatment. Cervical radiculopathy with persistent radicular pain after conservative treatment and progressive or profound motor weakness may require surgery. Options for surgical management are extensive. Each technique has strengths and weaknesses, so the choice will depend on the patient's clinical profile and the surgeon's judgment. PMID:21430971

  3. Improvement in pain after lumbar surgery in cancer patients with mechanical radiculopathy.

    PubMed

    Moliterno, Jennifer; Veselis, Clinton A; Hershey, Michael A; Lis, Eric; Laufer, Ilya; Bilsky, Mark H

    2014-10-01

    Lumbar metastases can result in spinal instability and mechanical radiculopathy, characterized by radicular pain produced by axial loading. This pain pattern represents a definitive symptom of neoplastic instability and may serve as a reliable indication for surgical stabilization. We examined the results of surgical decompression and fixation in the treatment of mechanical radiculopathy. A retrospective clinical study. An internally maintained spine neurosurgery database was queried between February 2002 and April 2010. Patients were identified and deemed eligible for inclusion in this study based on the presence of all the following: metastatic tumor, lumbar surgery, and lumbar radiculopathy. Visual analog scale (VAS) of pain and Eastern Cooperative Oncology Group (ECOG) status. The Memorial Sloan-Kettering Cancer Center Department of Neurosurgery operative database was queried over an 8-year period to identify all patients with spinal metastases who underwent lumbar surgery. Only patients whose operative indication included mechanical radiculopathy were included. Pre- and postoperative pain was assessed with the VAS of pain, whereas pre- and postoperative performance status was evaluated using the ECOG. Fifty-five patients were included in the cohort. L2 and L3 were the most common levels involved, and most patients underwent multilevel posterior decompression and instrumented fusion. After surgery, 98% of patients reported pain relief. A significant difference between average pre- and postoperative pain scores was found (p<.01). Overall, 41.5% of patients experienced improvement in their ECOG score postoperatively. Mechanical radiculopathy in patients with spinal metastases represents a highly reliable surgical indication. Spinal decompression and fixation is an effective treatment for pain palliation in this patient population. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Using the modified Delphi method to establish a new Chinese clinical consensus of the treatments for cervical radiculopathy.

    PubMed

    Zang, Lei; Fan, Ning; Hai, Yong; Lu, S B; Su, Q J; Yang, J C; Du, Peng; Gao, Y J

    2015-06-01

    Although cervical radiculopathy is very common, there is no standard treatment for this condition, with little high-level evidence available to guide the treatment choice. Thus, this study aimed to review the current data on the management of cervical radiculopathy; and, further, to establish a new Chinese clinical consensus of the treatments for cervical radiculopathy using the Delphi method. First, a systematic review of the previously established treatment guidelines and of articles related to cervical radiculopathy was conducted to establish a protocol for the clinical consensus of the treatment for cervical radiculopathy. Second, from February 2012 to June 2014, we performed a modified Delphi survey in which the current professional opinions from 30 experienced experts, representing almost all of the Chinese provinces, were gathered. Three rounds were performed, and consensus was defined as ≥70% agreement. Consensus of the treatments for cervical radiculopathy was reached on seven aspects, including the proportion of patients requiring only non-surgical therapies; the effectiveness of neck immobilization, physiotherapy, pharmacologic treatment; surgical indications; contraindications; surgery. The modified Delphi study conducted herein reached a consensus concerning several treatment issues for cervical radiculopathy. In the absence of high-level evidence, at present, these expert opinion findings will help guide health care providers to define the appropriate treatment in their regions. Items with no consensus provide excellent areas for future research.

  5. Sacral Stress Fracture Mimicking Lumbar Radiculopathy in a Mounted Police Officer: Case Report and Literature Review.

    PubMed

    Bednar, Drew A; Almansoori, Khaled

    2015-10-01

    Study Design Case report and review of the literature. Objective To present a unique case of L5 radiculopathy caused by a sacral stress fracture without neurologic compression. Methods We present our case and its clinical evolution and review the available literature on similar pathologies. Results Relief of the unusual mechanical loading causing sacral stress fracture led to rapid resolution of radiculopathy. Conclusion L5 radiculopathy can be caused by a sacral stress fracture and can be relieved by simple mechanical treatment of the fracture.

  6. Salvage of cervical motor radiculopathy using peripheral nerve transfer reconstruction.

    PubMed

    Afshari, Fardad T; Hossain, Taushaba; Miller, Caroline; Power, Dominic M

    2018-05-10

    Motor nerve transfer surgery involves re-innervation of important distal muscles using either an expendable motor branch or a fascicle from an adjacent functioning nerve. This technique is established as part of the reconstructive algorithm for traumatic brachial plexus injuries. The reproducible outcomes of motor nerve transfer surgery have resulted in exploration of the application of this technique to other paralysing conditions. The objective of this study is to report feasibility and increase awareness about nerve transfer as a method of improving upper limb function in patients with cervical motor radiculopathy of different aetiology. In this case series we report 3 cases with different modes of injury to the spinal nerve roots with significant and residual motor radiculopathy that have been successfully treated with nerve transfer surgery with good functional outcomes. The cases involved iatrogenic nerve root injury, tumour related root compression and degenerative root compression. Nerve transfer surgery may offer reliable reconstruction for paralysis when there has been no recovery following a period of conservative management. However the optimum timing of nerve transfer intervention is not yet identified for patients with motor radiculopathy.

  7. Optimal Duration of Conservative Management Prior to Surgery for Cervical and Lumbar Radiculopathy: A Literature Review

    PubMed Central

    Alentado, Vincent J.; Lubelski, Daniel; Steinmetz, Michael P.; Benzel, Edward C.; Mroz, Thomas E.

    2014-01-01

    Study Design Literature review. Objective Since the 1970s, spine surgeons have commonly required 6 weeks of failed conservative treatment prior to considering surgical intervention for various spinal pathologies. It is unclear, however, if this standard has been validated in the literature. The authors review the natural history, outcomes, and cost-effectiveness studies relating to the current standard of 6 weeks of nonoperative care prior to surgery for patients with spinal pathologies. Methods A systematic Medline search from 1953 to 2013 was performed to identify natural history, outcomes, and cost-effectiveness studies relating to the optimal period of conservative management prior to surgical intervention for both cervical and lumbar radiculopathy. Demographic information, operative indications, and clinical outcomes are reviewed for each study. Results A total of 5,719 studies were identified; of these, 13 studies were selected for inclusion. Natural history studies demonstrated that 88% of patients with cervical radiculopathy and 70% of patients with lumbar radiculopathy showed improvement within 4 weeks following onset of symptoms. Outcomes and cost-effectiveness studies supported surgical intervention within 8 weeks of symptom onset for both cervical and lumbar radiculopathy. Conclusions There are limited studies supporting any optimal duration of conservative treatment prior to surgery for cervical and lumbar radiculopathy. Therefore, evidence-based conclusions cannot be made. Based on the available literature, we suggest that an optimal timing for surgery following cervical radiculopathy is within 8 weeks of onset of symptoms. A shorter period of 4 weeks may be appropriate based on natural history studies. Additionally, we found that optimal timing for surgery following lumbar radiculopathy is between 4 and 8 weeks. A prospective study is needed to explicitly identify the optimal duration of conservative therapy prior to surgery so that costs

  8. Back pain was less explained than leg pain: a cross-sectional study using magnetic resonance imaging in low back pain patients with and without radiculopathy.

    PubMed

    Jensen, Ole Kudsk; Nielsen, Claus Vinther; Sørensen, Joan Solgaard; Stengaard-Pedersen, Kristian

    2015-12-03

    Cross-sectional studies have shown associations between lumbar degenerative manifestations on magnetic resonance imaging (MRI) and low back pain (LBP). Disc herniations and other degenerative manifestations, however, frequently occur in asymptomatic individuals. The purpose of this cross-sectional study was to analyze for associations between pain intensity and degenerative manifestations and other pain variables in patients for whom prognostic factors have been published previously. Included were 141 consecutive patients with and without radiculopathy, all sick-listed 1-4 months due to low back pain and subsequently examined by MRI of the lumbar spine. Using different methods of grouping the degenerative manifestations, linear regression analyses were performed with the intensity of back + leg pain, back pain and leg pain as dependent variables covering actual pain and pain the preceding 2 weeks. The clinical classification into +/- radiculopathy was established before and independently of the standardised description of MRI findings. Radiculopathy was present in 43 % of the patients. Pain was best explained using rank-ordered degenerative manifestations on MRI. Back pain and leg pain were differently associated, and back pain was less explained than leg pain in the multivariate analyses (15 % vs. 31 % of the variation). Back pain intensity was higher in patients with type 1 Modic changes and in some patients with nerve root touch, but was not associated with disc herniations. Leg pain intensity was well explained by disc herniations causing MRI nerve root compromise and radiculopathy. In patients with radiculopathy, nerve root touch caused as much leg pain as nerve root displacement or compression. High intensity zones and osteophytes were not associated with back pain, but only associated with leg pain in patients with radiculopathy. Tender points explained some of the back pain, and widespread pain explained leg pain in some of the patients without

  9. Long-term quality of life after posterior cervical foraminotomy for radiculopathy.

    PubMed

    Faught, Ryan W; Church, Ephraim W; Halpern, Casey H; Balmuri, Usha; Attiah, Mark A; Stein, Sherman C; Dante, Stephen J; Welch, William C; Simeone, Frederick A

    2016-03-01

    Cervical radiculopathy may cause symptoms and loss of function that can lead to a significant reduction in health related quality of life (HRQOL). As part of a comprehensive review of long-term outcomes, we examined HRQOL in a large cohort of patients undergoing posterior cervical foraminotomy (FOR) for radiculopathy. 338 patients who underwent FOR between 1990 and 2009 participated in a telephone interview designed to measure symptomatic and functional improvements following surgery. We also administered the EQ-5D, a standardized tool for assessing HRQOL. We analyzed this data for associations between patient and treatment characteristics, improvements in symptoms and function, and HRQOL as measured by the EQ-5D. Mean follow-up was 10.0 years. The average EQ-5D at follow-up was 0.81±0.18, and improvements in pain, weakness and function as well as ability to return to work correlated with improved EQ-5D score (p<0.0001). There was no correlation between length of follow-up and EQ-5D score (p=0.980). Additionally, there was no difference between mean EQ-5D score for soft disc versus osteophyte pathology (0.84 versus 0.81, p=0.21). These data provide evidence that FOR for cervical radiculopathy is associated with improved HRQOL at long-term follow-up. The lack of correlation between length of follow-up and HRQOL suggests that FOR is a durable treatment option. Moreover, FOR is associated with improved HRQOL whether radiculopathy is due to soft disc or osteophyte pathology. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Dimensions Underlying Measures of Disability, Personal Factors, and Health Status in Cervical Radiculopathy

    PubMed Central

    Halvorsen, Marie; Kierkegaard, Marie; Harms-Ringdahl, Karin; Peolsson, Anneli; Dedering, Åsa

    2015-01-01

    Abstract This cross-sectional study sought to identify dimensions underlying measures of impairment, disability, personal factors, and health status in patients with cervical radiculopathy. One hundred twenty-four patients with magnetic resonance imaging-verified cervical radiculopathy, attending a neurosurgery clinic in Sweden, participated. Data from clinical tests and questionnaires on disability, personal factors, and health status were used in a principal-component analysis (PCA) with oblique rotation. The PCA supported a 3-component model including 14 variables from clinical tests and questionnaires, accounting for 73% of the cumulative percentage. The first component, pain and disability, explained 56%. The second component, health, fear-avoidance beliefs, kinesiophobia, and self-efficacy, explained 9.2%. The third component including anxiety, depression, and catastrophizing explained 7.6%. The strongest-loading variables of each dimension were “present neck pain intensity,” “fear avoidance,” and “anxiety.” The three underlying dimensions identified and labeled Pain and functioning, Health, beliefs, and kinesiophobia, and Mood state and catastrophizing captured aspects of importance for cervical radiculopathy. Since the variables “present neck pain intensity,” “fear avoidance,” and “anxiety” had the strongest loading in each of the three dimensions; it may be important to include them in a reduced multidimensional measurement set in cervical radiculopathy. PMID:26091482

  11. Correlation of thermal deficit with clinical parameters and functional status in patients with unilateral lumbosacral radiculopathy.

    PubMed

    Dimitrijevic, I M; Kocic, M N; Lazovic, M P; Mancic, D D; Marinkovic, O K; Zlatanovic, D S

    2016-08-01

    Lumbosacral radiculopathy is a pathological process that refers to the dysfunction of one or more spinal nerve roots in the lumbosacral region of the spine. Some studies have shown that infrared thermography can estimate the severity of the clinical manifestation of unilateral lumbosacral radiculopathy. This study aimed to examine the correlation of the regional thermal deficit of the affected lower extremity with pain intensity, mobility of the lumbar spine, and functional status in patients with unilateral lumbosacral radiculopathy. This cross-sectional study was conducted at the Clinic for Physical Medicine and Rehabilitation of the Clinical Center Niš, Serbia. A total of 69 patients with unilateral lumbosacral radiculopathy of discogenic origin were recruited, with the following clinical parameters evaluated: (1) pain intensity by using a visual analogue scale, separately at rest and during active movement; (2) mobility of the lumbar spine by Schober test and the fingertip-to-floor test; and (3) functional status by the Oswestry Disability Index. Temperature differences between the symmetrical regions of the lower extremities were detected by infrared thermography. A quantitative analysis of thermograms determined the regions of interest with maximum thermal deficit. Correlation of maximum thermal deficit with each tested parameter was then determined. A significant and strong positive correlation was found between the regional thermal deficit and pain intensity at rest, as well as pain during active movements (rVAS - rest=0.887, rVAS - activity=0.890; P<0.001). The regional thermal deficit significantly and strongly correlated with the Oswestry Disability Index score and limited mobility of the lumbar spine (P<0.001). In patients with unilateral lumbosacral radiculopathy, the values of regional thermal deficit of the affected lower extremity are correlated with pain intensity, mobility of the lumbar spine, and functional status of the patient.

  12. Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

    PubMed

    Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

    2016-06-01

    No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

  13. Single Shot Epidural Injection for Cervical and Lumbosaccral Radiculopathies: A Preliminary Study

    PubMed Central

    Nawani, Digambar Prasad; Asthana, Veena

    2010-01-01

    Background Epidural steroid injection is an established treatment modality for intervertebral disc prolapse leading to radiculopathy. In cases where two levels of radiculopathy are present, two separate injections are warranted. Herein, we present our experience of management of such cases with a single epidural injection of local anaesthetic, tramadol and methylprednisolone, and table tilt for management of both radiculopathies. Methods 50 patients of either sex aged between 35-65 years presenting with features of cervical and lumbar radiculopathic pain were included and were subjected to single lumbar epidural injection of local anaesthetic, tramadol and methylprednisolone, in the lateral position. The table was then tilted in the trendelberg position with a tilt of 25 degrees, and patients were maintained for 10 minutes before being turned supine. All patients were administered 3 such injections with an interval of 2 weeks between subsequent injections, and pain relief was assessed with a visual analogue scale. Immediate complications after the block were assessed. Results Immediate and post procedural complications observed were nausea and vomiting (20%), painful injection site (4%), hypotension (10%) and high block (4%). Pain relief was assessed after the three injections by three grades: 37 (74%) had complete resolution of symptoms; 18% had partial relief and 8% did not benefit from the procedure. Conclusions This technique may be used as an alternative technique for pain relief in patients with unilateral cervical and lumbar radiculopathies. PMID:21217889

  14. Value of repeat CT scans in low back pain and radiculopathy.

    PubMed

    Schroeder, Josh E; Barzilay, Yair; Kaplan, Leon; Itshayek, Eyal; Hiller, Nurith

    2016-02-01

    We assessed the clinical value of repeat spine CT scan in 108 patients aged 18-60 years who underwent repeat lumbar spine CT scan for low back pain or radiculopathy from January 2008 to December 2010. Patients with a neoplasm or symptoms suggesting underlying disease were excluded from the study. Clinical data was retrospectively reviewed. Index examinations and repeat CT scan performed at a mean of 24.3 ± 11.3 months later were compared by a senior musculoskeletal radiologist. Disc abnormalities (herniation, sequestration, bulge), spinal stenosis, disc space narrowing, and bony changes (osteophytes, fractures, other changes) were documented. Indications for CT scan were low back pain (60 patients, 55%), radiculopathy (46 patients, 43%), or nonspecific back pain (two patients, 2%). A total of 292 spine pathologies were identified in 98 patients (90.7%); in 10 patients (9.3%) no spine pathology was seen on index or repeat CT scan. At repeat CT scan, 269/292 pathologies were unchanged (92.1%); 10/292 improved (3.4%), 8/292 worsened (2.8%, disc herniation or spinal stenosis), and five new pathologies were identified. No substantial therapeutic change was required in patients with worsened or new pathology. Added diagnostic value from repeat CT scan performed within 2-3 years was rare in patients suffering chronic or recurrent low back pain or radiculopathy, suggesting that repeat CT scan should be considered only in patients with progressive neurologic deficits, new neurologic complaints, or signs implying serious underlying conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Effect of transforaminal epidural polydeoxyribonucleotide injections on lumbosacral radiculopathy: A case report.

    PubMed

    Kang, Keum Nae; Kim, Tae Woong; Koh, Jin Woo; Oh, Han Byeol; Mun, Jong-Uk; Seo, Mi Sook; Kim, Young Uk

    2017-06-01

    Transforaminal epidural glucocorticoids administration is widely performed for the management of lumbosacral radiculopathy. However, it may worsen the condition of patients with type 2 diabetes mellitus (DM). Polydeoxyribonucleotide (PDRN) was recently noted as a substitute for glucocorticoids. A 44-year-old male patient was admitted to our pain clinic with symptoms of low back pain with severe pain and tingling sensation of left posterolateral leg. He had type 2 DM medicated with Glimepiride and Metformin. Blood glucose level was 367 mg/dL. He declined to use glucocorticoid. He was diagnosed as left foraminal disc protrusion at L4-5, left subarticular disc protrusion at L5-S1. Fluoroscopically guided transforaminal epidural PDRN injections were carried out. The patient was followed up for more than 6 months and demonstrated good improvement in lumbosacral radiculopathy without any complications. This is the first successful report on epidural injection of PDRN.

  16. Stretching of roots contributes to the pathophysiology of radiculopathies.

    PubMed

    Berthelot, Jean-Marie; Laredo, Jean-Denis; Darrieutort-Laffite, Christelle; Maugars, Yves

    2018-01-01

    To perform a synthesis of articles addressing the role of stretching on roots in the pathophysiology of radiculopathy. Review of relevant articles on this topic available in the PubMed database. An intraoperative microscopy study of patients with sciatica showed that in all patients the hernia was adherent to the dura mater of nerve roots. During the SLR (Lasègue's) test, the limitation of nerve root movement occurs by periradicular adhesive tissue, and temporary ischemic changes in the nerve root induced by the root stretching cause transient conduction disturbances. Spinal roots are more frail than peripheral nerves, and other mechanical stresses than root compression can also induce radiculopathy, especially if they also impair intraradicular blood flow, or the function of the arachnoid villi intimately related to radicular veins. For instance arachnoiditis, the lack of peridural fat around the thecal sac, and epidural fibrosis following surgery, can all promote sciatica, especially in patients whose sciatic trunks also stick to piriformis or internus obturator muscles. Indeed, stretching of roots is greatly increased by adherence at two levels. As excessive traction of nerve roots is not shown by imaging, many physicians have unlearned to think in terms of microscopic and physiologic changes, although nerve root compression in the lumbar MRI is lacking in more than 10% of patients with sciatica. It should be reminded that, while compression of a spinal nerve root implies stretching of this root, the reverse is not true: stretching of some roots can occur without any visible compression. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  17. The characteristic clinical symptoms of C-4 radiculopathy caused by ossification of the posterior longitudinal ligament.

    PubMed

    Katsumi, Keiichi; Yamazaki, Akiyoshi; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Endo, Naoto

    2014-05-01

    Cervical radiculopathy of the C2-4 spinal nerves is a rare condition and is poorly documented in terms of clinical symptoms, hindering its detection during initial patient screening based on imaging diagnostics. The authors describe in detail the clinical symptoms and successful surgical treatment of a patient diagnosed with isolated C-4 radiculopathy. This 41-year-old man suffered from sleep disturbance because of pain behind the right ear, along the right clavicle, and at the back of his neck on the right side. The Jackson and Spurling tests were positive, with pain radiating to the area behind the patient's ear. Unlike in cases of radiculopathy involving the C5-8 spinal nerves, no loss of upper-extremity motor function was seen. Magnetic resonance imaging showed foraminal stenosis at the C3-4 level on the right side, and multiplanar reconstruction CT revealed a beak-type ossification of the posterior longitudinal ligament in the foraminal region at the same level. In the absence of intracranial lesions or spinal cord compressive lesions, the positive Jackson and Spurling tests and the C3-4 foraminal stenosis were indicative of isolated C-4 radiculopathy. Microscopic foraminotomy was performed at the C3-4 vertebral level and the ossified lesion was resected. The patient's symptoms completely resolved immediately after surgery. To the authors' knowledge, this report is the first to describe the symptomatic features of isolated C-4 radiculopathy, in a case in which the diagnosis has been confirmed by both radiological findings and surgical outcome. Based on this case study, the authors conclude that the characteristic symptoms of C-4 radiculopathy are the presence of pain behind the ear and in the clavicular region in the absence of upper-limb involvement.

  18. Outcome of L5 radiculopathy after reduction and instrumented transforaminal lumbar interbody fusion of high-grade L5-S1 isthmic spondylolisthesis and the role of intraoperative neurophysiological monitoring.

    PubMed

    Schär, Ralph T; Sutter, Martin; Mannion, Anne F; Eggspühler, Andreas; Jeszenszky, Dezsö; Fekete, Tamas F; Kleinstück, Frank; Haschtmann, Daniel

    2017-03-01

    To evaluate the incidence and course of iatrogenic L5 radiculopathy after reduction and instrumented fusion of high-grade L5-S1 isthmic spondylolisthesis and the role of intraoperative neurophysiological monitoring (IONM). Consecutive patients treated for high-grade spondylolisthesis with IONM from 2005 to 2013 were screened for eligibility. Prospectively collected clinical and surgical data as well as radiographic outcomes were analyzed retrospectively. Patients completed the multidimensional Core Outcome Measures Index (COMI) before and at 3, 12, and 24 months after surgery. Seventeen patients were included, with a mean age of 26.3 (±9.5) years. Mean preoperative L5-S1 slip was 72% (±21%) and was reduced to 19% (±13%) postoperatively. Mean loss of reduction at last follow-up [mean 19 months (±14, range 3-48 months)] was 3% (±4.3%). Rate of new L5 radiculopathy with motor deficit (L5MD) after surgery was 29% (five patients). Four patients fully recovered after 3 months, one patient was lost to neurologic follow-up. IONM sensitivity and specificity for postoperative L5MD was 20 and 100%, respectively. COMI, back pain and leg pain scores showed significant (p < 0.001) improvements at 3 months postoperatively, which were retained up to 24 months postoperatively. Transient L5 radiculopathy after reduction and instrumented fusion of high-grade spondylolisthesis is frequent. With IONM the risk of irreversible L5 radiculopathy is minimal. If IONM signal changes recover, full clinical recovery is expected within 3 months. Overall, patient-reported outcome of reduction and instrumented fusion of high-grade spondylolisthesis showed clinically important improvement.

  19. Surgical and Functional Outcomes After Multilevel Cervical Fusion for Degenerative Disc Disease Compared With Fusion for Radiculopathy: A Study of Workers' Compensation Population.

    PubMed

    Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

    2017-05-01

    Retrospective cohort comparative study. To evaluate presurgical and surgical factors that affect return to work (RTW) status after multilevel cervical fusion, and to compare outcomes after multilevel cervical fusion for degenerative disc disease (DDD) versus radiculopathy. Cervical fusion provides more than 90% of symptomatic relief for radiculopathy and myelopathy. However, cervical fusion for DDD without radiculopathy is considered controversial. In addition, multilevel fusion is associated with poorer surgical outcomes with increased levels fused. Data of cervical comorbidities was collected from Ohio Bureau of Workers' Compensation for subjects with work-related injuries. The study population included subjects who underwent multilevel cervical fusion. Patients with radiculopathy or DDD were identified. Multivariate logistic regression was performed to identify factors that affect RTW status. Surgical and functional outcomes were compared between groups. Stable RTW status within 3 years after multilevel cervical fusion was negatively affected by: fusion for DDD, age > 55 years, preoperative opioid use, initial psychological evaluation before surgery, injury-to-surgery > 2 years and instrumentation.DDD group had lower rate of achieving stable RTW status (P= 0.0001) and RTW within 1 year of surgery (P= 0.0003) compared with radiculopathy group. DDD patients were less likely to have a stable RTW status [odds ratio, OR = 0.63 (0.50-0.79)] or RTW within 1 year after surgery [OR = 0.65 (0.52-0.82)].DDD group had higher rate of opioid use (P= 0.001), and higher rate of disability after surgery (P= 0.002). Multiple detriments affect stable RTW status after multilevel cervical fusion including DDD. DDD without radiculopathy was associated with lower RTW rates, less likelihood to return to work, higher disability, and higher opioid use after surgery. Multilevel cervical fusion for DDD may be counterproductive. Future studies should investigate further

  20. A descriptive study of the utilization of physical therapy for postoperative rehabilitation in patients undergoing surgery for lumbar radiculopathy.

    PubMed

    Louw, Adriaan; Puentedura, Emilio J; Diener, Ina

    2016-11-01

    To determine the referral patterns, utilization and indications for postoperative physical therapy (PT) for lumbar radiculopathy. At least 50 % of patients following lumbar surgery (LS) for radiculopathy are referred for PT to address postoperative pain and disability. Very little is known regarding factors following LS that predict referral to PT, patient perceptions, satisfaction of postoperative PT and predictors of success for PT following LS for radiculopathy. Sixty-five patients who underwent LS for radiculopathy completed outcome measures on pain and disability prior to, and 1, 3, 6 and 12 months after LS. They also completed a questionnaire regarding postoperative PT at the 12-month follow-up. The majority of patients (59.32 %) attended PT after LS for an average of 14 visits and rated PT favorably. Forty-five percent of the patients who did not attend PT after LS were of the opinion that they would have benefitted from PT after LS, and 62.5 % of these patients reported the surgeon not discussing postoperative PT after LS. Patients with longer duration of symptoms prior to surgery, with greater leg pain scores 1 month after surgery, and who did not feel as well prepared for surgery at the 1 year follow-up were more likely to receive PT, but this did not result in significantly better outcomes on any measure at any follow-up period and did not predict attendance in PT after LS. There is a need to determine if a subgroup of patients following LS exists who will respond favorably to postoperative PT.

  1. Cost-Utility Analysis of Anterior Cervical Discectomy and Fusion With Plating (ACDFP) Versus Posterior Cervical Foraminotomy (PCF) for Patients With Single-level Cervical Radiculopathy at 1-Year Follow-up.

    PubMed

    Alvin, Matthew D; Lubelski, Daniel; Abdullah, Kalil G; Whitmore, Robert G; Benzel, Edward C; Mroz, Thomas E

    2016-03-01

    A retrospective 1-year cost-utility analysis. To determine the cost-effectiveness of anterior cervical discectomy and fusion with plating (ACDFP) in comparison with posterior cervical foraminotomy (PCF) for patients with single-level cervical radiculopathy. Cervical radiculopathy due to cervical spondylosis is commonly treated by either PCF or ACDFP for patients who are refractory to nonsurgical treatment. Although some have suggested superior outcomes with ACDFP as compared with PCF, the former is also associated with greater costs. The present study analyzes the cost-effectiveness of ACDFP versus PCF for patients with single-level cervical radiculopathy. Forty-five patients who underwent ACDFP and 25 patients who underwent PCF for single-level cervical radiculopathy were analyzed. One-year postoperative health outcomes were assessed based on Visual Analogue Scale, Pain Disability Questionnaire, Patient Health Questionnaire, and EuroQOL-5 Dimensions questionnaires to analyze the comparative effectiveness of each procedure. Direct medical costs were estimated using Medicare national payment amounts and indirect costs were based on patient missed work days and patient income. Postoperative 1-year cost/utility ratios and the incremental cost-effectiveness ratio (ICER) were calculated to assess for cost-effectiveness using a threshold of $100,000/QALY gained. The 1-year cost-utility ratio for the PCF cohort was significantly lower ($79,856/QALY gained) than that for the ACDFP cohort ($131,951/QALY gained) (P<0.01). In calculating the 1-year ICER, as the ACDFP cohort showed lower QALY gained than the PCF cohort, the ICER was negative and is not reported, meaning that ACDFP was dominated by PCF. Statistically significant and clinically relevant improvements (through minimum clinically important differences) were seen in both cohorts. Although both cohorts showed improved health outcomes, ACDFP was not cost-effective relative to the threshold of $100,000/QALY gained at 1

  2. The course and prognostic factors of symptomatic cervical disc herniation with radiculopathy: a systematic review of the literature.

    PubMed

    Wong, Jessica J; Côté, Pierre; Quesnele, Jairus J; Stern, Paula J; Mior, Silvano A

    2014-08-01

    Cervical spine disc herniation is a disabling source of cervical radiculopathy. However, little is known about its course and prognosis. Understanding the course and prognosis of symptomatic cervical disc herniation is necessary to guide patients' expectations and assist clinicians in managing patients. To describe the natural history, clinical course, and prognostic factors of symptomatic cervical disc herniations with radiculopathy. Systematic review of the literature and best evidence synthesis. A systematic search of MEDLINE, EMBASE, CINAHL, SportsDiscus, and the Cochrane Central Register of Controlled Trials from inception to 2013 was conducted to retrieve eligible articles. Eligible articles were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. The results from articles with low risk of bias were analyzed using best evidence synthesis principles. We identified 1,221 articles. Of those, eight articles were eligible and three were accepted as having a low risk of bias. Two studies pertained to course and one study pertained to prognosis. Most patients with symptomatic cervical disc herniations with radiculopathy initially present with intense pain and moderate levels of disability. However, substantial improvements tend to occur within the first 4 to 6 months post-onset. Time to complete recovery ranged from 24 to 36 months in, approximately, 83% of patients. Patients with a workers' compensation claim appeared to have a poorer prognosis. Our best evidence synthesis describes the best available evidence on the course and prognosis of cervical disc herniations with radiculopathy. Most patients with symptomatic cervical spine disc herniation with radiculopathy recover. Possible recurrences and time to complete recovery need to be further studied. More studies are also needed to understand the prognostic factors for this condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Factors Associated With Work Ability in Patients Undergoing Surgery for Cervical Radiculopathy.

    PubMed

    Ng, Eunice; Johnston, Venerina; Wibault, Johanna; Löfgren, Håkan; Dedering, Åsa; Öberg, Birgitta; Zsigmond, Peter; Peolsson, Anneli

    2015-08-15

    Cross-sectional study. To investigate the factors associated with work ability in patients undergoing surgery for cervical radiculopathy. Surgery is a common treatment of cervical radiculopathy in people of working age. However, few studies have investigated the impact on the work ability of these patients. Patients undergoing surgery for cervical radiculopathy (n = 201) were recruited from spine centers in Sweden to complete a battery of questionnaires and physical measures the day before surgery. The associations between various individual, psychological, and work-related factors and self-reported work ability were investigated by Spearman rank correlation coefficient, multivariate linear regression, and forward stepwise regression analyses. Factors that were significant (P < 0.05) in each statistical analysis were entered into the successive analysis to reveal the factors most related to work ability. Work ability was assessed using the Work Ability Index. The mean Work Ability Index score was 28 (SD, 9.0). The forward stepwise regression analysis revealed 6 factors significantly associated with work ability, which explained 62% of the variance in the Work Ability Index. Factors highly correlated with greater work ability included greater self-efficacy in performing self-cares, lower physical load on the neck at work, greater self-reported chance of being able to work in 6 months' time, greater use of active coping strategies, lower frequency of hand weakness, and higher health-related quality of life. Psychological, work-related and individual factors were significantly associated with work ability in patients undergoing surgery for cervical radiculopathy. High self-efficacy was most associated with greater work ability. Consideration of these factors by surgeons preoperatively may provide optimal return to work outcomes after surgery. 3.

  4. Electrodiagnostic Examination of the Tibial Nerve in Clinically Normal Ferrets

    PubMed Central

    Bianchi, Ezio; Callegari, Daniela; Ravera, Manuela; Dondi, Maurizio

    2010-01-01

    Tibial nerves of 10 normal domestic ferrets (Mustela putorius furo) were evaluated by means of electrodiagnostic tests: motor nerve conduction studies (MNCSs), supramaximal repetitive nerve stimulation (SRNS), F waves, and cord dorsum potentials (CDPs). Values of conduction velocity, proximal and distal compound muscular action potentials, and amplitudes of MNCS were, respectively, 63.25 ± 7.56 m/sec, 10.79 ± 2.75 mV, and 13.02 ± 3.41 mV. Mean decrements in amplitude and area of compound muscular action potentials of wave 9 with low frequency SRNS were 0.3 ± 3.83% and 0.1 ± 3.51%. The minimum latency of the F waves and the F ratio were, respectively, 8.49 ± 0.65 ms and 1.92 ± 0.17. Onset latency of CDP was 1.99 ± 0.03 ms. These tests may help in diagnosing neuromuscular disorders and in better characterizing the hindlimb paresis reported in many ferrets with systemic illnesses. PMID:20706690

  5. Anterior Transposition of Anomalous Tortuous Vertebral Artery Causing Cervical Radiculopathy: A Report of 2 Cases and Review of Literature.

    PubMed

    Wang, Doris D; Burkhardt, Jan-Karl; Magill, Stephen T; Lawton, Michael T

    2017-05-01

    Cervical radiculopathy secondary to compression from vertebral artery (VA) tortuosity is a rare entity. We describe successful transposition through an anterolateral approach of tortuous VA loops causing cervical radiculopathy. Two patients with cervical radiculopathy (first case at C5-6 and second case at C3-4) secondary to anomalous VA loop compression underwent anterolateral approaches to the cervical spine for decompression and VA transposition. The anterior transverse foramina were drilled to unroof the VA loop, which was dissected free from the exiting nerve root. In both cases, the affected cervical nerve root was successfully decompressed with both radiographic and clinical improvements in radiculopathy symptoms. We found 8 other cases of VA transposition via either an anterolateral approach or a posterolateral approach described in the literature. Our second case of anterolateral VA transposition at the C3-4 level is the first case at this level and the highest level reported in the literature. Decompression using an anterolateral approach with direct microvascular transposition of the VA is a safe and effective treatment of this pathology and addresses the cause of radiculopathy more directly than the posterolateral approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The cutaneous silent period is preserved in cervical radiculopathy: significance for the diagnosis of cervical myelopathy

    PubMed Central

    Kofler, Markus; Stetkarova, Ivana; Stokic, Dobrivoje S.

    2010-01-01

    Electromyographic (EMG) activity from voluntarily contracting hand muscles undergoes transient suppression following nociceptive fingertip stimulation. This suppression is mediated by a spinal inhibitory reflex designated the cutaneous silent period (CSP). The CSP is abolished or altered in a variety of myelopathic conditions. However, before the CSP can gain acceptance as an aid in the diagnosis of myelopathy, the contribution of non-myelopathic conditions that can interrupt the afferent pathways responsible for the CSP needs to be considered. Accordingly, we examined the effect of radiculopathy on the CSP. Nociceptive stimulation was applied to thumb (C6 dermatome), middle (C7) and little (C8) fingers of 23 patients with cervical radiculopathy. Four or more CSP responses were recorded in abductor pollicis brevis muscle following digital stimulation. The patients had C6 (n = 10), C7 (n = 7), or C8 (n = 6) radiculopathy documented by EMG. A complete CSP was elicited in 21 of 23 patients with comparable latencies and durations irrespective of digit stimulated. We conclude that the CSP is preserved in radiculopathy, probably because afferent impulses are carried by smaller, slower conducting ‘injury-resistant’ A-delta fibers. These results provide important missing evidence that ensures specificity of CSP alterations in the diagnosis of cervical myelopathy. The finding that the CSP is spared in radiculopathy should open the door for investigators and clinicians to adopt this simple spinal inhibitory reflex as a physiologic aid in the diagnosis of spinal cord dysfunction. PMID:21132557

  7. Experimental study of brachial plexus and vessel compression: evaluation of combined central and peripheral electrodiagnostic approach.

    PubMed

    Yang, Chaoqun; Xu, Jianguang; Chen, Jie; Li, Shulin; Cao, Yu; Zhu, Yi; Xu, Lei

    2017-08-01

    We sought to investigate the reliability of a new electrodiagnostic method for identifying Electrodiagnosis of Brachial Plexus & Vessel Compression Syndrome (BPVCS) in rats that involves the application of transcranial electrical stimulation motor evoked potentials (TES-MEPs) combined with peripheral nerve stimulation compound muscle action potentials (PNS-CMAPs). The latencies of the TES-MEP and PNS-CMAP were initially elongated in the 8-week group. The amplitudes of TES-MEP and PNS-CMAP were initially attenuated in the 16-week group. The isolateral amplitude ratio of the TES-MEP to the PNS-CMAP was apparently decreased, and spontaneous activities emerged at 16 weeks postoperatively. Superior and inferior trunk models of BPVCS were created in 72 male Sprague Dawley (SD) rats that were divided into six experimental groups. The latencies, amplitudes and isolateral amplitude ratios of the TES-MEPs and PNS-CMAPs were recorded at different postoperative intervals. Electrophysiological and histological examinations of the rats' compressed brachial plexus nerves were utilized to establish preliminary electrodiagnostic criteria for BPVCS.

  8. Carpal tunnel syndrome: Investigating the sensitivity of initial-diagnosis with electro-diagnostic tests in 600 cases and associated risk factors especially manual milking.

    PubMed

    Tunç, Abdulkadir; Güngen, Belma Doğan

    2017-01-01

    Electro-diagnostic studies are the most reliable methods in diagnosis of carpal tunnel syndrome (CTS). Although there are many risk factors associated with CTS, there are a limited number of studies in the literature indicating that manual milking, which is frequently seen in Turkey, is a risk factor for CTS. The purpose of this study was to evaluate demographic findings of cases referred due to initial diagnosis of CTS as well as aetiological data especially manual milking and to investigate the sensitivity of initial diagnosis of CTS. Six hundred patients, who were referred to our electromyography laboratory due to initial diagnosis of CTS, were included. Demographic findings, duration of complaints, existence of diabetes mellitus, and manual milking histories of all patients were recorded. Sensitivity of initial diagnosis was investigated based on electro-diagnostic test results. According to electro-diagnostic test results, 289 of the patients were diagnosed with CTS (48.17%). 110 (18.3%) of 600 patients had a history of manual milking. In 94 of this group (85.4%), CTS was detected. Statistically significant correlation was found between CTS and age, female gender, duration of complaints, obesity and manual milking. This study confirms that manual milking is an important risk factor for CTS in addition to female gender, age, symptom duration and obesity. The fact that sensitivity of initial diagnosis of CTS was found to be low according to electro-diagnostic test results indicates importance of detailed clinical evaluation.

  9. Risk factor of contralateral radiculopathy following microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion.

    PubMed

    Yang, Yang; Liu, Zhong-Yu; Zhang, Liang-Ming; Dong, Jian-Wen; Xie, Pei-Gen; Chen, Rui-Qiang; Yang, Bu; Liu, Chang; Liu, Bin; Rong, Li-Min

    2017-12-08

    Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar degenerative disease; however, some patients show contralateral radiculopathy postoperatively. This study aims to investigate its risk factor. A total of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were divided into symptomatic and asymptomatic groups according to the presence of postoperative contralateral radiculopathy. Both preoperative and postoperative radiographic parameters, as well as their changes were compared between the two groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA). Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or bilateral canal decompression through unilateral route) were also analyzed as potential risk factors. Receiver operating characteristic (ROC) curve was drawn for the risk factor to determine the optimal threshold for predicting postoperative contralateral radiculopathy. Besides, clinical outcome assessment, involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics Association Score (JOA) and Oswestry Disability Index (ODI), was also compared between the two groups before surgery and at final follow-up (at least 3 months after the surgery for asymptomatic patients or final treatments of contralateral radiculopathy for symptomatic cases). Postoperative contralateral radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and postoperative CFA as well as its change were significantly decreased in symptomatic group compared with asymptomatic group (all P < 0.05). For the remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative and change values showed no statistical difference between the two groups (all P > 0.05). Neither screw breach nor decompression method revealed

  10. Bias in the physical examination of patients with lumbar radiculopathy

    PubMed Central

    2010-01-01

    Background No prior studies have examined systematic bias in the musculoskeletal physical examination. The objective of this study was to assess the effects of bias due to prior knowledge of lumbar spine magnetic resonance imaging findings (MRI) on perceived diagnostic accuracy of the physical examination for lumbar radiculopathy. Methods This was a cross-sectional comparison of the performance characteristics of the physical examination with blinding to MRI results (the 'independent group') with performance in the situation where the physical examination was not blinded to MRI results (the 'non-independent group'). The reference standard was the final diagnostic impression of nerve root impingement by the examining physician. Subjects were recruited from a hospital-based outpatient specialty spine clinic. All adults age 18 and older presenting with lower extremity radiating pain of duration ≤ 12 weeks were evaluated for participation. 154 consecutively recruited subjects with lumbar disk herniation confirmed by lumbar spine MRI were included in this study. Sensitivities and specificities with 95% confidence intervals were calculated in the independent and non-independent groups for the four components of the radiculopathy examination: 1) provocative testing, 2) motor strength testing, 3) pinprick sensory testing, and 4) deep tendon reflex testing. Results The perceived sensitivity of sensory testing was higher with prior knowledge of MRI results (20% vs. 36%; p = 0.05). Sensitivities and specificities for exam components otherwise showed no statistically significant differences between groups. Conclusions Prior knowledge of lumbar MRI results may introduce bias into the pinprick sensory testing component of the physical examination for lumbar radiculopathy. No statistically significant effect of bias was seen for other components of the physical examination. The effect of bias due to prior knowledge of lumbar MRI results should be considered when an isolated

  11. Bias in the physical examination of patients with lumbar radiculopathy.

    PubMed

    Suri, Pradeep; Hunter, David J; Katz, Jeffrey N; Li, Ling; Rainville, James

    2010-11-30

    No prior studies have examined systematic bias in the musculoskeletal physical examination. The objective of this study was to assess the effects of bias due to prior knowledge of lumbar spine magnetic resonance imaging findings (MRI) on perceived diagnostic accuracy of the physical examination for lumbar radiculopathy. This was a cross-sectional comparison of the performance characteristics of the physical examination with blinding to MRI results (the 'independent group') with performance in the situation where the physical examination was not blinded to MRI results (the 'non-independent group'). The reference standard was the final diagnostic impression of nerve root impingement by the examining physician. Subjects were recruited from a hospital-based outpatient specialty spine clinic. All adults age 18 and older presenting with lower extremity radiating pain of duration ≤ 12 weeks were evaluated for participation. 154 consecutively recruited subjects with lumbar disk herniation confirmed by lumbar spine MRI were included in this study. Sensitivities and specificities with 95% confidence intervals were calculated in the independent and non-independent groups for the four components of the radiculopathy examination: 1) provocative testing, 2) motor strength testing, 3) pinprick sensory testing, and 4) deep tendon reflex testing. The perceived sensitivity of sensory testing was higher with prior knowledge of MRI results (20% vs. 36%; p = 0.05). Sensitivities and specificities for exam components otherwise showed no statistically significant differences between groups. Prior knowledge of lumbar MRI results may introduce bias into the pinprick sensory testing component of the physical examination for lumbar radiculopathy. No statistically significant effect of bias was seen for other components of the physical examination. The effect of bias due to prior knowledge of lumbar MRI results should be considered when an isolated sensory deficit on examination is used in

  12. Effect of different surgical methods on headache associated with cervical spondylotic myelopathy and/or radiculopathy.

    PubMed

    Sun, Yuqing; Muheremu, Aikeremujiang; Yan, Kai; Yu, Jie; Zheng, Shan; Tian, Wei

    2015-09-23

    Anterior cervical discectomy and fusion, total disk replacement and open door laminoplasty have been widely used to treat patients with cervical spondylotic myelopathy and/or radiculopathy. In our clinical practice, many patients with cervical spondylosis also complain of headache, and wish to know if the surgical treatment for cervical spondylosis can also alleviate this symptom. Considering that there is no literature concerning this extra benefit of surgical manipulation on cervical spondylosis, we have carried out this retrospective study. Among the patients treated with anterior cervical discectomy and fusion, total disk replacement and open door laminoplasty in our institute for cervical spondylotic myelopathy and/or radiculopathy between February 2002 to March 2011, 108 of whom that have complained about headache at the same time were included in this study. Those patients were followed by 25 to 145 months. Severity of headache before the surgery and at the last follow up was recorded by VAS pain scores and compared among the patients with different surgical methods using SPSS17.0 software. One way ANOVA was used to compare VAS scores between the groups, paired sample t-tests were used to compare the differences in a group at different time points. Headache was significantly alleviated in all groups (P < 0.01). Respectively, 75.0% of the patients in the ACDF group, 84.6% of the patients in the TDR group and 82.2% of the patients in the laminoplasty group were significantly relieved of the headache after the surgery. No significant differences were found with the VAS score at the last follow up among the groups (P > 0.05). No significant differences were found among the groups comparing the degree of alleviation of VAS scores before and after the surgery (P > 0.05). Considering that all the three procedures in the current study have achieved similar effect on alliviating headache in patients with cevical myelopathy, and that what they have in

  13. Muscle activation timing and balance response in chronic lower back pain patients with associated radiculopathy.

    PubMed

    Frost, Lydia R; Brown, Stephen H M

    2016-02-01

    Patients with chronic low back pain and associated radiculopathy present with neuromuscular symptoms both in their lower back and down their leg; however, investigations of muscle activation have so far been isolated to the lower back. During balance perturbations, it is necessary that lower limb muscles activate with proper timing and sequencing along with the lower back musculature to efficiently regain balance control. Patients with chronic low back pain and radiculopathy and matched controls completed a series of balance perturbations (rapid bilateral arm raise, unanticipated and anticipated sudden loading, and rapid rise to toe). Muscle activation timing and sequencing as well as kinetic response to the perturbations were analyzed. Patients had significantly delayed lower limb muscle activation in rapid arm raise trials as compared to controls. In sudden loading trials, muscle activation timing was not delayed in patients; however, some differences in posterior chain muscle activation sequencing were present. Patients demonstrated less anterior-posterior movement in unanticipated sudden loading trials, and greater medial-lateral movement in rise to toe trials. Patients with low back pain and radiculopathy demonstrated some significant differences from control participants in terms of muscle activation timing, sequencing, and overall balance control. The presence of differences between patients and controls, specifically in the lower limb, indicates that radiculopathy may play a role in altering balance control in these patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain.

    PubMed

    Shamji, Mohammed F; Guha, Daipayan; Paul, Darcia; Shcharinsky, Alina

    2017-09-01

    The pathophysiology of lumbar radiculopathy includes both mechanical compression and biochemical irritation of apposed neural elements. Inflammatory and immune cytokines have been implicated, induced by systemic exposure of immune-privileged intervertebral disc tissue. Surgical intervention provides improved symptoms and quality of life, but persistent postoperative neuropathic pain (PPNP) afflicts a significant fraction of patients. To compare the inflammatory and immune phenotypes among patients undergoing structural surgery for lumbar radiculopathy and spinal cord stimulation for neuropathic pain. Consecutive patients undergoing surgical intervention for lumbar radiculopathy or neuropathic pain were studied. Demographic data included age, gender, and VAS and neuropathic pain scores. Serum was evaluated for cytokine levels (IL-6, Il-17, TNF-α) and cellular content [white blood cell (WBC)/differential, lymphocyte subtypes]. The primary analysis differentiated molecular and cellular profiles between radiculopathy and neuropathic pain patients. Subgroup analysis within the surgical radiculopathy population compared those patients achieving relief of symptoms and those with PPNP. Heightened IL-6, Il-17, and TNF-α levels were observed for the lumbar radiculopathy group compared with the neuropathic pain group. This was complemented by higher WBC count and a greater fraction of Th17 lymphocytes among radiculopathy patients. In the lumbar discectomy subgroup, pain relief was seen among patients with preoperatively elevated IL-17 levels. Those patients with PPNP refractory to surgical discectomy exhibited normal cytokine levels. Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery. Copyright © 2017 by the Congress of Neurological Surgeons

  15. Contralateral radiculopathy after transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: A Case Series.

    PubMed

    Hu, Hong-Tao; Ren, Liang; Sun, Xian-Ze; Liu, Feng-Yu; Yu, Jin-He; Gu, Zhen-Fang

    2018-04-01

    Transforaminal lumbar interbody fusion (TLIF) is an effective treatment for patients with degenerative lumbar disc disorder. Contralateral radiculopathy, as a complication of TLIF, has been recognized in this institution, but is rarely reported in the literature. In this article, we report 2 cases of contralateral radiculopathy after TLIF in our institution and its associated complications. In the 2 cases, the postoperative computed tomography (CT) and magnetic resonance image (MRI) showed obvious upward movement of the superior articular process, leading to contralateral foraminal stenosis. Revision surgery was done at once to partially resect the opposite superior facet and to relieve nerve root compression. After revision surgery, the contralateral radiculopathy disappeared. Contralateral radiculopathy is an avoidable potential complication. It is very important to create careful preoperative plans and to conscientiously plan the use of intraoperative techniques. In case of postoperative contralateral leg pain, the patients should be examined by CT and MRI. If CT and MRI show that the superior articular process significantly migrated upwards, which leads to contralateral foraminal stenosis, revision surgery should be done at once to partially resect the contralateral superior facet so as to relieve nerve root compression and avoid possible long-term impairment.

  16. Reliability of cervical radiculopathy, its congruence between patient history and medical imaging evidence of disc herniation and its role in surgical decision.

    PubMed

    Mostofi, Keyvan; Khouzani, Reza Karimi

    2016-10-01

    The incidence of cervical disc herniation is estimated about 5.5/100,000, and they lead to surgical intervention in 26 %. Cervical disc herniation causes radiculopathy, which defines by radicular pain and sensory deficit and maybe weakness following the path of the affected nerves. Classically, cervical radiculopathy is expected to follow its specific dermatome-C4, C5, C6, C7 and C8. We investigate patients who present with discrepancy between classical radiculopathy and imaging findings in the daily practice of our profession. We reviewed the medical records of 102 patients with cervical radiculopathy, caused by cervical disc herniation. All patients had surgery. We found an apparent discrepancy between clinical and radiological findings, patients complained of radiculopathy on one side, and magnetic resonance imaging (MRI) scan or CT scan finding on the other side in ten patients (10.2 %). We did not found any other abnormalities in preoperative and post-operative period. All patients underwent cervical diskectomy via anterior approach. Six weeks after surgery eight patients (80 %) recovered completely, and 3 months after all ten patients (100 %) had been relieved totally. The aim of this paper is review of this medical concept and management of radiculopathy in patients with this discrepancy. As far as we know, the subject has not yet been touched in this light in medical literature. The discrepancy between clinical radiculopathy and disc herniation level on MRI or on CT scan is not rare. Management of this discrepancy requires further investigation to avoid missing diagnosis and treatment failure.

  17. CURCUMIN ALLEVIATES LUMBAR RADICULOPATHY BY REDUCING NEUROINFLAMMATION, OXIDATIVE STRESS AND NOCICEPTIVE FACTORS

    PubMed Central

    Xiao, L.; Ding, M.; Fernandez, A.; Zhao, P.; Jin, L.; Li, X.

    2017-01-01

    Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (µCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe

  18. Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors.

    PubMed

    Xiao, L; Ding, M; Fernandez, A; Zhao, P; Jin, L; Li, X

    2017-05-09

    Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (μCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe

  19. The validity of using an electrocutaneous device for pain assessment in patients with cervical radiculopathy.

    PubMed

    Abbott, Allan; Ghasemi-Kafash, Elaheh; Dedering, Åsa

    2014-10-01

    The purpose of this study was to evaluate the validity and preference for assessing pain magnitude with electrocutaneous testing (ECT) compared to the visual analogue scale (VAS) and Borg CR10 scale in men and women with cervical radiculopathy of varying sensory phenotypes. An additional purpose was to investigate ECT sensory and pain thresholds in men and women with cervical radiculopathy of varying sensory phenotypes. This is a cross-sectional study of 34 patients with cervical radiculopathy. Scatterplots and linear regression were used to investigate bivariate relationships between ECT, VAS and Borg CR10 methods of pain magnitude measurement as well as ECT sensory and pain thresholds. The use of the ECT pain magnitude matching paradigm for patients with cervical radiculopathy with normal sensory phenotype shows good linear association with arm pain VAS (R(2) = 0.39), neck pain VAS (R(2) = 0.38), arm pain Borg CR10 scale (R(2) = 0.50) and neck pain Borg CR10 scale (R(2) = 0.49) suggesting acceptable validity of the procedure. For patients with hypoesthesia and hyperesthesia sensory phenotypes, the ECT pain magnitude matching paradigm does not show adequate linear association with rating scale methods rendering the validity of the procedure as doubtful. ECT for sensory and pain threshold investigation, however, provides a method to objectively assess global sensory function in conjunction with sensory receptor specific bedside examination measures.

  20. Dimensions Underlying Measures of Disability, Personal Factors, and Health Status in Cervical Radiculopathy: A Cross-Sectional Study.

    PubMed

    Halvorsen, Marie; Kierkegaard, Marie; Harms-Ringdahl, Karin; Peolsson, Anneli; Dedering, Åsa

    2015-06-01

    This cross-sectional study sought to identify dimensions underlying measures of impairment, disability, personal factors, and health status in patients with cervical radiculopathy. One hundred twenty-four patients with magnetic resonance imaging-verified cervical radiculopathy, attending a neurosurgery clinic in Sweden, participated. Data from clinical tests and questionnaires on disability, personal factors, and health status were used in a principal-component analysis (PCA) with oblique rotation. The PCA supported a 3-component model including 14 variables from clinical tests and questionnaires, accounting for 73% of the cumulative percentage. The first component, pain and disability, explained 56%. The second component, health, fear-avoidance beliefs, kinesiophobia, and self-efficacy, explained 9.2%. The third component including anxiety, depression, and catastrophizing explained 7.6%. The strongest-loading variables of each dimension were "present neck pain intensity," "fear avoidance," and "anxiety." The three underlying dimensions identified and labeled Pain and functioning, Health, beliefs, and kinesiophobia, and Mood state and catastrophizing captured aspects of importance for cervical radiculopathy. Since the variables "present neck pain intensity," "fear avoidance," and "anxiety" had the strongest loading in each of the three dimensions; it may be important to include them in a reduced multidimensional measurement set in cervical radiculopathy.

  1. The effect of cervical traction combined with neural mobilization on pain and disability in cervical radiculopathy. A case report.

    PubMed

    Savva, Christos; Giakas, Giannis

    2013-10-01

    Cervical radiculopathy is the result of cervical nerve root pathology that may lead to chronic pain and disability. Although manual therapy interventions including cervical traction and neural mobilization have been advocated to decrease pain and disability caused by cervical radiculopathy, their analgesic effect has been questioned due to the low quality of research evidence. The purpose of this paper is to present the effect of cervical traction combined with neural mobilization on pain and disability in a patient experiencing cervical radiculopathy. A 52-year-old woman presented with a 2 month history of neurological cervico-brachial pain and whose presentation was consistent with cervical radiculopathy. Cervical traction and a slider neural mobilization of the medial nerve were applied simultaneously to reduce the patient's pain and disability measured at baseline and at 2 and 4 weeks using the Numeric Pain Rating Scale, the Neck Disability Index and the Patient-Specific Functional Scale. Improvements in all outcome measures were noted over a period of four weeks. Scores in all outcome measures revealed that the patient's pain had almost disappeared and that she was able to perform her household chores and job tasks without difficulties and limitations. In conclusion, the findings of this study support that the application of cervical traction combined with neural mobilization can produce significant improvements in terms of pain and disability in cervical radiculopathy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Distal Predominance of Electrodiagnostic Abnormalities in Early Stage Amyotrophic Lateral Sclerosis.

    PubMed

    Shayya, Luay; Babu, Suma; Pioro, Erik P; Li, Jianbo; Li, Yuebing

    2018-05-09

    We compare the electrodiagnostic (EDX) yield of limb muscles in revealing lower motor neuron (LMN) dysfunction by electromyography (EMG) in early stage amyotrophic lateral sclerosis (ALS). Single-site retrospective review Results: This study includes 122 consecutive patients with possible ALS as defined by revised El Escorial Criteria. Distal limb muscles show more frequent EMG abnormalities than proximal muscles. EDX yield is higher in the limb where weakness begins and when clinical signs of LMN dysfunction are evident. Adoption of Awaji criteria increases the yield of EMG positive segments significantly in the cervical (p<0.0005) and lumbosacral regions (P<0.0001), and upgrades 19 patients into probable and 1 patient into definite categories. Electromyographic abnormalities are distal limb-predominant in early stage ALS. A redefinition of an EDX-positive cervical or lumbosacral segment, with an emphasis on distal limb muscles, may result in an earlier ALS diagnosis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  3. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy.

    PubMed

    Kreiner, D Scott; Hwang, Steven W; Easa, John E; Resnick, Daniel K; Baisden, Jamie L; Bess, Shay; Cho, Charles H; DePalma, Michael J; Dougherty, Paul; Fernand, Robert; Ghiselli, Gary; Hanna, Amgad S; Lamer, Tim; Lisi, Anthony J; Mazanec, Daniel J; Meagher, Richard J; Nucci, Robert C; Patel, Rakesh D; Sembrano, Jonathan N; Sharma, Anil K; Summers, Jeffrey T; Taleghani, Christopher K; Tontz, William L; Toton, John F

    2014-01-01

    The objective of the North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Lumbar Disc Herniation with Radiculopathy is to provide evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of lumbar disc herniation with radiculopathy. The guideline is intended to reflect contemporary treatment concepts for symptomatic lumbar disc herniation with radiculopathy as reflected in the highest quality clinical literature available on this subject as of July 2011. The goals of the guideline recommendations are to assist in delivering optimum efficacious treatment and functional recovery from this spinal disorder. To provide an evidence-based educational tool to assist spine specialists in the diagnosis and treatment of lumbar disc herniation with radiculopathy. Systematic review and evidence-based clinical guideline. This guideline is a product of the Lumbar Disc Herniation with Radiculopathy Work Group of NASS' Evidence-Based Guideline Development Committee. The work group consisted of multidisciplinary spine care specialists trained in the principles of evidence-based analysis. A literature search addressing each question and using a specific search protocol was performed on English-language references found in Medline, Embase (Drugs and Pharmacology), and four additional evidence-based databases to identify articles. The relevant literature was then independently rated using the NASS-adopted standardized levels of evidence. An evidentiary table was created for each of the questions. Final recommendations to answer each clinical question were developed via work group discussion, and grades were assigned to the recommendations using standardized grades of recommendation. In the absence of Level I to IV evidence, work group consensus statements have been developed using a modified nominal group technique, and these statements are clearly identified as such in the guideline

  4. Pure neuritic leprosy presenting as ulnar nerve neuropathy: a case report of electrodiagnostic, radiographic, and histopathological findings.

    PubMed

    Payne, Russell; Baccon, Jennifer; Dossett, John; Scollard, David; Byler, Debra; Patel, Akshal; Harbaugh, Kimberly

    2015-11-01

    Hansen's disease, or leprosy, is a chronic infectious disease with many manifestations. Though still a major health concern and leading cause of peripheral neuropathy in the developing world, it is rare in the United States, with only about 150 cases reported each year. Nevertheless, it is imperative that neurosurgeons consider it in the differential diagnosis of neuropathy. The causative organism is Mycobacterium leprae, which infects and damages Schwann cells in the peripheral nervous system, leading first to sensory and then to motor deficits. A rare presentation of Hansen's disease is pure neuritic leprosy. It is characterized by nerve involvement without the characteristic cutaneous stigmata. The authors of this report describe a case of pure neuritic leprosy presenting as ulnar nerve neuropathy with corresponding radiographic, electrodiagnostic, and histopathological data. This 11-year-old, otherwise healthy male presented with progressive right-hand weakness and numbness with no cutaneous abnormalities. Physical examination and electrodiagnostic testing revealed findings consistent with a severe ulnar neuropathy at the elbow. Magnetic resonance imaging revealed diffuse thickening and enhancement of the ulnar nerve and narrowing at the cubital tunnel. The patient underwent ulnar nerve decompression with biopsy. Pathology revealed acid-fast organisms within the nerve, which was pathognomonic for Hansen's disease. He was started on antibiotic therapy, and on follow-up he had improved strength and sensation in the ulnar nerve distribution. Pure neuritic leprosy, though rare in the United States, should be considered in the differential diagnosis of those presenting with peripheral neuropathy and a history of travel to leprosy-endemic areas. The long incubation period of M. leprae, the ability of leprosy to mimic other conditions, and the low sensitivity of serological tests make clinical, electrodiagnostic, and radiographic evaluation necessary for diagnosis

  5. Efficacy of Epidural Perineural Injection of Autologous Conditioned Serum in Unilateral Cervical Radiculopathy: A Pilot Study.

    PubMed

    Goni, Vijay G; Singh Jhala, Sampat; Gopinathan, Nirmal Raj; Behera, Prateek; Batra, Y K; R H H, Arjun; Guled, Uday; Vardhan, Harsha

    2015-08-15

    Prospective randomized pilot study. Evaluation of the efficacy of epidural perineural injection of autologous conditioned serum (ACS) versus methylprednisone (MPS) in unilateral cervical radiculopathy patients. Cervical radiculopathy is often treated by nonoperative and operative means. Guided injections of steroids have been used previously. We used ACS, an orthobiologic derived from patients' own blood in patients of unilateral cervical radiculopathy. Forty patients were equally allocated into ACS and MPS groups and were injected with 2.5 to 3 mL of ACS or MPS, respectively, under image guidance into the perineural area of the affected nerve root. They were followed up for 6 months with visual analogue scale for pain, neck pain disability scale in Hindi language, neck disability index, and Short Form of Health Survey-12 (SF-12). Patients who had received injections of ACS and MPS both had improvements in the scores of the evaluation tools. The improvement in the ACS patients was gradual and sustained during the entire study period whereas that in the MPS group had some deterioration over time. No major complications were noted among the 2 groups. Minor complications were noted in both the groups. ACS can be considered an equally good or better modality of nonoperative management in patients of unilateral cervical radiculopathy as MPS. The safety profile is good and the improvement seen is sustained over time. Thus, it may be offered to affected patients before offering them surgery. 2.

  6. Neuromuscular ultrasound imaging in low back pain patients with radiculopathy.

    PubMed

    Frost, Lydia R; Brown, Stephen H M

    2016-02-01

    Patients suffering from chronic low back pain with associated radiculopathy (LBP-R), or sciatica, experience neuromuscular symptoms in the lower back and leg; however, research to date has focussed solely on the lower back. To expand neuromuscular research of LBP-R patients into the lower limb, using ultrasound imaging. Case control study comparing LBP-R patients to matched healthy controls. LBP-R patients with disc bulge or herniation (L3/L4 to L5/S1) resulting in unilateral radiculopathy (n = 17) and healthy matched controls (n = 17) were recruited. High-resolution ultrasound imaging was used to investigate sciatic nerve structure, as well as the quality (relative magnitude of fat/fibrosis infiltration) and contraction (muscle thickening) of associated musculature in the lower back (paraspinals) and lower limb (biceps femoris, gastrocnemius, soleus). LBP-R patients had swollen sciatic nerves (increased cross sectional area), but this was not associated with evidence of reduced lower limb muscle quality. As compared to controls, LBP-R patients demonstrated less soleus muscle thickening during submaximal contraction; however, there were no impairments in the hamstring or lower back musculature. Ultrasound imaging was an effective method to detect sciatic nerve swelling in mild to moderately affected LBP-R patients. Nerve swelling was not associated with poorer muscle quality, nor consistently impaired muscle contraction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism

    PubMed Central

    2011-01-01

    of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity, imbalanced weight distribution, and gait compensations (P <0.1). Conclusions Our data indicate gait characterization has value for describing early limb dysfunctions in pre-clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development of gait compensations subsequent to lumbar radiculopathy in our model. PMID:21871102

  8. Resource utilization for non-operative cervical radiculopathy: Management by surgeons versus non-surgeons.

    PubMed

    Chung, Sophie H; Bohl, Daniel D; Paul, Jonathan T; Rihn, Jeffrey A; Harrop, James S; Ghogawala, Zoher; Hilibrand, Alan S; Grauer, Jonathan N

    2017-07-01

    To compare the estimated resource utilization for non-operative treatment of cervical radiculopathy if managed by surgeons versus non-surgeons. A Cervical Spine Research Society-sponsored survey was administered at a national spine surgery conference to surgeons and non-surgeons, as classified above. The survey asked questions regarding resource utilization and perceived costs for the "average patient" with cervical radiculopathy managed non-operatively. Resource utilization and perceived costs were compared between surgeon and non-surgeon participants, and between private practice and academic and/or hybrid groups that combine academic and private practices. In total, 101 of the 125 conference attendees participated in the survey (return rate 80.8%, of which 60% were surgeons). Surgeon and non-surgeon estimates for duration of non-operative care did not differ (3.3 versus 4.2 months, p=0.071). Estimates also did not differ for estimated number of physical therapy visits (10.5 versus 10.5, p=0.983), cervical injections (1.4 versus 1.7, p=0.272), chiropractic visits (3.1 versus 3.7, p=0.583), or perceived days off from work (14.9 versus 16.3, p=0.816). The only difference identified was that surgeon estimates of the number of physician visits while providing non-operative care were lower than non-surgeon estimates (3.2 versus 4.0, p=0.018). In terms of estimated costs, surgeon and non-surgeon were mostly similar (only difference being that surgeon estimates for the total cost of physician visits per patient were lower than non-surgeon estimates ($382 versus $579, p=0.007). Surgeon estimates for the percent of their patients that go on to receive surgery within 6 months were higher than non-surgeon estimates (28.6% versus 18.8%, p=0.018). Similarly, surgeon estimates for the percent of their patients to go on to receive surgery within 2 years were higher than non-surgeon estimates (37.8% versus 24.8%, p=0.013). Academic/hybrid and private practice group resource

  9. Results of posterior cervical foraminotomy for treatment of cervical spondylitic radiculopathy.

    PubMed

    Grieve, J P; Kitchen, N D; Moore, A J; Marsh, H T

    2000-02-01

    We evaluated the results of posterior cervical foraminotomy for spondylitic radiculopathy using a questionnaire sent to all 77 patients who had undergone surgery between 1990 and 1995 at our institution. Sixty-two patients (40 male) returned their questionnaires, one of whom had undergone two procedures (dealt with as separate events). Sixty patients complained of pre-operative arm pain; of these 42 (70%) had complete or > 75% resolution of their pain, 14 (23%) had < 75% improvement in their pain and four (7%) had the same or worsened pain at the time of the questionnaire. Sixteen patients (27%) reported initial improvement in symptoms with subsequent deterioration. The mean patient satisfaction score using a linear analogue scale from 0 to 10 was 7.5. Main postoperative complaints were neck pain (22%), persisting motor deficit (6%) and persisting sensory deficit (9%). One patient suffered nerve root damage at surgery. For unilateral and, in some cases, multi-level degenerative disease causing cervical radiculopathy, posterior cervical foraminotomy is a useful technique with the advantage of avoiding fusion, immobilization and the long-term risk of instability.

  10. Outcome of Percutaneous Lumbar Synovial Cyst Rupture in Patients with Lumbar Radiculopathy.

    PubMed

    Eshraghi, Yashar; Desai, Vimal; Cajigal Cajigal, Calvin; Tabbaa, Kutaiba

    2016-01-01

    Lumbar synovial cysts can result from spondylosis of facet joints. These cysts can encroach on adjacent nerve roots, causing symptoms of radiculopathy. Currently the only definitive treatment for these symptoms is surgery, which may involve laminectomy or laminotomy, with or without spinal fusion. Surgery has been reported to successfully relieve radicular pain in 83.5% of patients by Zhenbo et al. Little information is available concerning the efficacy and outcome of percutaneous fluoroscopic synovial cyst rupture for treatment of facet joint synovial cysts. The goal of this investigation was to assess the efficacy of fluoroscopically guided lumbar synovial cyst rupture, in particular for its relief of radicular symptoms and its potential to reduce the need for surgical intervention. Retrospective evaluation of a case series. University hospital and urban public health care system. With approval from the Institutional Review Board of Case Western Reserve University/ MetroHealth Medical Center, we reviewed the medical charts of patients with lumbar radiculopathy who underwent percutaneous lumbar synovial cyst rupture. The 30 patients in the cohort were treated by one pain specialist between 2006 and 2013. These patients were diagnosed with moderate to severe lower back pain, radiculopathy, and ranged in age from 42 to 80 years. Patients were followed up for a minimum of 6 months and up to 24 months. Pre- and post-procedure pain assessments were reviewed by clinical chart review. In addition post-procedure pain assessments and duration of pain relief were obtained with telephone interviews. Pain had been reported by the patients using a numeric rating scale of 0 - 10 (0 = no pain; 10 = worst possible pain). Charts were reviewed to determine if surgery was eventually performed to correct radicular symptoms. More than 6 months of pain relief was achieved in 14/30 patients (46%) and between one and 6 months of pain relief was achieved in 7/30 patients (23.3%). Nine

  11. Posterior Cervical Transfacet Fusion with Facetal Spacer for the Treatment of Single-Level Cervical Radiculopathy: A Randomized, Controlled Prospective Study.

    PubMed

    Lenzi, Jacopo; Nardone, Antonio; Passacantilli, Emiliano; Caporlingua, Alessandro; Lapadula, Gennaro; Caporlingua, Federico

    2017-04-01

    Single-level cervical radiculopathy may be treated conservatively with cervical tractions. Posterior cervical transfacet fusion with a facetal spacer is a viable option. The aim of the present study is to compare posterior cervical transfacet fusion with conservative physical treatment in single-level cervical radiculopathy. A total of 80 patients were randomized in 2 groups, a surgical group in which patients were given posterior cervical transfacet fusion and a traction group in which patients were treated conservatively with mechanical cervical tractions. Visual analog scale for arm and neck, Neck Disability Index, and Short Form-36 (SF-36) questionnaires were administered preoperatively and after treatment up to 12 months. After treatment, visual analog scale arm scores were greater in traction group (4.7 vs. 1.5 the day after treatment) and at follow-up controls (traction group vs. surgical group: 5.3 vs. 0.6 at 1 month, 3.6 vs. 0.3 at 6 months, 1.8 vs. 0.2 at 12 months). Neck Disability Index scores were lower in the surgical group (surgical group vs. traction group: 4.4 vs. 20.3 at 1 month, 1.3 vs. 10.5 at 6 months). SF-36 scores were greater in the surgical group (surgical group vs. traction group: 96 vs. 70 at 1 month, 96.5 vs. 82.6 at 6 months). Neck disability index and SF-36 scores were superimposable between the groups at 12-month follow-up. No adjacent-segment arthrosis or late complications were reported at 1-year follow-up in the surgical group. posterior cervical transfacet fusion is a safe and effective procedure to treat single-level cervical radiculopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Return to Work and Multilevel Versus Single-Level Cervical Fusion for Radiculopathy in a Workers' Compensation Setting.

    PubMed

    Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

    2017-01-15

    Retrospective comparative cohort study. Examine the impact of multilevel fusion on return to work (RTW) status and compare RTW status after multi- versus single-level cervical fusion for patients with work-related injury. Patients with work-related injuries in the workers' compensation systems have less favorable surgical outcomes. Cervical fusion provides a greater than 90% likelihood of relieving radiculopathy and stabilizing or improving myelopathy. However, more levels fused at index surgery are reportedly associated with poorer surgical outcomes than single-level fusion. Data was collected from the Ohio Bureau of Workers' Compensation (BWC) between 1993 and 2011. The study population included patients who underwent cervical fusion for radiculopathy. Two groups were constructed (multilevel fusion [MLF] vs. single-level fusion [SLF]). Outcomes measures evaluated were: RTW criteria, RTW <1year, reoperation, surgical complication, disability, and legal litigation after surgery. After accounting for a number of independent variables in the regression model, multilevel fusion was a negative predictor of successful RTW status within 3-year follow-up after surgery (OR = 0.82, 95% CI: 0.70-0.95, P <0.05).RTW criteria were met 62.9% of SLF group compared with 54.8% of MLF group. The odds of having a stable RTW for MLF patients were 0.71% compared with the SLF patients (95% CI: 0.61-0.83; P: 0.0001).At 1 year after surgery, RTW rate was 53.1% for the SLF group compared with 43.7% for the MLF group. The odds of RTW within 1 year after surgery for the MLF group were 0.69% compared with SLF patients (95% CI: 0.59-0.80; P: 0.0001).Higher rate of disability after surgery was observed in the MLF group compared with the SLF group (P: 0.0001) CONCLUSION.: Multilevel cervical fusion for radiculopathy was associated with poor return to work profile after surgery. Multilevel cervical fusion was associated with lower RTW rates, less likelihood of achieving stable return to

  13. Back school or brain school for patients undergoing surgery for lumbar radiculopathy? Protocol for a randomised, controlled trial.

    PubMed

    Ickmans, Kelly; Moens, Maarten; Putman, Koen; Buyl, Ronald; Goudman, Lisa; Huysmans, Eva; Diener, Ina; Logghe, Tine; Louw, Adriaan; Nijs, Jo

    2016-07-01

    Despite scientific progress with regard to pain neuroscience, perioperative education tends to stick to the biomedical model. This may involve, for example, explaining the surgical procedure or 'back school' (education that focuses on biomechanics of the lumbar spine and ergonomics). Current perioperative education strategies that are based on the biomedical model are not only ineffective, they can even increase anxiety and fear in patients undergoing spinal surgery. Therefore, perioperative pain neuroscience education is proposed as a dramatic shift in educating patients prior to and following surgery for lumbar radiculopathy. Rather than focusing on the surgical procedure, ergonomics or lumbar biomechanics, perioperative pain neuroscience education teaches people about the underlying mechanisms of pain, including the pain they will feel following surgery. The primary objective of the study is to examine whether perioperative pain neuroscience education ('brain school') is more effective than classic back school in reducing pain and improving pain inhibition in patients undergoing surgery for spinal radiculopathy. A secondary objective is to examine whether perioperative pain neuroscience education is more effective than classic back school in: reducing postoperative healthcare expenditure, improving functioning in daily life, increasing return to work, and improving surgical experience (ie, being better prepared for surgery, reducing incongruence between the expected and actual experience) in patients undergoing surgery for spinal radiculopathy. A multi-centre, two-arm (1:1) randomised, controlled trial with 2-year follow-up. People undergoing surgery for lumbar radiculopathy (n=86) in two Flemish hospitals (one tertiary care, university-based hospital and one regional, secondary care hospital) will be recruited for the study. All participants will receive usual preoperative and postoperative care related to the surgery for lumbar radiculopathy. The experimental

  14. Endurance and fatigue characteristics in the neck muscles during sub-maximal isometric test in patients with cervical radiculopathy.

    PubMed

    Halvorsen, Marie; Abbott, Allan; Peolsson, Anneli; Dedering, Åsa

    2014-03-01

    The aim of the study was to compare myoelectric manifestation in neck muscle endurance and fatigue characteristics during sub-maximal isometric endurance test in patients with cervical radiculopathy and asymptomatic subjects. An additional aim was to explore associations between primary neck muscle endurance, myoelectric fatigability, and self-rated levels of fatigue, pain and subjective health measurements in patients with cervical radiculopathy. Muscle fatigue in the ventral and dorsal neck muscles was assessed in patients with cervical radiculopathy and in an asymptomatic group during an isometric neck muscle endurance test in prone and supine. 46 patients and 34 asymptomatic subjects participated. Surface electromyography signals were recorded from the sternocleidomastoid, cervical paraspinal muscles and upper and middle trapezius bilaterally during the endurance test. Subjective health measurements were assessed with questionnaires. The results showed altered neck muscle endurance in several of the muscles investigated with greater negative median frequency slope, greater variability, side imbalance, lower endurance time and higher experience of fatigue among the cervical radiculopathy patients compared with healthy subjects. Endurance times were significantly lower in both prone and in supine positions between the patients compared to asymptomatic subjects. During the neck muscle endurance test, fatigues in the upper trapezius muscles during the prone test and in the sternocleidomastoid muscles during the supine test were of more importance than self-perceived pain, fatigue, disability and kinesiophobia in predicting neck muscle endurance (NME). NME testing in the primary neck muscles seems to be an important factor to take into consideration in rehabilitation.

  15. Return to work following surgery for lumbar radiculopathy: a systematic review.

    PubMed

    Huysmans, Eva; Goudman, Lisa; Van Belleghem, Griet; De Jaeger, Mats; Moens, Maarten; Nijs, Jo; Ickmans, Kelly; Buyl, Ronald; Vanroelen, Christophe; Putman, Koen

    2018-05-22

    Informing patients about postoperative return to work (RTW) expectations is of utmost importance because of the influence of realistic expectations on RTW outcomes. We aimed to give an overview of the duration of sick leave and RTW rates after surgery for lumbar radiculopathy and to list predictors of and factors related to RTW. A systematic review was carried out. A systematic literature search was conducted in PubMed, Web of Science, EMBASE, and SCOPUS. Full-text articles on RTW following surgery for lumbar radiculopathy were included through double-blind screening. Risk of bias was assessed using a modified version of the Downs and Black checklist. Sixty-three full-text articles (total sample size: 7,100 patients) were included. Risk of bias was scored low to high. Mean duration of sick leave ranged from 0.8 to 20 weeks. Within 0.1-240 months post surgery, 3%-100% of patients resumed work. Most important predictors for work resumption were preoperative work status, presence of comorbidities, age, sex and duration of preoperative symptoms. Duration of sick leave can be predicted by the preoperative level of pain or disability and presence of symptoms of depression, occupational mental stress, and lateral disc prolapse. Furthermore, less invasive surgical techniques were found to result in better RTW outcomes compared with more invasive techniques. Diverse results were found for RTW rates and duration of sick leave. Preoperative work status, presence of comorbidities, and several demographic factors were retrieved as predictors of RTW and duration of sick leave. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Acute-onset chronic inflammatory demyelinating polyneuropathy: An electrodiagnostic study.

    PubMed

    Anadani, Mohammad; Katirji, Bashar

    2015-11-01

    Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an increasingly recognized CIDP subtype. Differentiating A-CIDP from Guillain-Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes. We report 3 patients with A-CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long-term treatment of these patients and review the literature on EDx studies in this syndrome. Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy. Although several features may suggest the diagnosis of A-CIDP at initial presentation, close follow-up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A-CIDP from GBS patients. © 2015 Wiley Periodicals, Inc.

  17. Reliability, construct validity, and responsiveness of the neck disability index, patient-specific functional scale, and numeric pain rating scale in patients with cervical radiculopathy.

    PubMed

    Young, Ian A; Cleland, Joshua A; Michener, Lori A; Brown, Chris

    2010-10-01

    To examine the psychometric properties of the Neck Disability Index, Patient-Specific Functional Scale, and the Numeric Pain Rating Scale in a cohort of patients with cervical radiculopathy. A single-group repeated-measures design. Patients (n = 165) presenting to physical therapy with cervical radiculopathy completed the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale at the baseline examination and at a follow-up. At the time of follow-up, all patients also completed the Global Rating of Change, which was used to dichotomize patients as improved or stable. Baseline and follow-up scores were used to determine the test-retest reliability, construct validity, and minimal levels of detectable and clinically important change for the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale. Both the Neck Disability Index and Numeric Pain Rating Scale exhibited fair test-retest reliability, whereas the Patient-Specific Functional Scale exhibited poor reliability in patients with cervical radiculopathy. All three outcome measures showed adequate responsiveness in this patient population. The minimal detectable change was 13.4 for the Neck Disability Index, 3.3 for the Patient-Specific Functional Scale, and 4.1 for the Numeric Pain Rating Scale. The threshold for the minimal clinically important difference was 8.5 for the Neck Disability Index and 2.2 for both the Patient-Specific Functional Scale and Numeric Pain Rating Scale. In light of the varied distribution of symptoms in patients with cervical radiculopathy, future studies should investigate the psychometric properties of other neck-related disability measures in this patient population.

  18. [Randomized controlled trials of needle knife therapy combined with rotation traction manipulation for the treatment of cervical spondylotic radiculopathy].

    PubMed

    Zhou, Zhong-Liang; Su, Guo-Hong; Zheng, Bao-Zhu; Zuo, Yu-Zhu; Wei, Fu-Liang

    2016-09-25

    To compare the therapeutic effects between needle knife therapy combined with rotation traction manipulation and rotation traction manipulation for the treatment of cervical spondylotic radiculopathy. From November 2013 to June 2015, 80 patients with cervical spondylotic radiculopathy meeting the inclusion criteria were divided into two groups randomly:the control group in which 39 patients were treated with rotation traction manipulation, and the treatment group in which 41 patients were treated with needle knife combined with rotation traction manipulation. The patients in the control group were treated once dayly for 2 weeks, which was 1 course. The patients in the treatment group were treated with needle knife firstly once a week for 2 weeks, which was 1 course;then were treated with the same methods as the patients in the control group. The symptoms, signs score and the therapeutic effects of the two groups before and after treatment were observed. After treatment, symptoms and signs scores declined in both groups( P <0.05). The results of the treatment group were better than effects in the control group( P <0.05). In the treatment group, 19 patients got an excellent result, 16 good, 5 fair and 1 bad;while in the control group, 10 patients got an excellent result, 10 good, 16 fair and 3 bad;the results of the treatment group were better than the results of the control group( P <0.01). Needle knife combined with rotation traction manipulation is an effective method for the treatment of cervical spondylotic radiculopathy, which is better than using manipulation method simply. Needle knife therapy has follow advantages:improving local blood circulation, reducing local content of pain substance, increasing production of substances resisting pain, opening channels and collaterals, and make body reaching new static and dynamic balance on the new foundation.

  19. Effects of Qishe Pill, a compound traditional Chinese herbal medicine, on cervical radiculopathy: study protocol for a randomized controlled trial.

    PubMed

    Cui, Xue-Jun; Sun, Yue-Li; You, Sheng-Fu; Mo, Wen; Lu, Sheng; Shi, Qi; Wang, Yong-Jun

    2013-10-07

    Neck pain is a common symptom in most patients suffering from cervical radiculopathy. However, some conservative treatments are limited by their modest effectiveness. On the other hand, surgical intervention for cervical disc disorders is indicated when symptoms are refractory to conservative treatments and neurological symptoms are progressive. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. The purpose of the present study is to examine the efficacy and safety of Qishe Pill, a compound traditional Chinese herbal medicine, for neck pain in patients with cervical radiculopathy. A multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of the Qishe Pill is proposed. The study will include 240 patients from five sites across China and diagnosed with cervical radiculopathy, according to the following inclusion criteria: age 18 to 65 with pain or stiffness in the neck for at least 2 weeks (neck disability index score 25 or more) and accompanying arm pain that radiates distally from the elbow. Qualified participants will be randomly allocated into two groups: Qishe Pill group and placebo group. The prescription of the trial medications (Qishe Pill/placebo) are 3.75 g each twice a day for 28 consecutive days. The primary outcome is pain severity. Secondary outcomes are functional status, patient satisfaction, and adverse events as reported in the trial. Qishe Pill is composed of processed Radix Astragali, Muscone, Szechuan Lovage Rhizome, Radix Stephaniae Tetrandrae, Ovientvine, and Calculus Bovis Artifactus. According to modern research and preparation standards, Qishe Pill is developed to improve on the various symptoms of cervical radiculopathy, especially for neck pain. As it has a potential benefit in treating patients with neck pain, we designed a double-blind, prospective, randomized-controlled trial and would like to publish the results and

  20. The usefulness of electrodiagnostic studies in the diagnosis and management of neuromuscular disorders.

    PubMed

    Lindstrom, Heather; Ashworth, Nigel L

    2018-03-13

    This study seeks to evaluate the usefulness of electrodiagnostic (EDX) studies in terms of the patient's diagnosis and subsequent management and to identify patient groups in which EDX is particularly useful. The records of new patients referred to a single tertiary hospital EDX laboratory during 1 calendar year were reviewed to determine whether results of EDX studies led to a changed diagnosis and/or management plan. Logistic regression was used to determine whether any factors were associated with changed diagnosis or management. Results of EDX studies led to a change in diagnosis and a confirmation in diagnosis in 51.5% and 46.5% of the cases, respectively. Results of EDX studies led to a change in the management plan in 63.4% of all cases. The diagnosis and management plan were more likely to be changed in older patients and patients referred in hospital. EDX studies seem useful for confirming or changing the diagnosis and in guiding management in patients with suspected neuromuscular disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  1. A systematic review of the diagnostic accuracy of provocative tests of the neck for diagnosing cervical radiculopathy

    PubMed Central

    Pool, Jan J. M.; van Tulder, Maurits W.; Riphagen, Ingrid I.; de Vet, Henrica C. W.

    2006-01-01

    Clinical provocative tests of the neck, which position the neck and arm inorder to aggravate or relieve arm symptoms, are commonly used in clinical practice in patients with a suspected cervical radiculopathy. Their diagnostic accuracy, however, has never been examined in a systematic review. A comprehensive search was conducted in order to identify all possible studies fulfilling the inclusion criteria. A study was included if: (1) any provocative test of the neck for diagnosing cervical radiculopathy was identified; (2) any reference standard was used; (3) sensitivity and specificity were reported or could be (re-)calculated; and, (4) the publication was a full report. Two reviewers independently selected studies, and assessed methodological quality. Only six studies met the inclusion criteria, which evaluated five provocative tests. In general, Spurling’s test demonstrated low to moderate sensitivity and high specificity, as did traction/neck distraction, and Valsalva’s maneuver. The upper limb tension test (ULTT) demonstrated high sensitivity and low specificity, while the shoulder abduction test demonstrated low to moderate sensitivity and moderate to high specificity. Common methodological flaws included lack of an optimal reference standard, disease progression bias, spectrum bias, and review bias. Limitations include few primary studies, substantial heterogeneity, and numerous methodological flaws among the studies; therefore, a meta-analysis was not conducted. This review suggests that, when consistent with the history and other physical findings, a positive Spurling’s, traction/neck distraction, and Valsalva’s might be indicative of a cervical radiculopathy, while a negative ULTT might be used to rule it out. However, the lack of evidence precludes any firm conclusions regarding their diagnostic value, especially when used in primary care. More high quality studies are necessary in order to resolve this issue. PMID:17013656

  2. Postoperative Radiculopathy Caused by a Retained Fractured Pedicle Cannulation Probe and Its Mechanism of Extraction.

    PubMed

    Yuk, Frank; Steinberger, Jeremy; Skovrlj, Branko; Mascitelli, Justin; Cho, Samuel K; Caridi, John M

    2017-11-01

    Spine surgery relies heavily on technology and surgical instrumentation. Improperly used instrumentation can be detrimental to the patient. Despite multiple checkpoints to ensure that foreign bodies are not retained in surgery, numerous case reports have described retained foreign bodies; however, none of these cases involve retained instrumentation after open spine surgery. Of the retained objects, 4 were sponges and one was a Jamshidi needle fragment. Although smaller objects are more commonly the culprits, surgical instruments can break off, remain stuck, and cause clinical sequelae. This case presents a retained fractured pedicle finder as the cause of right L5 radiculopathy. To our knowledge, this report is the first to describe an instrumentation-associated postoperative radiculopathy. Because of the strength with which the object was impacted, its extraction proved difficult. The technique of removal using a mallet and osteotome in 4 directions to loosen its hold in the vertebral body. Attempts and eventual successful removal are described. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Individualized functional restoration as an adjunct to advice for lumbar disc herniation with associated radiculopathy. A preplanned subgroup analysis of a randomized controlled trial.

    PubMed

    Hahne, Andrew J; Ford, Jon J; Hinman, Rana S; Richards, Matthew C; Surkitt, Luke D; Chan, Alexander Y P; Slater, Sarah L; Taylor, Nicholas F

    2017-03-01

    Physical therapy is commonly sought by people with lumbar disc herniation and associated radiculopathy. It is unclear whether physical therapy is effective for this population. To determine the effectiveness of physical therapist-delivered individualized functional restoration as an adjunct to guideline-based advice in people with lumbar disc herniation and associated radiculopathy. This is a preplanned subgroup analysis of a multicenter parallel group randomized controlled trial. The study included 54 participants with clinical features of radiculopathy (6-week to 6-month duration) and imaging showing a lumbar disc herniation. Primary outcomes were activity limitation (Oswestry Disability Index) and separate 0-10 numerical pain rating scales for leg pain and back pain. Measures were taken at baseline and at 5, 10, 26, and 52 weeks. The participants were randomly allocated to receive either individualized functional restoration incorporating advice (10 sessions) or guideline-based advice alone (2 sessions) over a 10-week period. Treatment was administered by 11 physical therapists at private clinics in Melbourne, Australia. Between-group differences for activity limitation favored the addition of individualized functional restoration to advice alone at 10 weeks (7.7, 95% confidence interval [CI] 0.3-15.1) and 52 weeks (8.2, 95% CI 0.7-15.6), as well as back pain at 10 weeks (1.4, 95% CI 0.2-2.7). There were no significant differences between groups for leg pain at any follow-up. Several secondary outcomes also favored individualized functional restoration over advice. In participants with lumbar disc herniation and associated radiculopathy, an individualized functional restoration program incorporating advice led to greater reduction in activity limitation at 10- and 52-week follow-ups compared with guideline-based advice alone. Although back pain was significantly reduced at 10 weeks with individualized functional restoration, this effect was not maintained at

  4. [Minimally invasive approach for cervical spondylotic radiculopathy].

    PubMed

    Ding, Liang; Sun, Taicun; Huang, Yonghui

    2010-01-01

    To summarize the recent minimally invasive approach for cervical spondylotic radiculopathy (CSR). The recent literature at home and abroad concerning minimally invasive approach for CSR was reviewed and summarized. There were two techniques of minimally invasive approach for CSR at present: percutaneous puncture techniques and endoscopic techniques. The degenerate intervertebral disc was resected or nucleolysis by percutaneous puncture technique if CSR was caused by mild or moderate intervertebral disc herniations. The cervical microendoscopic discectomy and foraminotomy was an effective minimally invasive approach which could provide a clear view. The endoscopy techniques were suitable to treat CSR caused by foraminal osteophytes, lateral disc herniations, local ligamentum flavum thickening and spondylotic foraminal stenosis. The minimally invasive procedure has the advantages of simple handling, minimally invasive and low incidence of complications. But the scope of indications is relatively narrow at present.

  5. Muscle hypertrophy with complex repetitive discharges in C-6 radiculopathy.

    PubMed

    Rousseff, Rossen T; Tzvetanov, Plamen

    2005-08-01

    To report on a case of post-denervation muscle hypertrophy in an unusual distribution. A 52-year-old patient with severe flaccid paraparesis after polio developed unilateral C-6 radiculopathy that resolved with conservative treatment. Within 2 years marked hypertrophy, stiffness and pain in the muscles in the affected myotome developed. EMG discovered abundant complex repetitive discharges (CRD) within hypertrophic muscles. On biopsy, true hypertrophy of muscle fibers and some group atrophy was found. Steroid treatment relieved the symptoms and significantly suppressed the CRD. The possible causative role of CRD for hypertrophy in partially denervated muscle is discussed.

  6. The value transformation of health care: Impact on neuromuscular and electrodiagnostic medicine.

    PubMed

    Narayanaswami, Pushpa; Suk, Millie; Jones, Lyell K

    2017-10-01

    Beginning in 2017, most physicians who participate in Medicare are subject to the Medicare Access and CHIP Reauthorization Act (MACRA), the milestone legislation that signals the US health care system's transition from volume-based to value-based care. Here we review emerging trends in development of value-based healthcare systems in the US. MACRA and the resulting Quality Payment Program create 2 participation pathways, the Merit-based Incentive Payment System (MIPS) and the Advanced Alternative Payment Model (AAPM) pathway. Although there are several program incentives for AAPM participation, to date there have been few AAPM options for specialists. MIPS and its widening bonus and penalty window will likely be the primary participation pathway in the early years of the program. Value-based payment has the potential to reshape health care delivery in the United States, with implications for neuromuscular and electrodiagnostic (EDX) specialists. Meaningful quality measures are required for neuromuscular and EDX specialists. Muscle Nerve 56: 679-683, 2017. © 2017 Wiley Periodicals, Inc.

  7. Comparison between cervical disc arthroplasty and conservative treatment for patients with single level cervical radiculopathy at C5/6.

    PubMed

    He, Axiang; Xie, Dong; Qu, Bo; Cai, Xiaomin; Kong, Qin; Yang, Lili; Chen, Xiongsheng; Jia, Lianshun

    2018-01-31

    Cervical radiculopathy is a common disease that affects millions of people. Patients usually are managed by conservative therapy and surgical treatments. To compare the clinical outcomes between cervical disc arthroplasty (CDA) and conservative management for patients with single level cervical radiculopathy at C5/6. Seventy-two patients with cervical radiculopathy that only affect C5/6 joints were included and thirty-two of them received CDA surgery, and forty patients were treated with conservative management. All the patients were followed up around 4 years. Cervical curvature, cervical range of motion (CROM), horizontal displacement of cervical spine, and intervertebral gap were measured by radiological examination. All the patients have comparable disease severity based on pre-surgical radiological assessments. At the 4-year follow-up examination, patients with CDA surgery had less CROM at C5/6 level, while greater CROM at C4/5 level, than control group. Similarly, the horizontal displacement in CDA group decreased at C5/6 vertebrae, and increased at C4/5 level at the 4-year follow-up examination. The intervertebral gaps of patients in CDA group were larger than control group at one-year and last follow-up examination. CDA surgery stabilized C5/6 vertebrae and increased the CROM and horizontal displacement of upper adjacent C4/5 vertebrae. Copyright © 2018. Published by Elsevier Ltd.

  8. A Novel Technique for Cervical Facet Joint Hyperplasia-Spondylotic Radiculopathy by Laminar and Lateral Mass Screw Cofixations.

    PubMed

    Sheng, Sun-Ren; Wang, Ke; Nisar, Majid; Chen, Jiao-Xiang; Wu, Ai-Min; Wang, Xiang-Yang

    2018-02-01

    We sought to describe the novel technique and report the outcomes of cervical spondylotic radiculopathy caused by facet joint hyperplasia treated with minimally invasive surgery by laminar and lateral mass screw cofixations. In this retrospective study, patients with spondylotic radiculopathy caused by facet joint hyperplasia underwent this technique in our unit between January 2010 and June 2015. Hospital charts, magnetic resonance imaging studies, and follow-up records for all the patients were reviewed. Outcomes were assessed on the basis of neurologic status, magnetic resonance imaging, and visual analog scale for neck and radicular pain and by the short form-36 health survey questionnaire. Thirteen men and 5 women, aged 47-73 years (mean, 61.8 years), were included in this study. The follow-up time ranged from 19-50 months (mean, 32.4 months). The mean visual analog scale scores for radicular pain and neck pain, as well as the scores for all 8 domains of the short form-36 health survey questionnaire, showed significant improvements (P < 0.05). Cervical lordosis showed bending, whereas the height of the targeted disk segment showed no change (P > 0.05). Complications included 2 cases of neck pain that lasted for 3 months. Minimally invasive surgery by lamina and lateral mass screw cofixation is safe and effective for the treatment of cervical spondylotic radiculopathy caused by facet joint hyperplasia. In addition to sufficient decompression, this technique provides relative stability to the cervical spine. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Phantom Radiculopathy: Case Report and Review of the Literature.

    PubMed

    Croci, Davide; Fandino, Javier; Marbacher, Serge

    2016-06-01

    Phantom radicular pain is very uncommon. To the best of our knowledge, only 14 cases have been described in the literature. A review of the literature revealed the most common cause of phantom radicular pain to be lumbar disc herniation and, furthermore, that treatment with epidural steroid injection or surgical decompression relieves pain in almost all cases. A significant number of patients with superimposed phantom radiculopathy may be missed because of the high incidence of degenerative lumbar spine diseases in the adult population, as well as the fact that amputee patients very often present with mixed stump and phantom pain. We report a case of a patient presenting with new-onset phantom radicular pain (S1 left) 4 years after an above-the-knee amputation (left). Computed tomography myelography showed compression of the left S1 nerve root caused by recurrent disc herniation and scar tissue formation after previous discectomy at L5-S1. The patient experienced temporarily relief of the sciatic pain after a fluoroscopically-guided epidural transforaminal steroid injection. Subsequent microsurgical decompression led to complete remission of the phantom radicular pain. Amputees experiencing recurrent phantom radicular pain or new-onset superimposed pain deserve further radiologic evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Single-level anterior cervical discectomy and fusion versus minimally invasive posterior cervical foraminotomy for patients with cervical radiculopathy: a cost analysis.

    PubMed

    Mansfield, Haley E; Canar, W Jeffrey; Gerard, Carter S; O'Toole, John E

    2014-11-01

    Patients suffering from cervical radiculopathy in whom a course of nonoperative treatment has failed are often candidates for a single-level anterior cervical discectomy and fusion (ACDF) or posterior cervical foraminotomy (PCF). The objective of this analysis was to identify any significant cost differences between these surgical methods by comparing direct costs to the hospital. Furthermore, patient-specific characteristics were also considered for their effect on component costs. After obtaining approval from the medical center institutional review board, the authors conducted a retrospective cross-sectional comparative cohort study, with a sample of 101 patients diagnosed with cervical radiculopathy and who underwent an initial single-level ACDF or minimally invasive PCF during a 3-year period. Using these data, bivariate analyses were conducted to determine significant differences in direct total procedure and component costs between surgical techniques. Factorial ANOVAs were also conducted to determine any relationship between patient sex and smoking status to the component costs per surgery. The mean total direct cost for an ACDF was $8192, and the mean total direct cost for a PCF was $4320. There were significant differences in the cost components for direct costs and operating room supply costs. It was found that there was no statistically significant difference in component costs with regard to patient sex or smoking status. In the management of single-level cervical radiculopathy, the present analysis has revealed that the average cost of an ACDF is 89% more than a PCF. This increased cost is largely due to the cost of surgical implants. These results do not appear to be dependent on patient sex or smoking status. When combined with results from previous studies highlighting the comparable patient outcomes for either procedure, the authors' findings suggest that from a health care economics standpoint, physicians should consider a minimally invasive PCF

  11. C2 spondylotic radiculopathy: the nerve root impingement mechanism investigated by para-sagittal CT/MRI, dynamic rotational CT, intraoperative microscopic findings, and treated by microscopic posterior foraminotomy.

    PubMed

    Fujiwara, Yasushi; Izumi, Bunichiro; Fujiwara, Masami; Nakanishi, Kazuyoshi; Tanaka, Nobuhiro; Adachi, Nobuo; Manabe, Hideki

    2017-04-01

    C2 radiculopathy is known to cause occipito-cervical pain, but their pathology is unclear because of its rarity and unique anatomy. In this paper, we investigated the mechanism of C2 radiculopathy that underwent microscopic cervical foraminotomies (MCF). Three cases with C2 radiculopathy treated by MCF were investigated retrospectively. The mean follow-up period was 24 months. Pre-operative symptoms, imaging studies including para-sagittal CT and MRI, rotational dynamic CT, and intraoperative findings were investigated. There were 1 male and 2 females. The age of patients were ranged from 50 to 79 years. All cases had intractable occipito-cervical pain elicited by the cervical rotation. C2 nerve root block was temporally effective. There was unilateral spondylosis in symptomatic side without obvious atlatoaxial instability. Para-sagittal MRI and CT showed severe foraminal stenosis at C1-C2 due to the bony spur derived from the lateral atlanto-axial joints. In one case, dynamic rotational CT showed that the symptomatic foramen became narrower on rotational position. MCF was performed in all cases, and the C2 nerve root was impinged between the inferior edge of the C1 posterior arch and bony spur from the C1-C2 joint. After surgery, occipito-cervical pain disappeared. This study demonstrated that mechanical impingement of the C2 nerve root is one of the causes of occipito-cervical pain and it was successfully treated by microscopic resection of the inferior edge of the C1 posterior arch. Para-sagittal CT and MRI, rotational dynamic CT, and nerve root block were effective for diagnosis.

  12. Mineralization of the transverse ligament of the atlas causing compressive radiculopathy. Resolution following odontoidectomy and atlantoaxial arthrodesis.

    PubMed

    Hamilton, Leonard C; Driver, Colin; Tauro, Anna; Campbell, Gary; Fitzpatrick, Noel

    2016-05-18

    To describe a case of a Boxer dog with radiculopathy due to mineralization of the transverse ligament of the atlas and subsequent resorption and resolution of clinical signs after atlantoaxial arthrodesis and odontoidectomy. A five-year-old neutered female Boxer dog was presented with a four-month history of cervical hyperaesthesia refractory to medical management. Neurological examination and magnetic resonance imaging indicated a diagnosis of radiculopathy due to cervical nerve root impingement by dystrophic mineralization of the transverse ligament of the atlas. Odontoidectomy was performed by a ventral approach and atlantoaxial arthrodesis was achieved with a ventral composite polymethylmethacrylate and pin fixation. Atlantoaxial arthrodesis and progressive resorption of the mineralization following stabilization facilitated indirect decompression. The radioclinical diagnosis and response to arthrodesis was considered analogous to retro-odontoid pannus in the human. A clinical condition similar to retro-odontoid pannus may exist in the canine and may be amenable to atlantoaxial arthrodesis.

  13. Painless motor radiculopathy of the cervical spine: clinical and radiological characteristics and long-term outcomes after operative decompression.

    PubMed

    Siller, Sebastian; Kasem, Rami; Witt, Thomas-Nikolaus; Tonn, Joerg-Christian; Zausinger, Stefan

    2018-03-23

    OBJECTIVE Various neurological diseases are known to cause progressive painless paresis of the upper limbs. In this study the authors describe the previously unspecified syndrome of compression-induced painless cervical radiculopathy with predominant motor deficit and muscular atrophy, and highlight the clinical and radiological characteristics and outcomes after surgery for this rare syndrome, along with its neurological differential diagnoses. METHODS Medical records of 788 patients undergoing surgical decompression due to degenerative cervical spine diseases between 2005 and 2014 were assessed. Among those patients, 31 (3.9%, male to female ratio 4.8 to 1, mean age 60 years) presented with painless compressive cervical motor radiculopathy due to neuroforaminal stenosis without signs of myelopathy; long-term evaluation was available in 23 patients with 49 symptomatic foraminal stenoses. Clinical, imaging, and operative findings as well as the long-term course of paresis and quality of life were analyzed. RESULTS Presenting symptoms (mean duration 13.3 months) included a defining progressive flaccid radicular paresis (median grade 3/5) without any history of radiating pain (100%) and a concomitant muscular atrophy (78%); 83% of the patients were smokers and 17% patients had diabetes. Imaging revealed a predominantly anterior nerve root compression at the neuroforaminal entrance in 98% of stenoses. Thirty stenoses (11 patients) were initially decompressed via an anterior surgical approach and 19 stenoses (12 patients) via a posterior surgical approach. Overall reoperation rate due to new or recurrent stenoses was 22%, with time to reoperation shorter in smokers (p = 0.033). Independently of the surgical procedure chosen, long-term follow-up (mean 3.9 years) revealed a stable or improved paresis in 87% of the patients (median grade 4/5) and an excellent general performance and quality of life. CONCLUSIONS Painless cervical motor radiculopathy predominantly occurs

  14. Coexisting cervical spondylotic myelopathy and bilateral carpal tunnel syndromes.

    PubMed

    Epstein, N E; Epstein, J A; Carras, R

    1989-03-01

    In six patients, operations for bilateral carpal tunnel syndromes (CTS) were performed or were about to be performed without the awareness of the presence of underlying cervical spondylo-stenosis. Only later, when symptoms of myeloradiculopathy were recognized, was the diagnosis confirmed and decompressive laminectomy performed. Because the symptoms of CTS may resemble or be masked and accentuated by the cervical disorder, patients with the presumed diagnosis of bilateral CTS should undergo appropriate critical neurologic, electrodiagnostic, and neuroradiologic (magnetic resonance imaging, computed tomography, myelo-computed tomography) assessment. If these guidelines are followed, the radiculopathy caused by cervical pathology will be appropriately recognized and treated, possibly averting the need for carpal tunnel decompression or modifying treatment.

  15. Posterior epidural disc fragment masquerading as spinal tumor: Review of the literature.

    PubMed

    Park, Taejune; Lee, Ho Jun; Kim, Jae Seong; Nam, Kiyeun

    2018-03-09

    Posterior epidural lumbar disc fragment is infrequent because of anatomical barriers, and it is difficult to diagnose posterior epidural lumbar disc fragment because of its rare incidence and the ambiguity of radiologic evaluations. And it is difficult to differentiate it from other diseases such as spinal tumors. Differential diagnosis of posterior epidural lumbar disc fragment is clinically important because its diagnosis can affect treatment and prognosis. To investigate the incidence, anatomical concern, etiology, symptom, diagnostic tool, management and prognosis of posterior epidural lumbar disc fragment, we reviewed articles including case report. We performed a search of all clinical studies of posterior epidural lumbar disc fragment published to date. The following keywords were searched: Posterior epidural lumbar disc fragment, disc migration, posterior epidural disc, extradural migration, dorsal epidural migration, sequestrated disc, and disc fragment. We identified 40 patients of posterior epidural lumbar disc fragment from 28 studies. The most common presentation of posterior epidural lumbar disc fragment was sudden onset radiculopathy (70.0%), followed by cauda equina syndrome (27.5%). The most frequently used diagnostic modality was magnetic resonance imaging (MRI), conducted in 36 cases (90.0%), and followed by computed tomography in 14 cases (35.0%). After the imaging studies, the preoperative diagnoses were 45.0% masses, 20.0% lesions, and 12.5% tumors. Characteristic MRI findings in posterior epidural lumbar disc fragment are helpful for diagnosis; it typically displays low signals on T1-weighted images and high signals on T2-weighted images with respect to the parent disc. In addition, most of the disc fragments show peripheral rim enhancement on MRI with gadolinium administration. Electrodiagnostic testing is useful for verifying nerve damage. Surgical treatment was performed in all cases, and neurologic complications were observed in 12.5%. As

  16. Physical function outcome in cervical radiculopathy patients after physiotherapy alone compared with anterior surgery followed by physiotherapy: a prospective randomized study with a 2-year follow-up.

    PubMed

    Peolsson, Anneli; Söderlund, Anne; Engquist, Markus; Lind, Bengt; Löfgren, Håkan; Vavruch, Ludek; Holtz, Anders; Winström-Christersson, Annelie; Isaksson, Ingrid; Öberg, Birgitta

    2013-02-15

    Prospective randomized study. To investigate differences in physical functional outcome in patients with radiculopathy due to cervical disc disease, after structured physiotherapy alone (consisting of neck-specific exercises with a cognitive-behavioral approach) versus after anterior cervical decompression and fusion (ACDF) followed by the same structured physiotherapy program. No earlier studies have evaluated the effectiveness of a structured physiotherapy program or postoperative physical rehabilitation after ACDF for patients with magnetic resonance imaging-verified nerve compression due to cervical disc disease. Our prospective randomized study included 63 patients with radiculopathy and magnetic resonance imaging-verified nerve root compression, who were randomized to receive either ACDF in combination with physiotherapy or physiotherapy alone. For 49 of these patients, an independent examiner measured functional outcomes, including active range of neck motion, neck muscle endurance, and hand-related functioning before treatment and at 3-, 6-, 12-, and 24-month follow-ups. There were no significant differences between the 2 treatment alternatives in any of the measurements performed (P = 0.17-0.91). Both groups showed improvements over time in neck muscle endurance (P ≤ 0.01), manual dexterity (P ≤ 0.03), and right-handgrip strength (P = 0.01). Compared with a structured physiotherapy program alone, ACDF followed by physiotherapy did not result in additional improvements in neck active range of motion, neck muscle endurance, or hand-related function in patients with radiculopathy. We suggest that a structured physiotherapy program should precede a decision for ACDF intervention in patients with radiculopathy, to reduce the need for surgery. 2.

  17. Neck-specific training with a cognitive behavioural approach compared with prescribed physical activity in patients with cervical radiculopathy: a protocol of a prospective randomised clinical trial.

    PubMed

    Dedering, Åsa; Halvorsen, Marie; Cleland, Joshua; Svensson, Mikael; Peolsson, Anneli

    2014-08-12

    Patients with cervical radiculopathy often have neck- and arm pain, neurological changes, activity limitations and difficulties in returning to work. Most patients are not candidates for surgery but are often treated with different conservative approaches and may be sick-listed for long periods. The purpose of the current study is to compare the effectiveness of neck-specific training versus prescribed physical activity. The current protocol is a two armed intervention randomised clinical trial comparing the outcomes of patients receiving neck specific training or prescribed physical activity. A total of 144 patients with cervical radiculopathy will be randomly allocated to either of the two interventions. The interventions will be delivered by experienced physiotherapists and last 14 weeks. The primary outcome variable is neck- and arm pain intensity measured with a Visual Analogue Scale accompanied with secondary outcome measures of impairments and subjective health measurements collected before intervention and at 3, 6, 12 and 24 months after base-line assessment. We anticipate that the results of this study will provide evidence to support recommendations as to the effectiveness of conservative interventions for patients with cervical radiculopathy. ClinicalTrials.gov identifier: NCT01831271.

  18. Melorheostosis causing lumbar radiculopathy: a case report and a review of the literature.

    PubMed

    Saxena, Ankur; Neelakantan, Asha; Jampana, Ravi; Sangra, Meharpal

    2013-08-01

    Melorheostosis is a rare sclerosing bone disorder with a predilection for the appendicular skeleton. Involvement of the spine is infrequent and largely asymptomatic. Surgical treatment for spinal involvement is therefore uncommon with only one reported case of lumbar fusion for painful lumbosacral melorheostosis. We report a case of lumbar melorheostosis causing disabling radiculopathy treated with nerve root decompression. Melorheostosis of the lumbar spine causing radicular symptoms has not been reported before. Our message from the management of this particular patient is to consider surgical option in symptomatic individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Facetal distraction as treatment for single- and multilevel cervical spondylotic radiculopathy and myelopathy: a preliminary report.

    PubMed

    Goel, Atul; Shah, Abhidha

    2011-06-01

    The authors discuss their successful preliminary experience with 36 cases of cervical spondylotic disease by performing facetal distraction using specially designed Goel cervical facet spacers. The clinical and radiological results of treatment are analyzed. The mechanism of action of the proposed spacers and the rationale for their use are evaluated. Between 2006 and February 2010, 36 patients were treated using the proposed technique. Of these patients, 18 had multilevel and 18 had single-level cervical spondylotic radiculopathy and/or myelopathy. The average follow-up period was 17 months with a minimum of 6 months. The Japanese Orthopaedic Association classification system, visual analog scale (neck pain and radiculopathy), and Odom criteria were used to monitor the clinical status of the patient. The patients were prospectively analyzed. The technique of surgery involved wide opening of the facet joints, denuding of articular cartilage, distraction of facets, and forced impaction of Goel cervical facet spacers into the articular cavity. Additionally, the interspinous process ligaments were resected, and corticocancellous bone graft from the iliac crest was placed and was stabilized over the adjoining laminae and facets after adequately preparing the host bone. Eighteen patients underwent single-level, 6 patients underwent 2-level, and 12 patients underwent 3-level treatment. The alterations in the physical architecture of spine and canal dimensions were evaluated before and after the placement of intrafacet joint spacers and after at least 6 months of follow-up. All patients had varying degrees of relief from symptoms of pain, radiculopathy, and myelopathy. Analysis of radiological features suggested that the distraction of facets with the spacers resulted in an increase in the intervertebral foraminal dimension (mean 2.2 mm), an increase in the height of the intervertebral disc space (range 0.4-1.2 mm), and an increase in the interspinous distance (mean 2

  20. Quantitative sensory testing somatosensory profiles in patients with cervical radiculopathy are distinct from those in patients with nonspecific neck-arm pain.

    PubMed

    Tampin, Brigitte; Slater, Helen; Hall, Toby; Lee, Gabriel; Briffa, Noelle Kathryn

    2012-12-01

    The aim of this study was to establish the somatosensory profiles of patients with cervical radiculopathy and patients with nonspecific neck-arm pain associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles were compared to healthy control (HC) subjects and a positive control group comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimulation was performed in the maximal pain area, the corresponding dermatome and foot of 23 patients with painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7 dermatomal pain distribution, 31 HC and 22 patients with FM. For both neck-arm pain groups, all QST parameters were within the 95% confidence interval of HC data. Patients with cervical radiculopathy were characterised by localised loss of function (thermal, mechanical, vibration detection P<.009) in the maximal pain area and dermatome (thermal detection, vibration detection, pressure pain sensitivity P<.04), consistent with peripheral neuronal damage. Both neck-arm pain groups demonstrated increased cold sensitivity in their maximal pain area (P<.03) and the foot (P<.009), and this was also the dominant sensory characteristic in patients with NSNAP. Both neck-arm pain groups differed from patients with FM, the latter characterised by a widespread gain of function in most nociceptive parameters (thermal, pressure, mechanical pain sensitivity P<.027). Despite commonalities in pain characteristics between the 2 neck-arm pain groups, distinct sensory profiles were demonstrated for each group. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Comparison of Anterior Cervical Discectomy and Fusion versus Posterior Cervical Foraminotomy in the Treatment of Cervical Radiculopathy: A Systematic Review.

    PubMed

    Liu, Wei-Jun; Hu, Ling; Chou, Po-Hsin; Wang, Jun-Wen; Kan, Wu-Sheng

    2016-11-01

    Controversy remains over whether anterior cervical discectomy and fusion (ACDF) or posterior cervical foraminotomy (PCF) is superior for the treatment of cervical radiculopathy. We therefore performed a systematic review including three prospective randomized controlled trails (RCT) and seven retrospective comparative studies (RCoS) by searching PubMed and EMBASE. These studies were assessed on risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions, and the quality of evidence and level of recommendation were evaluated according to the GRADE approach. Clinical outcomes, complications, reoperation rates, radiological parameters, and cost/cost-utility were evaluated. The mean complication rate was 7% in the ACDF group and 4% in the PCF group, and the mean reoperation rate was 4% in the ACDF group and 6% in the PCF group within 2 years of the initial surgery. There was a strong level of recommendation that no difference existed in clinical outcome, complication rate and reoperation rate between the ACDF and the PCF group. There was conflicting evidence that the ACDF group had better clinical outcomes than the PCF group (one study with weak level of recommendation). PCF could preserve the range of motion (ROM) of the operated segment but did not increase the ROM of the adjacent segment (weak level of recommendation). Meanwhile, the average cost or cost-utility of the PCF group was significantly lower than that of the ACDF group (weak level of recommendation). In conclusion, the PCF was just as safe and effective as the ACDF in the treatment of cervical radiculopathy. Meanwhile, PCF might have lower medical cost than ACDF and decrease the incidence of adjacent segment disease. Based on the available evidence, PCF appears to be another good surgical approach in the treatment of cervical radiculopathy. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

  2. Low back pain, radiculopathy, and bilateral proximal hamstring ruptures: a case report.

    PubMed

    Deren, Matthew E; DeFroda, Steven F; Mukand, Nita H; Mukand, Jon A

    2015-12-01

    Low back pain (LBP) is a common complaint in the United States, with an incidence of 6.3%-15.4% and yearly recurrence in 54%-90% of patients.1 Trends show more frequent diagnostic testing, opioid use, and surgical intervention as the incidence of LBP increases.2 LBP is defined as pain at and near the lumbosacral region that can vary with physical activity and time. LBP is usually related to pathology of muscles, ligaments, spinal column joints, nerve roots, and the spinal cord. During the assessment of LBP, practitioners must also consider less common causes of pain in that region. For instance, patients with indolent or nighttime pain may have infectious or malignant processes. Referred pain from injuries to pelvic musculature or abdominal contents should be considered, especially following a traumatic event. One of these injuries, which can present as acute low back pain, is rupture of the proximal hamstring tendon. On rare occasion, concomitant LBP, radiculopathy, and hamstring injuries can occur;. This diagnostic challenge is described in the following case.

  3. Lumbosacral Radiculoplexopathy as the Initial Presentation of Lymphoma: A Report of 4 Cases.

    PubMed

    Marquardt, Robert J; Li, Yuebing

    2018-06-01

    To evaluate the clinical, laboratory, and radiological features of 4 cases of biopsy-proven lymphomatous lumbosacral radiculoplexopathy. Retrospective chart review. All patients suffered from diffuse large B-cell lymphoma. A mean diagnostic delay of 10 months was encountered. Presenting symptoms in all 4 patients included back pain, radicular leg pain, and leg weakness, similar to spondylotic radiculopathy. Electrodiagnostic study showed axon loss radiculoplexopathy and magnetic resonance imaging of the lumbar spine or pelvis demonstrated nerve or nerve root enhancement. Increased uptake by lumbosacral roots/plexus on fluorodeoxyglucose-positron emission tomography aided diagnosis in 3 cases. Cytology was positive in 1 of 10 cerebrospinal fluid samples. Combined chemotherapy and radiation treatment led to clinicoradiological improvement, with residual neurological symptoms in all patients. Lymphomatous lumbosacral radiculoplexopathy should be considered in patients with progressive lumbosacral radicular symptoms. Magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography, but not cerebrospinal fluid, are helpful in achieving early diagnosis. Treatment responses seem favorable.

  4. Virtual pathology of cervical radiculopathy based on 3D MR/CT fusion images: impingement, flattening or twisted condition of the compressed nerve root in three cases.

    PubMed

    Kamogawa, Junji; Kato, Osamu; Morizane, Tatsunori; Hato, Taizo

    2015-01-01

    There have been several imaging studies of cervical radiculopathy, but no three-dimensional (3D) images have shown the path, position, and pathological changes of the cervical nerve roots and spinal root ganglion relative to the cervical bony structure. The objective of this study was to introduce a technique that enables the virtual pathology of the nerve root to be assessed using 3D magnetic resonance (MR)/computed tomography (CT) fusion images that show the compression of the proximal portion of the cervical nerve root by both the herniated disc and the preforaminal or foraminal bony spur in patients with cervical radiculopathy. MR and CT images were obtained from three patients with cervical radiculopathy. 3D MR images were placed onto 3D CT images using a computer workstation. The entire nerve root could be visualized in 3D with or without the vertebrae. The most important characteristic evident on the images was flattening of the nerve root by a bony spur. The affected root was constricted at a pre-ganglion site. In cases of severe deformity, the flattened portion of the root seemed to change the angle of its path, resulting in twisted condition. The 3D MR/CT fusion imaging technique enhances visualization of pathoanatomy in cervical hidden area that is composed of the root and intervertebral foramen. This technique provides two distinct advantages for diagnosis of cervical radiculopathy. First, the isolation of individual vertebra clarifies the deformities of the whole root groove, including both the uncinate process and superior articular process in the cervical spine. Second, the tortuous or twisted condition of a compressed root can be visualized. The surgeon can identify the narrowest face of the root if they view the MR/CT fusion image from the posterolateral-inferior direction. Surgeons use MR/CT fusion images as a pre-operative map and for intraoperative navigation. The MR/CT fusion images can also be used as educational materials for all hospital

  5. Ultrasonography has a diagnostic value in the assessment of cervical radiculopathy: A prospective pilot study.

    PubMed

    Takeuchi, Mikinobu; Wakao, Norimitsu; Hirasawa, Atsuhiko; Murotani, Kenta; Kamiya, Mitsuhiro; Osuka, Koji; Takayasu, Masakazu

    2017-08-01

    This study investigated the diagnostic accuracy of the difference in the cross-sectional areas (CSAs) of affected cervical nerve roots (NRs) for diagnosing cervical radiculopathy (CR). In total, 102 CR patients and 219 healthy volunteers were examined with ultrasound. The CSA of the cervical NR at each level was measured on the affected side and the contralateral side in CR patients by blinded ultrasonographic technicians. The difference between the CSAs of CR patients and normal volunteers and the difference in the laterality of CSA at the same affected level (ΔCSA) were calculated for each cervical level. The CSAs of the affected NRs in CR patients were significantly larger than those of the unaffected NRs in CR patients and those of the control group at the C5, C6 and C7 levels (P<0.005). ΔCSA was also significantly larger in the CR group at all levels (P<0.001). A receiver operating characteristic analysis demonstrated that the threshold values were 9.6 mm 2 (CSA) for C5NR and 15 mm 2 for both C6NR and C7NR. This study revealed that the CSAs of affected NRs were enlarged and that the laterality of the CSA (ΔCSA) was greater in CR patients than in control patients. • Cervical radiculopathy is diagnosed through ultrasonographic measurement of the CSAs. • The CSAs of affected nerve roots were significantly enlarged. • The ΔCSA in the CR group was significantly higher than in the control group. • Diagnostic CSA and ΔCSA thresholds were identified.

  6. Study protocol for a randomised controlled multicentre study: the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy.

    PubMed

    Broekema, A E H; Kuijlen, J M A; Lesman-Leegte, G A T; Bartels, R H M A; van Asselt, A D I; Vroomen, P C A J; van Dijk, J M C; Reneman, M F; Soer, R; Groen, R J M

    2017-01-05

    Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. NTR5536, pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not

  7. A 5- to 8-year randomized study on the treatment of cervical radiculopathy: anterior cervical decompression and fusion plus physiotherapy versus physiotherapy alone.

    PubMed

    Engquist, Markus; Löfgren, Håkan; Öberg, Birgitta; Holtz, Anders; Peolsson, Anneli; Söderlund, Anne; Vavruch, Ludek; Lind, Bengt

    2017-01-01

    OBJECTIVE The aim of this study was to evaluate the 5- to 8-year outcome of anterior cervical decompression and fusion (ACDF) combined with a structured physiotherapy program as compared with that following the same physiotherapy program alone in patients with cervical radiculopathy. No previous prospective randomized studies with a follow-up of more than 2 years have compared outcomes of surgical versus nonsurgical intervention for cervical radiculopathy. METHODS Fifty-nine patients were randomized to ACDF surgery with postoperative physiotherapy (30 patients) or to structured physiotherapy alone (29 patients). The physiotherapy program included general and specific exercises as well as pain coping strategies. Outcome measures included neck disability (Neck Disability Index [NDI]), neck and arm pain intensity (visual analog scale [VAS]), health state (EQ-5D questionnaire), and a patient global assessment. Patients were followed up for 5-8 years. RESULTS After 5-8 years, the NDI was reduced by a mean score% of 21 (95% CI 14-28) in the surgical group and 11% (95% CI 4%-18%) in the nonsurgical group (p = 0.03). Neck pain was reduced by a mean score of 39 mm (95% CI 26-53 mm) compared with 19 mm (95% CI 7-30 mm; p = 0.01), and arm pain was reduced by a mean score of 33 mm (95% CI 18-49 mm) compared with 19 mm (95% CI 7-32 mm; p = 0.1), respectively. The EQ-5D had a mean respective increase of 0.29 (95% CI 0.13-0.45) compared with 0.14 (95% CI 0.01-0.27; p = 0.12). Ninety-three percent of patients in the surgical group rated their symptoms as "better" or "much better" compared with 62% in the nonsurgical group (p = 0.005). Both treatment groups experienced significant improvement over baseline for all outcome measures. CONCLUSIONS In this prospective randomized study of 5- to 8-year outcomes of surgical versus nonsurgical treatment in patients with cervical radiculopathy, ACDF combined with physiotherapy reduced neck disability and neck pain more effectively than

  8. [Efficacy of transforaminal lumbar epidural steroid injections in patients with lumbar radiculopathy].

    PubMed

    Çetin, Mehmet Fatih; Karaman, Haktan; Ölmez Kavak, Gönül; Tüfek, Adnan; Baysal Yildirim, Zeynep

    2012-01-01

    This study looks into the efficacy and safety of the transforaminal lumbar epidural steroid injection (TLESI) applied to patients with radiculopathy due to lumbar disk herniation. The patients' files which were applied TLESI, were retrospectively scanned. Patients who did not respond to one-month conservative treatment and who were detected to have bulging or protruding lumbar disk herniation as a result of imaging methods were included in the study. All applications were performed with C-arm fluoroscopy under local anesthesia by outpatient method. In all cases, a mix of 80 mg triamsinolone and 0.25% bupivacaine, was transforaminally injected to the anterior epidural area. Initial VAS pain scores were compared with the values of the 1, 3 and 6th months after the application. Patient satisfaction was determined through scoring. Furthermore, early and late term complications were collected for evaluation. A total of 222 patients were administered TLESI 460 times (average: 2.1, repeat interval: 1-6 times). The applications were carried out most frequently at the levels of L4-L5 and L5-S1. While the initial VAS score average was 8.2±0.7, after TLESI, it was 5.0±1.6, 4.8±1.5 and 5.1±1.5 in the 1, 3 and 6th months, respectively. 63.9% of the patients (n=142) defined the treatment as 'good and excellent'. No major complications were experienced and the overall minor complication rate was 11.1%. It was seen that TLESI was an efficient and safe method in the short and medium term.

  9. Clinical effect of acupuncture on cervical spondylotic radiculopathy: results of a case series.

    PubMed

    Nakajima, Miwa; Inoue, Motohiro; Itoi, Megumi; Kitakoji, Hiroshi

    2013-12-01

    To observe the effectiveness of acupuncture applied to the cervical region of patients with upper extremity radicular symptoms due to cervical spondylotic radiculopathy (CSR). 15 subjects diagnosed with CSR and with upper extremity pain and/or paraesthesiae for 13.1±18.0 months were selected. The 15 patients had 16 affected limbs and scored a total of 17 symptom scores of pain and/or paraesthesiae. All patients were treated with acupuncture once a week for 4 weeks at up to 10 sites in the cervical paraspinal region centred on the affected area. The severity of the symptoms was recorded using a visual analogue scale (VAS) and functional evaluation was conducted using a Neck Disability Index (NDI). A significant reduction over time was seen for both mean VAS (p<0.0001) and NDI (p<0.0001). Changes were still significant at 4-week follow-up. A 50% reduction in symptoms was scored for 15 of the 17 symptoms scored. Favourable results were seen in nearly 90% of cases. These results show that acupuncture treatment to the cervical region may be effective as a conservative therapy for treating CSR.

  10. Accuracy of clinical neurological examination in diagnosing lumbo-sacral radiculopathy: a systematic literature review.

    PubMed

    Tawa, Nassib; Rhoda, Anthea; Diener, Ina

    2017-02-23

    Lumbar radiculopathy remains a clinical challenge among primary care clinicians in both assessment and diagnosis. This often leads to misdiagnosis and inappropriate treatment of patients resulting in poor health outcomes, exacerbating this already debilitating condition. This review evaluated 12 primary diagnostic accuracy studies that specifically assessed the performance of various individual and grouped clinical neurological tests in detecting nerve root impingement, as established in the current literature. Eight electronic data bases were searched for relevant articles from inception until July 2016. All primary diagnostic studies which investigated the accuracy of clinical neurological test (s) in diagnosing lumbar radiculopathy among patients with low back and referred leg symptoms were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the 'Quality Assessment of Diagnostic tests Accuracy Studies' criteria. A total of 12 studies which investigated standard components of clinical neurological examination of (sensory, motor, tendon reflex and neuro-dynamics) of the lumbo-sacral spine were included. The mean inter-observer agreement on quality assessment by two independent reviewers was fair (k = 0.3 - 0.7). The diagnostic performance of sensory testing using MR imaging as a reference standard demonstrated a sensitivity (confidence interval 95%) 0.61 (0.47-0.73) and a specificity of 0.63 (0.38-0.84). Motor tests sensitivity was poor to moderate, ranging from 0.13 (0.04-0.31) to 0.61 (0.36-0.83). Generally, the diagnostic performance of reflex testing was notably good with specificity ranging from (confidence interval 95%) 0.60 (0.51-0.69) to 0.93 (0.87-0.97) and sensitivity ranging from 0.14 (0.09-0.21) to 0.67 (0.21-0.94). Femoral nerve stretch test had a high sensitivity of (confidence interval 95%) 1.00 (0.40-1.00) and specificity of 0.83 (0.52-0.98) while SLR test recorded a mean

  11. Shi-style cervical manipulations for cervical radiculopathy

    PubMed Central

    Cui, Xue-jun; Yao, Min; Ye, Xiu-lan; Wang, Ping; Zhong, Wei-hong; Zhang, Rui-chun; Li, Hui-ying; Hu, Zhi-jun; Tang, Zhan-ying; Wang, Wei-min; Qiao, Wei-ping; Sun, Yue-li; Li, Jun; Gao, Yang; Shi, Qi; Wang, Yongjun

    2017-01-01

    Abstract Background: There is a lack of high-quality evidence supporting the use of manipulation therapy for patients with cervical radiculopathy (CR). This study aimed to evaluate the effectiveness of Shi-style cervical manipulations (SCMs) versus mechanical cervical traction (MCT) for CR. Methods: This was a randomized, open-label, controlled trial carried out at 5 hospitals in patients with CR for at least 2 weeks and neck pain. The patients received 6 treatments of SCM (n = 179) or MCT (n = 180) over 2 weeks. The primary outcome was participant-rated disability (neck disability index), measured 2 weeks after randomization. The secondary outcomes were participant-rated pain (visual analog scale) and health-related quality of life (36-Item Short Form Health Survey [SF-36]). Assessments were performed before, during, and after (2, 4, 12, and 24 weeks) intervention. Results: After 2 weeks of treatment, the SCM group showed a greater improvement in participant-rated disability compared with the control group (P = .018). The SCM group reported less disability compared with the control group (P < .001) during the 26-week follow-up. The difference was particularly important at 6 months (mean −28.91 ± 16.43, P < .001). Significant improvements in SF-36 were noted in both groups after 2 weeks of treatment, but there were no differences between the 2 groups. Conclusion: SCM could be a better option than MCT for the treatment of CR-related pain and disability. PMID:28767566

  12. Comparison of 2-limb versus 3-limb electrodiagnostic studies in the evaluation of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Vo, Mary L; Hanineva, Aneliya; Chin, Russell L; Carey, Bridget T; Latov, Norman; Langsdorf, Jennifer A

    2015-04-01

    European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic (EDx) criteria for the definite diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) require the presence of demyelinating findings (DF) in at least 2 nerves. Data are lacking, however, regarding the optimal number of nerves to test. We retrospectively reviewed EDx data from 53 patients with CIDP and compared the number of DF found on 2- and 3-limb testing. A median of 3 (range 2-5) DF were found on 2-limb testing compared with 5 (range 4-7) DF when 3 limbs were evaluated. Two-limb EDx studies were sufficient to diagnose definite CIDP in 92.3% of typical, 84.2% of asymmetric, and 66.7% of distal phenotypes. Testing a third limb increased diagnostic certainty in 11 patients (20.8%) to definite CIDP. Three-limb testing may increase diagnostic sensitivity of definite CIDP, especially in patients with atypical phenotypes. Larger prospective studies are needed to better assess the benefit of performing 3-limb EDx studies. © 2014 Wiley Periodicals, Inc.

  13. Clinical and Radiographic Results of Indirect Decompression and Posterior Cervical Fusion for Single-Level Cervical Radiculopathy Using an Expandable Implant with 2-Year Follow-Up.

    PubMed

    Siemionow, Kris; Janusz, Piotr; Phillips, Frank M; Youssef, Jim A; Isaacs, Robert; Tyrakowski, Marcin; McCormack, Bruce

    2016-11-01

    Background  Indirect posterior cervical nerve root decompression and fusion performed by placing bilateral posterior cervical cages in the facet joints from a posterior approach has been proposed as an option to treat select patients with cervical radiculopathy. The purpose of this study was to report 2-year clinical and radiologic results of this treatment method. Methods  Patients who failed nonsurgical management for single-level cervical radiculopathy were recruited. Surgical treatment involved a posterior approach with decortication of the lateral mass and facet joint at the treated level followed by placement of the DTRAX Expandable Cage (Providence Medical Technology, Lafayette, California, United States) into both facet joints. Iliac crest bone autograft was mixed with demineralized bone matrix and used in all cases. The Neck Disability Index (NDI), visual analog scale (VAS) for neck and arm pain, and SF-12 v.2 questionnaire were evaluated preoperatively and 2 years postoperatively. Segmental (treated level) and overall C2-C7 cervical lordosis, disk height, adjacent segment degeneration, and fusion were assessed on computed tomography scans and radiographs acquired preoperatively and 2 years postoperatively. Results  Overall, 53 of 60 enrolled patients were available at 2-year follow-up. There were 35 females and 18 males with a mean age of 53 years (range: 40-75 years). The operated level was C3-C4 ( N  = 3), C4-C5 ( N  = 6), C5-C6 ( N  = 36), and C6-C7 ( N  = 8). The mean preoperative and 2-year scores were NDI: 32.3 versus 9.1 ( p  < 0.0001); VAS Neck Pain: 7.4 versus 2.6 ( p  < 0.0001); VAS Arm Pain: 7.4 versus 2.6 ( p  < 0.0001); SF-12 Physical Component Summary: 34.6 versus 43.6 ( p  < 0.0001), and SF-12 Mental Component Summary: 40.8 versus 51.4 ( p  < 0.0001). No significant changes in overall or segmental lordosis were noted after surgery. Radiographic fusion rate was 98.1%. There was no device failure

  14. Obtaining T1-T2 distribution functions from 1-dimensional T1 and T2 measurements: The pseudo 2-D relaxation model

    NASA Astrophysics Data System (ADS)

    Williamson, Nathan H.; Röding, Magnus; Galvosas, Petrik; Miklavcic, Stanley J.; Nydén, Magnus

    2016-08-01

    We present the pseudo 2-D relaxation model (P2DRM), a method to estimate multidimensional probability distributions of material parameters from independent 1-D measurements. We illustrate its use on 1-D T1 and T2 relaxation measurements of saturated rock and evaluate it on both simulated and experimental T1-T2 correlation measurement data sets. Results were in excellent agreement with the actual, known 2-D distribution in the case of the simulated data set. In both the simulated and experimental case, the functional relationships between T1 and T2 were in good agreement with the T1-T2 correlation maps from the 2-D inverse Laplace transform of the full 2-D data sets. When a 1-D CPMG experiment is combined with a rapid T1 measurement, the P2DRM provides a double-shot method for obtaining a T1-T2 relationship, with significantly decreased experimental time in comparison to the full T1-T2 correlation measurement.

  15. [Clinical observation on improvement of motion range of cervical spine of patients with cervical spondylotic radiculopathy treated with rotation-traction manipulation and neck pain particles and cervical neck pain rehabilitation exercises].

    PubMed

    Zhen, Peng-Chao; Zhu, Li-Guo; Gao, Jing-Hua; Yu, Jie; Feng, Min-Shan; Wei, Xu; Wang, Shang-Quan

    2010-10-01

    To observe the effects of two different therapies on patients whose cervical function were restricted due to cervical spondylotic radiculopathy. Form April 2008 to October 2009, 71 cases with cervical spondylotic radiculopathy were divided into group A (36 cases) and group B (35 cases). Among them, 22 cases were male and 49 cases were female, ranging in age form 45 to 65 years with an average of 52.27 years, course of disease was from 3 days to 5 years. The patients in group A were treated with rotation-traction manipulation, neck pain particles and cervical rehabilitation exercises; and the patients in group B were treated with cervical traction, Diclofenac sodium sustained release tablets and wearing neck collar. Theapeutic time was two weeks. The cervical anteflexion, extension, left and right lateral bending, left and right rotative activity were measured by helmet-style activities instrument before and after treatment (at the 1, 3, 5, 7, 9, 11, 13 days and 1 month after treatment respectively). There were no difference between two groups in cervical activity in all directions before treatment (P > 0.05). Compared with the beginning, cervical anteflexion and extension showed significant difference at the 5th day after treatment in group A (P < 0.01). In group B, cervical anteflexion showed significant difference at the 13th day after treatment (P < 0.05), but at the 1 month after treatment, the significant difference disappeared (P > 0.05); cervical extension showed significant difference at the 7th day after treatment compared with the beginning (P < 0.05). Compared with the beginning,left lateral bending showed significant difference at the 1st day after treatment in group A (P < 0.05) and at the 5th day after treatment in group B (P < 0.01). Both in group A or B, right lateral bending, left and right rotative activity showed significant difference at the same time after treatment, either the 3rd day (P < 0.05) or the 5th day (P < 0.05). Compared between

  16. High-resolution nuclear magnetic resonance spectroscopic study of metabolites in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

    PubMed Central

    Morio, Yasuo; Meshitsuka, Shunsuke; Yamane, Koji; Nanjo, Yoshiro; Teshima, Ryota

    2010-01-01

    There have been few reports describing substances related to oxidative and intermediary metabolism in the cerebrospinal fluid (CSF) in patients with spinal degenerative disorders. This study investigated whether the concentrations of metabolites in the CSF differed between patients with spinal degenerative disorders and controls, and whether the concentrations of these metabolites correlated with the severity of symptoms. CSF samples were obtained from 30 patients with cervical myelopathy (Group M), 30 patients with lumbar radiculopathy (Group R), and 10 volunteers (control). Metabolites in these CSF samples were measured by nuclear magnetic resonance spectroscopy. There were no differences in the concentrations of lactate, alanine, acetate, glutamate, pyruvate, or citrate between Groups M and R, between Group M and the control, or between Group R and the control. In Group M, neither symptom duration nor the Japanese Orthopaedic Association score correlated with the concentration of any metabolite. In Group R, the symptom duration positively correlated with the concentration of lactate, glutamate, and citrate in CSF. The duration of nerve root block showed a negative correlation with the concentrations of acetate in CSF of the patients in Group R. In patients with lumbar radiculopathy, there is a possibility of increased aerobic metabolic activity or decreased gluconeogenic activity in patients with shorter symptom duration, and increased aerobic metabolic activity in patients with severe inflammation around a nerve root. PMID:20490871

  17. Energy Impairments in Older Adults with Low Back Pain and Radiculopathy: A Matched Case-Control Study.

    PubMed

    Coyle, Peter C; Pugliese, Jenifer M; Sions, J Megan; Eskander, Mark S; Schrack, Jennifer A; Hicks, Gregory E

    2018-04-23

    To investigate the impact that the presence of chronic low back pain with radiculopathy (CLBPR) may have on 1) energy efficiency and 2) energy capacity among community-dwelling older adults. Matched case-control study. Clinical research laboratory. 38 community-dwelling older adults (60-85 years) with (n=19) and without (n=19) CLBPR were included in this analysis. Participants were matched between-groups on age (± 5 years), sex, and diabetic status. Not applicable. Energy cost of walking at self-selected speed (i.e. energy efficiency) and Peak Walking VO2 (i.e. energy capacity). Older adults with CLBPR had a higher energy cost of walking at self-selected speed (p=.009) and lower Peak Walking VO2 (p=.050), compared to those without pain. Older adults with CLBPR may benefit from specific rehabilitative interventions that target these potentially modifiable energetic outcomes, thereby reducing the risk of mobility decline. Future studies should identify which mechanisms specifically contribute to diminished energy efficiency and capacity among older adults with CLBPR. Copyright © 2018. Published by Elsevier Inc.

  18. An awake, minimally-invasive, fully-endoscopic surgical technique for treating lumbar radiculopathy secondary to heterotopic foraminal bone formation after a minimally invasive transforaminal lumbar interbody fusion with BMP: technical note

    PubMed Central

    2018-01-01

    One complication associated with recombinant human bone morphogenetic protein (rhBMP-2) use in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is heterotopic bone growth at the neural foramen which results in the compression of neural structures. Here we present an awake, minimally invasive surgical approach for treating the radiculopathy that results from this excessive bone growth in the foramen. A 42-year-old male underwent a lumbar 4–sacral 1 MIS-TLIF by another surgeon. He did well in the initial postoperative period, but he began to note right leg pain and numbness in an L5 dermatomal pattern. The pain continued for 2 years despite interventional pain management, and he began to note left foot dorsiflexion weakness. An electromyography (EMG) showed a left L5 radiculopathy and a CT Lumbar spine demonstrated excessive bone growth in the right L4–5 neural foramen. The patient underwent an awake, endoscopic foraminotomy procedure utilizing a blunt tipped manual shaver drill system. The patient’s radicular symptoms improved immediately, and he remained asymptomatic at the 1 year follow up. Heterotopic foraminal bone growth is one potential complication of rhBMP-2 use in the MIS-TLIF procedure. The endoscopic procedure described here is a minimally invasive surgical option that can be performed in an awake patient and is suggested a unique salvage or rescue procedure to be considered for the treatment of this potential rhBMP-2 complication. PMID:29732437

  19. [Innovation in differential diagnosis and monitoring of rational therapy in patients with lumbosacral radiculopathies].

    PubMed

    Zhivolupov, S A; Vorob'eva, M N; Samartsev, I N; Rashidov, N A

    2014-01-01

    Unfortunately, nowadays there are no reliable ways to predict the outcomes of the conservative treatment in patients with dorsopathies. Otherwise, we could identify patients that demand intensive treatment including therapeutic blockades. We approbated and modified a method for assessment of radicular latency duration in patients with lumbosacral radiculopathies to evaluate its diagnostic value and the possibility of using in monitoring of effectiveness of conservative treatment. We studied the effectiveness of conservative treatment in 60 patients with lumbosacral dorsopathies, including 35 patients manifested with exacerbation of sciatica and 25 patients diagnosed with failed back surgery syndrome (FBSS). There was a definite resistance to treatment in patients with FBSS. The complex management of patients, including neuromidin and epidural glucocorticoid blockades, demonstrated the greater effectiveness. The evaluation of radicular latency duration with neuromidin test turned out to have important predictive value which could be used to stratify treatment of patients with dorsopathies.

  20. Preoperative therapeutic neuroscience education for lumbar radiculopathy: a single-case fMRI report.

    PubMed

    Louw, Adriaan; Puentedura, Emilio J; Diener, Ina; Peoples, Randal R

    2015-01-01

    Therapeutic neuroscience education (TNE) has been shown to be effective in the treatment of mainly chronic musculoskeletal pain conditions. This case study aims to describe the changes in brain activation on functional magnetic resonance imaging (fMRI) scanning, before and after the application of a newly-designed preoperative TNE program. A 30-year-old female with a current acute episode of low back pain (LBP) and radiculopathy participated in a single preoperative TNE session. She completed pre- and post-education measures including visual analog scale (VAS) for LBP and leg pain; Oswestry Disability Index (ODI); Fear Avoidance Beliefs Questionnaire (FABQ); Pain Catastrophizing Scale (PCS) and a series of Likert-scale questions regarding beliefs and attitudes to lumbar surgery (LS). After a 30-minute TNE session, ODI decreased by 10%, PCS decreased by 10 points and her beliefs and attitudes shifted positively regarding LS. Immediately following TNE straight leg raise increased by 7° and forward flexion by 8 cm. fMRI testing following TNE revealed 3 marked differences compared to pre-education scanning: (1) deactivation of the periaqueductal gray area; (2) deactivation of the cerebellum; and (3) increased activation of the motor cortex. The immediate positive fMRI, psychometric and physical movement changes may indicate a cortical mechanism of TNE for patients scheduled for LS.

  1. Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

    PubMed

    Turan, Turgay; Efiloğlu, Özgür; Günaydin, Bilal; Özkanli, Şeyma; Nikerel, Emrah; Atiş, Gökhan; Çaşkurlu, Turhan; Yildirim, Asif

    2018-01-01

    To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy. Copyright® by the International Brazilian Journal of Urology.

  2. Increased pain sensitivity is not associated with electrodiagnostic findings in women with carpal tunnel syndrome.

    PubMed

    de la Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César; Laguarta-Val, Sofia; Alonso-Blanco, Cristina; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Pareja, Juan A

    2011-01-01

    To determine the differences in widespread pressure pain and thermal hypersensitivity in women with minimal, moderate, and severe carpal tunnel syndrome (CTS) and healthy controls. A total of 72 women with CTS (19 with minimal, 18 with moderate, and 35 with severe) and 19 healthy age-matched women participated. Pressure pain thresholds were bilaterally assessed over the median, ulnar, and radial nerves, the C5 to C6 zygapophyseal joint, the carpal tunnel, and the tibialis anterior muscle. In addition, warm and cold detection thresholds and heat and cold pain thresholds were bilaterally assessed over the carpal tunnel and the thenar eminence. All outcome parameters were assessed by an assessor blinded to the participant's condition. No significant differences in pain parameters among patients with minimal, moderate, and severe CTS were found. The results showed that PPT were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, C5 to C6 zygapophyseal joint, and the tibialis anterior muscle in patients with minimal, moderate, or severe CTS as compared with healthy controls (all, P<0.001). In addition, patients with CTS also showed lower heat pain threshold and reduced cold pain threshold compared with controls (P<0.001). No significant sensory differences between minimal, moderate, or severe CTS were found. The similar widespread pressure and thermal hypersensitivity in patients with minimal, moderate, or severe CTS and pain intensity suggests that increased pain sensitivity is not related to electrodiagnostic findings.

  3. Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

    NASA Astrophysics Data System (ADS)

    Hu, Fengqin; Zhao, Yong Sheng

    2012-09-01

    Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

  4. Cervical radiculopathy: a systematic review on treatment by spinal manipulation and measurement with the Neck Disability Index

    PubMed Central

    Rodine, Robert J.; Vernon, Howard

    2012-01-01

    Cervical radiculopathy (CR), while less common than conditions with neck pain alone, can be a significant cause of neck pain and disability; thus the determination of adequate treatment options for patients is essential. Currently, inadequate scientific literature restricts specific conservative management recommendations for CR. Despite a paucity of evidence for high-velocity low-amplitude (HVLA) spinal manipulation in the treatment for CR, this strategy has been frequently labeled as contraindicated. Scientific support for appropriate outcome measures for CR is equally deficient. While more scientific data is needed to draw firm conclusions, the present review suggests that spinal manipulation may be cautiously considered as a therapeutic option for patients suffering from CR. With respect to outcome measures, the Neck Disability Index appears well-suited for spinal manipulative treatment of CR. PMID:22457538

  5. Prolonged Preoperative Opioid Therapy Associated With Poor Return to Work Rates After Single-Level Cervical Fusion for Radiculopathy for Patients Receiving Workers' Compensation Benefits.

    PubMed

    Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

    2017-01-15

    Retrospective comparative cohort study. Examine the effect of prolonged preoperative opioid use on return to work (RTW) status after single-level cervical fusion for radiculopathy. The use of opioids has a dramatic effect in a workers' compensation population. The costs of claims that involved opioids in the management plan are catastrophic particularly for those undergoing spinal surgical procedure. Data of patients who underwent single-level cervical fusion for radiculopathy and had received opioid prescriptions before surgery were retrospectively collected from Ohio Bureau of Workers' Compensation between 1993 and 2011 after work-related injury. Then, based on opioid use duration, short-term use (STO) group (<3 mo), intermediate-term use (ITO) group (3-6 mo), and long-term use (LTO) group (>6 mo) were constructed. A multivariate logistic regression analysis was used to determine whether successful RTW status was achieved. Chi-square and analysis of variance tests were used to compare other secondary outcomes after surgery. Prolonged preoperative opioid use was a negative predictor of successful RTW status (odds ratio = 0.73; 95% confidence interval: 0.55-0.98; P value: 0.04). Prolonged preoperative opioid use was associated with increasingly lower rates of achieving stable RTW status (P < 0.05) and RTW within 1 year after surgery (P < 0.05). The odds of achieving successful RTW status were 0.49 (0.25-0.94) for ITO, and 0.40 (0.24-0.68) for LTO compared with STO group. The odds of RTW less than 1 year after surgery were 0.43 (0.21-0.88) for ITO and 0.36 (0.21-0.62) for LTO compared with STO group. Prolonged preoperative opioid use was also associated with increasingly higher net medical costs (P < 0.01), and disability benefits awarded after surgery (P < 0.01). Prolonged preoperative opioid use was associated with poor functional outcomes after cervical fusion. STO and earlier inclusion of the surgical approach in the management plan may offer

  6. A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance-the T1 Mapping and ECV Standardization in cardiovascular magnetic resonance (T1MES) program.

    PubMed

    Captur, Gabriella; Gatehouse, Peter; Keenan, Kathryn E; Heslinga, Friso G; Bruehl, Ruediger; Prothmann, Marcel; Graves, Martin J; Eames, Richard J; Torlasco, Camilla; Benedetti, Giulia; Donovan, Jacqueline; Ittermann, Bernd; Boubertakh, Redha; Bathgate, Andrew; Royet, Celine; Pang, Wenjie; Nezafat, Reza; Salerno, Michael; Kellman, Peter; Moon, James C

    2016-09-22

    T 1 mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T 1 mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T 1 and T 2 in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformité Européene (CE) marking. The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently-doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T 1 maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the B 1 field. T 1 and T 2 values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15-30 °C the short-T 1 tubes were more stable with temperature than the long-T 1 tubes. A batch of 69 phantoms was mass-produced with random sampling of

  7. Diagnostic Quality of 3D T2-SPACE Compared with T2-FSE in the Evaluation of Cervical Spine MRI Anatomy.

    PubMed

    Chokshi, F H; Sadigh, G; Carpenter, W; Allen, J W

    2017-04-01

    Spinal anatomy has been variably investigated using 3D MRI. We aimed to compare the diagnostic quality of T2 sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with T2-FSE sequences for visualization of cervical spine anatomy. We predicted that T2-SPACE will be equivalent or superior to T2-FSE for visibility of anatomic structures. Adult patients undergoing cervical spine MR imaging with both T2-SPACE and T2-FSE sequences for radiculopathy or myelopathy between September 2014 and February 2015 were included. Two blinded subspecialty-trained radiologists independently assessed the visibility of 12 anatomic structures by using a 5-point scale and assessed CSF pulsation artifact by using a 4-point scale. Sagittal images and 6 axial levels from C2-T1 on T2-FSE were reviewed; 2 weeks later and after randomization, T2-SPACE was evaluated. Diagnostic quality for each structure and CSF pulsation artifact visibility on both sequences were compared by using a paired t test. Interobserver agreement was calculated (κ). Forty-five patients were included (mean age, 57 years; 40% male). The average visibility scores for intervertebral disc signal, neural foramina, ligamentum flavum, ventral rootlets, and dorsal rootlets were higher for T2-SPACE compared with T2-FSE for both reviewers ( P < .001). Average scores for remaining structures were either not statistically different or the superiority of one sequence was discordant between reviewers. T2-SPACE showed less degree of CSF flow artifact ( P < .001). Interobserver variability ranged between -0.02-0.20 for T2-SPACE and -0.02-0.30 for T2-FSE (slight to fair agreement). T2-SPACE may be equivalent or superior to T2-FSE for the evaluation of cervical spine anatomic structures, and T2-SPACE shows a lower degree of CSF pulsation artifact. © 2017 by American Journal of Neuroradiology.

  8. 26 CFR 1.382-1T - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false [Reserved] 1.382-1T Section 1.382-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-1T [Reserved] ...

  9. T9 versus T10 as the upper instrumented vertebra for correction of adult deformity-rationale and recommendations.

    PubMed

    Hey, Hwee Weng Dennis; Tan, Kimberly-Anne; Neo, Christabel Shao-En; Lau, Eugene Tze-Chun; Choong, Denise Ai-Wen; Lau, Leok-Lim; Liu, Gabriel Ka-Po; Wong, Hee-Kit

    2017-05-01

    Adult spinal deformity correction sometimes involves long posterior pedicle screw constructs extending from the lumbosacral spine to the thoracic vertebra. As fusion obliterates motion and places supraphysiological stress on adjacent spinal segments, it is crucial to ascertain the ideal upper instrumented vertebra (UIV) to minimize risk of proximal junctional failure (PJF). The T10 vertebra is often chosen to allow bridging of the thoracolumbar junction into the immobile thoracic vertebrae on the basis that it is the lowest immobile thoracic vertebra strut by the rib cage. This study aimed to characterize the range of motion (ROM) of each vertebral segment from T7 to S1 to determine if T10 is truly the lowest immobile thoracic vertebra. This is a prospective, comparative study. Seventy-nine adults (mean age of 45.4 years) presenting with low back pain or lower limb radiculopathy or both, without previous spinal intervention, metastases, fractures, infection, or congenital deformities of the spine, were included in the study. A ROM >5° across two vertebral segments as determined by the Cobb method from radiographs. Lumbar flexion-extension and neutral erect radiographs were obtained in randomized order using a slot scanner. Segmental ROM was measured from T7-T8 to L5-S1 and analyzed for significant differences using t tests. Age, gender, radiographical indices such as standard spinopelvic parameters, sagittal vertical axis (SVA), C7-T12 SVA, T1 slope, thoracic kyphosis (TK), and lumbar lordosis (LL) were studied via multivariate analysis to identify predictive factors for >5° change in ROM at the various segmental levels. There were no sources of funding and no conflicts of interest associated with this study. In the thoracolumbar spine, significant decreases in ROM when compared with the adjacent caudad segment occurs up to T9-T10, with mean total ROM of 1.98±1.47° (p<.001) seen in T9-T10, 2.19±1.67° (p<.001) in T10-T11, and 3.92±3.21°(p<.001) in T11-T12

  10. Dectin-1 diversifies Aspergillus fumigatus–specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation

    PubMed Central

    Hohl, Tobias M.; Collins, Nichole; Leiner, Ingrid; Gallegos, Alena; Saijo, Shinobu; Coward, Jesse W.; Iwakura, Yoichiro

    2011-01-01

    Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus–infected wild-type mice reduces IFN-γ and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-γ or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus–infected mice. Transient deletion of monocyte-derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus–specific CD4 T cells. Our findings indicate that Dectin-1–mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-γ in innate cells, thereby decreasing T-bet expression in A. fumigatus–specific CD4 T cells and enabling Th17 differentiation. PMID:21242294

  11. Ultra-low field T1 vs. T1rho at 3T and 7T: study of rotationally immobilized protein gels and animal brain tissues

    NASA Astrophysics Data System (ADS)

    Dong, Hui; Inglis, Ben; Barr, Ian; Clarke, John

    2015-03-01

    Clinical magnetic resonance imaging (MRI) machines operating in static fields of typically 1.5 T or 3 T can capture information on slow molecular dynamics utilizing the so-called T1rho technique. This technique, in which a radiofrequency (RF) spin-lock field is applied with microtesla amplitude, has been used, for example, to determine the onset time of stroke in studies on rats. The long RF pulse, however, may exceed the specific absorption rate (SAR) limit, putting subjects at risk. Ultra-low-field (ULF) MRI, based on Superconducting Quantum Interference Devices (SQUIDs), directly detects proton signals at a static magnetic field of typically 50-250 μT. Using our ULF MRI system with adjustable static field of typically 55 to 240 μT, we systematically measured the T1 and T2 dispersion profiles of rotationally immobilized protein gels (bovine serum albumin), ex vivo pig brains, and ex vivo rat brains with induced stroke. Comparing the ULF results with T1rho dispersion obtained at 3 T and 7 T, we find that the degree of protein immobilization determines the frequency-dependence of both T1 and T1rho. Furthermore, T1rho and ULF T1 show similar results for stroke, suggesting that ULF MRI may be used to image traumatic brain injury with negligible SAR. This research was supported by the Henry H. Wheeler, Jr. Brain Imaging Center and the Donaldson Trust.

  12. Local T1-T2 distribution measurements in porous media

    NASA Astrophysics Data System (ADS)

    Vashaee, S.; Li, M.; Newling, B.; MacMillan, B.; Marica, F.; Kwak, H. T.; Gao, J.; Al-harbi, A. M.; Balcom, B. J.

    2018-02-01

    A novel slice-selective T1-T2 measurement is proposed to measure spatially resolved T1-T2 distributions. An adiabatic inversion pulse is employed for slice-selection. The slice-selective pulse is able to select a quasi-rectangular slice, on the order of 1 mm, at an arbitrary position within the sample. The method does not employ conventional selective excitation in which selective excitation is often accomplished by rotation of the longitudinal magnetization in the slice of interest into the transverse plane, but rather a subtraction based on CPMG data acquired with and without adiabatic inversion slice selection. T1 weighting is introduced during recovery from the inversion associated with slice selection. The local T1-T2 distributions measured are of similar quality to bulk T1-T2 measurements. The new method can be employed to characterize oil-water mixtures and other fluids in porous media. The method is beneficial when a coarse spatial distribution of the components is of interest.

  13. Spinal Subdural Haematoma.

    PubMed

    Manish K, Kothari; Chandrakant, Shah Kunal; Abhay M, Nene

    2015-01-01

    Spinal Subdural hematoma is a rare cause of radiculopathy and spinal cord compression syndromes. It's early diagnosis is essential. Chronological appearance of these bleeds vary on MRI. A 56 year old man presented with progressive left lower limb radiculopathy and paraesthesias with claudication of three days duration. MRI revealed a subdural space occupying lesion compressing the cauda equina at L5-S1 level producing a 'Y' shaped dural sac (Y sign), which was hyperintense on T1W imaging and hypointense to cord on T2W image. The STIR sequence showed hyperintensity to cord. There was no history of bleeding diathesis. The patient underwent decompressive durotomy and biopsy which confirmed the diagnosis. Spinal subdural hematoma may present with rapidly progressive neurological symptoms. MRI is the investigation of choice. The knowledge of MRI appearance with respect to the chronological stage of the bleed is essential to avoid diagnostic and hence surgical dilemma.

  14. Diagnostic Accuracy of the Neck Tornado Test as a New Screening Test in Cervical Radiculopathy.

    PubMed

    Park, Juyeon; Park, Woo Young; Hong, Seungbae; An, Jiwon; Koh, Jae Chul; Lee, Youn-Woo; Kim, Yong Chan; Choi, Jong Bum

    2017-01-01

    The Spurling test, although a highly specific provocative test of the cervical spine in cervical radiculopathy (CR), has low to moderate sensitivity. Thus, we introduced the neck tornado test (NTT) to examine the neck and the cervical spine in CR. The aim of this study was to introduce a new provocative test, the NTT, and compare the diagnostic accuracy with a widely accepted provocative test, the Spurling test. Retrospective study. Medical records of 135 subjects with neck pain (CR, n = 67; without CR, n = 68) who had undergone cervical spine magnetic resonance imaging and been referred to the pain clinic between September 2014 and August 2015 were reviewed. Both the Spurling test and NTT were performed in all patients by expert examiners. Sensitivity, specificity, and accuracy were compared for both the Spurling test and the NTT. The sensitivity of the Spurling test and the NTT was 55.22% and 85.07% ( P < 0.0001); specificity, 98.53% and 86.76% ( P = 0.0026); accuracy, 77.04% and 85.93% ( P = 0.0423), respectively. The NTT is more sensitive with superior diagnostic accuracy for CR diagnosed by magnetic resonance imaging than the Spurling test.

  15. The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd-DOTA-peptides.

    PubMed

    Cao, Limin; Li, Binbin; Yi, Peiwei; Zhang, Hailu; Dai, Jianwu; Tan, Bo; Deng, Zongwu

    2014-04-01

    Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T1 contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T1 relaxation rate which is in favor of T1-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T1 contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T1 contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T1 contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T1 contrast enhancement effect is discussed. Our results suggest that T1 contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T1-relaxation and T2-relaxation processes/rates. Both T1 and particularly T2 relaxation rate have to be taken into account to interpret T1 contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. A Movement system impairment approach to evaluation and treatment of a person with lumbar radiculopathy: A case report.

    PubMed

    Miller, Eileen; Sahrmann, Shirley A; Avers, Dale

    2017-03-01

    There are several systems of classification and treatment of patients with low back pain (LBP) based on assessment of the effect of lumbar postures and movements on symptoms. The efficacy of one of these systems, The Movement System Impairment (MSI) method, has not yet been demonstrated in the literature. The purpose of this case report is to describe the approach of the MSI method for an individual with lumbar radiculopathy. A 79-year-old woman with a history of chronic LBP was referred to PT with a physician's diagnosis of sciatica. The patient was classified utilizing a standardized MSI evaluation. She was instructed to modify her daily postures and movements, as well as perform specific exercises to address these impairments. Her Oswestry LBP disability score improved by over 30% and pain level per the NPRS improved by 3 out of 10 points. Despite the challenges of advanced joint degeneration and neurological involvement, this approach of identifying and addressing specific movement impairments appeared helpful for this older individual.

  17. Electronic properties of in-plane phase engineered 1T'/2H/1T' MoS2

    NASA Astrophysics Data System (ADS)

    Thakur, Rajesh; Sharma, Munish; Ahluwalia, P. K.; Sharma, Raman

    2018-04-01

    We present the first principles studies of semi-infinite phase engineered MoS2 along zigzag direction. The semiconducting (2H) and semi-metallic (1T') phases are known to be stable in thin-film MoS2. We described the electronic and structural properties of the infinite array of 1T'/2H/1T'. It has been found that 1T'phase induced semi-metallic character in 2H phase beyond interface but, only Mo atoms in 2H phase domain contribute to the semi-metallic nature and S atoms towards semiconducting state. 1T'/2H/1T' system can act as a typical n-p-n structure. Also high holes concentration at the interface of Mo layer provides further positive potential barriers.

  18. Simultaneous acquisition for T2 -T2 Exchange and T1 -T2 correlation NMR experiments

    NASA Astrophysics Data System (ADS)

    Montrazi, Elton T.; Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Barsi-Andreeta, Mariane; Bonagamba, Tito J.

    2018-04-01

    The NMR measurements of longitudinal and transverse relaxation times and its multidimensional correlations provide useful information about molecular dynamics. However, these experiments are very time-consuming, and many researchers proposed faster experiments to reduce this issue. This paper presents a new way to simultaneously perform T2 -T2 Exchange and T1 -T2 correlation experiments by taking the advantage of the storage time and the two steps phase cycling used for running the relaxation exchange experiment. The data corresponding to each step is either summed or subtracted to produce the T2 -T2 and T1 -T2 data, enhancing the information obtained while maintaining the experiment duration. Comparing the results from this technique with traditional NMR experiments it was possible to validate the method.

  19. Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

    PubMed

    Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

    2018-03-01

    Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This

  20. Effects of B1 inhomogeneity correction for three-dimensional variable flip angle T1 measurements in hip dGEMRIC at 3 T and 1.5 T.

    PubMed

    Siversson, Carl; Chan, Jenny; Tiderius, Carl-Johan; Mamisch, Tallal Charles; Jellus, Vladimir; Svensson, Jonas; Kim, Young-Jo

    2012-06-01

    Delayed gadolinium-enhanced MRI of cartilage is a technique for studying the development of osteoarthritis using quantitative T(1) measurements. Three-dimensional variable flip angle is a promising method for performing such measurements rapidly, by using two successive spoiled gradient echo sequences with different excitation pulse flip angles. However, the three-dimensional variable flip angle method is very sensitive to inhomogeneities in the transmitted B(1) field in vivo. In this study, a method for correcting for such inhomogeneities, using an additional B(1) mapping spin-echo sequence, was evaluated. Phantom studies concluded that three-dimensional variable flip angle with B(1) correction calculates accurate T(1) values also in areas with high B(1) deviation. Retrospective analysis of in vivo hip delayed gadolinium-enhanced MRI of cartilage data from 40 subjects showed the difference between three-dimensional variable flip angle with and without B(1) correction to be generally two to three times higher at 3 T than at 1.5 T. In conclusion, the B(1) variations should always be taken into account, both at 1.5 T and at 3 T. Copyright © 2011 Wiley-Liss, Inc.

  1. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    PubMed

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  2. Use of a multimodal conservative management protocol for the treatment of a patient with cervical radiculopathy

    PubMed Central

    Radpasand, Mohsen

    2011-01-01

    Objective The purpose of this study is to describe and discuss the treatment of a cervical disk herniation using a sequential multimodal conservative management approach. Clinical Features A 40-year-old man had complaints of headache and severe sharp neck pain radiating to his left shoulder down to his arm, forearm, and hand. Results of electromyography/nerve conduction studies were abnormal. Magnetic resonance imaging revealed a large disk protrusion at C5-C6 with indentation of the thecal sac and a spur at the posterior margin. Moderate left neural foraminal narrowing was present at C5-C6 with narrowed intervertebral disk space at C5-C6 and C6-C7. Intervention and Outcome High-velocity, low-amplitude chiropractic manipulation; electrotherapy; ice; and exercise were used for treatment. The Neck Disability Index was used as a primary and electromyography/nerve conduction studies as a secondary outcome measurement. Based on the Neck Disability Index, there was an overall 89.65% symptoms improvement from the baseline. Conclusions This case study demonstrated possible beneficial effects of the multimodal treatment approach in a patient with cervical radiculopathy. PMID:22027207

  3. Cervical Radiculopathy: Effectiveness of Adding Traction to Physical Therapy-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Romeo, Antonio; Vanti, Carla; Boldrini, Valerio; Ruggeri, Martina; Guccione, Andrew A; Pillastrini, Paolo; Bertozzii, Lucia

    2018-04-01

    Cervical radiculopathy (CR) is a common cervical spine disorder. Cervical traction (CT) is a frequently recommended treatment for patients with CR. The purpose of this study was to conduct a review and meta-analysis of randomized controlled trials (RCTs) on the effect of CT combined with other physical therapy procedures versus physical therapy procedures alone on pain and disability. Data were obtained from COCHRANE Controlled Trials Register, PubMed, CINAHL, Scopus, ISI Web of Science, and PEDro, from their inception to July 2016. All RCTs on symptomatic adults with CR, without any restriction regarding publication time or language, were considered. Two reviewers selected the studies, conducted the quality assessment, and extracted the results. Meta-analysis employed a random-effects model. The evidence was assessed using GRADE criteria. Five studies met the inclusion criteria. Mechanical traction had a significant effect on pain at short- and intermediate-terms (g = -0.85 [95% CI = -1.63 to -0.06] and g = -1.17 [95% CI = -2.25 to -0.10], respectively) and significant effects on disability at intermediate term (g = -1.05; 95% CI = -1.81 to -0.28). Manual traction had significant effects on pain at short- term (g = -0.85; 95% CI = -1.39 to -0.30). The most important limitation of the present work is the lack of homogeneity in CR diagnostic criteria among the included studies. In light of these results, the current literature lends some support to the use of the mechanical and manual traction for CR in addition to other physical therapy procedures for pain reduction, but yielding lesser effects on function/disability.

  4. Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-γ Pathway.

    PubMed

    Sun, Wen; Zheng, Kang; Liu, Bin; Fan, Danping; Luo, Hui; Qu, Xiaoyuan; Li, Li; He, Xiaojuan; Yi, Jianfeng; Lu, Cheng

    2017-01-01

    Cervical spondylotic radiculopathy (CSR) is the most general form of spinal degenerative disease and is characterized by pain and numbness of the neck and arm. Gentongping (GTP) granule, as a classical Chinese patent medicine, has been widely used in curing CSR, whereas the underlying mechanism remains unclear. Therefore, the aim of this study is to explore the pharmacological mechanisms of GTP on CSR. The rat model of CSR was induced by spinal cord injury (SCI). Our results showed that GTP could significantly alleviate spontaneous pain as well as ameliorate gait. The HE staining and Western blot results showed that GTP could increase the quantity of motoneuron and enhance the activation of peroxisome proliferator-activated receptor gamma (PPAR- γ ) in the spinal cord tissues. Meanwhile, immunofluorescence staining analysis indicated that GTP could reduce the expression of TNF- α in the spinal cord tissues. Furthermore, the protein level of Bax was decreased whereas the protein levels of Bcl-2 and NF200 were increased after the GTP treatment. These findings demonstrated that GTP might modulate the PPAR- γ pathway by inhibiting the inflammatory response and apoptosis as well as by protecting the cytoskeletal integrity of the spinal cord, ultimately play a neuroprotective role in CSR.

  5. Diagnostic Accuracy of the Neck Tornado Test as a New Screening Test in Cervical Radiculopathy

    PubMed Central

    Park, Juyeon; Park, Woo Young; Hong, Seungbae; An, Jiwon; Koh, Jae Chul; Lee, Youn-Woo; Kim, Yong Chan; Choi, Jong Bum

    2017-01-01

    Background: The Spurling test, although a highly specific provocative test of the cervical spine in cervical radiculopathy (CR), has low to moderate sensitivity. Thus, we introduced the neck tornado test (NTT) to examine the neck and the cervical spine in CR. Objectives: The aim of this study was to introduce a new provocative test, the NTT, and compare the diagnostic accuracy with a widely accepted provocative test, the Spurling test. Design: Retrospective study. Methods: Medical records of 135 subjects with neck pain (CR, n = 67; without CR, n = 68) who had undergone cervical spine magnetic resonance imaging and been referred to the pain clinic between September 2014 and August 2015 were reviewed. Both the Spurling test and NTT were performed in all patients by expert examiners. Sensitivity, specificity, and accuracy were compared for both the Spurling test and the NTT. Results: The sensitivity of the Spurling test and the NTT was 55.22% and 85.07% (P < 0.0001); specificity, 98.53% and 86.76% (P = 0.0026); accuracy, 77.04% and 85.93% (P = 0.0423), respectively. Conclusions: The NTT is more sensitive with superior diagnostic accuracy for CR diagnosed by magnetic resonance imaging than the Spurling test. PMID:28824298

  6. Use of the Rat Grimace Scale to Evaluate Neuropathic Pain in a Model of Cervical Radiculopathy.

    PubMed

    Philips, Blythe H; Weisshaar, Christine L; Winkelstein, Beth A

    2017-02-01

    Although neck and low-back pain are common sources of neuropathic pain with high societal costs, the pathophysiology of neuropathic pain is not well-defined. Traditionally, most rodent pain studies rely on evoked reflex-based testing to measure pain. However, these testing methods do not reveal spontaneous pain, particularly early after injury. The rat grimace scale (RGS) for quantifying spontaneous pain has been validated after visceral, incisional, orthopedic, and inflammatory insults but not neuropathic pain. The current study used a rat model of radiculopathy to investigate the time course of RGS, the effect of the NSAID meloxicam on RGS, and the reliability and consistency of RGS across testers. RGS values at baseline and at 3, 6, 24, and 48 h after cervical nerve root compression (NRC) that induced robust evoked pain responses were compared with those obtained after sham surgery. The RGS was also evaluated at 6 h after NRC in another set of rats that had received meloxicam treatment prior to surgery. At 6 h, NRC induced higher RGS scores (1.27 ± 0.18) than did sham surgery (0.93 ± 0.20), and scores remained above baseline for as long as 48 h. Treatment with meloxicam before NRC reduced RGS at 6 h to sham levels, which were lower than those of injury without treatment. The RGS was associated with very good interobserver reliability (intraclass correlation coefficient, 0.91) and excellent internal consistency (Cronbach α, 0.87). These findings suggest that RGS is a useful approach to identifying and monitoring acute neuropathic pain in rats.

  7. Three-dimensional kinematic stress magnetic resonance image analysis shows promise for detecting altered anatomical relationships of tissues in the cervical spine associated with painful radiculopathy.

    PubMed

    Jaumard, N V; Udupa, J K; Siegler, S; Schuster, J M; Hilibrand, A S; Hirsch, B E; Borthakur, A; Winkelstein, B A

    2013-10-01

    For some patients with radiculopathy a source of nerve root compression cannot be identified despite positive electromyography (EMG) evidence. This discrepancy hampers the effective clinical management for these individuals. Although it has been well-established that tissues in the cervical spine move in a three-dimensional (3D) manner, the 3D motions of the neural elements and their relationship to the bones surrounding them are largely unknown even for asymptomatic normal subjects. We hypothesize that abnormal mechanical loading of cervical nerve roots during pain-provoking head positioning may be responsible for radicular pain in those cases in which there is no evidence of nerve root compression on conventional cervical magnetic resonance imaging (MRI) with the neck in the neutral position. This biomechanical imaging proof-of-concept study focused on quantitatively defining the architectural relationships between the neural and bony structures in the cervical spine using measurements derived from 3D MR images acquired in neutral and pain-provoking neck positions for subjects: (1) with radicular symptoms and evidence of root compression by conventional MRI and positive EMG, (2) with radicular symptoms and no evidence of root compression by MRI but positive EMG, and (3) asymptomatic age-matched controls. Function and pain scores were measured, along with neck range of motion, for all subjects. MR imaging was performed in both a neutral position and a pain-provoking position. Anatomical architectural data derived from analysis of the 3D MR images were compared between symptomatic and asymptomatic groups, and the symptomatic groups with and without imaging evidence of root compression. Several differences in the architectural relationships between the bone and neural tissues were identified between the asymptomatic and symptomatic groups. In addition, changes in architectural relationships were also detected between the symptomatic groups with and without imaging

  8. Modeling T1 and T2 relaxation in bovine white matter

    NASA Astrophysics Data System (ADS)

    Barta, R.; Kalantari, S.; Laule, C.; Vavasour, I. M.; MacKay, A. L.; Michal, C. A.

    2015-10-01

    The fundamental basis of T1 and T2 contrast in brain MRI is not well understood; recent literature contains conflicting views on the nature of relaxation in white matter (WM). We investigated the effects of inversion pulse bandwidth on measurements of T1 and T2 in WM. Hybrid inversion-recovery/Carr-Purcell-Meiboom-Gill experiments with broad or narrow bandwidth inversion pulses were applied to bovine WM in vitro. Data were analysed with the commonly used 1D-non-negative least squares (NNLS) algorithm, a 2D-NNLS algorithm, and a four-pool model which was based upon microscopically distinguishable WM compartments (myelin non-aqueous protons, myelin water, non-myelin non-aqueous protons and intra/extracellular water) and incorporated magnetization exchange between adjacent compartments. 1D-NNLS showed that different T2 components had different T1 behaviours and yielded dissimilar results for the two inversion conditions. 2D-NNLS revealed significantly more complicated T1/T2 distributions for narrow bandwidth than for broad bandwidth inversion pulses. The four-pool model fits allow physical interpretation of the parameters, fit better than the NNLS techniques, and fits results from both inversion conditions using the same parameters. The results demonstrate that exchange cannot be neglected when analysing experimental inversion recovery data from WM, in part because it can introduce exponential components having negative amplitude coefficients that cannot be correctly modeled with nonnegative fitting techniques. While assignment of an individual T1 to one particular pool is not possible, the results suggest that under carefully controlled experimental conditions the amplitude of an apparent short T1 component might be used to quantify myelin water.

  9. Electrodiagnostic Evaluation of Individuals Implanted With Extracellular Matrix for the Treatment of Volumetric Muscle Injury: Case Series

    PubMed Central

    Han, Nami; Yabroudi, Mohammad A.; Stearns-Reider, Kristen; Helkowski, Wendy; Sicari, Brian M.; Rubin, J. Peter; Badylak, Stephen F.; Boninger, Michael L.

    2016-01-01

    Background Electrodiagnosis can reveal the nerve and muscle changes following surgical placement of an extracellular matrix (ECM) bioscaffold for treatment of volumetric muscle loss (VML). Objective The purpose of this study was to characterize nerve conduction study (NCS) and electromyography (EMG) changes following ECM bioscaffold placement in individuals with VML. The ability of presurgical NCS and EMG to be used as a tool to help identify candidates who are likely to display improvements postsurgically also was explored. Design A longitudinal case series design was used. Methods The study was conducted at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Eight individuals with a history of chronic VML participated. The intervention was surgical placement of an ECM bioscaffold at the site of VML. The strength of the affected region was measured using a handheld dynamometer, and electrophysiologic evaluation was conducted on the affected limb with standard method of NCS and EMG. All measurements were obtained the day before surgery and repeated 6 months after surgery. Results Seven of the 8 participants had a preoperative electrodiagnosis of incomplete mononeuropathy within the site of VML. After ECM treatment, 5 of the 8 participants showed improvements in NCS amplitude or needle EMG parameters. The presence of electrical activity within the scaffold remodeling site was concomitant with clinical improvement in muscle strength. Limitations This study had a small sample size, and participants served as their own controls. The electromyographers and physical therapists performing the evaluation were not blinded. Conclusions Electrodiagnostic data provide objective evidence of physiological improvements in muscle function following ECM placement at sites of VML. Future studies are warranted to further investigate the potential of needle EMG as a predictor of successful outcomes following ECM treatment for VML. PMID:26564252

  10. Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

    PubMed

    Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

    2018-05-01

    The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

  11. Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy

    PubMed Central

    Wood, John C.; Otto-Duessel, Maya; Aguilar, Michelle; Nick, Hanspeter; Nelson, Marvin D.; Coates, Thomas D.; Pollack, Harvey; Moats, Rex

    2010-01-01

    Background Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. Methods and Results Twelve gerbils underwent iron dextran loading (200 mg · kg−1 · wk−1) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis. Conclusions MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans. PMID:16027257

  12. Breath-hold black-blood T1rho mapping improves liver T1rho quantification in healthy volunteers.

    PubMed

    Wáng, Yì Xiáng J; Deng, Min; Lo, Gladys G; Liang, Dong; Yuan, Jing; Chen, Weitian

    2018-03-01

    Background Recent researches suggest that T1rho may be a non-invasive and quantitative technique for detecting and grading liver fibrosis. Purpose To compare a multi-breath-hold bright-blood fast gradient echo (GRE) imaging and a single breath-hold single-shot fast spin echo (FSE) imaging with black-blood effect for liver parenchyma T1rho measurement and to study liver physiological T1rho value in healthy volunteers. Material and Methods The institutional Ethics Committee approved this study. 28 healthy participants (18 men, 10 women; age = 29.6 ± 5.1 years) underwent GRE liver T1rho imaging, and 20 healthy participants (10 men, 10 women; age = 36.9 ± 10.3 years) underwent novel black-blood FSE liver T1rho imaging, both at 3T with spin-lock frequency of 500 Hz. The FSE technique allows simultaneous acquisition of four spin lock times (TSLs; 1 ms, 10 ms, 30 ms, 50msec) in 10 s. Results For FSE technique the intra-scan repeatability intraclass correlation coefficient (ICC) was 0.98; while the inter-scan reproducibility ICC was 0.82 which is better than GRE technique's 0.76. Liver T1rho value in women tended to have a higher value than T1rho values in men (FSE: 42.28 ± 4.06 ms for women and 39.13 ± 2.12 ms for men; GRE: 44.44 ± 1.62 ms for women and 42.36 ± 2.00 ms for men) and FSE technique showed liver T1rho value decreased slightly as age increased. Conclusion Single breath-hold black-blood FSE sequence has better scan-rescan reproducibility than multi-breath-hold bright-blood GRE sequence. Gender and age dependence of liver T1rho in healthy participants is observed, with young women tending to have a higher T1rho measurement.

  13. T1ρ Dispersion in Articular Cartilage

    PubMed Central

    Besier, Thor F.; Pauly, John M.; Smith, R. Lane; Delp, Scott L.; Beaupre, Gary S.; Gold, Garry E.

    2015-01-01

    Objective This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? Design Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. Results Cartilage initial elastic modulus, E0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). Conclusions T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water–protein interactions, are dependent on the cartilage structure, and were correlated in this study. PMID:26069714

  14. T-cell receptor transfer for boosting HIV-1-specific T-cell immunity in HIV-1-infected patients.

    PubMed

    Mummert, Christiane; Hofmann, Christian; Hückelhoven, Angela G; Bergmann, Silke; Mueller-Schmucker, Sandra M; Harrer, Ellen G; Dörrie, Jan; Schaft, Niels; Harrer, Thomas

    2016-09-10

    Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8 T cells derived from healthy donors. So far, it is unknown whether the transfer of HIV-1-specific TCRs is capable to reprogram CD8 T cells of HIV-1-infected patients. To assess the efficiency of TCR-transfer by mRNA electroporation and the functionality of reprogramed T cells in HIV-1-infected patients, we performed an in-vitro analysis of TCR-transfer into T cells from HIV-1-infected patients in various stages of disease and from healthy controls. Peripheral blood mononuclear cells from 16 HIV-1-infected patients (nine HLA-A02-positive, seven HLA-A02-negative) and from five healthy controls were electroporated with mRNA-constructs encoding TCRs specific for the HLA-A02/HIV-1-gag p17 epitope SLYNTVATL (SL9). Functionality of the TCRs was measured by γIFN-ELISpot assays. SL9/TCR transfection into peripheral blood mononuclear cells from both HLA-A02-positive and HLA-A02-negative HIV-1-infected patients and from healthy blood donors reprogramed T cells for recognition of SL9-presenting HLA-A02-positive cells in γIFN-ELISpot assays. SL9/TCR-transfer into T cells from an immunodeficient AIDS patient could induce recognition of SL9-expressing target cells only after reversion of T-cell dysfunction by antiretroviral therapy. The transfer of HIV-1-p17-specific TCRs into T cells is functional both in HIV-1-infected patients as well as in healthy blood donors. TCR-transfer is a promising method to boost the immune system against HIV-1.

  15. Hybridized 1T/2H MoS2 Having Controlled 1T Concentrations and its use in Supercapacitors.

    PubMed

    Thi Xuyen, Nguyen; Ting, Jyh-Ming

    2017-12-06

    Molybdenum disulfide (MoS 2 ) nanoflowers consisting of hybridized 1T/2H phases have been synthesized by using a microwave-assisted hydrothermal (MTH) method. The concentration of the 1T phase, ranging from 40 % to 73 %, is controlled by simply adjusting the ratio of the Mo and S precursors. By using the hybridized 1T/2H MoS 2 as an electrode material, it was demonstrated that the resulting supercapacitor performance is dominated by the 1T phase concentration. It was found that a supercapacitor with 73 % 1T phase exhibits excellent capacitance of 259 F g -1 and great cyclic stability after 1000 cycles. The formation mechanism of the MHT-synthesized hybridized 1T/2H MoS 2 is also reported. More importantly, the mechanism also explains the observed relationship between the 1T phase concentration and the ratio of the Mo and S precursors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

    PubMed

    Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

    2016-10-11

    The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

  17. T1 hyperintense disc in alkaptonuria.

    PubMed

    Sag, Alan A; Silbergleit, Richard; Olson, Rick E; Wilson, Jon; Krishnan, Anant

    2012-10-01

    Case report. To report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation. A 46-year-old man without previous diagnosis of alkaptonuria underwent evaluation for progressive back pain revealing a T1-hyperintense disc herniation at the L3-L4 level. Discectomy recovered a blackened disc that was pathologically confirmed to be nucleus pulposus with alkaptonuric involvement. The differential diagnosis of a T1-hyperintense, T2-hypointense disc on magnetic resonance imaging is discussed, with emphasis on the pathophysiology of alkaptonuria. A single patient is reported. Pathologically proven patient presentation with radiological and pathological images. We report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation.

  18. Ultrasonography for the diagnosis of tendinitis and electromyography for the diagnosis of peripheral neuropathy and upper limb radiculopathy: rheumatologists' perspectives.

    PubMed

    Helfenstein, Milton; Ferreira, Mario Soares; Maia, Anna Beatriz Assad; Siena, César Augusto Fávaro; Techy, Antonio

    2013-01-01

    To ascertain the value ascribed by Brazilian rheumatologists to ultrasonography (US) for diagnosing tendinitis and to electromyography (EMG) for diagnosing peripheral neuropathy and upper limb radiculopathy. In total, 165 rheumatologists answered an anonymous survey (sent via the internet) concerning the two exams, with respect to the following characteristics: reliability, diagnostic accuracy, the importance and necessity of these tests for diagnostic The study revealed that most of the rheumatologists recognised that these exams are operator-dependent, that clinicians do not rely entirely on the results, that these exams are not mandatory for the diagnoses listed, and that professionals who perform these exams should be better trained to provide reliable results. The Brazilian rheumatologists believe the following: the results of these exams should be interpreted with caution and are not definitive for diagnosis; musculoskeletal US and EMG should be performed by trained professionals; and there must be better preparation of the professionals who perform these exams.

  19. Measurement of T1 of human arterial and venous blood at 7T.

    PubMed

    Rane, Swati D; Gore, John C

    2013-04-01

    Techniques for measuring cerebral perfusion require accurate longitudinal relaxation (T1) of blood, an MRI parameter that is field dependent. T1 of arterial and venous human blood was measured at 7T using three different sources - pathology laboratory, blood bank and in vivo. The T1 of venous blood was measured from sealed samples from a pathology lab and in vivo. Samples from a blood bank were oxygenated and mixed to obtain different physiological concentrations of hematocrit and oxygenation. T1 relaxation times were estimated using a three-point fit to a simple inversion recovery equation. At 37°C, the T1 of blood at arterial pO2 was 2.29±0.1s and 2.07±0.12 at venous pO2. The in vivo T1 of venous blood, in three subjects, was slightly longer at 2.45±0.11s. T1 of arterial and venous blood at 7T was measured and found to be significantly different. The T1 values were longer in vivo than in vitro. While the exact cause for the discrepancy is unknown, the additives in the blood samples, degradation during experiment, oxygenation differences, and the non-stagnant nature of blood in vivo could be potential contributors to the lower values of T1 in the venous samples. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

    PubMed

    Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Chen, Bailiang; De Verbizier, Jacques; Beaumont, Marine; Badr, Sammy; Cotten, Anne; Blum, Alain

    2017-12-01

    To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

  1. Comparison of contrast-enhanced T1-weighted FLAIR with BLADE, and spin-echo T1-weighted sequences in intracranial MRI.

    PubMed

    Alkan, Ozlem; Kizilkiliç, Osman; Yildirim, Tülin; Alibek, Sedat

    2009-06-01

    We compared periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER, BLADE) MR technique with spin echo (SE) technique for evaluation of artifacts, and detection and delineation of brain lesions. Contrast-enhanced T1-weighted fluid attenuated inversion recovery (FLAIR) images with BLADE technique (CE T1W-FLAIR BLADE) and contrast-enhanced T1-weighted SE (CE T1W-SE) were performed in 50 patients with intracranial enhancing lesions. These techniques were compared by two neuroradiologists for qualitative analysis of artifacts, lesion detectability, lesion delineation from adjacent structures, and preferred imaging technique; and for quantitative variables, i.e., lesion-to-background and lesion-to-cerebrospinal fluid (CSF) contrast-to-noise (CNR) ratios. Reader agreement was assessed by kappa statistics. All lesions depicted with the CE T1W-SE were also detected with the CE T1W-FLAIR BLADE technique. Delineation of lesions was better on CE T1W-FLAIR BLADE in the majority of patients. Flow-related artifacts were considerably reduced with CE T1W-FLAIR BLADE. A star-like artifact at the level of the 4(th) ventricle was noted on CE T1W-FLAIR BLADE but not on CE T1W-SE. The lesion-to-background CNR and lesion-to-CSF CNR did not show a statistically significant difference between the two techniques. CE T1W-FLAIR BLADE images were preferred by the observers over the CE T1w-SE images, indicating good interobserver agreement (k = 0.70). CE T1W-FLAIR BLADE technique is superior to CE T1WSE for delineation of lesions and reduction of flow-related artifacts, especially within the posterior fossa, and is preferred by readers. CE T1W-FLAIR BLADE may be an alternative approach to imaging, especially for posterior fossa lesions.

  2. Taste responses in mice lacking taste receptor subunit T1R1

    PubMed Central

    Kusuhara, Yoko; Yoshida, Ryusuke; Ohkuri, Tadahiro; Yasumatsu, Keiko; Voigt, Anja; Hübner, Sandra; Maeda, Katsumasa; Boehm, Ulrich; Meyerhof, Wolfgang; Ninomiya, Yuzo

    2013-01-01

    The T1R1 receptor subunit acts as an umami taste receptor in combination with its partner, T1R3. In addition, metabotropic glutamate receptors (brain and taste variants of mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate the function of T1R1 and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock-out (T1R1−/−) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1-expressing cells. Gustatory nerve recordings demonstrated that T1R1−/− mice exhibited a serious deficit in inosine monophosphate-elicited synergy but substantial residual responses to glutamate alone in both chorda tympani and glossopharyngeal nerves. Interestingly, chorda tympani nerve responses to sweeteners were smaller in T1R1−/− mice. Taste cell recordings demonstrated that many mCherry-expressing taste cells in T1R1+/− mice responded to sweet and umami compounds, whereas those in T1R1−/− mice responded to sweet stimuli. The proportion of sweet-responsive cells was smaller in T1R1−/− than in T1R1+/− mice. Single-cell RT-PCR demonstrated that some single mCherry-expressing cells expressed all three T1R subunits. Chorda tympani and glossopharyngeal nerve responses to glutamate were significantly inhibited by addition of mGluR antagonists in both T1R1−/− and T1R1+/− mice. Conditioned taste aversion tests demonstrated that both T1R1−/− and T1R1+/− mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1-expressing cells mainly contribute to umami taste synergism and partly to sweet sensitivity and that mGluRs are involved in the detection of umami compounds. PMID:23339178

  3. Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

    PubMed Central

    Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

    2009-01-01

    Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

  4. Cardiac T1 Imaging

    PubMed Central

    Jerosch-Herold, Michael; Kwong, Raymond Y.

    2014-01-01

    T1 mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extra-cellular volume (expansion), and most recently cardiomyocyte hypertrophy. The MRI pulse sequence techniques developed for these applications have had to address at least two important considerations for cardiac applications: measure magnetization inversion recoveries during cardiac motion with sufficient temporal resolution for the shortest expected T1 values, and, secondly, obtain these measurements within a time during which a patient can comfortably suspend breathing. So-called Look-Locker techniques, and variants thereof, which all sample multiple points of a magnetization recovery after each magnetization preparation have therefore become a mainstay in this field. The rapid pace of advances and new findings based on cardiac T1 mapping for assessment of diffuse fibrosis, or myocardial edema show that these techniques enrich the capabilities of MRI for myocardial tissue profiling, which is arguably unmatched by other cardiac imaging modalities. PMID:24509619

  5. Impact of Age and Duration of Symptoms on Surgical Outcome of Single-Level Microscopic Anterior Cervical Discectomy and Fusion in the Patients with Cervical Spondylotic Radiculopathy.

    PubMed

    Omidi-Kashani, Farzad; Ghayem Hasankhani, Ebrahim; Ghandehari, Reza

    2014-01-01

    We aim to evaluate the impact of age and duration of symptoms on surgical outcome of the patients with cervical spondylotic radiculopathy (CSR) who had been treated by single-level microscopic anterior cervical discectomy and fusion (ACDF). We retrospectively evaluated 68 patients (48 female and 20 male) with a mean age of 41.2 ± 4.3 (ranged from 24 to 72 years old) in our Orthopedic Department, Imam Reza Hospital. They were followed up for 31.25 ± 4.1 months (ranged from 25 to 65 months). Pain and disability were assessed by Visual Analogue Scale (VAS) and Neck Disability Index (NDI) questionnaires in preoperative and last follow-up visits. Functional outcome was eventually evaluated by Odom's criteria. Surgery could significantly improve pain and disability from preoperative 6.2 ± 1.4 and 22.2 ± 6.2 to 3.5 ± 2.0 and 8.7 ± 5.2 (1-21) at the last follow-up visit, respectively. Satisfactory outcomes were observed in 89.7%. Symptom duration of more and less than six months had no effect on surgical outcome, but the results showed a statistically significant difference in NDI improvement in favor of the patients aged more than 45 years (P = 0.032), although pain improvement was similar in the two groups.

  6. Yang-Baxter deformations of W2,4 × T1,1 and the associated T-dual models

    NASA Astrophysics Data System (ADS)

    Sakamoto, Jun-ichi; Yoshida, Kentaroh

    2017-08-01

    Recently, for principal chiral models and symmetric coset sigma models, Hoare and Tseytlin proposed an interesting conjecture that the Yang-Baxter deformations with the homogeneous classical Yang-Baxter equation are equivalent to non-abelian T-dualities with topological terms. It is significant to examine this conjecture for non-symmetric (i.e., non-integrable) cases. Such an example is the W2,4 ×T 1 , 1 background. In this note, we study Yang-Baxter deformations of type IIB string theory defined on W2,4 ×T 1 , 1 and the associated T-dual models, and show that this conjecture is valid even for this case. Our result indicates that the conjecture would be valid beyond integrability.

  7. Reflex-based grasping, skilled forelimb reaching, and electrodiagnostic evaluation for comprehensive analysis of functional recovery-The 7-mm rat median nerve gap repair model revisited.

    PubMed

    Stößel, Maria; Rehra, Lena; Haastert-Talini, Kirsten

    2017-10-01

    The rat median nerve injury and repair model gets increasingly important for research on novel bioartificial nerve grafts. It allows follow-up evaluation of the recovery of the forepaw functional ability with several sensitive techniques. The reflex-based grasping test, the skilled forelimb reaching staircase test, as well as electrodiagnostic recordings have been described useful in this context. Currently, no standard values exist, however, for comparison or comprehensive correlation of results obtained in each of the three methods after nerve gap repair in adult rats. Here, we bilaterally reconstructed 7-mm median nerve gaps with autologous nerve grafts (ANG) or autologous muscle-in-vein grafts (MVG), respectively. During 8 and 12 weeks of observation, functional recovery of each paw was separately monitored using the grasping test (weekly), the staircase test, and noninvasive electrophysiological recordings from the thenar muscles (both every 4 weeks). Evaluation was completed by histomorphometrical analyses at 8 and 12 weeks postsurgery. The comprehensive evaluation detected a significant difference in the recovery of forepaw functional motor ability between the ANG and MVG groups. The correlation between the different functional tests evaluated precisely displayed the recovery of distinct levels of forepaw functional ability over time. Thus, this multimodal evaluation model represents a valuable preclinical model for peripheral nerve reconstruction approaches.

  8. Clinical heterogeneity of type 1 diabetes (T1D) found in Asia.

    PubMed

    Park, Yongsoo; Wintergerst, Kupper A; Zhou, Zhiguang

    2017-10-01

    Diabetes mellitus among young patients in Asia is caused by a complex set of factors. Although type 1 diabetes (T1D) remains the most common form of diabetes in children, the recent unabated increase in obesity has resulted in the emergence of type 2 diabetes (T2D) as a new type of diabetes among adolescents and young adults. In addition to the typical autoimmune type 1 diabetes (T1aD) and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1bD). Additional forms have been described, including fulminant T1D (FT1D). Although most diagnoses of T1D are classified as T1aD, fulminant T1D exists as a hyper-acute subtype of T1D that affects older children, without associated autoimmunity. Patient with this rare aetiology of diabetes showed a complete loss of β-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults is a form of autoimmune-mediated diabetes, usually diagnosed during the insulin-dependent stage that follows a non-insulin requiring phase, which can be diagnosed earlier based on anti-islet autoantibody positivity. Some reports discuss T1bD. Others are elaborating on the presence of "atypical T1b diabetes," such as Flatbush diabetes. The prevalence of diabetes mellitus in young adults continues to rise in Asian populations as T2D increases. With improved characterization of patients with diabetes, the range of diabetic subgroups will become even more diverse in the future. Distinguishing T1D, T2D, and other forms of diabetes in young patients is challenging in Asian populations, as the correct diagnosis is clinically important and has implications for prognosis and management. Despite aetiological heterogeneity in the usual clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds as well as measuring islet autoantibodies and fasting plasma C

  9. Identification of novel gammadelta T-cell subsets following bacterial infection in the absence of Vgamma1+ T cells: homeostatic control of gammadelta T-cell responses to pathogen infection by Vgamma1+ T cells.

    PubMed

    Newton, Darren J; Andrew, Elizabeth M; Dalton, Jane E; Mears, Rainy; Carding, Simon R

    2006-02-01

    Although gammadelta T cells are a common feature of many pathogen-induced immune responses, the factors that influence, promote, or regulate the response of individual gammadelta T-cell subsets to infection is unknown. Here we show that in the absence of Vgamma1+ T cells, novel subsets of gammadelta T cells, expressing T-cell receptor (TCR)-Vgamma chains that normally define TCRgammadelta+ dendritic epidermal T cells (DETCs) (Vgamma5+), intestinal intraepithelial lymphocytes (iIELs) (Vgamma7+), and lymphocytes associated with the vaginal epithelia (Vgamma6+), are recruited to the spleen in response to bacterial infection in TCR-Vgamma1-/- mice. By comparison of phenotype and structure of TCR-Vgamma chains and/or -Vdelta chains expressed by these novel subsets with those of their epithelium-associated counterparts, the Vgamma6+ T cells elicited in infected Vgamma1-/- mice were shown to be identical to those found in the reproductive tract, from where they are presumably recruited in the absence of Vgamma1+ T cells. By contrast, Vgamma5+ and Vgamma7+ T cells found in infected Vgamma1-/- mice were distinct from Vgamma5+ DETCs and Vgamma7+ iIELs. Functional analyses of the novel gammadelta T-cell subsets identified for infected Vgamma1-/- mice showed that whereas the Vgamma5+ and Vgamma7+ subsets may compensate for the absence of Vgamma1+ T cells by producing similar cytokines, they do not possess cytocidal activity and they cannot replace the macrophage homeostasis function of Vgamma1+ T cells. Collectively, these findings identify novel subsets of gammadelta T cells, the recruitment and activity of which is under the control of Vgamma1+ T cells.

  10. Predictors of associated autoimmune diseases (AAID) in families with type 1 diabetes (T1D). Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

    PubMed Central

    Wägner, Ana M; Santana, Ángelo; Hernández, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Didac

    2011-01-01

    Background Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAID) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAID in the Type 1 Diabetes Genetics Consortium (T1DGC) data set. Methods 3263 families with at least 2 siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD and anti-IA-2 were measured and HLA-genotyping was performed. Siblings with T1D with and without AAID were compared and a multivariate regression analysis was performed to find predictors of AAID. T1D-associated HLA haplotypes were defined as the 4 most susceptible and protective, respectively. Results AAID was present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, and there was a female predominance and more family history of AAID in the group with AAID, as well as more frequent anti-GAD and less frequent anti-IA2 positivity. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAID. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAID. Conclusions In patients with T1D, the presence of AAID is associated with female predominance, more frequent family history of AAID, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. PMID:21744463

  11. Comparison of post-contrast 3D-T1-MPRAGE, 3D-T1-SPACE and 3D-T2-FLAIR MR images in evaluation of meningeal abnormalities at 3-T MRI.

    PubMed

    Jeevanandham, Balaji; Kalyanpur, Tejas; Gupta, Prashant; Cherian, Mathew

    2017-06-01

    This study was to assess the usefulness of newer three-dimensional (3D)-T 1 sampling perfection with application optimized contrast using different flip-angle evolutions (SPACE) and 3D-T 2 fluid-attenuated inversion recovery (FLAIR) sequences in evaluation of meningeal abnormalities. 78 patients who presented with high suspicion of meningeal abnormalities were evaluated using post-contrast 3D-T 2 -FLAIR, 3D-T 1 magnetization-prepared rapid gradient-echo (MPRAGE) and 3D-T 1 -SPACE sequences. The images were evaluated independently by two radiologists for cortical gyral, sulcal space, basal cisterns and dural enhancement. The diagnoses were confirmed by further investigations including histopathology. Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images yielded significantly more information than MPRAGE images (p < 0.05 for both SPACE and FLAIR images) in detection of meningeal abnormalities. SPACE images best demonstrated abnormalities in dural and sulcal spaces, whereas FLAIR was useful for basal cisterns enhancement. Both SPACE and FLAIR performed equally well in detection of gyral enhancement. In all 10 patients, where both SPACE and T 2 -FLAIR images failed to demonstrate any abnormality, further analysis was also negative. The 3D-T 1 -SPACE sequence best demonstrated abnormalities in dural and sulcal spaces, whereas FLAIR was useful for abnormalities in basal cisterns. Both SPACE and FLAIR performed holds good for detection of gyral enhancement. Post-contrast SPACE and FLAIR sequences are superior to the MPRAGE sequence for evaluation of meningeal abnormalities and when used in combination have the maximum sensitivity for leptomeningeal abnormalities. The negative-predictive value is nearly 100%, where no leptomeningeal abnormality was detected on these sequences. Advances in knowledge: Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images are more useful than 3D-T 1 -MPRAGE images in evaluation of meningeal abnormalities.

  12. Characterization of RUNX1T1, an Adipogenesis Regulator in Ovine Preadipocyte Differentiation.

    PubMed

    Deng, Kaiping; Ren, Caifang; Liu, Zifei; Gao, Xiaoxiao; Fan, Yixuan; Zhang, Guomin; Zhang, Yanli; Ma, Ei-Samahy; Wang, Feng; You, Peihua

    2018-04-26

    Runt-related transcription factor 1 translocation partner 1 (RUNX1T1), a potential novel regulator of adipogenesis, exists in two splice variants: a long (RUNX1T1-L) and a short (RUNX1T1-S) isoform. However, there is no data showing the existence of RUNX1T1 in ovine subcutaneous fat at different stages of developmental and its role on ovine adipogenesis. Therefore, the objectives of this study were to evaluate the presence of RUNX1T1 in subcutaneous fat of five-day-old to 24-month-old sheep and to investigate the role of RUNX1T1 in ovine adipogenesis. In this study, we detected a 1829 bp cDNA fragment of RUNX1T1 which contains a 1815 bp coding sequence that encodes 602-amino acid and 14 bp of 5' untranslated region, respectively. The amino acid sequence of RUNX1T1 has 31.18⁻94.21% homology with other species' protein sequences. During fat development, the RUNX1T1 protein expression was higher in subcutaneous fat of 24-month-old Hu sheep. In addition, the expression of RUNX1T1-L mRNA decreased first, then subsequently increased during ovine preadipocyte differentiation. Knockdown of RUNX1T1-L in ovine preadipocytes promoted preadipocyte differentiation and lipid accumulation. Taken together, our data suggests that RUNX1T1 is an important functional molecule in adipogenesis. Moreover, it showed for the first time that RUNX1T1-L was negatively correlated with the ovine preadipocyte differentiation.

  13. Function in patients with cervical radiculopathy or chronic whiplash-associated disorders compared with healthy volunteers.

    PubMed

    Peolsson, Anneli; Ludvigsson, Maria Landén; Wibault, Johanna; Dedering, Åsa; Peterson, Gunnel

    2014-05-01

    The purposes of this study were to examine whether any differences in function and health exist between patients with cervical radiculopathy (CR) due to disk disease scheduled for surgery and patients with chronic whiplash-associated disorders (WADs) and to compare measures of patients' physical function with those obtained from healthy volunteers. This is a cross-sectional study of patients with CR (n = 198) and patients with chronic WAD (n = 215). Patient data were compared with raw data previously obtained from healthy people. Physical measures included cervical active range of motion, neck muscle endurance, and hand grip strength. Self-rated measures included pain intensity (visual analog scale), neck disability (Neck Disability Index), self-efficacy (Self-Efficacy Scale), and health-related quality of life (EuroQol 5-dimensional self-classifier). Patient groups exhibited significantly lower performance than the healthy group in all physical measures (P < .0005) except for neck muscle endurance in flexion for women (P > .09). There was a general trend toward worse results in the CR group than the WAD group, with significant differences in neck active range of motion, left hand strength for women, pain intensity, Neck Disability Index, EuroQol 5-dimensional self-classifier, and Self-Efficacy Scale (P < .0001). Patients had worse values than healthy individuals in almost all physical measures. There was a trend toward worse results for CR than WAD patients. Copyright © 2014 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  14. Limb-shaking transient ischemic attack masquerading as lumbar radiculopathy from pericallosal artery stenosis treated successfully with intracranial angioplasty and stenting.

    PubMed

    Kalia, Junaid; Wolfe, Thomas; Zaidat, Osama O

    2010-03-01

    The pericallosal artery is rarely associated with intracranial atherosclerotic disease and, until recently, was usually not amenable to endovascular therapy with balloon angioplasty and stenting. We present an elderly patient with postural left leg-shaking episodes secondary to pericallosal artery stenosis, which was treated initially with primary intracranial balloon angioplasty, and subsequently, angioplasty and stenting as a result of recurrent stenosis. Both procedures were preformed without complications, and the patient remained free of symptoms on 6-month follow-up. This case demonstrates unique clinical and neuroendovascular aspects; the isolated postural leg-shaking transient ischemic attacks, initially mistaken for radiculopathy and local joint etiology, were found later to be cerebrovascular ischemic in origin. Moreover, the correlation between the findings of computed tomography perfusion and angiography localized the lesion into the medial frontal lobe and pericallosal artery territory. In addition, the technical aspect provides insight into the current state of neuroendovascular techniques, addressing the difficulty of access into very small and distal intracranial arteries affected by stenosis. Copyright 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

    PubMed

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  16. White matter fiber-based analysis of T1w/T2w ratio map

    NASA Astrophysics Data System (ADS)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  17. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon.

    PubMed

    Kendig, Derek M; Hurst, Norman R; Bradley, Zachary L; Mahavadi, Sunila; Kuemmerle, John F; Lyall, Vijay; DeSimone, John; Murthy, Karnam S; Grider, John R

    2014-12-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5'-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1(-/-) mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. Copyright © 2014 the American Physiological Society.

  18. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

    PubMed Central

    Kendig, Derek M.; Hurst, Norman R.; Bradley, Zachary L.; Mahavadi, Sunila; Kuemmerle, John F.; Lyall, Vijay; DeSimone, John; Murthy, Karnam S.

    2014-01-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5′-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1−/− mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. PMID:25324508

  19. Electrodiagnostic studies in presumptive primary hypothyroidism and polyneuropathy in dogs with reevaluation during hormone replacement therapy.

    PubMed

    Giza, Elżbieta Gabriela; Płonek, Marta; Nicpoń, Józef Marian; Wrzosek, Marcin Adam

    2016-05-21

    Peripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated polyneuropathy in dogs are very limited and usually lack a reevaluation after hormone replacement therapy. The objective of this study was to perform a detailed, retrospective analysis of electromyographic (EMG), motor nerve conduction velocity (MNCV), F-wave and brainstem auditory evoked response (BAER) findings in 24 dogs with presumptive primary hypothyroidism and polyneuropathy with a comparison of the results before and after initiation of levothyroxine treatment with the assessment of the clinical outcome. The results obtained from hypothyroid dogs showed a significant reduction in MNCV at a proximal-distal and middle-distal stimulation, decreased amplitudes of compound muscle action potentials (CMAP), an increased CMAP duration and a prolonged distal latency prior to treatment. Fifty percent of the dogs had an increased F-wave latency. A normal BAER recording was found in 78 % of the hypothyroid patients without vestibular impairment. Bilaterally increased peak V latencies and increased interpeak I-V latencies were found in the remaining individuals. Dogs with concurrent vestibular impairment had ipsilaterally increased peak latencies with normal interpeak latencies and decreased amplitudes of wave I and II. A comparison of the findings before and after 2 months of treatment revealed a decrease in the pathological activity on EMG, an improvement of proximal, middle and distal CMAP amplitudes and an increase in the proximal-distal conduction velocity in all dogs. F-wave latency improved in 38 % of dogs. The BAER reexamination revealed a persistent prolongation of peak I, II, III and V latencies and decreased wave I amplitude on the affected side in all dogs manifesting vestibular signs. Conversely, in dogs without vestibular signs, the peak V and interpeak I-V latencies decreased to normal values

  20. The Transforming Growth Factor-β1 (TGF-β1) Gene Polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and Susceptibility to Postmenopausal Osteoporosis

    PubMed Central

    Sun, Jiajia; Zhang, Chi; Xu, Lei; Yang, Mingyuan; Yang, Huilin

    2015-01-01

    Abstract The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-β1 (TGF-β1) gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk. PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-β1 gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and PMOP risk have been reported; however, some of these results are controversial. A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-β1 T869C and TGF-β1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations. Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-β1 T869C and TGF-β1 T29C polymorphisms and PMOP (TGF-β1 T869C—C vs T: OR = 1.18, 95% CI = 1.02–1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01–1.88, P = 0.042; CC vs CT/TT: OR = 1.39, 95% CI = 1.09–1.76, P = 0.008; TGF-β1 T29C—CT vs TT: OR = 1.25, 95% CI = 1.02–1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02–1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-β1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01–1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01–1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03–1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI

  1. T1 and T2 Mapping in Cardiology: "Mapping the Obscure Object of Desire".

    PubMed

    Mavrogeni, Sophie; Apostolou, Dimitris; Argyriou, Panayiotis; Velitsista, Stella; Papa, Lilika; Efentakis, Stelios; Vernardos, Evangelos; Kanoupaki, Mikela; Kanoupakis, George; Manginas, Athanassios

    The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing. © 2017 S. Karger AG, Basel.

  2. RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

    PubMed

    Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

    2015-12-01

    The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

  3. Lumbar subcutaneous edema and degenerative spinal disease in patients with low back pain: a retrospective MRI study.

    PubMed

    Quattrocchi, C C; Giona, A; Di Martino, A; Gaudino, F; Mallio, C A; Errante, Y; Occhicone, F; Vitali, M A; Zobel, B B; Denaro, V

    2015-08-01

    This study was designed to determine the association between LSE, spondylolisthesis, facet arthropathy, lumbar canal stenosis, BMI, radiculopathy and bone marrow edema at conventional lumbar spine MR imaging. This is a retrospective radiological study; 441 consecutive patients with low back pain (224 men and 217 women; mean age 57.3 years; mean BMI 26) underwent conventional lumbar MRI using a 1.5-T magnet (Avanto, Siemens). Lumbar MR images were reviewed by consensus for the presence of LSE, spondylolisthesis, facet arthropathy, lumbar canal stenosis, radiculopathy and bone marrow edema. Descriptive statistics and association studies were conducted using STATA software 11.0. Association studies have been performed using linear univariate regression analysis and multivariate regression analysis, considering LSE as response variable. The overall prevalence of LSE was 40%; spondylolisthesis (p = 0.01), facet arthropathy (p < 0.001), BMI (p = 0.008) and lumbar canal stenosis (p < 0.001) were included in the multivariate regression model, whereas bone marrow edema, radiculopathy and age were not. LSE is highly associated with spondylolisthesis, facet arthropathy and BMI, suggesting underestimation of its clinical impact as an integral component in chronic lumbar back pain. Longitudinal simultaneous X-ray/MRI studies should be conducted to test the relationship of LSE with lumbar spinal instability and low back pain.

  4. Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML.

    PubMed

    Zampini, Matteo; Tregnago, Claudia; Bisio, Valeria; Simula, Luca; Borella, Giulia; Manara, Elena; Zanon, Carlo; Zonta, Francesca; Serafin, Valentina; Accordi, Benedetta; Campello, Silvia; Buldini, Barbara; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

    2018-05-01

    The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

  5. mTORC1 promotes T-bet phosphorylation to regulate Th1 differentiation

    PubMed Central

    Chornoguz, Olesya; Hagan, Robert S.; Haile, Azeb; Arwood, Matthew L.; Gamper, Christopher J.; Banerjee, Arnob; Powell, Jonathan D.

    2017-01-01

    CD4+ T cells lacking the mTORC1 activator Rheb fail to secrete IFNγ under Th1 polarizing conditions. We hypothesized that this phenotype is due to defects in regulation of the canonical Th1 transcription factor T-bet at the level of protein phosphorylation downstream of mTORC1. To test this hypothesis, we employed targeted mass-spectrometry proteomic analysis – multiple reaction monitoring mass spectrometry (MRM-MS). We used MRM-MS to detect and quantify predicted phospho-peptides derived from T-bet. By analyzing activated murine WT and Rheb deficient CD4+ T cells, as well as murine CD4+ T cells activated in the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to identify 6 T-bet phosphorylation sites. Five of these are novel, and 4 sites are consistently dephosphorylated in both Rheb deficient CD4+ T-cells and T-cells treated with rapamycin, suggesting mTORC1 signaling controls their phosphorylation. Alanine mutagenesis of each of the 6 phosphorylation sites was tested for the ability to impair IFNγ expression. Single phosphorylation site mutants still support induction of IFNγ expression, however simultaneous mutation of 3 of the mTORC1-dependent sites results in significantly reduced IFNγ expression. The reduced activity of the triple mutant T-bet is associated with its failure to recruit chromatin remodeling complexes to the Ifng gene promoter. These results establish a novel mechanism by which mTORC1 regulates Th1 differentiation, through control of T-bet phosphorylation. PMID:28424242

  6. Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

    PubMed

    Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

    2017-09-01

    To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P < 0.001). The Michelson Contrast equation showed that contrast differences between these two regions for the ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P < 0.001). Finally, the ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

  7. Intralesional hemorrhage and thrombosis without rupture in a pure spinal epidural cavernous angioma: a rare cause of acute lumbal radiculopathy

    PubMed Central

    Riemenschneider, Markus; Herdmann, Jörg

    2010-01-01

    Pure spinal epidural cavernous angiomas are extremely rare lesions, and their normal shape is that of a fusiform mass in the dorsal aspects of the spinal canal. We report a case of a lumbo-sacral epidural cavernous vascular malformation presenting with acute onset of right-sided S1 radiculopathy. Clinical aspects, imaging, intraoperative findings, and histology are demonstrated. The patient, a 27-year-old man presented with acute onset of pain, paraesthesia, and numbness within the right leg corresponding to the S1 segment. An acute lumbosacral disc herniation was suspected, but MRI revealed a cystic lesion with the shape of a balloon, a fluid level and a thickened contrast-enhancing wall. Intraoperatively, a purple-blue tumor with fibrous adhesions was located between the right S1 and S2 nerve roots. Macroscopically, no signs of epidural bleedings could be denoted. After coagulation of a reticular venous feeder network and dissection of the adhesions the rubber ball-like lesion was resected in total. Histology revealed a prominent venous vessel with a pathologically thickened, amuscular wall surrounded by smaller, hyalinized, venous vessels arranged in a back-to-back position typical for the diagnosis of a cavernous angioma. Lumina were partially occluded by thrombi. The surrounding fibrotic tissue showed signs of recurrent bleedings. There was no obvious mass hemorrhage into the surrounding tissue. In this unique case, the pathologic mechanism was not the usual rupture of the cavernous angioma with subsequent intraspinal hemorrhage, but acute mass effect by intralesional bleedings and thrombosis with subsequent increase of volume leading to nerve root compression. Thus, even without a sudden intraspinal hemorrhage a spinal cavernous malformation can cause acute symptoms identical to the clinical features of a soft disc herniation. PMID:20213297

  8. Measurement of T1 of the Ultrashort T2* Components in White Matter of the Brain at 3T

    PubMed Central

    Du, Jiang; Sheth, Vipul; He, Qun; Carl, Michael; Chen, Jun; Corey-Bloom, Jody; Bydder, Graeme M.

    2014-01-01

    Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32±0.09 ms, and a short mean T1 of 226±46 ms were demonstrated for the healthy volunteers at 3T. PMID:25093859

  9. 26 CFR 1.923-1T - Temporary regulations; exempt foreign trade income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Temporary regulations; exempt foreign trade income. 1.923-1T Section 1.923-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Earned Income of Citizens of United States § 1.923-1T Temporary regulations; exempt foreign trade...

  10. 26 CFR 1.923-1T - Temporary regulations; exempt foreign trade income.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 10 2012-04-01 2012-04-01 false Temporary regulations; exempt foreign trade income. 1.923-1T Section 1.923-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Earned Income of Citizens of United States § 1.923-1T Temporary regulations; exempt...

  11. Saturation-inversion-recovery: A method for T1 measurement

    NASA Astrophysics Data System (ADS)

    Wang, Hongzhi; Zhao, Ming; Ackerman, Jerome L.; Song, Yiqiao

    2017-01-01

    Spin-lattice relaxation (T1) has always been measured by inversion-recovery (IR), saturation-recovery (SR), or related methods. These existing methods share a common behavior in that the function describing T1 sensitivity is the exponential, e.g., exp(- τ /T1), where τ is the recovery time. In this paper, we describe a saturation-inversion-recovery (SIR) sequence for T1 measurement with considerably sharper T1-dependence than those of the IR and SR sequences, and demonstrate it experimentally. The SIR method could be useful in improving the contrast between regions of differing T1 in T1-weighted MRI.

  12. A novel enterocin T1 with anti-Pseudomonas activity produced by Enterococcus faecium T1 from Chinese Tibet cheese.

    PubMed

    Liu, Hui; Zhang, Lanwei; Yi, Huaxi; Han, Xue; Gao, Wei; Chi, Chunliang; Song, Wei; Li, Haiying; Liu, Chunguang

    2016-02-01

    An enterocin-producing Enterococcus faecium T1 was isolated from Chinese Tibet cheese. The enterocin was purified by SP-Sepharose and reversed phase HPLC. It was identified as unique from other reported bacteriocins based on molecular weight (4629 Da) and amino acid compositions; therefore it was subsequently named enterocin T1. Enterocin T1 was stable at 80-100 °C and over a wide pH range, pH 3.0-10.0. Protease sensitivity was observed to trypsin, pepsin, papain, proteinase K, and pronase E. Importantly, enterocin T1 was observed to inhibit the growth of numerous Gram-negative and Gram-positive bacteria including Pseudomonas putida, Pseudomonas aeruginosa, Pseudomonas fluorescens, Escherichia coli, Salmonella typhimurium, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Listeria monocytogenes. Take together, these results suggest that enterocin T1 is a novel bacteriocin with the potential to be used as a bio-preservative to control Pseudomonas spp. in food.

  13. Hybrid nanotrimers for dual T 1 and T 2-weighted magnetic resonance imaging

    DOE PAGES

    Cheng, Kai; Yang, Meng; Zhang, Ruiping; ...

    2014-10-04

    Development of multifunctional nanoparticle-based probes for dual T 1- and T 2-weighted magnetic resonance imaging (MRI) could allow us to image and diagnose the tumors or other abnormalities in an exceptionally accurate and reliable manner. In this study, by fusing distinct nanocrystals via solid-state interfaces, we built hybrid heteronanostructures to combine both T 1 and T 2- weighted contrast agents together for MRI with high accuracy and reliability. The resultant hybrid heterotrimers showed high stability in physiological conditions and could induce both simultaneous positive and negative contrast enhancements in MR images. Small animal positron emission tomography imaging study revealed thatmore » the hybrid heterostructures displayed favorable biodistribution and were suitable for in vivo imaging. Furthermore, their potential as dual contrast agents for T 1 and T 2-weighted MRI was further demonstrated by in vitro and in vivo imaging and relaxivity measurements.« less

  14. Tax Protein-induced Expression of Antiapoptotic Bfl-1 Protein Contributes to Survival of Human T-cell Leukemia Virus Type 1 (HTLV-1)-infected T-cells*♦

    PubMed Central

    Macaire, Héloïse; Riquet, Aurélien; Moncollin, Vincent; Biémont-Trescol, Marie-Claude; Duc Dodon, Madeleine; Hermine, Olivier; Debaud, Anne-Laure; Mahieux, Renaud; Mesnard, Jean-Michel; Pierre, Marlène; Gazzolo, Louis; Bonnefoy, Nathalie; Valentin, Hélène

    2012-01-01

    Human T lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). ATLL is a severe malignancy with no effective treatment. HTLV-1 regulatory proteins Tax and HTLV-1 basic leucine zipper factor (HBZ) play a major role in ATLL development, by interfering with cellular functions such as CD4+ T-cell survival. In this study, we observed that the expression of Bfl-1, an antiapoptotic protein of the Bcl-2 family, is restricted to HTLV-1-infected T-cell lines and to T-cells expressing both Tax and HBZ proteins. We showed that Tax-induced bfl-1 transcription through the canonical NF-κB pathway. Moreover, we demonstrated that Tax cooperated with c-Jun or JunD, but not JunB, transcription factors of the AP-1 family to stimulate bfl-1 gene activation. By contrast, HBZ inhibited c-Jun-induced bfl-1 gene activation, whereas it increased JunD-induced bfl-1 gene activation. We identified one NF-κB, targeted by RelA, c-Rel, RelB, p105/p50, and p100/p52, and two AP-1, targeted by both c-Jun and JunD, binding sites in the bfl-1 promoter of T-cells expressing both Tax and HBZ. Analyzing the potential role of antiapoptotic Bcl-2 proteins in HTLV-1-infected T-cell survival, we demonstrated that these cells are differentially sensitive to silencing of Bfl-1, Bcl-xL, and Bcl-2. Indeed, both Bfl-1 and Bcl-xL knockdowns decreased the survival of HTLV-1-infected T-cell lines, although no cell death was observed after Bcl-2 knockdown. Furthermore, we demonstrated that Bfl-1 knockdown sensitizes HTLV-1-infected T-cells to ABT-737 or etoposide treatment. Our results directly implicate Bfl-1 and Bcl-xL in HTLV-1-infected T-cell survival and suggest that both Bfl-1 and Bcl-xL represent potential therapeutic targets for ATLL treatment. PMID:22553204

  15. Whole brain myelin mapping using T1- and T2-weighted MR imaging data

    PubMed Central

    Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

    2014-01-01

    Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approach is a retrospective calibration algorithm, applied to bias-corrected T1-w and T2-w images, that relies on image intensities outside the brain. This permits standardizing the intensity histogram of the ratio image, thereby allowing for across-subject statistical analyses. Quantitative comparisons of image histograms within and across different datasets confirmed the effectiveness of our normalization procedure. Not only did the calibrated T1-w/T2-w images exhibit a comparable intensity range, but also the shape of the intensity histograms was largely corresponding. We also assessed the reliability and specificity of the ratio image compared to other MR-based techniques, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), and fluid-attenuated inversion recovery (FLAIR). With respect to these other techniques, T1-w/T2-w had consistently high values, as well as low inter-subject variability, in brain structures where myelin is most abundant. Overall, our results suggested that the T1-w/T2-w technique may be a valid tool supporting the non-invasive mapping of myelin in the brain. Therefore, it might find important applications in the study of brain development, aging and disease. PMID:25228871

  16. The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

    PubMed

    Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung; de Jong, Petrus R; Kim, Peter; Han, Tiffany; Yu, Timothy; To, Keith; Takahashi, Naoki; Boland, Brigid S; Chang, John T; Ho, Samuel B; Herdman, Scott; Corr, Maripat; Franco, Alessandra; Sharma, Sonia; Dong, Hui; Akopian, Armen N; Raz, Eyal

    2017-09-01

    Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca 2+ )-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models). We performed electrophysiological and Ca 2+ imaging studies to analyse TRPA1 and TRPV1 functions in CD4+ T cells. We used genetic and pharmacological approaches to evaluate TRPV1 contribution to the phenotype of Trpa1 -/- CD4+ T cells. We also analysed TRPA1 and TRPV1 gene expression and TRPA1 + TRPV1 + T cell infiltration in colonic biopsies from patients with IBD. We identified a protective role for TRPA1 in T-cell-mediated colitis. We demonstrated the functional expression of TRPA1 on the plasma membrane of CD4+ T cells and identified that Trpa1 -/- CD4+ T cells have increased T-cell receptor-induced Ca 2+ influx, activation profile and differentiation into Th1-effector cells. This phenotype was abrogated upon genetic deletion or pharmacological inhibition of the TRPV1 channel in mouse and human CD4+ T cells. Finally, we found differential regulation of TRPA1 and TRPV1 gene expression as well as increased infiltration of TRPA1 + TRPV1 + T cells in the colon of patients with IBD. Our study indicates that TRPA1 inhibits TRPV1 channel activity in CD4+ T cells, and consequently restrains CD4+ T-cell activation and colitogenic responses. These findings may therefore have therapeutic implications for human IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Programmed death-1 controls T cell survival by regulating oxidative metabolism1

    PubMed Central

    Tkachev, Victor; Goodell, Stefanie; Opipari, Anthony W.; Hao, Ling-Yang; Franchi, Luigi; Glick, Gary D.; Ferrara, James L.M.; Byersdorfer, Craig A.

    2015-01-01

    The co-inhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly up-regulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1HiROSHi phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and total cellular ROS levels and PD-1 driven increases in ROS were dependent upon the oxidation of fatty acids, as treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by anti-oxidants. Furthermore, PD-1 driven changes in ROS were fundamental to establishing a cell’s susceptibility to subsequent metabolic inhibition, as blockade of PD-1 decreased the efficacy of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing reactive oxygen species in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti-PD-1 therapies in the clinic. PMID:25972478

  18. Comparison of axial T1 spin-echo and T1 fat-saturation magnetic resonance imaging techniques in the diagnosis of chondromalacia patellae.

    PubMed

    Vanarthos, W J; Pope, T L; Monu, J U

    1994-12-01

    To test the diagnostic value of T1 spin-echo and T1 fat-saturated magnetic resonance images (MRIs), we reviewed axial T1-weighted images with and without fat saturation in 20 patients with clinically suspected chondromalacia of the patella. All scans were obtained on 1.5-MR units. The scans were randomly ordered and reviewed independently at different times by two radiologists without knowledge of the arthroscopy results. The sensitivity of the individual techniques for detecting grade 3 or 4 chondromalacia patellae was 92% for fat-saturated axial T1-weighted images alone, and 67% for axial T1-weighted images without fat saturation. The sensitivity of the combined techniques was 100% for grades 3 and 4 and 90% for all grades (0 to 4). Chondromalacia patellae is diagnosed more accurately by using T1 fat saturation than by using T1 spin-echo images. With a combination of the two techniques, accuracy is 90% to 100%.

  19. Saturation pulse design for quantitative myocardial T1 mapping.

    PubMed

    Chow, Kelvin; Kellman, Peter; Spottiswoode, Bruce S; Nielles-Vallespin, Sonia; Arai, Andrew E; Salerno, Michael; Thompson, Richard B

    2015-10-01

    Quantitative saturation-recovery based T1 mapping sequences are less sensitive to systematic errors than the Modified Look-Locker Inversion recovery (MOLLI) technique but require high performance saturation pulses. We propose to optimize adiabatic and pulse train saturation pulses for quantitative T1 mapping to have <1 % absolute residual longitudinal magnetization (|MZ/M0|) over ranges of B0 and [Formula: see text] (B1 scale factor) inhomogeneity found at 1.5 T and 3 T. Design parameters for an adiabatic BIR4-90 pulse were optimized for improved performance within 1.5 T B0 (±120 Hz) and [Formula: see text] (0.7-1.0) ranges. Flip angles in hard pulse trains of 3-6 pulses were optimized for 1.5 T and 3 T, with consideration of T1 values, field inhomogeneities (B0 = ±240 Hz and [Formula: see text]=0.4-1.2 at 3 T), and maximum achievable B1 field strength. Residual MZ/M0 was simulated and measured experimentally for current standard and optimized saturation pulses in phantoms and in-vivo human studies. T1 maps were acquired at 3 T in human subjects and a swine using a SAturation recovery single-SHot Acquisition (SASHA) technique with a standard 90°-90°-90° and an optimized 6-pulse train. Measured residual MZ/M0 in phantoms had excellent agreement with simulations over a wide range of B0 and [Formula: see text]. The optimized BIR4-90 reduced the maximum residual |MZ/M0| to <1 %, a 5.8× reduction compared to a reference BIR4-90. An optimized 3-pulse train achieved a maximum residual |MZ/M0| <1 % for the 1.5 T optimization range compared to 11.3 % for a standard 90°-90°-90° pulse train, while a 6-pulse train met this target for the wider 3 T ranges of B0 and [Formula: see text]. The 6-pulse train demonstrated more uniform saturation across both the myocardium and entire field of view than other saturation pulses in human studies. T1 maps were more spatially homogeneous with 6-pulse train SASHA than the reference 90°-90°-90° SASHA in both

  20. Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing.

    PubMed

    Shirazi-Beechey, Soraya P; Daly, Kristian; Al-Rammahi, Miran; Moran, Andrew W; Bravo, David

    2014-06-01

    Luminal nutrient sensing by G-protein-coupled receptors (GPCR) expressed on the apical domain of enteroendocrine cells activates intracellular pathways leading to secretion of gut hormones that control vital physiological processes such as digestion, absorption, food intake and glucose homeostasis. The taste 1 receptor (T1R) family of GPCR consists of three members: T1R1; T1R2; T1R3. Expression of T1R1, T1R2 and T1R3 at mRNA and protein levels has been demonstrated in the intestinal tissue of various species. It has been shown that T1R2-T1R3, in association with G-protein gustducin, is expressed in intestinal K and L endocrine cells, where it acts as the intestinal glucose (sweet) sensor. A number of studies have demonstrated that activation of T1R2-T1R3 by natural sugars and artificial sweeteners leads to secretion of glucagon-like peptides 1&2 (GLP-1 and GLP-2) and glucose dependent insulinotropic peptide (GIP). GLP-1 and GIP enhance insulin secretion; GLP-2 increases intestinal growth and glucose absorption. T1R1-T1R3 combination co-expressed on the apical domain of cholecystokinin (CCK) expressing cells is a luminal sensor for a number of L-amino acids; with amino acid-activation of the receptor eliciting CCK secretion. This article focuses on the role of the gut-expressed T1R1, T1R2 and T1R3 in intestinal sweet and L-amino acid sensing. The impact of exploiting T1R2-T1R3 as a nutritional target for enhancing intestinal glucose absorption and gut structural maturity in young animals is also highlighted.

  1. 26 CFR 1.7519-3T - Effective date (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Effective date (temporary). 1.7519-3T Section 1.7519-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES The Tax Court § 1.7519-3T Effective date (temporary). The provisions of §§ 1.7519-1T...

  2. Three-dimensional T1rho-weighted MRI at 1.5 Tesla.

    PubMed

    Borthakur, Arijitt; Wheaton, Andrew; Charagundla, Sridhar R; Shapiro, Erik M; Regatte, Ravinder R; Akella, Sarma V S; Kneeland, J Bruce; Reddy, Ravinder

    2003-06-01

    To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner. Copyright 2003

  3. MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

    PubMed

    Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

    2017-04-01

    To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  4. The Absence of Interleukin 1 Receptor–Related T1/St2 Does Not Affect T Helper Cell Type 2 Development and Its Effector Function

    PubMed Central

    Hoshino, Katsuaki; Kashiwamura, Shin-ichiro; Kuribayashi, Kozo; Kodama, Taku; Tsujimura, Tohru; Nakanishi, Kenji; Matsuyama, Tomohiro; Takeda, Kiyoshi; Akira, Shizuo

    1999-01-01

    T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2−/−) mice and examined the roles of T1/ST2. Naive CD4+ T cells isolated from T1/ST2−/− mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2−/− mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow–derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells. PMID:10562328

  5. T1ρ MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration

    PubMed Central

    Witschey, Walter RT; Borthakur, Arijitt; Fenty, Matt; Kneeland, J Bruce; Lonner, Jess H; McArdle, Erin L.; Sochor, Matt; Reddy, Ravinder

    2010-01-01

    9 asymptomatic subjects and 6 patients underwent T1ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2–3 months post-arthroscopy using sagittal T1-weighted and axial and coronal T1ρ MRI from which spatial T1ρ relaxation maps were calculated from segmented T1-weighted images. Median T1ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (p < 0.001) and median T1ρ exceeded asymptomatic articular cartilage median T1ρ by 2.5 to 9.2 ms. In 8 observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1ρ was elevated in 5, but in all observations, large foci of increased T1ρ were observed. It was determined that T1ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. PMID:20432308

  6. High phase-purity 1T'-MoS2- and 1T'-MoSe2-layered crystals

    NASA Astrophysics Data System (ADS)

    Yu, Yifu; Nam, Gwang-Hyeon; He, Qiyuan; Wu, Xue-Jun; Zhang, Kang; Yang, Zhenzhong; Chen, Junze; Ma, Qinglang; Zhao, Meiting; Liu, Zhengqing; Ran, Fei-Rong; Wang, Xingzhi; Li, Hai; Huang, Xiao; Li, Bing; Xiong, Qihua; Zhang, Qing; Liu, Zheng; Gu, Lin; Du, Yonghua; Huang, Wei; Zhang, Hua

    2018-06-01

    Phase control plays an important role in the precise synthesis of inorganic materials, as the phase structure has a profound influence on properties such as conductivity and chemical stability. Phase-controlled preparation has been challenging for the metallic-phase group-VI transition metal dichalcogenides (the transition metals are Mo and W, and the chalcogens are S, Se and Te), which show better performance in electrocatalysis than their semiconducting counterparts. Here, we report the large-scale preparation of micrometre-sized metallic-phase 1T'-MoX2 (X = S, Se)-layered bulk crystals in high purity. We reveal that 1T'-MoS2 crystals feature a distorted octahedral coordination structure and are convertible to 2H-MoS2 following thermal annealing or laser irradiation. Electrochemical measurements show that the basal plane of 1T'-MoS2 is much more active than that of 2H-MoS2 for the electrocatalytic hydrogen evolution reaction in an acidic medium.

  7. DJ-1/Park7 Sensitive Na+ /H+ Exchanger 1 (NHE1) in CD4+ T Cells.

    PubMed

    Zhou, Yuetao; Shi, Xiaolong; Chen, Hong; Zhang, Shaqiu; Salker, Madhuri S; Mack, Andreas F; Föller, Michael; Mak, Tak W; Singh, Yogesh; Lang, Florian

    2017-11-01

    DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na + /H + exchanger 1 (NHE1). ROS formation in CD4 + T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-1 is expressed in CD4 + T cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ-1 and NHE1 transcript, and protein levels were quantified by qRT-PCR and Western blotting, respectively, intracellular pH (pH i ) utilizing bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed in CD4 + T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4 + T cells from DJ-1 deficient mice than in CD4 + T cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1 deficient CD4 + T cells, and blunted the difference between DJ-1 -/- and DJ-1 +/+ CD4 + T cells, an observation pointing to a role of ROS in the up-regulation of NHE1 in DJ-1 -/- CD4 + T cells. In conclusion, DJ-1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4 + T cells. J. Cell. Physiol. 232: 3050-3059, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3 T

    PubMed Central

    Li, Yan; Srinivasan, Radhika; Ratiney, Helene; Lu, Ying; Chang, Susan M.; Nelson, Sarah J.

    2011-01-01

    Purpose To measure T1 and T2 relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. Materials and Methods Twenty-three patients with gliomas and ten volunteers were studied with single voxel 2D J-resolved PRESS using a 3T MR scanner. Voxels were chosen in normal appearing white matter and in regions of tumor. The T1 and T2 of choline containing compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) were estimated. Results Metabolite T1 relaxation values in gliomas were not significantly different from values in normal white matter. The T2 of Cho and Cr were statistically significantly longer for Grade 4 gliomas than for normal white matter but the T2 of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P<0.001). Conclusion The differential increase in T2 for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MRSI data, where limited time is available and only one echo time can be used. PMID:18666155

  9. Definitive Radiotherapy for T1-T2 Squamous Cell Carcinoma of Pyriform Sinus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rabbani, Anna; Amdur, Robert J.; Mancuso, Anthony A.

    2008-10-01

    Purpose: To report the long-term results after definitive radiotherapy (RT) for T1-T2 pyriform sinus squamous cell carcinoma. Patients and Methods: The data from 123 patients with T1-T2 pyriform sinus squamous cell carcinoma treated with RT with or without neck dissection between November 1964 and June 2003 were analyzed. The median follow-up for all patients was 3.2 years, and the median follow-up for living patients was 10.7 years. Results: The 5-year local control, locoregional control, freedom from distant metastasis, cause-specific survival, and overall survival rate was 85%, 70%, 75%, 61%, and 35%, respectively. The ultimate local control rate, including successful salvagemore » of RT failure, for T1 and T2 cancer patients was 96% and 94%, respectively. The overall local control rate with a functional larynx was 83%. Pretreatment computed tomography tumor volume data were available for 55 patients. The median computed tomography tumor volume was 4.2 cm{sup 3} (range, 0-22.4). Local control was worse for patients with a tumor volume >6.5 cm{sup 3} compared with those with a smaller tumor volume. Of the 123 patients, 16% developed moderate to severe acute (2%), late (9%), or postoperative (5%) complications. Conclusions: Local control with larynx preservation after definitive RT for T1-T2 pyriform sinus squamous cell carcinoma likely results in local control and survival similar to that after total laryngectomy or larynx-conserving surgery. Two-thirds of our living patients retained a functional larynx.« less

  10. TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax.

    PubMed

    Ma, Guangyong; Yasunaga, Jun-ichirou; Akari, Hirofumi; Matsuoka, Masao

    2015-02-17

    Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-κB and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.

  11. Early postnatal myelin content estimate of white matter via T1w/T2w ratio

    NASA Astrophysics Data System (ADS)

    Lee, Kevin; Cherel, Marie; Budin, Francois; Gilmore, John; Zaldarriaga Consing, Kirsten; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Glasser, Matthew F.; Van Essen, David C.; Buss, Claudia; Styner, Martin

    2015-03-01

    To develop and evaluate a novel processing framework for the relative quantification of myelin content in cerebral white matter (WM) regions from brain MRI data via a computed ratio of T1 to T2 weighted intensity values. We employed high resolution (1mm3 isotropic) T1 and T2 weighted MRI from 46 (28 male, 18 female) neonate subjects (typically developing controls) scanned on a Siemens Tim Trio 3T at UC Irvine. We developed a novel, yet relatively straightforward image processing framework for WM myelin content estimation based on earlier work by Glasser, et al. We first co-register the structural MRI data to correct for motion. Then, background areas are masked out via a joint T1w and T2 foreground mask computed. Raw T1w/T2w-ratios images are computed next. For purpose of calibration across subjects, we first coarsely segment the fat-rich facial regions via an atlas co-registration. Linear intensity rescaling based on median T1w/T2w-ratio values in those facial regions yields calibrated T1w/T2wratio images. Mean values in lobar regions are evaluated using standard statistical analysis to investigate their interaction with age at scan. Several lobes have strongly positive significant interactions of age at scan with the computed T1w/T2w-ratio. Most regions do not show sex effects. A few regions show no measurable effects of change in myelin content change within the first few weeks of postnatal development, such as cingulate and CC areas, which we attribute to sample size and measurement variability. We developed and evaluated a novel way to estimate white matter myelin content for use in studies of brain white matter development.

  12. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived...

  13. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived...

  14. Enforced IL-10 Expression Confers Type 1 Regulatory T Cell (Tr1) Phenotype and Function to Human CD4+ T Cells

    PubMed Central

    Andolfi, Grazia; Fousteri, Georgia; Rossetti, Maura; Magnani, Chiara F; Jofra, Tatiana; Locafaro, Grazia; Bondanza, Attilio; Gregori, Silvia; Roncarolo, Maria-Grazia

    2012-01-01

    Type 1 regulatory T (Tr1) cells are an inducible subset of CD4+ Tr cells characterized by high levels of interleukin (IL)-10 production and regulatory properties. Several protocols to generate human Tr1 cells have been developed in vitro. However, the resulting population includes a significant fraction of contaminating non-Tr1 cells, representing a major bottleneck for clinical application of Tr1 cell therapy. We generated an homogeneous IL-10–producing Tr1 cell population by transducing human CD4+ T cells with a bidirectional lentiviral vector (LV) encoding for human IL-10 and the marker gene, green fluorescent protein (GFP), which are independently coexpressed. The resulting GFP+ LV-IL-10–transduced human CD4+ T (CD4LV-IL-10) cells expressed, upon T-cell receptor (TCR) activation, high levels of IL-10 and concomitant low levels of IL-4, and markers associated with IL-10. Moreover, CD4LV-IL-10 T cells displayed typical Tr1 features: the anergic phenotype, the IL-10, and transforming growth factor (TGF)-β dependent suppression of allogeneic T-cell responses, and the ability to suppress in a cell-to-cell contact independent manner in vitro. CD4LV-IL-10 T cells were able to control xeno graft-versus-host disease (GvHD), demonstrating their suppressive function in vivo. These results show that constitutive over-expression of IL-10 in human CD4+ T cells leads to a stable cell population that recapitulates the phenotype and function of Tr1 cells. PMID:22692497

  15. The XENON1T dark matter experiment

    NASA Astrophysics Data System (ADS)

    Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Antunes, B.; Arneodo, F.; Balata, M.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breskin, A.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Chiarini, A.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Corrieri, R.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; Gangi, P. Di; Giovanni, A. Di; Diglio, S.; Disdier, J.-M.; Doets, M.; Duchovni, E.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Franco, D.; Front, D.; Fulgione, W.; Rosso, A. Gallo; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Giboni, K.-L.; Goetzke, L. W.; Grandi, L.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Huhmann, C.; Itay, R.; James, A.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Maier, R.; Manfredini, A.; Maris, I.; Undagoitia, T. Marrodán; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morå, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Orlandi, D.; Othegraven, R.; Pakarha, P.; Parlati, S.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; García, D. Ramírez; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Santos, J. M. F. dos; Saldanha, R.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Lavina, L. Scotto; Selvi, M.; Shagin, P.; Shockley, E.; Silva, M.; Simgen, H.; Sivers, M. v.; Stern, M.; Stein, A.; Tatananni, D.; Tatananni, L.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Upole, N.; Vargas, M.; Wack, O.; Walet, R.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wittweg, C.; Wulf, J.; Ye, J.; Zhang, Y.

    2017-12-01

    The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.

  16. Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion.

    PubMed

    Utz, U; Banks, D; Jacobson, S; Biddison, W E

    1996-02-01

    Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers, show very high precursor frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific T cells were demonstrated to be directed predominantly against one HTLV-1 epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An analysis of the T-cell receptor (TCR) repertoire of these cells revealed an absence of restricted variable (V) region usage. Different combinations of TCR V alpha and V beta genes were utilized between, but also within, the individual patients for the recognition of Tax11-19. Sequence analysis of the TCR showed evidence for an oligoclonal expansion of few founder T cells in each patient. Apparent structural motifs were identified for the CDR3 regions of the TCR beta chains. One T-cell clone could be detected within the same patient over a period of 3 years. We suggest that these in vivo clonally expanded T cells might play a role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific TCR which may elucidate the nature of the T cells that infiltrate the central nervous system in HAM/TSP patients.

  17. Individual T1-weighted/T2-weighted ratio brain networks: Small-worldness, hubs and modular organization

    NASA Astrophysics Data System (ADS)

    Wu, Huijun; Wang, Hao; Lü, Linyuan

    Applying network science to investigate the complex systems has become a hot topic. In neuroscience, understanding the architectures of complex brain networks was a vital issue. An enormous amount of evidence had supported the brain was cost/efficiency trade-off with small-worldness, hubness and modular organization through the functional MRI and structural MRI investigations. However, the T1-weighted/T2-weighted (T1w/T2w) ratio brain networks were mostly unexplored. Here, we utilized a KL divergence-based method to construct large-scale individual T1w/T2w ratio brain networks and investigated the underlying topological attributes of these networks. Our results supported that the T1w/T2w ratio brain networks were comprised of small-worldness, an exponentially truncated power-law degree distribution, frontal-parietal hubs and modular organization. Besides, there were significant positive correlations between the network metrics and fluid intelligence. Thus, the T1w/T2w ratio brain networks open a new avenue to understand the human brain and are a necessary supplement for future MRI studies.

  18. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis.

    PubMed

    Chae, Wook-Jin; Park, Jong-Hyun; Henegariu, Octavian; Yilmaz, Saliha; Hao, Liming; Bothwell, Alfred L M

    2017-10-01

    Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3 + regulatory T (Treg) cells use Dickkopf-1 (DKK-1) to regulate T-cell-mediated tolerance in the T-cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4 + T-cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymus-derived Treg cells showed a robust expression of DKK-1 but not in naive or effector CD4 T cells. DKK-1 expression in Foxp3 + Treg cells was further increased upon T-cell receptor stimulation in vitro and in vivo. Interestingly, Foxp3 + Treg cells expressed DKK-1 in the cell membrane and the functional inhibition of DKK-1 using DKK-1 monoclonal antibody abrogated the suppressor function of Foxp3 + Treg cells. DKK-1 expression was dependent on de novo protein synthesis and regulated by the mitogen-activated protein kinase pathway but not by the canonical Wnt pathway. Taken together, our results highlight membrane-bound DKK-1 as a novel Treg-derived mediator to maintain immunological tolerance in T-cell-mediated autoimmune colitis. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  19. [Laser debulking surgery prior to radiotherapy for T1T2 carcinoma of the hypopharynx].

    PubMed

    Mori, K; Chijiwa, K; Umeno, H; Umeno, T; Sakamoto, K

    2000-09-01

    The local control rate for T1-T2 carcinomas of the hypopharynx is rather high whereas the overall survival rate is unsatisfactory, irrespective of treatment modalities. Radical radiotherapy has yielded a local control rate of 40-70% and an overall 5-year survival of 30-50%, while surgical treatment with or without postoperative radiotherapy has yielded a local control rate of 60-90% and an overall 5-year survival rate of 30-60%. Based on these reasons, for the patients with minor hypopharyngeal lesions, such as T1-T2 carcinomas, in the Kurume University Hospital radiotherapy has often been selected as a first choice instead of partial pharyngectomy. If the primary lesion is exophytic and has a large volume, laser debulking surgery has been employed prior to radiotherapy to improve the local control rate. The purpose of the present study is to describe the details of laser debulking surgery prior to radiotherapy (LDSR) for the treatment of T1-T2 carcinomas of the hypopharynx. In addition, the preliminary results for this treatment procedure will also be compared with the results of partial pharyngectomies preserving the larynx (PPPL) that were performed in the Kurume University Hospital. In this study 20 patients (T1: 4, T2: 16) who had undergone PPPL and 16 patients (T1: 4, T2: 12) who had undergone LDSR were included. For patients undergoing PPPL, the 5-year local control rate, 5-year larynx conservation rate and disease specific 5-year survival rate were 83.6%, 70.4%, and 75.0%, respectively, whereas for patients undergoing LDSR these were 87.1%, 93.8%, 87.5% respectively. Although the treatment outcomes by LDSR did not show a significant drastic improvement compared with those by PPPL, the quality of life of the patients undergoing LDSR was not aggravated. LDSR may thus be preferable to PPPL for selected cases of T1-T2 carcinomas of the hypopharynx.

  20. Spatial Distribution and Relationship of T1ρ and T2 Relaxation Times in Knee Cartilage With Osteoarthritis

    PubMed Central

    Li, Xiaojuan; Pai, Alex; Blumenkrantz, Gabrielle; Carballido-Gamio, Julio; Link, Thomas; Ma, Benjamin; Ries, Michael; Majumdar, Sharmila

    2009-01-01

    T1ρ and T2 relaxation time constants have been proposed to probe biochemical changes in osteoarthritic cartilage. This study aimed to evaluate the spatial correlation and distribution of T1ρ and T2 values in osteoarthritic cartilage. Ten patients with osteoarthritis (OA) and 10 controls were studied at 3T. The spatial correlation of T1ρ and T2 values was investigated using Z-scores. The spatial variation of T1ρ and T2 values in patellar cartilage was studied in different cartilage layers. The distribution of these relaxation time constants was measured using texture analysis parameters based on gray-level co-occurrence matrices (GLCM). The mean Z-scores for T1ρ and T2 values were significantly higher in OA patients vs. controls (P < 0.05). Regional correlation coefficients of T1ρ and T2 Z-scores showed a large range in both controls and OA patients (0.2– 0.7). OA patients had significantly greater GLCM contrast and entropy of T1ρ values than controls (P < 0.05). In summary, T1ρ and T2 values are not only increased but are also more heterogeneous in osteoarthritic cartilage. T1ρ and T2 values show different spatial distributions and may provide complementary information regarding cartilage degeneration in OA. PMID:19319904

  1. Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

    PubMed

    Smith, Kimberly R; Spector, Alan C

    2017-10-01

    Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1 ) detectable when both receptor subunits are absent and 2 ) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose. Copyright © 2017 the American Physiological Society.

  2. Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

    PubMed

    Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

    2018-01-01

    Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

  3. PD-1 regulates extrathymic regulatory T-cell differentiation

    PubMed Central

    Chen, Xiufen; Fosco, Dominick; Kline, Douglas E.; Meng, Liping; Nishi, Saki; Savage, Peter A.; Kline, Justin

    2014-01-01

    Regulatory T (Treg) cells and the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway are both critical for maintaining peripheral tolerance to self antigens. A significant subset of Treg cells constitutively expresses PD-1, which prompted an investigation into the role of PD-1/PD-L1 interactions in Treg-cell development, function and induction in vivo. The phenotype and abundance of Treg cells was not significantly altered in PD-1-deficient mice. The thymic development of polyclonal and monospecific Treg cells was not negatively impacted by PD-1 deficiency. The suppressive function of PD-1−/− Treg cells was similar to their PD-1+/+ counterparts both in vitro and in vivo. However, in three different in vivo experimental settings, PD-1−/− conventional CD4+ T cells demonstrated a strikingly diminished tendency toward differentiation into peripherally induced Treg (pTreg) cells. Our results demonstrate that PD-1 is dispensable for thymic (tTreg) Treg-cell development and suppressive function, but is critical for the extrathymic differentiation of pTreg cells in vivo. These data suggest that antibody blockade of the PD-1/PD-L1 pathway may augment T-cell responses by acting directly on conventional T cells, and also by suppressing the differentiation of pTreg cells. PMID:24975127

  4. Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

    NASA Astrophysics Data System (ADS)

    Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

    2018-04-01

    Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

  5. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis.

    PubMed

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2017-05-01

    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  6. Correlation study between facet joint cartilage and intervertebral discs in early lumbar vertebral degeneration using T2, T2* and T1ρ mapping

    PubMed Central

    Zhang, Yi; Hu, Jianzhong; Duan, Chunyue; Hu, Ping; Lu, Hongbin; Peng, Xianjing

    2017-01-01

    Recent advancements in magnetic resonance imaging have allowed for the early detection of biochemical changes in intervertebral discs and articular cartilage. Here, we assessed the feasibility of axial T2, T2* and T1ρ mapping of the lumbar facet joints (LFJs) to determine correlations between cartilage and intervertebral discs (IVDs) in early lumbar vertebral degeneration. We recruited 22 volunteers and examined 202 LFJs and 101 IVDs with morphological (sagittal and axial FSE T2-weighted imaging) and axial biochemical (T2, T2* and T1ρ mapping) sequences using a 3.0T MRI scanner. IVDs were graded using the Pfirrmann system. Mapping values of LFJs were recorded according to the degeneration grades of IVDs at the same level. The feasibility of T2, T2* and T1ρ in IVDs and LFJs were analyzed by comparing these mapping values across subjects with different rates of degeneration using Kruskal-Wallis tests. A Pearson’s correlation analysis was used to compare T2, T2* and T1ρ values of discs and LFJs. We found excellent reproducibility in the T2, T2* and T1ρ values for the nucleus pulposus (NP), anterior and posterior annulus fibrosus (PAF), and LFJ cartilage (intraclass correlation coefficients 0.806–0.955). T2, T2* and T1ρ mapping (all P<0.01) had good Pfirrmann grade performances in the NP with IVD degeneration. LFJ T2* values were significantly different between grades I and IV (PL = 0.032, PR = 0.026), as were T1ρ values between grades II and III (PL = 0.002, PR = 0.006) and grades III and IV (PL = 0.006, PR = 0.001). Correlations were moderately negative for T1ρ values between LFJ cartilage and NP (rL = −0.574, rR = −0.551), and between LFJ cartilage and PAF (rL = −0.551, rR = −0.499). T1ρ values of LFJ cartilage was weakly correlated with T2 (r = 0.007) and T2* (r = −0.158) values. Overall, we show that axial T1ρ effectively assesses early LFJ cartilage degeneration. Using T1ρ analysis, we propose a link between LFJ degeneration and IVD NP or

  7. The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential.

    PubMed

    Sprous, Dennis; Palmer, Kyle R

    2010-01-01

    Taste signaling is a critical determinant of ingestive behaviors and thereby linked to obesity and related metabolic dysfunctions. Recent evidence of taste signaling pathways in the gut suggests the link to be more direct, raising the possibility that taste receptor systems could be regarded as therapeutic targets. T1R2/T1R3, the G protein coupled receptor that mediates sweet taste, and the TRPM5 ion channel have been the focus of discovery programs seeking novel compounds that could be useful in modifying taste. We review in this chapter the hypothesis of gastrointestinal taste signaling and discuss the potential for T1R2/T1R3 and TRPM5 as targets of therapeutic intervention in obesity and diabetes. Critical to the development of a drug discovery program is the creation of libraries that enhance the likelihood of identifying novel compounds that modulate the target of interest. We advocate a computer-based chemoinformatic approach for assembling natural and synthetic compound libraries as well as for supporting optimization of structure activity relationships. Strategies for discovering modulators of T1R2/T1R3 and TRPM5 using methods of chemoinformatics are presented herein. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Revisiting the human polypeptide GalNAc-T1 and T13 paralogs

    PubMed Central

    Festari, María Florencia; Trajtenberg, Felipe; Berois, Nora; Pantano, Sergio; Revoredo, Leslie; Kong, Yun; Solari-Saquieres, Patricia; Narimatsu, Yoshiki; Freire, Teresa; Bay, Sylvie; Robello, Carlos; Bénard, Jean; Gerken, Thomas A; Clausen, Henrik; Osinaga, Eduardo

    2017-01-01

    Polypeptide GalNAc-transferases (GalNAc-Ts) constitute a family of 20 human glycosyltransferases (comprising 9 subfamilies), which initiate mucin-type O-glycosylation. The O-glycoproteome is thought to be differentially regulated via the different substrate specificities and expression patterns of each GalNAc-T isoforms. Here, we present a comprehensive in vitro analysis of the peptide substrate specificity of GalNAc-T13, showing that it essentially overlaps with the ubiquitous expressed GalNAc-T1 isoform found in the same subfamily as T13. We have also identified and partially characterized nine splice variants of GalNAc-T13, which add further complexity to the GalNAc-T family. Two variants with changes in their lectin domains were characterized by in vitro glycosylation assays, and one (Δ39Ex9) was inactive while the second one (Ex10b) had essentially unaltered activity. We used reverse transcription-polymerase chain reaction analysis of human neuroblastoma cell lines, normal brain and a small panel of neuroblastoma tumors to demonstrate that several splice variants (Ex10b, ΔEx9, ΔEx2-7 and ΔEx6/8-39bpEx9) were highly expressed in tumor cell lines compared with normal brain, although the functional implications remain to be unveiled. In summary, the GalNAc-T13 isoform is predicted to function similarly to GalNAc-T1 against peptide substrates in vivo, in contrast to a prior report, but is unique by being selectively expressed in the brain. PMID:27913570

  9. Outcomes of T1b esophageal adenocarcinoma patients.

    PubMed

    Tian, Jianmin; Prasad, Ganapathy A; Lutzke, Lori S; Lewis, Jason T; Wang, Kenneth K

    2011-12-01

    Esophagectomy is usually recommended for patients with submucosal esophageal adenocarcinoma (T1b EAC) because of the potential for lymph node metastasis (LNM). Endoscopic management often differs based on the risk of metastasis. There is limited information on the difference in outcomes for T1b-EAC with and without esophagectomy. To investigate (1) the outcomes of T1b EAC treatments with and without esophagectomy and (2) the percentage of LNM at esophagectomy for T1b-EAC. Retrospective cohort. A tertiary Barrett's esophagus unit. Sixty-eight T1b EAC patients based on EMR histology. Esophagectomy and endoscopic therapies. Survival duration and mortality rate. A total of 68 patients had T1b EAC; cumulative mortality rate was 30.9% and median survival duration was 39.5 months. Thirty-nine underwent esophagectomy and 29 did not. Among patients who underwent esophagectomy, 13 (33.3%) had LNM, and the mortality rate was 50.0% and 11.1% for those with and without LNM, respectively (P < .01). For those with and without esophagectomy, the cumulative mortality rates were 25.6% and 37.9%, and median survival duration was 48.9 and 34.8 months, respectively. There was no statistical difference in Charlson comorbidity index, number of EMRs, mortality rate, or survival duration. In Cox proportional hazard model analysis, the hazard ratio for esophagectomy was 0.5 (P = .21). Retrospective, nonrandomized small sample size cohort. Among the patients with T1b EAC found in EMR specimens who underwent esophagectomy, one third had regional LNM. In our small series, patients who underwent esophagectomy did not have a significantly different survival duration from that of those who did not, indicating that these patients may have similar outcomes [corrected]. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  10. 46 CFR 34.13-1 - Application-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 34.13-1 Section 34.13-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Steam Smothering Systems § 34.13-1 Application—T/ALL. Steam smothering fire extinguishing systems are not permitted on...

  11. 46 CFR 34.15-1 - Application-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 34.15-1 Section 34.15-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Carbon Dioxide Extinguishing Systems, Details § 34.15-1 Application—T/ALL. (a) Where a carbon dioxide extinguishing system is...

  12. 46 CFR 34.25-1 - Application-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 34.25-1 Section 34.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Water Spray Extinguishing Systems, Details § 34.25-1 Application—T/ALL. (a) Where a water spray extinguishing system is...

  13. 46 CFR 34.25-1 - Application-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL. 34.25-1 Section 34.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Water Spray Extinguishing Systems, Details § 34.25-1 Application—T/ALL. (a) Where a water spray extinguishing system is...

  14. 46 CFR 34.17-1 - Application-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL. 34.17-1 Section 34.17-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Fixed Foam Extinguishing Systems, Details § 34.17-1 Application—T/ALL. (a) Where a fixed foam extinguishing system is...

  15. 46 CFR 34.17-1 - Application-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 34.17-1 Section 34.17-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Fixed Foam Extinguishing Systems, Details § 34.17-1 Application—T/ALL. (a) Where a fixed foam extinguishing system is...

  16. 46 CFR 34.13-1 - Application-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL. 34.13-1 Section 34.13-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Steam Smothering Systems § 34.13-1 Application—T/ALL. Steam smothering fire extinguishing systems are not permitted on...

  17. 26 CFR 1.709-1T - Treatment of organizational expenses and syndication costs (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... syndication costs (temporary). 1.709-1T Section 1.709-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... § 1.709-1T Treatment of organizational expenses and syndication costs (temporary). (a) [Reserved] For... organizational expenses for two or more taxable years. (3) Liquidation of partnership. If there is a winding up...

  18. Radiculopathy in the setting of lumbar nerve root compression due to an extradural intraforaminal lipoma: a report of 3 cases.

    PubMed

    Loriaux, Daniel B; Adogwa, Owoicho; Gottfried, Oren N

    2015-07-01

    A true adult spinal lipoma is an exceedingly rare cause of lumbar compression neuropathy. Only 5 cases of true extradural intraforaminal lipomas have been documented in the medical literature. The diagnostic criteria and treatment guidelines for this specific lipoma have yet to be established. This report features 3 histologically confirmed cases of extradural intraforaminal spinal lipomas that recently presented to the authors' practice. In addition, the literature was surveyed to include the 5 previously reported cases of true adult extradural intraforaminal spinal lipomas. The consistency in presentation, response to surgical intervention, and postoperative recovery in these 8 cases supports surgical intervention at the time of diagnosis. The authors' findings support elevated clinical suspicion, efficient diagnosis based on MRI, and early surgical intervention for this rare pathological entity. All cases presented in this report were symptomatic and occurred in the absence of other significant pathologies such as general spinal epidural lipomatosis, intradural lesions, tethering, or severe degenerative stenosis or herniated discs. The clinical, neuroradiological, and histological findings characteristic of a true adult extradural intraforaminal lipoma are emphasized to differentiate this lesion from the more common etiologies for lumbar compression neuropathy. Heightened awareness and clinical suspicion for the focal, foraminal spinal lipoma as a cause of radiculopathy symptoms will enable more efficient diagnosis and treatment.

  19. 46 CFR 34.60-1 - Application-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL. 34.60-1 Section 34.60-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Fire Axes § 34.60-1 Application—T/ALL. (a) The provisions of this subpart shall apply to all tankships. (b) [Reserved] ...

  20. 46 CFR 34.60-1 - Application-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 34.60-1 Section 34.60-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Fire Axes § 34.60-1 Application—T/ALL. (a) The provisions of this subpart shall apply to all tankships. (b) [Reserved] ...

  1. T1 correlates age: A short-TE MR relaxometry study in vivo on human cortical bone free water at 1.5T.

    PubMed

    Akbari, Atena; Abbasi-Rad, Shahrokh; Rad, Hamidreza Saligheh

    2016-02-01

    Large pores of human cortical bone (>30μm) are filled with fluids, essentially consisting of water, suggesting that cortical bone free water can be considered as a reliable surrogate measure of cortical bone porosity and hence quality. Signal from such pores can be reliably captured using Short Echo Time (STE) pulse sequence with echo-time in the range of 1-1.5msec (which should be judiciously selected correspond to T2(⁎) value of free water molecules). Furthermore, it is well-known that cortical bone T1-relaxivity is a function of its geometry, suggesting that cortical bone free water increases with age. In this work, we quantified cortical bone free water longitudinal relaxation time (T1) by a Dual-TR technique using STE pulse sequence. In the sequel, we investigated relationship between STE-derived cortical bone free water T1-values and age in a group of healthy volunteers (thirty subjects covering the age range of 20-70years) at 1.5T. Preliminary results showed that cortical bone free water T1 highly correlates with age (r(2)=0.73, p<0.0001), representing cortical bone free water T1 as a reliable indicator of cortical bone porosity and age-related deterioration. It can be concluded that STE-MRI can be utilized as proper alternative in quantifying cortical bone porosity parameters in-vivo, with the advantages of widespread clinical availability and being cost-effective. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles.

    PubMed

    Xiao, Ning; Gu, Wei; Wang, Hao; Deng, Yunlong; Shi, Xin; Ye, Ling

    2014-03-01

    To overcome the negative contrast limitations of iron oxide-based contrast agents and to improve the biocompatibility of Gd-chelate contrast agents, PEGylated Gd-doped iron oxide (PEG-GdIO) NPs as a T1-T2 dual-modal contrast agent were synthesized by the polyol method. The transverse relaxivity (r2) and longitudinal relaxivity (r1) of PEG-GdIO were determined to be 66.9 and 65.9 mM(-1) s(-1), respectively. The high r1 value and low r2/r1 ratio make PEG-GdIO NPs suitable as a T1-T2 dual-modal contrast agent. The in vivo MRI demonstrated a brighter contrast enhancement in T1-weighted image and a simultaneous darken effect in T2-weighted MR image compared to the pre-contrast image in the region of glioma. Furthermore, the biocompatibility of PEG-GdIO NPs was confirmed by the in vitro MTT cytotoxicity and in vivo histological analyses (H&E). Therefore, PEG-GdIO NPs hold great potential in T1-T2 dual-modal imaging for the diagnosis of brain glioma. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. 26 CFR 1.846-4T - Effective dates (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Effective dates (temporary). 1.846-4T Section 1.846-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Other Insurance Companies § 1.846-4T Effective dates (temporary). (a) [Reserved...

  4. 46 CFR 31.40-1 - Application-T/ALL

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL 31.40-1 Section 31.40-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS INSPECTION AND CERTIFICATION Certificates Under International Convention for Safety of Life at Sea, 1974 § 31.40-1 Application—T/ALL The provisions of this...

  5. 46 CFR 32.56-1 - Application-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 32.56-1 Section 32.56-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS SPECIAL EQUIPMENT, MACHINERY, AND HULL....56-1 Application—T/ALL. (a)This subpart applies to all tankships that have a keel laying date on or...

  6. 46 CFR 31.40-1 - Application-T/ALL

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL 31.40-1 Section 31.40-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS INSPECTION AND CERTIFICATION Certificates Under International Convention for Safety of Life at Sea, 1974 § 31.40-1 Application—T/ALL The provisions of this...

  7. 46 CFR 32.56-1 - Application-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL. 32.56-1 Section 32.56-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS SPECIAL EQUIPMENT, MACHINERY, AND HULL....56-1 Application—T/ALL. (a)This subpart applies to all tankships that have a keel laying date on or...

  8. [Influence of electroacupuncture with penetration needling method on comprehensive pain score in patients with cervical spondylotic radiculopathy].

    PubMed

    Wan, Bi-Jiang; Huang, Wei; Zhang, Ya-Xi; Zhang, Huang-Sheng

    2013-05-01

    To compare the efficacy differences among electroacupuncture with penetration needling method, Jiaji electroacupuncture and Jing fukang granule for cervical spondylotic radiculopathy (CSR) and to explore the best therapeutic method. One hundred and sixty patients with CSR were randomly divided into 3 groups. Sixty patients in electroacupuncture with penetration needling method group (group A) were treated by electroacupuncture with penetration needling method, and C4 Jiaji-to-C7 Jiaji, Jianwaishu (SI 14)-to-Quyuan (SI 13), Tianzong (SI 11)-to-Naoshu (SI 10), Shousanli (LI 10)-to-Xialian (LI 8) were selected, once a day. Sixty patients in Jiaji electroacupuncture group (group B) were treated by Jiaji electroacupuncture at C4 Jiaji-to-C7 Jiaji, once a day. Fourty patients in Jing fukang granule group (group C) were treated by oral administration of Jing fukang granule, 1 bag each time, twice each day. Six days as a course, the 3 groups were all treated for two courses. The simplified MPQ (SF-MPQ) scale which was internationally accepted was adopt to evaluate the improving situations in pain. After treatment, pain rating idex (PRI), visual analogue scale (VAS), present pain intensity (PPI) and the total pain score were significantly improved in the group A and B compared with those before treatment (all P < 0.01), which was also improved in the group C (all P < 0.05). Compared with the group C, all the scores were significantly improved in the group A (all P < 0.01), the improvement of PRI, VAS, PPI and total pain score in the group B was superior to those in the group C (all P < 0.05), and all the improvements in the group A were superior to those in the group B (P < 0.05, P < 0.01). Electroacupuncture with penetration needling method can relive pain rapaidly in patients with CSR, which is superior to Jiaji electroacupuncture and Jing fukang granule in improving the comprehensive pain scores.

  9. Bilateral deficits in fine motor control and pinch grip force are not associated with electrodiagnostic findings in women with carpal tunnel syndrome.

    PubMed

    de la Llave-Rincón, Ana Isabel; Fernández-de-Las-Peñas, César; Pérez-de-Heredia-Torres, Marta; Martínez-Perez, Almudena; Valenza, Marie Carmen; Pareja, Juan A

    2011-06-01

    : The aim of this study was to analyze the differences in deficits in fine motor control and pinch grip force between patients with minimal, moderate/mild, or severe carpal tunnel syndrome (CTS) and healthy age- and hand dominance-matched controls. : A case-control study was conducted. The subtests of the Purdue Pegboard Test (one-hand and bilateral pin placements and assemblies) and pinch grip force between the thumb and the remaining four fingers of the hand were bilaterally evaluated in 66 women with minimal (n = 16), moderate (n = 16), or severe (n = 34) CTS and in 20 age- and hand-matched healthy women. The differences among the groups were analyzed using different mixed models of analysis of variance. : A two-way mixed analysis of variance revealed significant differences between groups, not depending on the presence of unilateral or bilateral symptoms (side), for the one-hand pin placement subtest: patients showed bilateral lower scores compared with controls (P < 0.001), without differences among those with minimal, moderate, or severe CTS (P = 0.946). The patients also exhibited lower scores in bilateral pin placement (P < 0.001) and assembly (P < 0.001) subtests, without differences among them. The three-way analysis of variance revealed significant differences among groups (P < 0.001) and fingers (P < 0.001), not depending on the presence of unilateral/bilateral symptoms (P = 0.684), for pinch grip force: patients showed bilateral lower pinch grip force in all fingers compared with healthy controls, without differences among those with minimal, moderate, or severe CTS. : The current study revealed similar bilateral deficits in fine motor control and pinch grip force in patients with minimal, moderate, or severe CTS, supporting that fine motor control deficits are a common feature of CTS not associated with electrodiagnostic findings.

  10. Magnetic resonance evaluation of cardiac thrombi and masses by T1 and T2 mapping: an observational study.

    PubMed

    Caspar, Thibault; El Ghannudi, Soraya; Ohana, Mickaël; Labani, Aïssam; Lawson, Aubrietia; Ohlmann, Patrick; Morel, Olivier; De Mathelin, Michel; Roy, Catherine; Gangi, Afshin; Germain, Philippe

    2017-04-01

    The purpose of this work was to evaluate CMR T1 and T2 mapping sequences in patients with intracardiac thrombi and masses in order to assess T1 and T2 relaxometry usefulness and to allow better etiological diagnosis. This observational study of patients scheduled for routine CMR was performed from September 2014 to August 2015. All patients referred to our department for a 1.5 T CMR were screened to participate. T1 mapping were acquired before and after Gadolinium injection; T2 mapping images were obtained before injection. 41 patients were included. 22 presented with cardiac thrombi and 19 with cardiac masses. The native T1 of thrombi was 1037 ± 152 ms (vs 1032 ± 39 ms for myocardium, p = 0.88; vs 1565 ± 88 ms for blood pool, p < 0.0001). T2 were 74 ± 13 ms (vs 51 ± 3 ms for myocardium, p < 0.0001; vs 170 ± 32 ms for blood pool, p < 0.0001). Recent thrombi had a native T1 shorter than old thrombi (911 ± 177 vs 1169 ± 107 ms, p = 0.01). The masses having a shorter T1 than the myocardium were lipomas (278 ± 29 ms), calcifications (621 ± 218 ms), and melanoma (736 ms). All other masses showed T1 values higher than myocardial T1, with T2 consistently >70 ms. T1 and T2 mapping CMR sequences can be useful and represent a new approach for the evaluation of cardiac thrombi and masses.

  11. [Clinical study of cervical spondylotic radiculopathy treated with massage therapy combined with Magnetic sticking therapy at the auricular points and the cost comparison].

    PubMed

    Wang, Saina; Sheng, Feng; Pan, Yunhua; Xu, Feng; Wang, Zhichao; Cheng, Lei

    2015-08-01

    To compare the clinical efficacy on cervical spondylotic radiculopathy between the combined therapy of massage and magnetic-sticking at the auricular points and the simple massage therapy, and conduct the health economics evaluation. Seventy-two patients of cervical spondylotic radiculopathy were randomized into a combined therapy group, and a simple massage group, 36 cases in each one. Finally, 35 cases and 34 cases were met the inclusive criteria in the corresponding groups separately. In the combined therapy group, the massage therapy and the magnetic sticking therapy at auricular points were combined in the treatment. Massage therapy was mainly applied to Fengchi (GB 20), Jianjing (GB 21), Jianwaishu (SI 14), Jianyu (LI 15) and Quchi (LI 11). The main auricular points for magnetic sticking pressure were Jingzhui (AH13), Gan (On12) Shen (CO10), Shenmen (TF4), Pizhixia (AT4). In the simple massage group, the simple massage therapy was given, the massage parts and methods were the same as those in the combined therapy group. The treatment was given once every two days, three times a week, for 4 weeks totally. The cervical spondylosis effect scale and the simplified McGill pain questionnaire were adopted to observe the improvements in the clinical symptoms, clinical examination, daily life movement, superficial muscular pain in the neck and the health economics cost in the patients of the two groups. The effect was evaluated in the two groups. The effective rate and the clinical curative rate in the combined therapy group were better than those in the control group [100. 0% (35/35) vs 85. 3% (29/34), 42. 9% (15/35) vs 17. 6% (6/34), both P<0. 05]. The scores of the spontaneous symptoms, clinical examnation, daily life movement and superficialmuscular pain in the neck were improved apparently after treatment as compared with those before treatment in the patients of the two groups (all P<0. 001). In terms of the improvements in the spontaneous symptoms, clinical

  12. Repeatability of magnetic resonance fingerprinting T1 and T2 estimates assessed using the ISMRM/NIST MRI system phantom.

    PubMed

    Jiang, Yun; Ma, Dan; Keenan, Kathryn E; Stupic, Karl F; Gulani, Vikas; Griswold, Mark A

    2017-10-01

    The purpose of this study was to evaluate accuracy and repeatability of T 1 and T 2 estimates of a MR fingerprinting (MRF) method using the ISMRM/NIST MRI system phantom. The ISMRM/NIST MRI system phantom contains multiple compartments with standardized T 1 , T 2 , and proton density values. Conventional inversion-recovery spin echo and spin echo methods were used to characterize the T 1 and T 2 values in the phantom. The phantom was scanned using the MRF-FISP method over 34 consecutive days. The mean T 1 and T 2 values were compared with the values from the spin echo methods. The repeatability was characterized as the coefficient of variation of the measurements over 34 days. T 1 and T 2 values from MRF-FISP over 34 days showed a strong linear correlation with the measurements from the spin echo methods (R 2  = 0.999 for T 1 ; R 2  = 0.996 for T 2 ). The MRF estimates over the wide ranges of T 1 and T 2 values have less than 5% variation, except for the shortest T 2 relaxation times where the method still maintains less than 8% variation. MRF measurements of T 1 and T 2 are highly repeatable over time and across wide ranges of T 1 and T 2 values. Magn Reson Med 78:1452-1457, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  13. Myeloradicular damage in traumatic cervical disc herniation.

    PubMed

    Bucciero, A; Carangelo, B; Cerillo, A; Gammone, V; Panagiotopoulos, K; Vizioli, L

    1998-12-01

    The literature on pure traumatic disc herniation is now voluminous but diversity of opinion exists regarding frequency, pathogenesis and management of this type of lesion. As a further contribution to the solution of the question it is thus justified to report our series of cervical traumatic disc herniation. During the period from January 1986 to December 1994, 41 patients (25 males and 16 females, between the ages of 24 and 51 years) with traumatic cervical disc herniations were operated on by anterior approach. Twenty-six (63.4%) patients presented with radicular syndrome, 3 (7.3%) with medullary symptoms and signs, and 12 (29.3%) with myeloradiculopathy. Disc herniation was at the C3/4 level in 4 (9.7%) cases, at the C4/5 level in 7 (17.1%) cases, at the C5/6 level in 24 (58.5%) cases, and at the C6/7 level in 8 (19.5%) cases. In 6 (40%) patients suffering from myelopathy (with or without radiculopathy) an area of high MR signal intensity was observed within the cervical cord on T2-weighted images; such area corresponded at the level of cord compression by disc and was not demonstrated on T1-weighted images. All patients underwent discectomy without bone grafting. Among patients with radiculopathy, 27 (71%) experienced complete relief of preoperative symptomatology, and 11 (29%) minor pain and/or neurological deficits without interference with work activities. The myelopathy completely disappeared in 11 (73.3%) cases whereas remained unchanged in 3 (20%); 1 patient with myelopathy experienced amelioration of preoperative specific symptoms and signs. The results of surgery for cervical radiculopathy due to traumatic disc herniation are satisfactory since 92 to 100% of the patients postoperatively regain prior activities, an observation we have confirmed with our own series. The results in cases of myelopathy are less satisfactory: although approximately 73% of our patients with myelopathy reported total relief of preoperative symptomatology, published reports

  14. HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells

    PubMed Central

    Araya, Natsumi; Sato, Tomoo; Ando, Hitoshi; Tomaru, Utano; Yoshida, Mari; Coler-Reilly, Ariella; Yagishita, Naoko; Yamauchi, Junji; Hasegawa, Atsuhiko; Kannagi, Mari; Hasegawa, Yasuhiro; Takahashi, Katsunori; Kunitomo, Yasuo; Tanaka, Yuetsu; Nakajima, Toshihiro; Nishioka, Kusuki; Utsunomiya, Atae; Jacobson, Steven; Yamano, Yoshihisa

    2014-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) is linked to multiple diseases, including the neuroinflammatory disease HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. Evidence suggests that HTLV-1, via the viral protein Tax, exploits CD4+ T cell plasticity and induces transcriptional changes in infected T cells that cause suppressive CD4+CD25+CCR4+ Tregs to lose expression of the transcription factor FOXP3 and produce IFN-γ, thus promoting inflammation. We hypothesized that transformation of HTLV-1–infected CCR4+ T cells into Th1-like cells plays a key role in the pathogenesis of HAM/TSP. Here, using patient cells and cell lines, we demonstrated that Tax, in cooperation with specificity protein 1 (Sp1), boosts expression of the Th1 master regulator T box transcription factor (T-bet) and consequently promotes production of IFN-γ. Evaluation of CSF and spinal cord lesions of HAM/TSP patients revealed the presence of abundant CD4+CCR4+ T cells that coexpressed the Th1 marker CXCR3 and produced T-bet and IFN-γ. Finally, treatment of isolated PBMCs and CNS cells from HAM/TSP patients with an antibody that targets CCR4+ T cells and induces cytotoxicity in these cells reduced both viral load and IFN-γ production, which suggests that targeting CCR4+ T cells may be a viable treatment option for HAM/TSP. PMID:24960164

  15. The effects of neural mobilization on cervical radiculopathy patients' pain, disability, ROM, and deep flexor endurance.

    PubMed

    Kim, Dong-Gyu; Chung, Sin Ho; Jung, Ho Bal

    2017-09-22

    Cervical radiculopathy (CR) is a disease of the cervical spine and a space-occupying lesion that occurs because of pathological problems with cervical nerve roots. Nerve root injury to produce functional disability. The purpose of this study was to examine the effects of neural mobilization with manual cervical traction (NMCT) compared with manual cervical traction (MCT) on pain, functional disability, muscle endurance, and range of motion (ROM) in individuals with CR patients. A blinded randomized clinical trial was conducted. Thirty CR patients were divided into two groups - those who received NMCT and those who received MCT. The intervention was applied three times per week for eight weeks. It was measured in order to determine the pain and functional disability in patients with CR. The numeric pain rating scale (NPRS), neck disability index (NDI), ROM, and deep flexor endurance of patients were measured prior to the experiment, four weeks, and eight weeks after the experiment to compare the time points. A repeated-measures analysis of variance was used to compare differences within each group prior to the experiment. And Bonferroni test was performed to examine the significance of each time point. There were significant differences within each group prior to the intervention, four weeks after the intervention, and eight weeks after the intervention in NPRS, NDI, ROM, and deep flexor endurance (P< 0.05). NPRS and NDI more decreased, and, ROM and deep flexor endurance increased in the NMCT group than the MCT group (P< 0.05). These results suggest that the NMCT can pain relief, recovery from neck disability, ROM, and deep flexor endurance for patients with CR.

  16. Engineering T Cells to Functionally Cure HIV-1 Infection.

    PubMed

    Leibman, Rachel S; Riley, James L

    2015-07-01

    Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure.

  17. Distinct Contributions of T1R2 and T1R3 Taste Receptor Subunits to the Detection of Sweet Stimuli

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nie,Y.; Vigues, S.; Hobbs, J.

    2005-01-01

    The molecular mechanisms by which G protein-coupled receptor (GPCR)-type chemosensory receptors of animals selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes, though little is known about the relative contributions of individual subunits to receptor functions. This study showed that each of the two subunits in the mammalian heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli, though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in mice.more » Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.« less

  18. Glycine transporters GlyT1 and GlyT2 are differentially modulated by glycogen synthase kinase 3β.

    PubMed

    Jiménez, Esperanza; Núñez, Enrique; Ibáñez, Ignacio; Zafra, Francisco; Aragón, Carmen; Giménez, Cecilio

    2015-02-01

    Inhibitory glycinergic neurotransmission is terminated by the specific glycine transporters GlyT1 and GlyT2 which actively reuptake glycine from the synaptic cleft. GlyT1 is associated with both glycinergic and glutamatergic pathways, and is the main regulator of the glycine levels in the synapses. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is vital to preserve the quantal glycine content in synaptic vesicles. Therefore, to control glycinergic neurotransmission efficiently, GlyT1 and GlyT2 activity must be regulated by diverse neuronal and glial signaling pathways. In this work, we have investigated the possible functional modulation of GlyT1 and GlyT2 by glycogen synthase kinase 3 (GSK3β). This kinase is involved in mood stabilization, neurodegeneration and plasticity at excitatory and inhibitory synapses. The co-expression of GSK3β with GlyT1 or GlyT2 in COS-7 cells and Xenopus laevis oocytes, leads to inhibition and stimulation of GlyT1 and GlyT2 activities, respectively, with a decrease of GlyT1, and an increase in GlyT2 levels at the plasma membrane. The specificity of these changes is supported by the antagonism exerted by a catalytically inactive form of the kinase and through inhibitors of GSK3β such as lithium chloride and TDZD-8. GSK3β also increases the incorporation of 32Pi into GlyT1 and decreases that of GlyT2. The pharmacological inhibition of the endogenous GSK3β in neuron cultures of brainstem and spinal cord leads to an opposite modulation of GlyT1 and GlyT2.Our results suggest that GSK3β is important for stabilizing and/or controlling the expression of functional GlyTs on the neural cell surface. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Notch ligands Delta1 and Jagged1 transmit distinct signals to T-cell precursors

    PubMed Central

    Lehar, Sophie M.; Dooley, James; Farr, Andrew G.; Bevan, Michael J.

    2009-01-01

    Signaling through the Notch pathway plays an essential role in inducing T-lineage commitment and promoting the maturation of immature thymocytes. Using an in vitro culture system, we show that 2 different classes of Notch ligands, Jagged1 or Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells expressing either Jagged1 or Delta1 inhibit the differentiation of DN1 thymocytes into the B-cell lineage, but only the Delta1-expressing stromal cells promote the proliferation and maturation of T-cell progenitors through the early double-negative (DN) stages of thymocyte development. Whereas the majority of bone marrow-derived stem cells do not respond to Jagged1 signals, T-cell progenitors respond to Jagged1 signals during a brief window of their development between the DN1 and DN3 stages of thymic development. During these stages, Jagged1 signals can influence the differentiation of immature thymocytes along the natural killer (NK) and γδ T-cell lineages. PMID:15486060

  20. Relationship Between T1 Slope and Cervical Alignment Following Multilevel Posterior Cervical Fusion Surgery: Impact of T1 Slope Minus Cervical Lordosis.

    PubMed

    Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2016-04-01

    Retrospective study. To assess the relationship between sagittal alignment of the cervical spine and patient-reported health-related quality-of-life scores following multilevel posterior cervical fusion, and to explore whether an analogous relationship exists in the cervical spine using T1 slope minus C2-C7 lordosis (T1S-CL). A recent study demonstrated that, similar to the thoracolumbar spine, the severity of disability increases with sagittal malalignment following cervical reconstruction surgery. From 2007 to 2013, 38 consecutive patients underwent multilevel posterior cervical fusion for cervical stenosis, myelopathy, and deformities. Radiographic measurements included C0-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), T1 slope, and T1S-CL. Pearson correlation coefficients were calculated between pairs of radiographic measures and health-related quality-of-life. C2-C7 SVA positively correlated with neck disability index (NDI) scores (r = 0.495). C2-C7 lordosis (P = 0.001) and T1S-CL (P = 0.002) changes correlated with NDI score changes after surgery. For significant correlations between C2-C7 SVA and NDI scores, regression models predicted a threshold C2-C7 SVA value of 50 mm, beyond which correlations were most significant. The T1S-CL also correlated positively with C2-C7 SVA and NDI scores (r = 0.871 and r = 0.470, respectively). Results of the regression analysis indicated that a C2-C7 SVA value of 50 mm corresponded to a T1S-CL value of 26.1°. This study showed that disability of the neck increased with cervical sagittal malalignment following surgical reconstruction and a greater T1S-CL mismatch was associated with a greater degree of cervical malalignment. Specifically, a mismatch greater than 26.1° corresponded to positive cervical sagittal malalignment, defined as C2-C7 SVA greater than 50 mm. 3.

  1. Effect of 3,5,3'-Triiodothyronine (T3) administration on dio1 gene expression and T3 metabolism in normal and type 1 deiodinase-deficient mice.

    PubMed

    Maia, A L; Kieffer, J D; Harney, J W; Larsen, P R

    1995-11-01

    The type 1 deiodinase (D1) catalyzes the monodeiodination of T4 to produce T3, the active thyroid hormone. In the C3H mouse, hepatic D1 and the dio1 messenger RNA (mRNA) are only 10% that in the C57 strain, the common phenotype. Low activity cosegregated with a series of five GCT repeats located in the 5'-flanking region of the C3H dio1 gene that impaired C3H promoter potency and provided a partial explanation for the lower D1. The present studies were performed to search for additional explanations for low D1 activity in C3H mice. Previous studies have shown that T3 up-regulates the dio1 gene. Therefore, loss of the capacity to respond to endogenous T3 is a possible additional cause of the lower D1 levels in the C3H mice. The hepatic C3H dio1 mRNA increases 10- to 20 fold after T3 administration. The t3 effect occurs at a transplantation level and T3 does not alter the dio1 mRNA half-life. Despite the transcriptional response to T3, no functional thyroid response elements were identified in the 1.5-kilobase 5'-flanking region of either the C57 or C3H dio1 gene. After the same dose of exogenous T3, both dio1 mRNA and D1 of the C3H mouse respond to a greater extent than those of the C57 strain. This can be explained in part by the reduction in T3 clearance due to the lower D1 levels in C3H mice in which higher concentrations of circulating T3 are maintained. The decrease in serum T3 levels and T3 production observed in fasting and systemic illness in both human and experimental animals has been attributed in part to a decrease in hepatic D1. In contrast, despite markedly lower hepatic and renal D1 levels, serum T3 concentrations remain normal in C3H mice. The present studies suggest that the absence of stress-induced hypothalamic-pituitary suppression that allows T4 production to be maintained together with the reduced clearance of T3 and T4 via inner ring deiodination compensate for the D1 deficiency.

  2. 26 CFR 1.1502-13T - Intercompany transactions (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... January 1 of Year 4, in an independent transaction, S distributes all of its assets to P in a complete..., the T1 stock becomes a successor asset to the T stock. On January 1 of Year 9, in an independent... are made to reflect any events occurring before the formation of new T and to reflect any assets not...

  3. T1ρ MR Imaging of Human Musculoskeletal System

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Magnetic resonance imaging (MRI) offers the direct visualization of human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium etc. Conventional MR imaging techniques based on T1- and T2-weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article, we will focus on cartilage biochemical composition, basic principles of T1ρ MR imaging, implementation of T1ρ pulse sequences, biochemical validation, and summarize the potential applications of T1ρ MR imaging technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we will also review the potential advantages, challenges, and future prospects of T1ρ MR imaging for widespread clinical translation. PMID:24935818

  4. Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression.

    PubMed

    Callaerts-Vegh, Zsuzsanna; Moechars, Diederik; Van Acker, Nathalie; Daneels, Guy; Goris, Ilse; Leo, Sandra; Naert, Arne; Meert, Theo; Balschun, Detlef; D'Hooge, Rudi

    2013-05-15

    The excitatory neurotransmitter l-glutamate is transported into synaptic vesicles by vesicular glutamate transporters (VGluTs) to transmit glutamatergic signals. Changes in their expression have been linked to various brain disorders including schizophrenia, Parkinson's, and Alzheimer's disease. Deleting either the VGluT1 or VGluT2 gene leads to profound developmental and neurological complications and early death, but mice heterozygous for VGluT1 or VGluT2 are viable and thrive. Acquisition, retention and extinction of conditioned visuospatial and emotional responses were compared between VGluT1(+/-) and VGluT2(+/-) mice, and their wildtype littermates, using different water maze procedures, appetitive scheduled conditioning, and conditioned fear protocols. The distinct brain expression profiles of the VGluT1 and -2 isoforms particularly in telencephalic structures, such as neocortex, hippocampus and striatum, are reflected in very specific behavioral changes. VGluT2(+/-) mice were unimpaired in spatial learning tasks and fear extinction. Conversely, VGluT1(+/-) mice displayed spatial extinction learning deficits and markedly impaired fear extinction. These data indicate that VGluT1, but not VGluT2, plays a role in the neural processes underlying inhibitory learning. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells.

    PubMed

    Li, Deguan; Chen, Renxiang; Wang, Yi-Wen; Fornace, Albert J; Li, Heng-Hong

    2018-05-01

    In this study we addressed the question whether radiation-induced adverse effects on T cell activation are associated with alterations of T cell checkpoint receptors. Expression levels of checkpoint receptors on T cell subpopulations were analyzed at multiple post-radiation time points ranging from one to four weeks in mice receiving a single fraction of 1 or 4 Gy of γ-ray. T cell activation associated metabolic changes were assessed. Our results showed that prior irradiation resulted in significant elevated expression of programmed cell death protein 1 (PD-1) in both CD4+ and CD8+ populations, at all three post-radiation time points. T cells with elevated PD-1 mostly were either central memory or naïve cells. In addition, the feedback induction of PD-1 expression in activated T cells declined after radiation. Taken together, the elevated PD-1 level observed at weeks after radiation exposure is connected to T cell dysfunction. Recent preclinical and clinical studies have showed that a combination of radiotherapy and T cell checkpoint blockade immunotherapy including targeting the programmed death-ligand 1 (PD-L1)/PD-1 axis may potentiate the antitumor response. Understanding the dynamic changes in PD-1 levels in T cells after radiation should help in the development of a more effective therapeutic strategy.

  6. Comparison of T2, T1rho, and diffusion metrics in assessment of liver fibrosis in rats.

    PubMed

    Zhang, Hui; Yang, Qihua; Yu, Taihui; Chen, Xiaodong; Huang, Jingwen; Tan, Cui; Liang, Biling; Guo, Hua

    2017-03-01

    To evaluate the value of T 2 , T 1 rho, and diffusion metrics in assessment of liver fibrosis in rats. Liver fibrosis in a rat model (n = 72) was induced by injection of carbon tetrachloride (CCl 4 ) at 3T. T 2 , T 1 rho, and diffusion parameters (apparent diffusion coefficient (ADC), D true ) via spin echo (SE) diffusion-weighted imaging (DWI) and stimulated echo acquisition mode (STEAM) DWI with three diffusion times (DT: 80, 106, 186 msec) were obtained in surviving rats with hepatic fibrosis (n = 52) and controls (n = 8). Liver fibrosis stage (F0-F6) was identified based on pathological results using the traditional liver fibrosis staging method for rodents. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analysis were employed to determine the diagnostic accuracy. Mean T 2 , T 1 rho, ADC, and D true with DT = 186 msec correlated with the severity of fibrosis with r = 0.73, 0.83, -0.83, and -0.85 (all P < 0.001), respectively. The average areas under the ROC curve at different stages for T 1 rho and diffusion parameters (DT = 186 msec) were larger than those of T 2 and SE DWI (0.92, 0.92, and 0.92 vs. 0.86, 0.82, and 0.83). The corresponding average sensitivity and specificity for T 1 rho and diffusion parameters with a long DT were larger (89.35 and 88.90, 88.36 and 89.97, 90.16 and 87.13) than T 2 and SE DWI (90.28 and 79.93, 85.30 and 77.64, 78.21 and 82.41). The performances of T 1 rho and D true (DT = 186 msec) were comparable (average AUC: 0.92 and 0.92). Among the evaluated sequences, T 1 rho and STEAM DWI with a long DT may serve as superior imaging biomarkers for assessing liver fibrosis and monitoring disease severity. 1 J. Magn. Reson. Imaging 2017;45:741-750. © 2016 International Society for Magnetic Resonance in Medicine.

  7. Short-term stability of T1 and T2 relaxation measures in multiple sclerosis normal appearing white matter.

    PubMed

    Liang, Alice L W; Vavasour, Irene M; Mädler, Burkhard; Traboulsee, Anthony L; Lang, Donna J; Li, David K B; MacKay, Alex L; Laule, Cornelia

    2012-06-01

    The presence of diffuse and widespread abnormalities within the 'normal appearing' white matter (NAWM) of multiple sclerosis (MS) brain has been established. T(1) histogram analysis has revealed increased T(1) (related to water content) in segmented NAWM, while quantitative assessment of T(2) relaxation measures has demonstrated decreased myelin water fraction (MWF, related to myelin content) and increased geometric mean T(2) (GMT(2)) of the intra/extracellular water pool. Previous studies with follow-up periods of 1-5 years have demonstrated longitudinal changes in T(1) histogram metrics over time; however, longitudinal changes in MWF and GMT(2) of segmented NAWM have not been examined. We examined the short-term evolution of MWF, GMT(2) and T(1) in MS NAWM based on monthly scanning over 6 months in 18 relapsing remitting (RR) MS subjects. Histogram metrics demonstrated short-term stability of T(1), MWF and remitting (RR) MS subjects. We observed no change in MWF, GMT(2) or T(1) histogram metrics in NAWM in RRMS over the course of 6 months. Longer follow-up periods may be required to establish demonstrable changes in NAWM based on of MWF, GMT(2) and T(1) metrics.

  8. Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

    PubMed

    Henninger, B; Kremser, C; Rauch, S; Eder, R; Zoller, H; Finkenstedt, A; Michaely, H J; Schocke, M

    2012-11-01

    To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms +  n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

  9. Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

    PubMed

    Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

    2014-01-01

    To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Balance chiropractic therapy for cervical spondylotic radiculopathy: study protocol for a randomized controlled trial.

    PubMed

    Yang, Feng; Li, Wen-Xiong; Liu, Zhu; Liu, Li

    2016-10-22

    Cervical spondylosis is a very common disorder and cervical spondylotic radiculopathy (CSR) is the most common form of spinal degenerative disease. Its clinical manifestations focus on pain and numbness of the neck and arm as well as restricted movement of the neck, which greatly affect the patient's life and work. The orthopedic of traditional Chinese medicine (TCM) theory holds that the basic pathologic change in spinal degenerative diseases is the imbalance between the dynamic system and the static system of the cervical spine. Based on this theory, some Chinese physicians have developed a balance chiropractic therapy (BCT) to treat CSR, which has been clinically examined for more than 50 years to effectively cure CSR. The purpose of this study is to evaluate the therapeutic effect and safety of BCT on CSR and to investigate the mechanism by which the efficacy is achieved. We propose a multicenter, parallel-group, randomized controlled trial to evaluate the efficacy and safety of BCT for CSR. Participants aged 18 to 65 years, who are in conformity with the diagnostic criteria of CSR and whose pain score on a Visual Analog Scale (VAS) is more than 4 points and less than 8 points, will be included and randomly allocated into two groups: a treatment group and a control group. Participants in the treatment group will be treated with BCT, while the control group will receive traction therapy (TT). The primary outcome is pain severity (measured with a VAS). Secondary outcomes will include cervical curvature (measured by the Borden Index), a composite of functional status (measured by the Neck Disability Index, NDI), patient health status (evaluated by the SF-36 health survey) and adverse events (AEs) as reported in the trial. If BCT can relieve neck pain without adverse effects, it may be a novel strategy for the treatment of CSR. Furthermore, the mechanism of BCT for CSR will be partially elucidated. Clinical Trials.gov Identifier: NCT02705131 . Registered on 9

  11. The impact of reliable prebolus T 1 measurements or a fixed T 1 value in the assessment of glioma patients with dynamic contrast enhancing MRI.

    PubMed

    Tietze, Anna; Mouridsen, Kim; Mikkelsen, Irene Klærke

    2015-06-01

    Accurate quantification of hemodynamic parameters using dynamic contrast enhanced (DCE) MRI requires a measurement of tissue T 1 prior to contrast injection (T 1). We evaluate (i) T 1 estimation using the variable flip angle (VFA) and the saturation recovery (SR) techniques and (ii) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a predefined T 1 value when differentiating high- from low-grade gliomas. The accuracy and precision of T 1 measurements, acquired by VFA and SR, were investigated by computer simulations and in glioma patients using an equivalence test (p > 0.05 showing significant difference). The permeability measure, K trans, cerebral blood flow (CBF), and - volume, V p, were calculated in 42 glioma patients, using fixed T 1 of 1500 ms or an individual T 1 measurement, using SR. The areas under the receiver operating characteristic curves (AUCs) were used as measures for accuracy to differentiate tumor grade. The T 1 values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T 1 introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high-grade from low-grade gliomas, (AUCfix = 0.906 and AUCind = 0.884 for K trans; AUCfix = 0.863 and AUCind = 0.856 for V p; p for AUC comparison > 0.05). T 1 measurements by VFA were less precise, and the SR method is preferable, when accurate parameter estimation is required. Semiquantitative DCE values, based on predefined T 1 values, were sufficient to perform tumor grading in our study.

  12. Organic Ferroelectric-Based 1T1T Random Access Memory Cell Employing a Common Dielectric Layer Overcoming the Half-Selection Problem.

    PubMed

    Zhao, Qiang; Wang, Hanlin; Ni, Zhenjie; Liu, Jie; Zhen, Yonggang; Zhang, Xiaotao; Jiang, Lang; Li, Rongjin; Dong, Huanli; Hu, Wenping

    2017-09-01

    Organic electronics based on poly(vinylidenefluoride/trifluoroethylene) (P(VDF-TrFE)) dielectric is facing great challenges in flexible circuits. As one indispensable part of integrated circuits, there is an urgent demand for low-cost and easy-fabrication nonvolatile memory devices. A breakthrough is made on a novel ferroelectric random access memory cell (1T1T FeRAM cell) consisting of one selection transistor and one ferroelectric memory transistor in order to overcome the half-selection problem. Unlike complicated manufacturing using multiple dielectrics, this system simplifies 1T1T FeRAM cell fabrication using one common dielectric. To achieve this goal, a strategy for semiconductor/insulator (S/I) interface modulation is put forward and applied to nonhysteretic selection transistors with high performances for driving or addressing purposes. As a result, high hole mobility of 3.81 cm 2 V -1 s -1 (average) for 2,6-diphenylanthracene (DPA) and electron mobility of 0.124 cm 2 V -1 s -1 (average) for N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDI-FCN 2 ) are obtained in selection transistors. In this work, we demonstrate this technology's potential for organic ferroelectric-based pixelated memory module fabrication. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Thy-1+ dendritic epidermal cells express T3 antigen and the T-cell receptor gamma chain.

    PubMed Central

    Stingl, G; Koning, F; Yamada, H; Yokoyama, W M; Tschachler, E; Bluestone, J A; Steiner, G; Samelson, L E; Lew, A M; Coligan, J E

    1987-01-01

    The murine epidermis is a heterogeneous epithelium composed of keratinocytes, melanocytes, Langerhans cells, and a recently described subpopulation (2-3%) of bone-marrow-derived leukocytes with a dendritic morphology and the cell surface phenotype Thy-1+, L3T4-, Lyt-2-. Previous studies have demonstrated that cell lines derived from freshly explanted Thy-1+ dendritic epidermal cells (DEC) have abundant mRNA for rearranged T-cell receptor (TCR) gamma-chain genes. Analysis of Thy-1+ DEC in situ, freshly isolated cell suspensions of Thy-1+ DEC, and long-term Thy-1+ DEC lines demonstrated that 100% of the Thy-1+ DEC reacted with a monoclonal antibody to the epsilon chain of the murine T3 complex and that 40-60% of resident Thy-1+ DEC were also reactive with an antiserum to the TCR gamma chain. Two Thy-1+ DEC lines expressed a disulfide-linked 70-kDa molecule that could be precipitated with an anti-gamma-chain antiserum and could be coprecipitated with an antiserum to the T3 delta chain; the molecule appeared as a single 34-kDa band under reducing conditions. The phenotype of Thy-1+ DEC (T3+, L3T4-, Lyt-2-, TCR gamma chain+) thus resembles that of the recently described subpopulation of murine and human lymphocytes that have been identified in the thymus, peripheral blood, and fetal blood. Images PMID:2885839

  14. 26 CFR 1.6662-5T - Substantial and gross valuation misstatements under chapter 1 (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... under chapter 1 (temporary). 1.6662-5T Section 1.6662-5T Internal Revenue INTERNAL REVENUE SERVICE..., Additional Amounts, and Assessable Penalties § 1.6662-5T Substantial and gross valuation misstatements under chapter 1 (temporary). (a)-(e)(3) [Reserved]. For further information, see § 1.6662-5(a) through (e)(3...

  15. Three-dimensional quantitative T1 and T2 mapping of the carotid artery: Sequence design and in vivo feasibility.

    PubMed

    Coolen, Bram F; Poot, Dirk H J; Liem, Madieke I; Smits, Loek P; Gao, Shan; Kotek, Gyula; Klein, Stefan; Nederveen, Aart J

    2016-03-01

    A novel three-dimensional (3D) T1 and T2 mapping protocol for the carotid artery is presented. A 3D black-blood imaging sequence was adapted allowing carotid T1 and T2 mapping using multiple flip angles and echo time (TE) preparation times. B1 mapping was performed to correct for spatially varying deviations from the nominal flip angle. The protocol was optimized using simulations and phantom experiments. In vivo scans were performed on six healthy volunteers in two sessions, and in a patient with advanced atherosclerosis. Compensation for patient motion was achieved by 3D registration of the inter/intrasession scans. Subsequently, T1 and T2 maps were obtained by maximum likelihood estimation. Simulations and phantom experiments showed that the bias in T1 and T2 estimation was < 10% within the range of physiological values. In vivo T1 and T2 values for carotid vessel wall were 844 ± 96 and 39 ± 5 ms, with good repeatability across scans. Patient data revealed altered T1 and T2 values in regions of atherosclerotic plaque. The 3D T1 and T2 mapping of the carotid artery is feasible using variable flip angle and variable TE preparation acquisitions. We foresee application of this technique for plaque characterization and monitoring plaque progression in atherosclerotic patients. © 2015 Wiley Periodicals, Inc.

  16. ZnT-1 enhances the activity and surface expression of T-type calcium channels through activation of Ras-ERK signaling.

    PubMed

    Mor, Merav; Beharier, Ofer; Levy, Shiri; Kahn, Joy; Dror, Shani; Blumenthal, Daniel; Gheber, Levi A; Peretz, Asher; Katz, Amos; Moran, Arie; Etzion, Yoram

    2012-07-15

    Zinc transporter-1 (ZnT-1) is a putative zinc transporter that confers cellular resistance from zinc toxicity. In addition, ZnT-1 has important regulatory functions, including inhibition of L-type calcium channels and activation of Raf-1 kinase. Here we studied the effects of ZnT-1 on the expression and function of T-type calcium channels. In Xenopus oocytes expressing voltage-gated calcium channel (CaV) 3.1 or CaV3.2, ZnT-1 enhanced the low-threshold calcium currents (I(caT)) to 182 ± 15 and 167.95 ± 9.27% of control, respectively (P < 0.005 for both channels). As expected, ZnT-1 also enhanced ERK phosphorylation. Coexpression of ZnT-1 and nonactive Raf-1 blocked the ZnT-1-mediated ERK phosphorylation and abolished the ZnT-1-induced augmentation of I(caT). In mammalian cells (Chinese hamster ovary), coexpression of CaV3.1 and ZnT-1 increased the I(caT) to 166.37 ± 6.37% compared with cells expressing CaV3.1 alone (P < 0.01). Interestingly, surface expression measurements using biotinylation or total internal reflection fluorescence microscopy indicated marked ZnT-1-induced enhancement of CaV3.1 surface expression. The MEK inhibitor PD-98059 abolished the ZnT-1-induced augmentation of surface expression of CaV3.1. In cultured murine cardiomyocytes (HL-1 cells), transient exposure to zinc, leading to enhanced ZnT-1 expression, also enhanced the surface expression of endogenous CaV3.1 channels. Consistently, in these cells, endothelin-1, a potent activator of Ras-ERK signaling, enhanced the surface expression of CaV3.1 channels in a PD-98059-sensitive manner. Our findings indicate that ZnT-1 enhances the activity of CaV3.1 and CaV3.2 through activation of Ras-ERK signaling. The augmentation of CaV3.1 currents by Ras-ERK activation is associated with enhanced trafficking of the channel to the plasma membrane.

  17. Quantitative water content mapping at clinically relevant field strengths: a comparative study at 1.5 T and 3 T.

    PubMed

    Abbas, Zaheer; Gras, Vincent; Möllenhoff, Klaus; Oros-Peusquens, Ana-Maria; Shah, Nadim Joni

    2015-02-01

    Quantitative water content mapping in vivo using MRI is a very valuable technique to detect, monitor and understand diseases of the brain. At 1.5 T, this technology has already been successfully used, but it has only recently been applied at 3T because of significantly increased RF field inhomogeneity at the higher field strength. To validate the technology at 3T, we estimate and compare in vivo quantitative water content maps at 1.5 T and 3T obtained with a protocol proposed recently for 3T MRI. The proposed MRI protocol was applied on twenty healthy subjects at 1.5 T and 3T; the same post-processing algorithms were used to estimate the water content maps. The 1.5 T and 3T maps were subsequently aligned and compared on a voxel-by-voxel basis. Statistical analysis was performed to detect possible differences between the estimated 1.5 T and 3T water maps. Our analysis indicates that the water content values obtained at 1.5 T and 3T did not show significant systematic differences. On average the difference did not exceed the standard deviation of the water content at 1.5 T. Furthermore, the contrast-to-noise ratio (CNR) of the estimated water content map was increased at 3T by a factor of at least 1.5. Vulnerability to RF inhomogeneity increases dramatically with the increasing static magnetic field strength. However, using advanced corrections for the sensitivity profile of the MR coils, it is possible to preserve quantitative accuracy while benefiting from the increased CNR at the higher field strength. Indeed, there was no significant difference in the water content values obtained in the brain at 1.5 T and 3T. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Runx1t1 (Runt-Related Transcription Factor 1; Translocated to, 1) Epigenetically Regulates the Proliferation and Nitric Oxide Production of Microglia

    PubMed Central

    Baby, Nimmi; Li, Yali; Ling, Eng-Ang; Lu, Jia; Dheen, S. Thameem

    2014-01-01

    Background Microglia, the resident immune cells of the brain, undergo rapid proliferation and produce several proinflammatory molecules and nitric oxide (NO) when activated in neuropathological conditions. Runx1t1 (Runt-related transcription factor 1, translocated to 1) has been implicated in recruiting histone deacetylases (HDACs) for transcriptional repression, thereby regulating cell proliferation. In the present study, Runx1t1 expression was shown to localize in amoeboid microglial cells of the postnatal rat brain, being hardly detectable in ramified microglia of the adult brain. Moreover, a marked expression of Runx1t1was induced and translocated to nuclei in activated microglia in vitro and in vivo. In view of these findings, it was hypothesized that Runx1t1 regulates microglial functions during development and in neuropathological conditions. Methods and Findings siRNA-mediated knockdown of Runx1t1 significantly decreased the expression level of cell cycle-related gene, cyclin-dependent kinase 4 (Cdk4) and proliferation index in activated BV2 microglia. It was also shown that HDAC inhibitor (HDACi) treatment mimics the effects of Runx1t1 knockdown on microglial proliferation, confirming that microglial proliferation is associated with Runx1t1 expression and HDACs activity. Further, Runx1t1 and HDACs were shown to promote neurotoxic effect of microglia by repressing expression of LAT2, L-aminoacid transporter-2 (cationic amino acid transporter, y+ system), which normally inhibits NO production. This was confirmed by chromatin immunoprecipitation (ChIP) assay, which revealed that Runx1t1 binds to the promoter region of LAT2 and this binding increased upon microglial activation. However, the enhanced binding of Runx1t1 to the LAT2 promoter could not repress the LAT2 expression when the BV2 microglia cells were treated with HDACi, indicating that Runx1t1 requires HDACs to transcriptionally repress the expression of LAT2. Conclusion/Interpretation In conclusion

  19. Eomesodermin Promotes the Development of Type-1 Regulatory T (TR1) Cells

    PubMed Central

    Zhang, Ping; Lee, Jason S.; Gartlan, Kate H.; Schuster, Iona S; Comerford, Iain; Varelias, Antiopi; Ullah, Md Ashik; Vuckovic, Slavica; Koyama, Motoko; Kuns, Rachel D.; Locke, Kelly R.; Beckett, Kirrilee J.; Olver, Stuart D.; Samson, Luke D.; de Oca, Marcela Montes; de Labastida Rivera, Fabian; Clouston, Andrew D.; Belz, Gabrielle T.; Blazar, Bruce R.; MacDonald, Kelli P.; McColl, Shaun R.; Thomas, Ranjeny; Engwerda, Christian R.; Degli-Esposti, Mariapia A.; Kallies, Axel; Tey, Siok-Keen; Hill, Geoffrey R.

    2017-01-01

    Type-1 regulatory T (TR1) cells are Foxp3-negative IL-10-producing CD4+ T cells with potent immune suppressive properties but their requirements for lineage development have remained elusive. Here we show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes) and are critical for the prevention of graft-versus-host disease (GVHD). We demonstrate that Eomes is required for TR1 cell differentiation during which it acts in concert with the transcription factor B-lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other Th lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage-derived IL-27. We thus define the cellular and transcriptional control of TR1 cell differentiation during bone marrow transplantation, opening new avenues to therapeutic manipulation. PMID:28738016

  20. The clinical identification of peripheral neuropathy among older persons.

    PubMed

    Richardson, James K

    2002-11-01

    To identify simple clinical rules for the detection of a diffuse peripheral neuropathy among older outpatients. Observational, blinded, controlled study. A tertiary-care electrodiagnostic laboratory and biomechanics laboratory. One hundred research subjects, 68 with electrodiagnostic evidence of peripheral neuropathy, between the ages of 50 and 80 years. Not applicable. One examiner, unaware of the results of electrodiagnostic testing, evaluated Achilles' and patellar reflexes, Romberg testing, semiquantified vibration, and position sense at the toe and ankle in all subjects, and unipedal stance time and the Michigan Diabetes Neuropathy Score in a subset of subjects. Significant group differences were present in all clinical measures tested. Three signs, Achilles' reflex (absent despite facilitation), vibration (128Hz tuning fork perceived for <10s), and position sense (<8/10 1-cm trials) at the toe, were the best predictors of peripheral neuropathy on both univariate and logistic regression (pseudo R(2)=.744) analyses. The presence of 2 or 3 signs versus 0 or 1 sign identified peripheral neuropathy with sensitivity, specificity, and positive and negative predictive values of 94.1%, 84.4%, 92.8%, and 87.1%, respectively. Values were similar among subgroups of subjects with and without diabetes mellitus. When other clinicians applied the technique to 12 more subjects, excellent interrater reliability regarding the presence of peripheral neuropathy (kappa=.833) and good to excellent interrater reliability for each sign (kappa range,.667-1.00) were shown. Among older persons, the presence of 2 or 3 of the 3 clinical signs strongly suggested electrodiagnostic evidence of a peripheral neuropathy, regardless of etiology. Age-related decline in peripheral nerve function need not be a barrier to the clinical recognition of a diffuse peripheral neuropathy among older persons. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of

  1. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.

    PubMed

    Wauson, Eric M; Guerra, Marcy L; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M; Cobb, Melanie H

    2015-08-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that G(I) is not central to either pathway. Although glucagon-like peptide 1, an agonist for a G(s-)coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca(2+) entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective G(q) inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for G(q). Inhibition of G(12/13) by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways.

  2. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells

    PubMed Central

    Wauson, Eric M.; Guerra, Marcy L.; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M.

    2015-01-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that Gi is not central to either pathway. Although glucagon-like peptide 1, an agonist for a Gs-coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca2+ entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective Gq inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for Gq. Inhibition of G12/13 by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways. PMID:26168033

  3. SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells.

    PubMed

    Stephen, Tom L; Payne, Kyle K; Chaurio, Ricardo A; Allegrezza, Michael J; Zhu, Hengrui; Perez-Sanz, Jairo; Perales-Puchalt, Alfredo; Nguyen, Jenny M; Vara-Ailor, Ana E; Eruslanov, Evgeniy B; Borowsky, Mark E; Zhang, Rugang; Laufer, Terri M; Conejo-Garcia, Jose R

    2017-01-17

    Despite the importance of programmed cell death-1 (PD-1) in inhibiting T cell effector activity, the mechanisms regulating its expression remain poorly defined. We found that the chromatin organizer special AT-rich sequence-binding protein-1 (Satb1) restrains PD-1 expression induced upon T cell activation by recruiting a nucleosome remodeling deacetylase (NuRD) complex to Pdcd1 regulatory regions. Satb1 deficienct T cells exhibited a 40-fold increase in PD-1 expression. Tumor-derived transforming growth factor β (Tgf-β) decreased Satb1 expression through binding of Smad proteins to the Satb1 promoter. Smad proteins also competed with the Satb1-NuRD complex for binding to Pdcd1 enhancers, releasing Pdcd1 expression from Satb1-mediated repression, Satb1-deficient tumor-reactive T cells lost effector activity more rapidly than wild-type lymphocytes at tumor beds expressing PD-1 ligand (CD274), and these differences were abrogated by sustained CD274 blockade. Our findings suggest that Satb1 functions to prevent premature T cell exhaustion by regulating Pdcd1 expression upon T cell activation. Dysregulation of this pathway in tumor-infiltrating T cells results in diminished anti-tumor immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Native T1 mapping of the heart - a pictorial review.

    PubMed

    Germain, Philippe; El Ghannudi, Soraya; Jeung, Mi-Young; Ohlmann, Patrick; Epailly, Eric; Roy, Catherine; Gangi, Afshin

    2014-01-01

    T1 mapping is now a clinically feasible method, providing pixel-wise quantification of the cardiac structure's T1 values. Beyond focal lesions, well depicted by late gadolinium enhancement sequences, it has become possible to discriminate diffuse myocardial alterations, previously not assessable by noninvasive means. The strength of this method includes the high reproducibility and immediate clinical applicability, even without the use of contrast media injection (native or pre-contrast T1). The two most important determinants of native T1 augmentation are (1) edema related to tissue water increase (recent infarction or inflammation) and (2) interstitial space increase related to fibrosis (infarction scar, cardiomyopathy) or to amyloidosis. Conversely, lipid (Anderson-Fabry) or iron overload diseases are responsible for T1 reduction. In this pictorial review, the main features provided by native T1 mapping are discussed and illustrated, with a special focus on the awaited clinical purpose of this unique, promising new method.

  5. Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

    PubMed

    Nguyen, Dang Khoa; Rochette, Emilie; Leroux, Jean-Maxime; Beaudoin, Gilles; Cossette, Patrick; Lassonde, Maryse; Guilbert, François

    2010-10-01

    High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.5 T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI. We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0 T MR study after a negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist. Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery. The frequency of detection of a new lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. P-body components, Dhh1 and Pat1, are involved in tRNA nuclear-cytoplasmic dynamics

    PubMed Central

    Hurto, Rebecca L.; Hopper, Anita K.

    2011-01-01

    The nuclear-cytoplasmic distribution of tRNA depends on the balance between tRNA nuclear export/re-export and retrograde tRNA nuclear import in Saccharomyces cerevisiae. The distribution of tRNA is sensitive to nutrient availability as cells deprived of various nutrients exhibit tRNA nuclear accumulation. Starvation induces numerous events that result in translational repression and P-body formation. This study investigated the possible coordination of these responses with tRNA nuclear-cytoplasmic distribution. Dhh1 and Pat1 function in parallel to promote translation repression and P-body formation in response to starvation. Loss of both, Dhh1 and Pat1, results in a failure to repress translation and to induce P-body formation in response to glucose starvation. This study reports that nutrient deprived dhh1 pat1 cells also fail to accumulate tRNA within nuclei. Conversely, inhibition of translation initiation and induction of P-body formation by overproduction of Dhh1 or Pat1 cause tRNA nuclear accumulation in nutrient-replete conditions. Also, loss of the mRNA decapping activator, Lsm1, causes tRNA nuclear accumulation. However, the coordination between P-body formation, translation repression, and tRNA distribution is limited to the early part of the P-body formation/translation repression pathway as loss of mRNA decapping or 5′ to 3′ degradation does not influence tRNA nuclear-cytoplasmic dynamics. The data provide the first link between P-body formation/translation initiation and tRNA nuclear-cytoplasmic dynamics. The current model is that Dhh1 and Pat1 function in parallel to promote starvation-induced tRNA nuclear accumulation. PMID:21398402

  7. NMR relaxation in natural soils: Fast Field Cycling and T1-T2 Determination by IR-MEMS

    NASA Astrophysics Data System (ADS)

    Haber-Pohlmeier, S.; Pohlmeier, A.; Stapf, S.; van Dusschoten, D.

    2009-04-01

    Soils are natural porous media of highest importance for food production and sustainment of water resources. For these functions, prominent properties are their ability of water retainment and transport, which are mainly controlled by pore size distribution. The latter is related to NMR relaxation times of water molecules, of which the longitudinal relaxation time can be determined non-invasively by fast-field cycling relaxometry (FFC) and both are obtainable by inversion recovery - multi-echo- imaging (IR-MEMS) methods. The advantage of the FFC method is the determination of the field dependent dispersion of the spin-lattice relaxation rate, whereas MRI at high field is capable of yielding spatially resolved T1 and T2 times. Here we present results of T1- relaxation time distributions of water in three natural soils, obtained by the analysis of FFC data by means of the inverse Laplace transformation (CONTIN)1. Kaldenkirchen soil shows relatively broad bimodal distribution functions D(T1) which shift to higher relaxation rates with increasing relaxation field. These data are compared to spatially resolved T1- and T2 distributions, obtained by IR-MEMS. The distribution of T1 corresponds well to that obtained by FFC.

  8. Therapeutic targeting of NOTCH1 signaling in T-ALL

    PubMed Central

    Palomero, Teresa; Ferrando, Adolfo

    2010-01-01

    The recent identification of activating mutations in NOTCH1 in the majority of T-cell acute lymphoblastic leukemias (T-ALL) has brought major interest towards targeting the NOTCH signaling pathway in this disease. Small molecule γ-secretase inhibitors (GSIs) which block a critical proteolytic step required for NOTCH1 activation can effectively block the activity of NOTCH1 mutant alleles. However, the clinical development of GSIs has been hampered by their low cytotoxicity against human T-ALL and the development of significant gastrointestinal toxicity derived from inhibition of NOTCH signaling in the gut. Improved understanding of the oncogenic mechanisms of NOTCH1 and the effects of NOTCH inhibition in leukemic cells and the intestinal epithelium are required for the design of effective anti-NOTCH1 therapies in T-ALL. PMID:19778842

  9. PAUSED Encodes the Arabidopsis Exportin-t Ortholog1

    PubMed Central

    Hunter, Christine A.; Aukerman, Milo J.; Sun, Hui; Fokina, Maria; Poethig, R. Scott

    2003-01-01

    Los1p/exportin-t (XPOT) mediates the nuclear export of tRNAs in yeast and mammals. The requirements for this transport pathway are unclear, however, because los1 mutations do not affect yeast growth, and the phenotype of XPOT mutations in mammals is unknown. Here, we show that PAUSED (PSD) is the Arabidopsis ortholog of LOS1/XPOT and is capable of rescuing the tRNA export defect of los1 in Brewer's yeast (Saccharomyces cerevisiae), suggesting that its function has been conserved. Putative null alleles of PSD disrupt the initiation of the shoot apical meristem and delay leaf initiation after germination, the emergence of the radicle and lateral roots, and the transition to flowering. Plants doubly mutant for psd and hasty, the Arabidopsis ortholog of exportin 5, are viable but have a more severe phenotype than either single mutant. These results suggest that PSD plays a role in tRNA export in Arabidopsis, but that at least one—and perhaps several—additional tRNA export pathways also exist. The PSD transcript is broadly expressed during development and is alternatively spliced in the 3′-untranslated region. No temporal or spatial difference in the abundance of different splice forms was observed. We propose that the mutant phenotype of psd reflects defects in developmental events and cell/tissue types that require elevated levels of protein synthesis and are therefore acutely sensitive to a reduction in tRNA export. PMID:12913168

  10. 26 CFR 1.41-6T - Aggregation of expenditures (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Aggregation of expenditures (temporary). 1.41-6T Section 1.41-6T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Credits Against Tax § 1.41-6T Aggregation of expenditures (temporary). (a) [Reserved] For further...

  11. GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain.

    PubMed

    Huang, Hung-Hsiang; Hassinen, Antti; Sundaram, Subha; Spiess, Andrej-Nikolai; Kellokumpu, Sakari; Stanley, Pamela

    2015-09-15

    Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP-L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis.

  12. Low programmed cell death-1 (PD-1) expression in peripheral CD4(+) T cells in Japanese patients with autoimmune type 1 diabetes.

    PubMed

    Fujisawa, R; Haseda, F; Tsutsumi, C; Hiromine, Y; Noso, S; Kawabata, Y; Mitsui, S; Terasaki, J; Ikegami, H; Imagawa, A; Hanafusa, T

    2015-06-01

    Programmed cell death-1 (PD-1) is a co-stimulatory molecule that inhibits T cell proliferation. We aimed to clarify PD-1 expression in CD4(+) T cells and the association between PD-1 expression and the 7785C/T polymorphism of PDCD1, with a focus on the two subtypes of type 1 diabetes, type 1A diabetes (T1AD) and fulminant type 1 diabetes (FT1D), in the Japanese population. We examined 22 patients with T1AD, 15 with FT1D, 19 with type 2 diabetes (T2D) and 29 healthy control (HC) subjects. Fluorescence-activated cell sorting (FACS) and real-time PCR were utilized to analyse PD-1 expression quantitatively. Genotyping of 7785C/T in PDCD1 was performed using the TaqMan method in a total of 63 subjects (21 with T1AD, 15 with FT1D and 27 HC). FACS revealed a significant reduction in PD-1 expression in CD4(+) T cells in patients with T1AD (mean: 4.2 vs. 6.0% in FT1D, P=0.0450; vs. 5.8% in T2D, P=0.0098; vs. 6.0% in HC, P=0.0018). PD-1 mRNA expression in CD4(+) T cells was also significantly lower in patients with T1AD than in the HC subjects. Of the 63 subjects, PD-1 expression was significantly lower in individuals with the 7785C/C genotype than in those with the C/T and T/T genotypes (mean: 4.1 vs. 5.9%, P=0.0016). Our results indicate that lower PD-1 expression in CD4(+) T-cells might contribute to the development of T1AD through T cell activation. © 2015 British Society for Immunology.

  13. 26 CFR 1.181-0T - Table of contents (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Table of contents (temporary). 1.181-0T Section...-0T Table of contents (temporary). This section lists the table of contents for §§ 1.181-1T through 1... deduction allowed. § 1.181-2TElection (temporary). (a) Time and manner of making election. (b) Election by...

  14. The lupus susceptibility gene Pbx1 regulates the balance between follicular helper T cell and regulatory T cell differentiation

    PubMed Central

    Choi, Seung-Chul; Hutchinson, Tarun E.; Titov, Anton A.; Seay, Howard R.; Li, Shiwu; Brusko, Todd M.; Croker, Byron P.; Salek-Ardakani, Shahram; Morel, Laurence

    2016-01-01

    Pbx1 controls chromatin accessibility to a large number of genes and is entirely conserved between mice and humans. The Pbx1-d dominant negative isoform is more frequent in the CD4+ T cells from lupus patients than from healthy controls. Pbx1-d is associated with the production of autoreactive T cells in mice carrying the Sle1a1 lupus susceptibility locus. Transgenic expression of Pbx1-d in CD4+ T cells reproduced the phenotypes of Sle1a1 mice, with increased inflammatory functions of CD4+ T cells and impaired regulatory T cell homeostasis. Pbx1-d Tg also expanded the number of follicular helper T cells in a cell-intrinsic and antigen-specific manner that was enhanced in recall responses, and resulted in TH1-biased antibodies. Moreover, Pbx1-d Tg CD4+ T cells upregulated the expression of miR-10a, miR-21 and miR-155, which have been implicated in Treg and TFH cell homeostasis. Our results suggest that Pbx1-d impacts lupus development by regulating effector T cell differentiation and promoting TFH cells at the expense of Treg cells. In addition, our results identify Pbx1 as a novel regulator of CD4+ T cell effector function. PMID:27296664

  15. Non-water-suppressed 1 H FID-MRSI at 3T and 9.4T.

    PubMed

    Chang, Paul; Nassirpour, Sahar; Avdievitch, Nikolai; Henning, Anke

    2018-08-01

    This study investigates metabolite concentrations using metabolite-cycled 1 H free induction decay (FID) magnetic resonance spectroscopic imaging (MRSI) at ultra-high fields. A non-lipid-suppressed and slice-selective ultra-short echo time (TE) 1 H FID MRSI sequence was combined with a low-specific absorption rate (SAR) asymmetric inversion adiabatic pulse to enable non-water-suppressed metabolite mapping using metabolite-cycling at 9.4T. The results were compared to a water-suppressed FID MRSI sequence, and the same study was performed at 3T for comparison. The scan times for performing single-slice metabolite mapping with a nominal voxel size of 0.4 mL were 14 and 17.5 min on 3T and 9.4T, respectively. The low-SAR asymmetric inversion adiabatic pulse enabled reliable non-water-suppressed metabolite mapping using metabolite cycling at both 3T and 9.4T. The spectra and maps showed good agreement with the water-suppressed FID MRSI ones at both field strengths. A quantitative analysis of metabolite ratios with respect to N-acetyl aspartate (NAA) was performed. The difference in Cre/NAA was statistically significant, ∼0.1 higher for the non-water-suppressed case than for water suppression (from 0.73 to 0.64 at 3T and from 0.69 to 0.59 at 9.4T). The difference is likely because of chemical exchange effects of the water suppression pulses. Small differences in mI/NAA were also statistically significant, however, are they are less reliable because the metabolite peaks are close to the water peak that may be affected by the water suppression pulses or metabolite-cycling inversion pulse. We showed the first implementation of non-water-suppressed metabolite-cycled 1 H FID MRSI at ultra-high fields. An increase in Cre/NAA was seen for the metabolite-cycled case. The same methodology was further applied at 3T and similar results were observed. Magn Reson Med 80:442-451, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society

  16. T1 and susceptibility contrast at high fields

    NASA Astrophysics Data System (ADS)

    Neelavalli, Jaladhar

    Clinical imaging at high magnetic field strengths (≥ 3Tesla) is sought after primarily due to the increased signal strength available at these fields. This increased SNR can be used to perform: (a) high resolution imaging in the same time as at lower field strengths; (b) the same resolution imaging with much faster acquisition; and (c) functional MR imaging (fMRI), dynamic perfusion and diffusion imaging with increased sensitivity. However they are also associated with increased power deposition (SAR) due to increase in imaging frequency and longer T1 relaxation times. Longer T1s mean longer imaging times for generating good T1 contrast images. On the other hand for faster imaging, at high fields fast spin echo or magnetization prepared sequences are conventionally proposed which are, however, associated with high SAR values. Imaging with low SAR is more and more important as we move towards high fields and particularly for patients with metallic implants like pacemakers or deep brain stimulator. The SAR limit acceptable for these patients is much less than the limit acceptable for normal subjects. A new method is proposed for imaging at high fields with good contrast with simultaneous reduction in power deposition. Further, T1 based contrast optimization problem in FLASH imaging is considered for tissues with different T1s but same spin densities. The solution providing optimal imaging parameters is simplified for quick and easy computation in a clinical setting. The efficacy of the simplification is evaluated and practical limits under which the simplification can be applied are worked out. The phase difference due to variation in magnetic susceptibility property among biological tissues is another unique source of contrast which is different from the conventional T1, T2 and T2* contrast. This susceptibility based phase contrast has become more and more important at high fields, partly due to contrast generation issues due to longer T 1s and shorter T2s and

  17. Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.

    PubMed

    Karur, Gauri R; Robison, Sean; Iwanochko, Robert M; Morel, Chantal F; Crean, Andrew M; Thavendiranathan, Paaladinesh; Nguyen, Elsie T; Mathur, Shobhit; Wasim, Syed; Hanneman, Kate

    2018-04-24

    Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P < .001]; 1192 msec ± 52 vs 1268 msec ± 55 [P < .001]; and 1221 msec ± 54 vs 1271 msec ± 37 [P = .001], respectively). A septal LV native T1 cutoff point of 1220 msec or lower distinguished AFD from HCM with sensitivity of 97%, specificity of 93%, and accuracy of 95%. Septal LV native T1 values differentiated AFD from HCM after adjustment for age, sex, and conventional imaging features (odds ratio, 0.94; 95% confidence interval: 0.91, 0.98; P = < .001). In a nested logistic regression model with age, sex, and conventional imaging features, model fit was significantly improved by the addition of septal LV native T1 values (χ 2 [df = 1] = 33.4; P < .001). Conclusion Cardiac MR imaging native T1 values at 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic

  18. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice

    PubMed Central

    Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F.; Vasselli, Joseph R.; Sclafani, Anthony

    2015-01-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. PMID:26157055

  19. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

    PubMed

    Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

    2015-09-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. Copyright © 2015 the American Physiological Society.

  20. 26 CFR 1.469-4T - Definition of activity (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Definition of activity (temporary). 1.469-4T Section 1.469-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxable Year for Which Deductions Taken § 1.469-4T Definition of activity (temporary). (a) Overview—(1)...

  1. 26 CFR 1.469-4T - Definition of activity (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Definition of activity (temporary). 1.469-4T Section 1.469-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxable Year for Which Deductions Taken § 1.469-4T Definition of activity (temporary). (a) Overview—(1)...

  2. 26 CFR 1.469-4T - Definition of activity (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Definition of activity (temporary). 1.469-4T Section 1.469-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxable Year for Which Deductions Taken § 1.469-4T Definition of activity (temporary). (a) Overview—(1)...

  3. 26 CFR 1.469-4T - Definition of activity (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Definition of activity (temporary). 1.469-4T Section 1.469-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxable Year for Which Deductions Taken § 1.469-4T Definition of activity (temporary). (a) Overview—(1)...

  4. p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells.

    PubMed

    Cereseto, A; Diella, F; Mulloy, J C; Cara, A; Michieli, P; Grassmann, R; Franchini, G; Klotman, M E

    1996-09-01

    Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53-regulated gene, p21waf1/cip1 (wild-type p53 activated fragment 1/cycling dependent kinases [cdks] interacting protein 1), in HTLV-I-infected T cells. We have found that the majority of HTLV-I-infected T cells have the wild-type p53 gene. However, its function in HTLV-I-transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21waf1/cip1, is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxl-1, a human T-cell line stably expressing Tax. Additionally, Tax induces upregulation of a p21waf1/cip1 promoter-driven luciferase gene in p53 null cells, and increases p21waf1/cip1 expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21waf1/cip1 in HTLV-I-infected cells. Dysregulation of p53 and p21waf1/cip1 proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

  5. Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths

    PubMed Central

    West, Janne; Blystad, Ida; Engström, Maria; Warntjes, Jan B. M.; Lundberg, Peter

    2013-01-01

    Background Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. Methods In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. Results Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001). Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. Conclusions Most of the brain was identically classified at the two field strengths, although some regional differences were observed. PMID:24066153

  6. Magnetic resonance fingerprinting using echo-planar imaging: Joint quantification of T1 and T2∗ relaxation times.

    PubMed

    Rieger, Benedikt; Zimmer, Fabian; Zapp, Jascha; Weingärtner, Sebastian; Schad, Lothar R

    2017-11-01

    To develop an implementation of the magnetic resonance fingerprinting (MRF) paradigm for quantitative imaging using echo-planar imaging (EPI) for simultaneous assessment of T 1 and T2∗. The proposed MRF method (MRF-EPI) is based on the acquisition of 160 gradient-spoiled EPI images with rapid, parallel-imaging accelerated, Cartesian readout and a measurement time of 10 s per slice. Contrast variation is induced using an initial inversion pulse, and varying the flip angles, echo times, and repetition times throughout the sequence. Joint quantification of T 1 and T2∗ is performed using dictionary matching with integrated B1+ correction. The quantification accuracy of the method was validated in phantom scans and in vivo in 6 healthy subjects. Joint T 1 and T2∗ parameter maps acquired with MRF-EPI in phantoms are in good agreement with reference measurements, showing deviations under 5% and 4% for T 1 and T2∗, respectively. In vivo baseline images were visually free of artifacts. In vivo relaxation times are in good agreement with gold-standard techniques (deviation T 1 : 4 ± 2%, T2∗: 4 ± 5%). The visual quality was comparable to the in vivo gold standard, despite substantially shortened scan times. The proposed MRF-EPI method provides fast and accurate T 1 and T2∗ quantification. This approach offers a rapid supplement to the non-Cartesian MRF portfolio, with potentially increased usability and robustness. Magn Reson Med 78:1724-1733, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  7. Evaluation of MRI sequences for quantitative T1 brain mapping

    NASA Astrophysics Data System (ADS)

    Tsialios, P.; Thrippleton, M.; Glatz, A.; Pernet, C.

    2017-11-01

    T1 mapping constitutes a quantitative MRI technique finding significant application in brain imaging. It allows evaluation of contrast uptake, blood perfusion, volume, providing a more specific biomarker of disease progression compared to conventional T1-weighted images. While there are many techniques for T1-mapping there is a wide range of reported T1-values in tissues, raising the issue of protocols reproducibility and standardization. The gold standard for obtaining T1-maps is based on acquiring IR-SE sequence. Widely used alternative sequences are IR-SE-EPI, VFA (DESPOT), DESPOT-HIFI and MP2RAGE that speed up scanning and fitting procedures. A custom MRI phantom was used to assess the reproducibility and accuracy of the different methods. All scans were performed using a 3T Siemens Prisma scanner. The acquired data processed using two different codes. The main difference was observed for VFA (DESPOT) which grossly overestimated T1 relaxation time by 214 ms [126 270] compared to the IR-SE sequence. MP2RAGE and DESPOT-HIFI sequences gave slightly shorter time than IR-SE (~20 to 30ms) and can be considered as alternative and time-efficient methods for acquiring accurate T1 maps of the human brain, while IR-SE-EPI gave identical result, at a cost of a lower image quality.

  8. Alternative Polyadenylation Regulates CELF1/CUGBP1 Target Transcripts Following T Cell Activation

    PubMed Central

    Beisang, Daniel; Reilly, Cavan; Bohjanen, Paul R.

    2014-01-01

    Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3′ end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3′ untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3′ end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression. We present a model whereby CELF1 regulates APA site selection following T cell activation through reversible binding to nearby GRE sequences. These findings provide insight into the role of APA in controlling cellular proliferation during biological processes such as development, oncogenesis and T cell activation PMID:25123787

  9. Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel.

    PubMed

    Wang, Guangyu; Strang, Candace; Pfaffinger, Paul J; Covarrubias, Manuel

    2007-05-04

    The thiol-based redox regulation of proteins plays a central role in cellular signaling. Here, we investigated the redox regulation at the Zn(2+) binding site (HX(5)CX(20)CC) in the intracellular T1-T1 inter-subunit interface of a Kv4 channel. This site undergoes conformational changes coupled to voltage-dependent gating, which may be sensitive to oxidative stress. The main results show that internally applied nitric oxide (NO) inhibits channel activity profoundly. This inhibition is reversed by reduced glutathione and suppressed by intracellular Zn(2+), and at least two Zn(2+) site cysteines are required to observe the NO-induced inhibition (Cys-110 from one subunit and Cys-132 from the neighboring subunit). Biochemical evidence suggests strongly that NO induces a disulfide bridge between Cys-110 and Cys-132 in intact cells. Finally, further mutational studies suggest that intra-subunit Zn(2+) coordination involving His-104, Cys-131, and Cys-132 protects against the formation of the inhibitory disulfide bond. We propose that the interfacial T1 Zn(2+) site of Kv4 channels acts as a Zn(2+)-dependent redox switch that may regulate the activity of neuronal and cardiac A-type K(+) currents under physiological and pathological conditions.

  10. Taste information derived from T1R-expressing taste cells in mice.

    PubMed

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-03-01

    The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination. © 2016 Authors; published by Portland Press Limited.

  11. Novel Biomarkers of Human GM1 Gangliosidosis Reflect the Clinical Efficacy of Gene Therapy in a Feline Model.

    PubMed

    Gray-Edwards, Heather L; Regier, Debra S; Shirley, Jamie L; Randle, Ashley N; Salibi, Nouha; Thomas, Sarah E; Latour, Yvonne L; Johnston, Jean; Golas, Gretchen; Maguire, Annie S; Taylor, Amanda R; Sorjonen, Donald C; McCurdy, Victoria J; Christopherson, Peter W; Bradbury, Allison M; Beyers, Ronald J; Johnson, Aime K; Brunson, Brandon L; Cox, Nancy R; Baker, Henry J; Denney, Thomas S; Sena-Esteves, Miguel; Tifft, Cynthia J; Martin, Douglas R

    2017-04-05

    GM1 gangliosidosis is a fatal neurodegenerative disease that affects individuals of all ages. Favorable outcomes using adeno-associated viral (AAV) gene therapy in GM1 mice and cats have prompted consideration of human clinical trials, yet there remains a paucity of objective biomarkers to track disease status. We developed a panel of biomarkers using blood, urine, cerebrospinal fluid (CSF), electrodiagnostics, 7 T MRI, and magnetic resonance spectroscopy in GM1 cats-either untreated or AAV treated for more than 5 years-and compared them to markers in human GM1 patients where possible. Significant alterations were noted in CSF and blood of GM1 humans and cats, with partial or full normalization after gene therapy in cats. Gene therapy improved the rhythmic slowing of electroencephalograms (EEGs) in GM1 cats, a phenomenon present also in GM1 patients, but nonetheless the epileptiform activity persisted. After gene therapy, MR-based analyses revealed remarkable preservation of brain architecture and correction of brain metabolites associated with microgliosis, neuroaxonal loss, and demyelination. Therapeutic benefit of AAV gene therapy in GM1 cats, many of which maintain near-normal function >5 years post-treatment, supports the strong consideration of human clinical trials, for which the biomarkers described herein will be essential for outcome assessment. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  12. Core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Li, Fenfen; Zhi, Debo; Luo, Yufeng; Zhang, Jiqian; Nan, Xiang; Zhang, Yunjiao; Zhou, Wei; Qiu, Bensheng; Wen, Longping; Liang, Gaolin

    2016-06-01

    T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes

  13. Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity.

    PubMed

    Vinciguerra, Manlio; Santini, Maria Paola; Claycomb, William C; Ladurner, Andreas G; Rosenthal, Nadia

    2009-12-10

    Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD(+)-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic.

  14. Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity

    PubMed Central

    Vinciguerra, Manlio; Santini, Maria Paola; Claycomb, William C.; Ladurner, Andreas G.; Rosenthal, Nadia

    2010-01-01

    Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD+-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic. PMID:20228935

  15. Cervical disc hernia operations through posterior laminoforaminotomy.

    PubMed

    Yolas, Coskun; Ozdemir, Nuriye Guzin; Okay, Hilmi Onder; Kanat, Ayhan; Senol, Mehmet; Atci, Ibrahim Burak; Yilmaz, Hakan; Coban, Mustafa Kemal; Yuksel, Mehmet Onur; Kahraman, Umit

    2016-01-01

    The most common used technique for posterolateral cervical disc herniations is anterior approach. However, posterior cervical laminotoforaminomy can provide excellent results in appropriately selected patients with foraminal stenosis in either soft disc prolapse or cervical spondylosis. The purpose of this study was to present the clinical outcomes following posterior laminoforaminotomy in patients with radiculopathy. We retrospectively evaluated 35 patients diagnosed with posterolateral cervical disc herniation and cervical spondylosis with foraminal stenosis causing radiculopathy operated by the posterior cervical keyhole laminoforaminotomy between the years 2010 and 2015. The file records and the radiographic images of the 35 patients were assessed retrospectively. The mean age was 46.4 years (range: 34-66 years). Of the patients, 19 were males and 16 were females. In all of the patients, the neurologic deficit observed was radiculopathy. The posterolaterally localized disc herniations and the osteophytic structures were on the left side in 18 cases and on the right in 17 cases. In 10 of the patients, the disc level was at C5-6, in 18 at C6-7, in 2 at C3-4, in 2 at C4-5, in 1 at C7-T1, in 1 patient at both C5-6 and C6-7, and in 1 at both C4-5 and C5-6. In 14 of these 35 patients, both osteophytic structures and protruded disc herniation were present. Intervertebral foramen stenosis was present in all of the patients with osteophytes. Postoperatively, in 31 patients the complaints were relieved completely and four patients had complaints of neck pain and paresthesia radiating to the arm (the success of operation was 88.5%). On control examinations, there was no finding of instability or cervical kyphosis. Posterior cervical laminoforaminotomy is an alternative appropriate choice in both cervical soft disc herniations and cervical stenosis.

  16. 26 CFR 1.181-6T - Effective date (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... first day of principal photography for which occurs on or after February 9, 2007, and before January 1...-between animation” in place of “principal photography”. Productions involving both animation and live-action photography may use either standard. (2) The applicability of §§ 1.181-1T through 1.181-5T expires...

  17. 26 CFR 1.181-6T - Effective date (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... first day of principal photography for which occurs on or after February 9, 2007, and before January 1...-between animation” in place of “principal photography”. Productions involving both animation and live-action photography may use either standard. (2) The applicability of §§ 1.181-1T through 1.181-5T expires...

  18. Role of interleukin 1 in antigen-specific T cell proliferation.

    PubMed

    Chu, E; Rosenwasser, L J; Dinarello, C A; Lareau, M; Geha, R S

    1984-03-01

    The role of interleukin 1 (IL 1) in human antigen-specific T cell proliferation was examined. Nylon wool-purified T cells proliferated in the presence of autologous monocytes (Mo.) pulsed for 18 h with tetanus toxoid (TT) antigen (Mo.TT). Irradiation of Mo.TT with ultraviolet (UV) light (72 J/m2) abolished their capacity to support T cell proliferation and drastically reduced their capacity to secrete IL 1 after stimulation with Staphylococcus albus. The defect in antigen presentation induced by UV irradiation of Mo.TT was reversed in a dose-dependent manner by the addition of two different preparations containing human interleukin 1 (IL 1). The first preparation consisted of supernatants of Mo. stimulated with Con A for 18 hr and in which Con A activity was blocked by alpha-D-methyl-mannoside (Mo.-Con A-Sup). The second preparation consisted of human IL 1 partially purified from supernatants of human peripheral blood mononuclear cells stimulated with S. albus. This IL 1 copurified with human leukocyte pyrogen (LP) and was termed IL 1/LP. Both IL 1-containing preparations enhanced the response of C57BL/6 mouse thymocytes to phytohemagglutinin. A rabbit antibody to human IL 1/LP inhibited the capacity of T cells to proliferate in response to Mo.TT and inhibited the capacity of Mo.-Con A-Sup to reconstitute the T cell response to UV-irradiated Mo.TT. IL 1/LP was not necessary for T cells to recognize the immunogenic moiety presented by Mo., because monolayers of UV-irradiated Mo.TT were equivalent to monolayers of unirradiated MO.TT in their capacity to adsorb TT-reactive T cells specifically. Furthermore, the addition of rabbit antibody to IL 1/LP did not interfere with the capacity of UV-irradiated Mo.TT to adsorb TT-reactive T cells. The results obtained in this study indicate that IL 1 is involved in optimal antigen-driven proliferation of human T lymphocytes.

  19. Cluster analysis of quantitative MRI T2 and T1ρ relaxation times of cartilage identifies differences between healthy and ACL-injured individuals at 3T.

    PubMed

    Monu, U D; Jordan, C D; Samuelson, B L; Hargreaves, B A; Gold, G E; McWalter, E J

    2017-04-01

    To identify focal lesions of elevated MRI T 2 and T 1ρ relaxation times in articular cartilage of an ACL-injured group using a novel cluster analysis technique. Eighteen ACL-injured patients underwent 3T MRI T 2 and T 1ρ relaxometry at baseline, 6 months and 1 year and six healthy volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or below T 2 and T 1ρ intensity and area thresholds were identified on a projection map of the 3D femoral cartilage surface. The total area of femoral cartilage plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA-) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured group were determined using the Wilcoxon signed rank test. %CA+ was greater in the ACL-injured patients than the healthy volunteers at 6 months and 1 year with average %CA+ of 5.2 ± 4.0% (p = 0.0054) and 6.6 ± 3.7% (p = 0.0041) for T 2 and 6.2 ± 7.1% (p = 0.063) and 8.2 ± 6.9% (p = 0.042) for T 1ρ , respectively. %CA- at 6 months and 1 year was 3.0 ± 1.8% (p > 0.1) and 5.9 ± 5.0% (p > 0.1) for T 2 and 4.4 ± 4.9% (p > 0.1) and 4.5 ± 4.6% (p > 0.1) for T 1ρ , respectively. With the proposed cluster analysis technique, we have quantified cartilage lesion coverage and demonstrated that the ACL-injured group had greater areas of elevated T 2 and T 1ρ relaxation times as compared to healthy volunteers. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Evaluation of multimodal segmentation based on 3D T1-, T2- and FLAIR-weighted images - the difficulty of choosing.

    PubMed

    Lindig, Tobias; Kotikalapudi, Raviteja; Schweikardt, Daniel; Martin, Pascal; Bender, Friedemann; Klose, Uwe; Ernemann, Ulrike; Focke, Niels K; Bender, Benjamin

    2018-04-15

    Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35.8 years, 19-66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28.1 years,19-40 years, 3 females), and 5 patients with left hippocampal sclerosis (LHS) (mean age 49.0 years, 25-67 years, 3 females) from a 3T scanner were evaluated. Segmentation based on T1-only, T1+T2, T1+FLAIR, T2+FLAIR, and T1+T2+FLAIR were compared in the healthy subjects. Clinical VBM results based on the different segmentation approaches for MCD and for LHS were compared. T1-only segmentation overestimated total intracranial volume by about 80ml compared to the other segmentation methods. This was due to misclassification of dura mater and vessels as GM and CSF. Significant differences were found for several anatomical regions: the occipital lobe, the basal ganglia/thalamus, the pre- and postcentral gyrus, the cerebellum, and the brainstem. None of the segmentation methods yielded completely satisfying results for the basal ganglia/thalamus and the brainstem. The best correlation with age could be found for the multimodal T1+T2+FLAIR segmentation. Highest T-scores for identification of LHS were found for T1+T2 segmentation, while highest T-scores for MCD were dependent on lesion and anatomical location. Multimodal segmentation is superior to T1-only segmentation and reduces the misclassification of dura mater and vessels as GM and CSF. Depending on the anatomical region and the pathology of interest (atrophy, lesion detection, etc.), different combinations of T1, T2 and FLAIR yield optimal results. Copyright © 2017 Elsevier

  1. 26 CFR 1.860G-2T - Other rules (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Other rules (temporary). 1.860G-2T Section 1.860G-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Real Estate Investment Trusts § 1.860G-2T Other rules (temporary). (a...

  2. 26 CFR 1.860G-2T - Other rules (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Other rules (temporary). 1.860G-2T Section 1.860G-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Real Estate Investment Trusts § 1.860G-2T Other rules (temporary). (a...

  3. Gene Polymorphisms of Glutathione S-Transferase T1/M1 in Egyptian Children and Adolescents with Type 1 Diabetes Mellitus.

    PubMed

    Barseem, Naglaa; Elsamalehy, Mona

    2017-06-01

    Oxidative stress plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). To evaluate the association of glutathione S-transferase mu 1 (GST M1) and glutathione S-transferase theta 1 (GST T1) polymorphisms with development of T1DM and disease-related risk factors. Measurement of fasting glucose, serum creatinine, lipid profile, and glycosylated hemoglobin (HbA1c), as well as evaluation of GST T1 and M1 genetic polymorphisms using polymerase chain reaction were done in 64 diabetic children and 41 controls. The diabetic group had significantly higher fasting glucose, HbA1c, and cholesterol levels. GST T1 null genotype was more frequent in the diabetic than the control group with 4.2-fold increased risk of T1DM (odds ratio=4.2; 95% confidence interval=1.6-11.5; p=0.03). Significant positive associations were found with lipid profile, HbA1c, and duration of illness but not with age, age at onset, and body mass index. Gene polymorphisms of the enzyme GST are associated with development of T1DM and disease-related risk factors.

  4. Assessment of myocardial fibrosis with T1 mapping MRI.

    PubMed

    Everett, R J; Stirrat, C G; Semple, S I R; Newby, D E; Dweck, M R; Mirsadraee, S

    2016-08-01

    Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. Copyright © 2016 The Royal College

  5. Role of PD-1 during effector CD8 T cell differentiation.

    PubMed

    Ahn, Eunseon; Araki, Koichi; Hashimoto, Masao; Li, Weiyan; Riley, James L; Cheung, Jeanne; Sharpe, Arlene H; Freeman, Gordon J; Irving, Bryan A; Ahmed, Rafi

    2018-05-01

    PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1 is also expressed transiently by activated CD8 T cells during acute viral infection, but the role of PD-1 in modulating T cell effector differentiation and function is not well defined. To address this question, we examined the expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis virus (LCMV) infection of mice. PD-1 was rapidly up-regulated in vivo upon activation of naive virus-specific CD8 T cells within 24 h after LCMV infection and in less than 4 h after peptide injection, well before any cell division had occurred. This rapid PD-1 expression by CD8 T cells was driven predominantly by antigen receptor signaling since infection with a LCMV strain with a mutation in the CD8 T cell epitope did not result in the increase of PD-1 on antigen-specific CD8 T cells. Blockade of the PD-1 pathway using anti-PD-L1 or anti-PD-1 antibodies during the early phase of acute LCMV infection increased mTOR signaling and granzyme B expression in virus-specific CD8 T cells and resulted in faster clearance of the infection. These results show that PD-1 plays an inhibitory role during the naive-to-effector CD8 T cell transition and that the PD-1 pathway can also be modulated at this stage of T cell differentiation. These findings have implications for developing therapeutic vaccination strategies in combination with PD-1 blockade.

  6. 26 CFR 1.103(n)-1T - Limitation on aggregrate amount of private activity bonds (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... activity bonds (temporary). 1.103(n)-1T Section 1.103(n)-1T Internal Revenue INTERNAL REVENUE SERVICE... Excluded from Gross Income § 1.103(n)-1T Limitation on aggregrate amount of private activity bonds (temporary). Q-1: What does section 103(n) provide? A-1: Interest on an issue of private activity bonds will...

  7. 26 CFR 1.103(n)-1T - Limitation on aggregrate amount of private activity bonds (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... activity bonds (temporary). 1.103(n)-1T Section 1.103(n)-1T Internal Revenue INTERNAL REVENUE SERVICE... Excluded from Gross Income § 1.103(n)-1T Limitation on aggregrate amount of private activity bonds (temporary). Q-1: What does section 103(n) provide? A-1: Interest on an issue of private activity bonds will...

  8. Measurement of the t anti-t production cross-section at √s = 1.96-TeV using lifetime tagging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khanov, Alexander

    2004-01-01

    A measurement of the tmore » $$\\bar{t}$$ production cross section in the lepton+jets channels with the D0 detector at √s = 1.96 TeV using the lifetime-tagging techniques is presented. The t$$\\bar{t}$$ cross section is estimated from the combination of the e+jets and μ+jets channels. The obtained result σ t$$\\bar{t}$$ = 7.47$$+ 1.22\\atop{-1.14}$$(stat)$$+ 1.65\\atop{-1.03}$$(syst) ± 0.49(lumi) pb is consistent with the Standard Model expectation.« less

  9. Synergistic antileukemic therapies in NOTCH1-induced T-ALL

    PubMed Central

    Sanchez-Martin, Marta; Ambesi-Impiombato, Alberto; Qin, Yue; Herranz, Daniel; Bansal, Mukesh; Girardi, Tiziana; Paietta, Elisabeth; Tallman, Martin S.; Rowe, Jacob M.; Califano, Andrea; Ferrando, Adolfo A.

    2017-01-01

    The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo. Mechanistically, network perturbation analyses showed eIF2A-phosphorylation–mediated inhibition of protein translation as a critical mediator of the antileukemic effects of withaferin A and its interaction with NOTCH1 inhibition. Overall, these results support a role for anti-NOTCH1 therapies and protein translation inhibitor combinations in the treatment of T-ALL. PMID:28174276

  10. Early Outcomes of Endoscopic Contralateral Foraminal and Lateral Recess Decompression via an Interlaminar Approach in Patients with Unilateral Radiculopathy from Unilateral Foraminal Stenosis.

    PubMed

    Kim, Hyeun Sung; Patel, Ravish; Paudel, Byapak; Jang, Jee-Soo; Jang, Il-Tae; Oh, Seong-Hoon; Park, Jae Eun; Lee, Sol

    2017-12-01

    Percutaneous endoscopic contralateral interlaminar lumbar foraminotomy (PECILF) for lumbar degenerative spinal stenosis is an established procedure. Better preservation of contralateral facet joint compared with that of the approach side has been shown with uniportal bilateral decompression. The aim of this retrospective case series was to analyze the early clinical and radiologic outcomes of stand-alone contralateral foraminotomy and lateral recess decompression using PECILF. Twenty-six consecutive patients with unilateral lower limb radiculopathy underwent contralateral foraminotomy and lateral recess decompression using PECILF. Their clinical outcomes were evaluated with visual analog scale leg pain score, Oswestry Disability Index, and the MacNab criteria. Completeness of decompression was documented with a postoperative magnetic resonance imaging. Mean age for the study group was 62.9 ± 9.2 years and the male/female ratio was 4:9. A total of 30 levels were decompressed, with 18 patients (60%) undergoing decompression at L4-L5, 9 at L5-S1 (30%), 2 at L3-L4 (6.7%), and 1 at L2-L3 (3.3%). Mean estimated blood loss was 27 ± 15 mL per level. Mean operative duration was 48 ± 12 minutes/level. Visual analog scale leg score improved from 7.7 ± 1 to 1.8 ± 0.8 (P < 0.0001). Oswestry Disability Index improved from 64.4 ± 5.8 to 21 ± 4.5 (P < 0.0001). Mean follow-up of the study was 13.7 ± 2.7 months. According to the MacNab criteria, 10 patients (38.5%) had good results, 14 patients (53.8%) had excellent results, and 2 patients (7.7%) had fair results. One patient required revision surgery. Facet-preserving contralateral foraminotomy and lateral recess decompression with PECILF is effective for treatment of lateral recess and foraminal stenosis. Thorough decompression with acceptable early clinical outcomes and minimal perioperative morbidity can be obtained with the contralateral endoscopic approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 26 CFR 1.904(g)-1T - Overall domestic loss and the overall domestic loss account (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... loss account (temporary). 1.904(g)-1T Section 1.904(g)-1T Internal Revenue INTERNAL REVENUE SERVICE... Without the United States § 1.904(g)-1T Overall domestic loss and the overall domestic loss account... reductions from such accounts for purposes of section 904(g). Section 1.904(g)-2T provides rules for...

  12. 26 CFR 1.904(g)-1T - Overall domestic loss and the overall domestic loss account (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... loss account (temporary). 1.904(g)-1T Section 1.904(g)-1T Internal Revenue INTERNAL REVENUE SERVICE... Without the United States § 1.904(g)-1T Overall domestic loss and the overall domestic loss account... reductions from such accounts for purposes of section 904(g). Section 1.904(g)-2T provides rules for...

  13. 26 CFR 1.904(g)-1T - Overall domestic loss and the overall domestic loss account (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... loss account (temporary). 1.904(g)-1T Section 1.904(g)-1T Internal Revenue INTERNAL REVENUE SERVICE... United States § 1.904(g)-1T Overall domestic loss and the overall domestic loss account (temporary). (a... accounts for purposes of section 904(g). Section 1.904(g)-2T provides rules for recapturing the balance in...

  14. The Discover artificial disc replacement versus fusion in cervical radiculopathy--a randomized controlled outcome trial with 2-year follow-up.

    PubMed

    Skeppholm, Martin; Lindgren, Lars; Henriques, Thomas; Vavruch, Ludek; Löfgren, Håkan; Olerud, Claes

    2015-06-01

    Several previous studies comparing artificial disc replacement (ADR) and fusion have been conducted with cautiously positive results in favor of ADR. This study is not, in contrast to most previous studies, an investigational device exemption study required by the Food and Drug Administration for approval to market the product in the United States. This study was partially funded with unrestricted institutional research grants by the company marketing the artificial disc used in this study. To compare outcomes between the concepts of an artificial disc to treatment with anterior cervical decompression and fusion (ACDF) and to register complications associated to the two treatments during a follow-up time of 2 years. This is a randomized controlled multicenter trial, including three spine centers in Sweden. The study included patients seeking care for cervical radiculopathy who fulfilled inclusion criteria. In total, 153 patients were included. Self-assessment with Neck Disability Index (NDI) as a primary outcome variable and EQ-5D and visual analog scale as secondary outcome variables. Patients were randomly allocated to either treatment with the Depuy Discover artificial disc or fusion with iliac crest bone graft and plating. Randomization was blinded to both patient and caregivers until time for implantation. Adverse events, complications, and revision surgery were registered as well as loss of follow-up. Data were available in 137 (91%) of the included and initially treated patients. Both groups improved significantly after surgery. NDI changed from 63.1 to 39.8 in an intention-to-treat analysis. No statistically significant difference between the ADR and the ACDF groups could be demonstrated with NDI values of 39.1 and 40.1, respectively. Nor in secondary outcome measures (EQ-5D and visual analog scale) could any statistically significant differences be demonstrated between the groups. Nine patients in the ADR group and three in the fusion group underwent

  15. Pancreatic Duct in Autoimmune Pancreatitis: Intraindividual Comparison of Magnetic Resonance Pancreatography at 1.5 T and 3.0 T.

    PubMed

    Kim, Jin Hee; Byun, Jae Ho; Kim, Myung-Hwan; Lee, Sung Koo; Kim, Song Cheol; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2017-08-01

    The aim of this study was to intraindividually compare magnetic resonance pancreatography (MRP) image quality at 1.5 T and 3.0 T when demonstrating main pancreatic duct (MPD) abnormalities in patients with autoimmune pancreatitis (AIP). Thirty prospectively enrolled patients with AIP underwent MRP at both 1.5 T and 3.0 T followed by endoscopic retrograde pancreatography before treatment. Two readers independently analyzed the MRP images and graded the visualization of MPD strictures and full-length MPD, using endoscopic retrograde pancreatography as the reference standard, as well as overall image artifacts on a 4-point scale. The contrast between the MPD and periductal area was calculated using a region-of-interest measurement. Visualization scores of MPD strictures and full-length MPD, and summed scores of each qualitative analysis, were significantly greater at 3.0-T MRP than at 1.5-T MRP for both readers (P ≤ 0.02). There were less image artifacts at 3.0 T compared with 1.5 T (P ≤ 0.052). The contrast between the MPD and periductal area was significantly greater at 3.0-T MRP than at 1.5-T MRP (P < 0.001). The MRP at 3.0 T was superior to 1.5-T MRP for demonstrating MPD abnormalities in AIP, with better image contrast and fewer image artifacts. Consequently, 3.0-T MRP may be useful for the diagnosis and management of patients with AIP.

  16. Europium-engineered iron oxide nanocubes with high T1 and T2 contrast abilities for MRI in living subjects

    NASA Astrophysics Data System (ADS)

    Yang, Lijiao; Zhou, Zijian; Liu, Hanyu; Wu, Changqiang; Zhang, Hui; Huang, Guoming; Ai, Hua; Gao, Jinhao

    2015-04-01

    Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver

  17. 26 CFR 1.709-1T - Treatment of organizational expenses and syndication costs (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... syndication costs (temporary). 1.709-1T Section 1.709-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... Treatment of organizational expenses and syndication costs (temporary). (a) [Reserved] For further guidance... organizational expenses for two or more taxable years. (3) Liquidation of partnership. If there is a winding up...

  18. Osmotic and aging effects in caviar oocytes throughout water and lipid changes assessed by 1H NMR T1 and T2 relaxation and MRI.

    PubMed

    Gussoni, Maristella; Greco, Fulvia; Vezzoli, Alessandra; Paleari, Maria Antonietta; Moretti, Vittorio Maria; Lanza, Barbara; Zetta, Lucia

    2007-01-01

    By combining NMR relaxation spectroscopy and magnetic resonance imaging techniques, unsalted (us) and salted (s) caviar (Acipenser transmontanus) oocytes were characterized over a storage period of up to 90 days. The aging and the salting effects on the two major cell constituents, water and lipids, were separately assessed. T1 and T2 decays were interpreted by assuming a two-site exchange model. At Day 0, two water compartments that were not in fast exchange were identified by the T1 relaxation measurements on the us oocytes. In the s samples, T1 decay was monoexponential. During the time of storage, an increment of the free water amount was found for the us oocytes, ascribed to an increased metabolism. T1 and T2 of the s oocytes shortened as a consequence of the osmotic stress produced by salting. Selective images showed the presence of water endowed with different regional mobility that severely changed during the storage. Lipid T1 relaxation decays collected on us and s samples were found to be biexponential, and the T1 values lengthened during storage. In us and s oocytes, the increased lipid mobility with the storage was ascribed to lipolysis. Selective images of us samples showed lipids that were confined to the cytoplasm for up to 60 days of storage.

  19. A systematic evaluation of three different cardiac T2-mapping sequences at 1.5 and 3T in healthy volunteers.

    PubMed

    Baeßler, Bettina; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Maintz, David; Bunck, Alexander C

    2015-11-01

    Previous studies showed that myocardial T2 relaxation times measured by cardiac T2-mapping vary significantly depending on sequence and field strength. Therefore, a systematic comparison of different T2-mapping sequences and the establishment of dedicated T2 reference values is mandatory for diagnostic decision-making. Phantom experiments using gel probes with a range of different T1 and T2 times were performed on a clinical 1.5T and 3T scanner. In addition, 30 healthy volunteers were examined at 1.5 and 3T in immediate succession. In each examination, three different T2-mapping sequences were performed at three short-axis slices: Multi Echo Spin Echo (MESE), T2-prepared balanced SSFP (T2prep), and Gradient Spin Echo with and without fat saturation (GraSEFS/GraSE). Segmented T2-Maps were generated according to the AHA 16-segment model and statistical analysis was performed. Significant intra-individual differences between mean T2 times were observed for all sequences. In general, T2prep resulted in lowest and GraSE in highest T2 times. A significant variation with field strength was observed for mean T2 in phantom as well as in vivo, with higher T2 values at 1.5T compared to 3T, regardless of the sequence used. Segmental T2 values for each sequence at 1.5 and 3T are presented. Despite a careful selection of sequence parameters and volunteers, significant variations of the measured T2 values were observed between field strengths, MR sequences and myocardial segments. Therefore, we present segmental T2 values for each sequence at 1.5 and 3T with the inherent potential to serve as reference values for future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Comparative Analysis between Total Disc Replacement and Posterior Foraminotomy for Posterolateral Soft Disc Herniation with Unilateral Radiculopathy : Clinical and Biomechanical Results of a Minimum 5 Years Follow-up

    PubMed Central

    Kim, Kyoung-Tae; Cho, Dae-Chul; Sung, Joo-Kyung; Kim, Young-Baeg; Kim, Du Hwan

    2017-01-01

    Objective To compare the clinical outcomes and biomechanical effects of total disc replacement (TDR) and posterior cervical foraminotomy (PCF) and to propose relative inclusion criteria. Methods Thirty-five patients who underwent surgery between 2006 and 2008 were included. All patients had single-level disease and only radiculopathy. The overall sagittal balance and angle and height of a functional segmental unit (FSU; upper and lower vertebral body of the operative lesion) were assessed by preoperative and follow-up radiographs. C2–7 range of motion (ROM), FSU, and the adjacent segment were also checked. Results The clinical outcome of TDR (group A) was tended to be superior to that of PCF (group B) without statistical significance. In the group A, preoperative and postoperative upper adjacent segment level motion values were 8.6±2.3 and 8.4±2.0, and lower level motion values were 8.4±2.2 and 8.3±1.9. Preoperative and postoperative FSU heights were 37.0±2.1 and 37.1±1.8. In the group B, upper level adjacent segment motion values were 8.1±2.6 and 8.2±2.8, and lower level motion values were 6.5±3.3 and 6.3±3.1. FSU heights were 37.1±2.0 and 36.2±1.8. The postoperative FSU motion and height changes were significant (p<0.05). The patient’s satisfaction rates for surgery were 88.2% in group A and 88.8% in group B. Conclusion TDR and PCF have favorable outcomes in patients with unilateral soft disc herniation. However, patients have different biomechanical backgrounds, so the patient’s biomechanical characteristics and economic status should be understood and treated using the optimal procedure. PMID:28061490

  1. 26 CFR 1.904(g)-0T - Outline of regulation provisions (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....904(g)-0T Section 1.904(g)-0T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....904(g)-0T Outline of regulation provisions (temporary). This section lists the headings for §§ 1.904(g)-1T through 1.904(g)-3T. § 1.904(g)-1TOverall domestic loss and the overall domestic loss account...

  2. 26 CFR 1.904(g)-0T - Outline of regulation provisions (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....904(g)-0T Section 1.904(g)-0T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....904(g)-0T Outline of regulation provisions (temporary). This section lists the headings for §§ 1.904(g)-1T through 1.904(g)-3T. § 1.904(g)-1TOverall domestic loss and the overall domestic loss account...

  3. Cardiac MOLLI T1 mapping at 3.0 T: comparison of patient-adaptive dual-source RF and conventional RF transmission.

    PubMed

    Rasper, Michael; Nadjiri, Jonathan; Sträter, Alexandra S; Settles, Marcus; Laugwitz, Karl-Ludwig; Rummeny, Ernst J; Huber, Armin M

    2017-06-01

    To prospectively compare image quality and myocardial T 1 relaxation times of modified Look-Locker inversion recovery (MOLLI) imaging at 3.0 T (T) acquired with patient-adaptive dual-source (DS) and conventional single-source (SS) radiofrequency (RF) transmission. Pre- and post-contrast MOLLI T 1 mapping using SS and DS was acquired in 27 patients. Patient wise and segment wise analysis of T 1 times was performed. The correlation of DS MOLLI measurements with a reference spin echo sequence was analysed in phantom experiments. DS MOLLI imaging reduced T 1 standard deviation in 14 out of 16 myocardial segments (87.5%). Significant reduction of T 1 variance could be obtained in 7 segments (43.8%). DS significantly reduced myocardial T 1 variance in 16 out of 25 patients (64.0%). With conventional RF transmission, dielectric shading artefacts occurred in six patients causing diagnostic uncertainty. No according artefacts were found on DS images. DS image findings were in accordance with conventional T 1 mapping and late gadolinium enhancement (LGE) imaging. Phantom experiments demonstrated good correlation of myocardial T 1 time between DS MOLLI and spin echo imaging. Dual-source RF transmission enhances myocardial T 1 homogeneity in MOLLI imaging at 3.0 T. The reduction of signal inhomogeneities and artefacts due to dielectric shading is likely to enhance diagnostic confidence.

  4. 26 CFR 1.409(p)-1T - Prohibited allocations of securities in an S corporation (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... corporation (temporary). 1.409(p)-1T Section 1.409(p)-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT..., Stock Bonus Plans, Etc. § 1.409(p)-1T Prohibited allocations of securities in an S corporation (temporary). (a) Organization of this section. Section 409(p) applies if a nonallocation year occurs in an...

  5. Critically re-evaluating a common technique: Accuracy, reliability, and confirmation bias of EMG.

    PubMed

    Narayanaswami, Pushpa; Geisbush, Thomas; Jones, Lyell; Weiss, Michael; Mozaffar, Tahseen; Gronseth, Gary; Rutkove, Seward B

    2016-01-19

    (1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG. Three experienced academic electromyographers interpreted 3 compact discs with 20 EMG videos (10 normal, 10 radiculopathy) in a blinded, standardized fashion without information regarding the nature of the study. The EMGs were interpreted 3 times (discs A, B, C) 1 month apart. Clinical information was provided only with disc C. Intrarater reliability was calculated by comparing interpretations in discs A and B, interrater reliability by comparing interpretation between reviewers. Confirmation bias was estimated by the difference in correct interpretations when clinical information was provided. Sensitivity was similar to previous reports (77%, confidence interval [CI] 63%-90%); specificity was 71%, CI 56%-85%. Intrarater reliability was good (κ 0.61, 95% CI 0.41-0.81); interrater reliability was lower (κ 0.53, CI 0.35-0.71). There was no substantial confirmation bias when clinical information was provided (absolute difference in correct responses 2.2%, CI -13.3% to 17.7%); the study lacked precision to exclude moderate confirmation bias. This study supports that (1) serial EMG studies should be performed by the same electromyographer since intrarater reliability is better than interrater reliability; (2) knowledge of clinical information does not bias EMG interpretation substantially; (3) EMG has moderate diagnostic accuracy for radiculopathy with modest specificity and electromyographers should exercise caution interpreting mild abnormalities. This study provides Class III evidence that EMG has moderate diagnostic accuracy and specificity for radiculopathy. © 2015 American Academy of Neurology.

  6. Critically re-evaluating a common technique

    PubMed Central

    Geisbush, Thomas; Jones, Lyell; Weiss, Michael; Mozaffar, Tahseen; Gronseth, Gary; Rutkove, Seward B.

    2016-01-01

    Objectives: (1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG. Methods: Three experienced academic electromyographers interpreted 3 compact discs with 20 EMG videos (10 normal, 10 radiculopathy) in a blinded, standardized fashion without information regarding the nature of the study. The EMGs were interpreted 3 times (discs A, B, C) 1 month apart. Clinical information was provided only with disc C. Intrarater reliability was calculated by comparing interpretations in discs A and B, interrater reliability by comparing interpretation between reviewers. Confirmation bias was estimated by the difference in correct interpretations when clinical information was provided. Results: Sensitivity was similar to previous reports (77%, confidence interval [CI] 63%–90%); specificity was 71%, CI 56%–85%. Intrarater reliability was good (κ 0.61, 95% CI 0.41–0.81); interrater reliability was lower (κ 0.53, CI 0.35–0.71). There was no substantial confirmation bias when clinical information was provided (absolute difference in correct responses 2.2%, CI −13.3% to 17.7%); the study lacked precision to exclude moderate confirmation bias. Conclusions: This study supports that (1) serial EMG studies should be performed by the same electromyographer since intrarater reliability is better than interrater reliability; (2) knowledge of clinical information does not bias EMG interpretation substantially; (3) EMG has moderate diagnostic accuracy for radiculopathy with modest specificity and electromyographers should exercise caution interpreting mild abnormalities. Classification of evidence: This study provides Class III evidence that EMG has moderate diagnostic accuracy and specificity for radiculopathy. PMID:26701380

  7. Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice

    PubMed Central

    1996-01-01

    Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin- associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP- 1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development. PMID:8879233

  8. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load

    PubMed Central

    Kløverpris, Henrik N.; McGregor, Reuben; McLaren, James E.; Ladell, Kristin; Stryhn, Anette; Koofhethile, Catherine; Brener, Jacqui; Chen, Fabian; Riddell, Lynn; Graziano, Luzzi; Klenerman, Paul; Leslie, Alasdair; Buus, Søren; Price, David A.; Goulder, Philip

    2014-01-01

    Objectives: Although CD8+ T cells play a critical role in the control of HIV-1 infection, their antiviral efficacy can be limited by antigenic variation and immune exhaustion. The latter phenomenon is characterized by the upregulation of multiple inhibitory receptors, such as programmed death-1 (PD-1), CD244 and lymphocyte activation gene-3 (LAG-3), which modulate the functional capabilities of CD8+ T cells. Design and methods: Here, we used an array of different human leukocyte antigen (HLA)-B∗15 : 03 and HLA-B∗42 : 01 tetramers to characterize inhibitory receptor expression as a function of differentiation on HIV-1-specific CD8+ T-cell populations (n = 128) spanning 11 different epitope targets. Results: Expression levels of PD-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of PD-1 on T-cell receptor (TCR) clonotypes within individual HIV-1-specific CD8+ T-cell populations was also apparent, independent of clonal dominance hierarchies. Positive correlations were detected between PD-1 expression and plasma viral load, which were reinforced by stratification for epitope sequence stability and dictated by effector memory CD8+ T cells. Conclusion: Collectively, these data suggest that PD-1 expression on HIV-1-specific CD8+ T cells tracks antigen load at the level of epitope specificity and TCR clonotype usage. These findings are important because they provide evidence that PD-1 expression levels are influenced by peptide/HLA class I antigen exposure. PMID:24906112

  9. 26 CFR 1.103(n)-2T - Private activity bond defined (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...(n)-2T Section 1.103(n)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....103(n)-2T Private activity bond defined (temporary). Q-1: What is the definition of the term “private activity bond”? A-1: In general, for purposes of §§ 1.103(n)-1T through 1.103(n)-6T, the term “private...

  10. Elevated Cyclic AMP Levels in T Lymphocytes Transformed by Human T-Cell Lymphotropic Virus Type 1

    PubMed Central

    Kress, Andrea K.; Schneider, Grit; Pichler, Klemens; Kalmer, Martina; Fleckenstein, Bernhard; Grassmann, Ralph

    2010-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of adult T-cell leukemia/lymphoma (ATLL), transforms CD4+ T cells to permanent growth through its transactivator Tax. HTLV-1-transformed cells share phenotypic properties with memory and regulatory T cells (T-reg). Murine T-reg-mediated suppression employs elevated cyclic AMP (cAMP) levels as a key regulator. This led us to determine cAMP levels in HTLV-1-transformed cells. We found elevated cAMP concentrations as a consistent feature of all HTLV-1-transformed cell lines, including in vitro-HTLV-1-transformed, Tax-transformed, and patient-derived cells. In transformed cells with conditional Tax expression, high cAMP levels coincided with the presence of Tax but were lost without it. However, transient ectopic expression of Tax alone was not sufficient to induce cAMP. We found specific downregulation of the cAMP-degrading phosphodiesterase 3B (PDE3B) in HTLV-1-transformed cells, which was independent of Tax in transient expression experiments. This is in line with the notion that PDE3B transcripts and cAMP levels are inversely correlated. Overexpression of PDE3B led to a decrease of cAMP in HTLV-1-transformed cells. Decreased expression of PDE3B was associated with inhibitory histone modifications at the PDE3B promoter and the PDE3B locus. In summary, Tax transformation and its continuous expression contribute to elevated cAMP levels, which may be regulated through PDE3B suppression. This shows that HTLV-1-transformed cells assume biological features of long-lived T-cell populations that potentially contribute to viral persistence. PMID:20573814

  11. T cell-dependent antibody production by Ly-1 B cells.

    PubMed

    Taki, S; Schmitt, M; Tarlinton, D; Förster, I; Rajewsky, K

    1992-05-04

    Through the use of a SCID transfer system, we have demonstrated that under certain conditions, the production of Ig by Ly-1 B cells can be modulated by T cells. This modulation can take the form of enhanced isotype production or isotype-switch induction and to some extent appears to be dependent on the activation state of the T cells. Furthermore we have shown that Ly-1 B cells can mount an idiotypically restricted T cell-dependent immune response to the antigen PC-KLH. This result suggests that the previous failure to observe T cell-dependent responses by Ly-1 B cells has been due to these B cells being "blind" to the antigens used and is not due to some inherent property of these B cells. When one considers the previous reports of the substantial contribution of Ly-1 B cells to the natural serum immunoglobulin levels and the ability of T cells to affect Ig production by Ly-1 B cells documented in this report, it is clear that the interaction of T cells with the Ly-1 B-cell population is important in determining the "natural" serum Ig repertoire of the mouse.

  12. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells.

    PubMed

    Arbore, Giuseppina; West, Erin E; Spolski, Rosanne; Robertson, Avril A B; Klos, Andreas; Rheinheimer, Claudia; Dutow, Pavel; Woodruff, Trent M; Yu, Zu Xi; O'Neill, Luke A; Coll, Rebecca C; Sher, Alan; Leonard, Warren J; Köhl, Jörg; Monk, Pete; Cooper, Matthew A; Arno, Matthew; Afzali, Behdad; Lachmann, Helen J; Cope, Andrew P; Mayer-Barber, Katrin D; Kemper, Claudia

    2016-06-17

    The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4(+) T cells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (T(H)1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to "innate immune cells" but is an integral component of normal adaptive T(H)1 responses. Copyright © 2016, American Association for the Advancement of Science.

  13. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells

    PubMed Central

    Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z.; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.; Rosenberg, Eric S.; Yu, Xu G.

    2017-01-01

    HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells. PMID:28628034

  14. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

    PubMed

    Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

    2017-06-30

    HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

  15. Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen

    PubMed Central

    Rafiq, S; Purdon, TJ; Daniyan, AF; Koneru, M; Dao, T; Liu, C; Scheinberg, DA; Brentjens, RJ

    2017-01-01

    CD19-directed chimeric antigen receptor (CAR) T cells are clinically effective in a limited set of leukemia patients. However, CAR T-cell therapy thus far has been largely restricted to targeting extracellular tumor-associated antigens (TAA). Herein, we report a T-cell receptor-mimic (TCRm) CAR, termed WT1-28z, that is reactive to a peptide portion of the intracellular onco-protein Wilms Tumor 1(WT1), as it is expressed on the surface of the tumor cell in the context of HLA-A*02:01. T cells modified to express WT1-28z specifically targeted and lysed HLA-A*02:01+ WT1+ tumors and enhanced survival of mice engrafted with HLA-A*02:01+, WT1+ leukemia or ovarian tumors. This in vivo functional validation of TCRm CAR T cells provides the proof-of-concept necessary to expand the range of TAA that can be effectively targeted for immunotherapy to include attractive intracellular targets, and may hold great potential to expand on the success of CAR T-cell therapy. PMID:27924074

  16. Development of t(8;21) and RUNX1-RUNX1T1 in the Philadelphia-positive clone of a patient with chronic myelogenous leukemia: additional evidence for multiple steps involved in disease progression.

    PubMed

    Najfeld, Vesna; Wisch, Nathaniel; Mascarenhas, John; Issa, Leonard; Tripodi, Joseph; Sidhu, Manpreet; Hoffman, Ronald

    2011-03-01

    A 65-year-old patient with a high hemoglobin and hematocrit was treated for 14 months with therapeutic phlebotomy when cytogenetics of bone marrow revealed 100% cells with the Ph chromosome and 45% of the Ph+ cells contained trisomy 8. Treatment with tyrosine kinase inhibitors did not reduce the BCR-ABL1 fusion positive clone. Instead, the Ph positive cells acquired further the t(8;21)/RUNX1-RUNX1T1, del(4q) and trisomy 15 chromosomal abnormalities which were resistant to further treatment. Literature review revealed eight other patients who either had t(9;22) and t(8;21) simultaneously or developed t(8;21) in the Ph positive clone. We conclude that there are rare patients with CML who either present in blast crisis with coexistence of t(9;22) and t(8;21) with or without +8, or progress to blast crisis with acquiring RUNX1-RUNX1T1 in the BCR-ABL1 clone which may or may not be therapy related and represent a later event in a multistep pathogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. T1 weighted brain images at 7 Tesla unbiased for Proton Density, T2* contrast and RF coil receive B1 sensitivity with simultaneous vessel visualization.

    PubMed

    Van de Moortele, Pierre-François; Auerbach, Edwards J; Olman, Cheryl; Yacoub, Essa; Uğurbil, Kâmil; Moeller, Steen

    2009-06-01

    At high magnetic field, MR images exhibit large, undesirable signal intensity variations commonly referred to as "intensity field bias". Such inhomogeneities mostly originate from heterogeneous RF coil B(1) profiles and, with no appropriate correction, are further pronounced when utilizing rooted sum of square reconstruction with receive coil arrays. These artifacts can significantly alter whole brain high resolution T(1)-weighted (T(1)w) images that are extensively utilized for clinical diagnosis, for gray/white matter segmentation as well as for coregistration with functional time series. In T(1) weighted 3D-MPRAGE sequences, it is possible to preserve a bulk amount of T(1) contrast through space by using adiabatic inversion RF pulses that are insensitive to transmit B(1) variations above a minimum threshold. However, large intensity variations persist in the images, which are significantly more difficult to address at very high field where RF coil B(1) profiles become more heterogeneous. Another characteristic of T(1)w MPRAGE sequences is their intrinsic sensitivity to Proton Density and T(2)(*) contrast, which cannot be removed with post-processing algorithms utilized to correct for receive coil sensitivity. In this paper, we demonstrate a simple technique capable of producing normalized, high resolution T(1)w 3D-MPRAGE images that are devoid of receive coil sensitivity, Proton Density and T(2)(*) contrast. These images, which are suitable for routinely obtaining whole brain tissue segmentation at 7 T, provide higher T(1) contrast specificity than standard MPRAGE acquisitions. Our results show that removing the Proton Density component can help in identifying small brain structures and that T(2)(*) induced artifacts can be removed from the images. The resulting unbiased T(1)w images can also be used to generate Maximum Intensity Projection angiograms, without additional data acquisition, that are inherently registered with T(1)w structural images. In addition

  18. From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor.

    PubMed

    Morini, Gabriella; Bassoli, Angela; Temussi, Piero A

    2005-08-25

    The sweet taste receptor, a heterodimeric G protein coupled receptor (GPCR) protein, formed by the T1R2 and T1R3 subunits, recognizes several sweet compounds including carbohydrates, amino acids, peptides, proteins, and synthetic sweeteners. Its similarity with the metabotropic glutamate mGluR1 receptor allowed us to build homology models. All possible dimers formed by combinations of the human T1R2 and T1R3 subunits, modeled on the A (closed) or B (open) chains of the extracellular ligand binding domain of the mGluR1 template, yield four ligand binding sites for low-molecular-weight sweeteners. These sites were probed by docking a set of molecules representative of all classes of sweet compounds and calculating the free energy of ligand binding. These sites are not easily accessible to sweet proteins, but docking experiments in silico showed that sweet proteins can bind to a secondary site without entering the deep cleft. Our models account for many experimental observations on the tastes of sweeteners, including sweetness synergy, and can help to design new sweeteners.

  19. Value of 3D MR lumbosacral radiculography in the diagnosis of symptomatic chemical radiculitis.

    PubMed

    Byun, W M; Ahn, S H; Ahn, M-W

    2012-03-01

    Radiologic methods for the diagnosis of chemical radiculitis associated with anular tears in the lumbar spine have been rare. Provocative diskography is one of the methods for diagnosing diskogenic chemical radiculitis but is invasive. A reliable imaging method for replacing provocative diskography and diagnosing chemical radiculitis is required. Our aim was to investigate the value of 3D MR radiculography depicted by rendering imaging in the diagnosis of symptomatic chemical radiculopathy associated with anular tears. The study population consisted of 17 patients (age range, 32-88 years) with unilateral radiculopathy. Symptomatic chemical radiculopathy was confirmed with provocative CT diskography and/or provocative selective nerve root block for agreement of sides and levels. Through adhering to the principles of selective excitation (Proset imaging), we acquired 3D coronal FFE sequences with selective water excitation. Morphologic changes in the ipsilateral symptomatic nerve root caused by chemical radiculopathy were compared with those in the contralateral nerve root on 3D MR lumbosacral radiculography. Pain reproduction at the contrast-leak level during diskography (n = 4) and selective nerve root injection (n = 13) showed concordant pain in all patients. All patients with symptomatic chemical radiculopathy showed nerve root swelling in both ipsilateral levels and sides on 3D MR radiculography. The most common nerve root affected by the chemical radiculopathy was the L5 nerve root (n = 13), while the most common segment exhibiting nerve root swelling was the exit nerve root (n = 16). All patients with radicular leg pain caused by chemical radiculopathy showed nerve root swelling on 3D MR radiculography. We believe that in cases without mechanical nerve root compression caused by disk herniation or stenosis in the lumbar spine, nerve root swelling on 3D MR radiculography in patients with radiculopathy associated with an anular tear may be relevant in the

  20. Decoding of exon splicing patterns in the human RUNX1-RUNX1T1 fusion gene.

    PubMed

    Grinev, Vasily V; Migas, Alexandr A; Kirsanava, Aksana D; Mishkova, Olga A; Siomava, Natalia; Ramanouskaya, Tatiana V; Vaitsiankova, Alina V; Ilyushonak, Ilia M; Nazarov, Petr V; Vallar, Laurent; Aleinikova, Olga V

    2015-11-01

    The t(8;21) translocation is the most widespread genetic defect found in human acute myeloid leukemia. This translocation results in the RUNX1-RUNX1T1 fusion gene that produces a wide variety of alternative transcripts and influences the course of the disease. The rules of combinatorics and splicing of exons in the RUNX1-RUNX1T1 transcripts are not known. To address this issue, we developed an exon graph model of the fusion gene organization and evaluated its local exon combinatorics by the exon combinatorial index (ECI). Here we show that the local exon combinatorics of the RUNX1-RUNX1T1 gene follows a power-law behavior and (i) the vast majority of exons has a low ECI, (ii) only a small part is represented by "exons-hubs" of splicing with very high ECI values, and (iii) it is scale-free and very sensitive to targeted skipping of "exons-hubs". Stochasticity of the splicing machinery and preferred usage of exons in alternative splicing can explain such behavior of the system. Stochasticity may explain up to 12% of the ECI variance and results in a number of non-coding and unproductive transcripts that can be considered as a noise. Half-life of these transcripts is increased due to the deregulation of some key genes of the nonsense-mediated decay system in leukemia cells. On the other hand, preferred usage of exons may explain up to 75% of the ECI variability. Our analysis revealed a set of splicing-related cis-regulatory motifs that can explain "attractiveness" of exons in alternative splicing but only when they are considered together. Cis-regulatory motifs are guides for splicing trans-factors and we observed a leukemia-specific profile of expression of the splicing genes in t(8;21)-positive blasts. Altogether, our results show that alternative splicing of the RUNX1-RUNX1T1 transcripts follows strict rules and that the power-law component of the fusion gene organization confers a high flexibility to this process. Copyright © 2015 Elsevier Ltd. All rights

  1. Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting.

    PubMed

    Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

    2015-12-01

    Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T 1 and T 2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T 1 and T 2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T 1 and T 2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored.

  2. Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting

    PubMed Central

    Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

    2016-01-01

    Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T1 and T2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T1 and T2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T1 and T2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored. PMID:26824078

  3. Depletion of Saccharomyces cerevisiae tRNAHis Guanylyltransferase Thg1p Leads to Uncharged tRNAHis with Additional m5C

    PubMed Central

    Gu, Weifeng; Hurto, Rebecca L.; Hopper, Anita K.; Grayhack, Elizabeth J.; Phizicky, Eric M.

    2005-01-01

    The essential Saccharomyces cerevisiae tRNAHis guanylyltransferase (Thg1p) is responsible for the unusual G−1 addition to the 5′ end of cytoplasmic tRNAHis. We report here that tRNAHis from Thg1p-depleted cells is uncharged, although histidyl tRNA synthetase is active and the 3′ end of the tRNA is intact, suggesting that G−1 is a critical determinant for aminoacylation of tRNAHis in vivo. Thg1p depletion leads to activation of the GCN4 pathway, most, but not all, of which is Gcn2p dependent, and to the accumulation of tRNAHis in the nucleus. Surprisingly, tRNAHis in Thg1p-depleted cells accumulates additional m5C modifications, which are delayed relative to the loss of G−1 and aminoacylation. The additional modification is likely due to tRNA m5C methyltransferase Trm4p. We developed a new method to map m5C residues in RNA and localized the additional m5C to positions 48 and 50. This is the first documented example of the accumulation of additional modifications in a eukaryotic tRNA species. PMID:16135808

  4. Platelet activation suppresses HIV-1 infection of T cells

    PubMed Central

    2013-01-01

    Background Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. Results We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Conclusions Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens. PMID:23634812

  5. Platelet activation suppresses HIV-1 infection of T cells.

    PubMed

    Solomon Tsegaye, Theodros; Gnirß, Kerstin; Rahe-Meyer, Niels; Kiene, Miriam; Krämer-Kühl, Annika; Behrens, Georg; Münch, Jan; Pöhlmann, Stefan

    2013-05-01

    Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.

  6. Cex1p facilitates Rna1p-mediated dissociation of the Los1p-tRNA-Gsp1p-GTP export complex.

    PubMed

    McGuire, Andrew T; Mangroo, Dev

    2012-02-01

    Nuclear tRNA export plays an essential role in key cellular processes such as regulation of protein synthesis, cell cycle progression, response to nutrient availability and DNA damage and development. Like other nuclear export processes, assembly of the nuclear tRNA export complex in the nucleus is dependent on Ran-GTP/Gsp1p-GTP, and dissociation of the export receptor-tRNA-Ran-GTP/Gsp1p-GTP complex in the cytoplasm requires RanBP1/Yrb1p and RanGAP/Rna1p to activate the GTPase activity of Ran-GTP/Gsp1p-GTP. The Saccharomyces cerevisiae Cex1p and Human Scyl1 have also been proposed to participate in unloading of the tRNA export receptors at the cytoplasmic face of the nuclear pore complex (NPC). Here, we provide evidence suggesting that Cex1p is required for activation of the GTPase activity of Gsp1p and dissociation of the receptor-tRNA-Gsp1p export complex in S. cerevisiae. The data suggest that Cex1p recruits Rna1p from the cytoplasm to the NPC and facilitates Rna1p activation of the GTPase activity of Gsp1p by enabling Rna1p to gain access to Gsp1p-GTP bound to the export receptor tRNA complex. It is possible that this tRNA unloading mechanism is conserved in evolutionarily diverse organisms and that other Gsp1p-GTP-dependent export processes use a pathway-specific component to recruit Rna1p to the NPC. © 2011 John Wiley & Sons A/S.

  7. SIRT1 Suppresses Human T-Cell Leukemia Virus Type 1 Transcription

    PubMed Central

    Tang, Hei-Man Vincent; Gao, Wei-Wei; Chan, Chi-Ping; Cheng, Yun; Deng, Jian-Jun; Yuen, Kit-San; Iha, Hidekatsu

    2015-01-01

    ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1)-associated diseases are poorly treatable, and HTLV-1 vaccines are not available. High proviral load is one major risk factor for disease development. HTLV-1 encodes Tax oncoprotein, which activates transcription from viral long terminal repeats (LTR) and various types of cellular promoters. Counteracting Tax function might have prophylactic and therapeutic benefits. In this work, we report on the suppression of Tax activation of HTLV-1 LTR by SIRT1 deacetylase. The transcriptional activity of Tax on the LTR was largely ablated when SIRT1 was overexpressed, but Tax activation of NF-κB was unaffected. On the contrary, the activation of the LTR by Tax was boosted when SIRT1 was depleted. Treatment of cells with resveratrol shunted Tax activity in a SIRT1-dependent manner. The activation of SIRT1 in HTLV-1-transformed T cells by resveratrol potently inhibited HTLV-1 proviral transcription and Tax expression, whereas compromising SIRT1 by specific inhibitors augmented HTLV-1 mRNA expression. The administration of resveratrol also decreased the production of cell-free HTLV-1 virions from MT2 cells and the transmission of HTLV-1 from MT2 cells to uninfected Jurkat cells in coculture. SIRT1 associated with Tax in HTLV-1-transformed T cells. Treatment with resveratrol prevented the interaction of Tax with CREB and the recruitment of CREB, CRTC1, and p300 to Tax-responsive elements in the LTR. Our work demonstrates the negative regulatory function of SIRT1 in Tax activation of HTLV-1 transcription. Small-molecule activators of SIRT1 such as resveratrol might be considered new prophylactic and therapeutic agents in HTLV-1-associated diseases. IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) causes a highly lethal blood cancer or a chronic debilitating disease of the spinal cord. Treatments are unsatisfactory, and vaccines are not available. Disease progression is associated with robust expression of HTLV-1 genes

  8. Preoperative detection of malignant liver tumors: Comparison of 3D-T2-weighted sequences with T2-weighted turbo spin-echo and single shot T2 at 1.5 T.

    PubMed

    Barat, Maxime; Soyer, Philippe; Dautry, Raphael; Pocard, Marc; Lo-Dico, Rea; Najah, Haythem; Eveno, Clarisse; Cassinotto, Christophe; Dohan, Anthony

    2018-03-01

    To assess the performances of three-dimensional (3D)-T2-weighted sequences compared to standard T2-weighted turbo spin echo (T2-TSE), T2-half-Fourier acquisition single-shot turbo spin-echo (T2-HASTE), diffusion weighted imaging (DWI) and 3D-T1-weighted VIBE sequences in the preoperative detection of malignant liver tumors. From 2012 to 2015, all patients of our institution undergoing magnetic resonance imaging (MRI) examination for suspected malignant liver tumors were prospectively included. Patients had contrast-enhanced 3D-T1-weighted, DWI, 3D-T2-SPACE, T2-HASTE and T2-TSE sequences. Imaging findings were compared with those obtained at follow-up, surgery and histopathological analysis. Sensitivities for the detection of malignant liver tumors were compared for each sequence using McNemar test. A subgroup analysis was conducted for HCCs. Image artifacts were analyzed and compared using Wilcoxon paired signed rank-test. Thirty-three patients were included: 13 patients had 40 hepatocellular carcinomas (HCC) and 20 had 54 liver metastases. 3D-T2-weighted sequences had a higher sensitivity than T2-weighted TSE sequences for the detection of malignant liver tumors (79.8% versus 68.1%; P < 0.001). The difference did not reach significance for HCC. T1-weighted VIBE and DWI had a higher sensitivity than T2-weighted sequences. 3D-T2-weighted-SPACE sequences showed significantly less artifacts than T2-weitghted TSE. 3D-T2-weighted sequences show very promising performances for the detection of liver malignant tumors compared to T2-weighted TSE sequences. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis

    PubMed Central

    Hwang, Seong-Hye; Jung, Seung-Hyun; Lee, Saseong; Choi, Susanna; Yoo, Seung-Ah; Park, Ji-Hwan; Hwang, Daehee; Shim, Seung Cheol; Sabbagh, Laurent; Kim, Ki-Jo; Park, Sung Hwan; Cho, Chul-Soo; Kim, Bong-Sung; Leng, Lin; Montgomery, Ruth R.; Bucala, Richard; Chung, Yeun-Jun; Kim, Wan-Uk

    2015-01-01

    Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell–dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA. PMID:26554018

  10. Further exploration of MRI techniques for liver T1rho quantification.

    PubMed

    Zhao, Feng; Yuan, Jing; Deng, Min; Lu, Pu-Xuan; Ahuja, Anil T; Wang, Yi-Xiang J

    2013-12-01

    With biliary duct ligation and CCl4 induced rat liver fibrosis models, recent studies showed that MR T1rho imaging is able to detect liver fibrosis, and the degree of fibrosis is correlated with the degree of elevation of the T1rho measurements, suggesting liver T1rho quantification may play an important role for liver fibrosis early detection and grading. It has also been reported it is feasible to obtain consistent liver T1rho measurement for human subjects at 3 Tesla (3 T), and preliminary clinical data suggest liver T1rho is increased in patients with cirrhosis. In these previous studies, T1rho imaging was used with the rotary-echo spin-lock pulse for T1rho preparation, and number of signal averaging (NSA) was 2. Due to the presence of inhomogeneous B0 field, artifacts may occur in the acquired T1rho-weighted images. The method described by Dixon et al. (Magn Reson Med 1996;36:90-4), which is a hard RF pulse with 135° flip angle and same RF phase as the spin-locking RF pulse is inserted right before and after the spin-locking RF pulse, has been proposed to reduce sensitivity to B0 field inhomogeneity in T1rho imaging. In this study, we compared the images scanned by rotary-echo spin-lock pulse method (sequence 1) and the pulse modified according to Dixon method (sequence 2). When the artifacts occurred in T1rho images, we repeated the same scan until satisfactory. We accepted images if artifact in liver was less than 10% of liver area by visual estimation. When NSA =2, the breath-holding duration for data acquisition of one slice scanning was 8 sec due to a delay time of 6,000 ms for magnetization restoration. If NSA =1, the duration was shortened to be 2 sec. In previous studies, manual region of interest (ROI) analysis of T1rho map was used. In this current study, histogram analysis was also applied to evaluate liver T1rho value on T1rho maps. MRI data acquisition was performed on a 3 T clinical scanner. There were 29 subjects with 61 examinations obtained

  11. 26 CFR 1.1291-9T - Deemed dividend election (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Special Rules for Determining Capital Gains and Losses § 1... shareholder as defined in § 1.1291-1T(b)(7) or an indirect shareholder as defined in § 1.1291-1T(b)(8). (k) Effective/applicability date—(1) [Reserved] For further guidance see § 1.1291-9(k)(1). (2) [Reserved] For...

  12. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing

    PubMed Central

    Jones, Christopher P.; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-01-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNALys3. Host cell tRNALys is selectively packaged into HIV-1 through a specific interaction between the major tRNALys-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNALys3 is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNALys and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNALys3 in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNALys to increase the efficiency of tRNALys3 annealing to viral RNA. PMID:23264568

  13. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

    PubMed

    Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

    2015-09-01

    Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Advanced Colloids Experiment (ACE-T1)

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ron; Brown, Dan; Eustace, John

    2015-01-01

    Increment 45 - 46 Science Symposium presentation of Advanced Colloids Experiment (ACE-T1) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

  15. Causes of Hand Tingling in Visual Display Terminal Workers

    PubMed Central

    Oh, Sein; Kim, Hyung Kuk; Kwak, Jehwan; Kim, Taikon; Jang, Seong Ho; Lee, Kyu Hoon; Kim, Mi Jung; Park, Si-Bog

    2013-01-01

    Objective To offer the basic data about the causes and distribution of hand tingling, symptoms and physical findings, and pressure pain threshold in desk workers. Methods Five physiatrists participated in the screening test composed of history and physical examination. A total of 876 desk workers were evaluated and of them 37 subjects with hand tingling were selected. For further analyzing, detailed history taking and meticulous physical examination were taken. Pressure pain threshold (PPT) at the infraspinatus, upper trapezius, flexor carpi radialis, rhomboideus, and flexor pollicis longus were examined. PPT measurements were repeated three times with two minute intervals by a pressure algometer. Electrodiagnostic study was done to detect potential neurologic abnormalities. Results The causes of hand tingling in order of frequency were: myofascial pain syndrome, 68%; cervical radiculopathy, 27%; rotator cuff syndrome, 11%; tenosynovitis, 8%; and carpal tunnel syndrome, 5%. The location of trigger points in the myofascial pain syndrome, which were proven to evoke a tingling sensation to the hand in order of frequency were: infraspinatus, 65.4%; upper trapezius, 57.7%; flexor carpi radialis, 38.5%; rhomboideus 15.4%; and flexor pollicis longus 11.5%. The PPT of the affected side was significantly lower than that of the unaffected side in myofascial pain syndrome (p<0.05). Conclusion The most common cause of hand tingling in desk workers was myofascial pain syndrome rather than carpal tunnel syndrome. Common trigger points to evoke hand tingling were in the infraspinatus and upper trapezius. PMID:23705117

  16. T1- or T2-weighted magnetic resonance imaging: what is the best choice to evaluate atrophy of the hippocampus?

    PubMed

    Fischbach-Boulanger, C; Fitsiori, A; Noblet, V; Baloglu, S; Oesterle, H; Draghici, S; Philippi, N; Duron, E; Hanon, O; Dietemann, J-L; Blanc, F; Kremer, S

    2018-05-01

    Magnetic resonance imaging is part of the diagnostic criteria for Alzheimer's disease (AD) through the evaluation of hippocampal atrophy. The objective of this study was to evaluate which sequence of T1-weighted (T1WI) and T2-weighted (T2WI) imaging allowed the best visual evaluation of hippocampal atrophy. Visual qualitative ratings of the hippocampus of 100 patients with mild cognitive impairment (MCI) and 50 patients with AD were made independently by four operators according to the medial temporal lobe atrophy score based either on T1WI or T2WI. These two evaluations were compared in terms of interobserver reproducibility, concordance with a quantitative volumetric measure, discrimination power between AD and MCI groups, and correlation with several neuropsychological tests. The medial temporal lobe atrophy score evaluated on either T1WI or T2WI exhibited similar interobserver variability and accordance with quantitative volumetric evaluation. However, the visual evaluation on T2WI seemed to provide better discrimination power between AD and MCI groups for both left (T1WI, P = 0.0001; T2WI, P = 7.072 × 10 -5 ) and right (T1WI, P = 0.008; T2WI, P = 0.001) hippocampus, and a higher overall correlation with neuropsychological tests. The present study suggests that T2WI provides a more adequate visual rating of hippocampal atrophy. © 2018 EAN.

  17. T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

    PubMed

    Greulich, Simon; Mayr, Agnes; Kitterer, Daniel; Latus, Joerg; Henes, Joerg; Steubing, Hannah; Kaesemann, Philipp; Patrascu, Alexandru; Greiser, Andreas; Groeninger, Stefan; Braun, Niko; Alscher, M Dominik; Sechtem, Udo; Mahrholdt, Heiko

    2017-01-06

    Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

  18. Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio in the cerebral cortex.

    PubMed

    Ritchie, Jacob; Pantazatos, Spiro P; French, Leon

    2018-07-01

    Magnetic resonance (MR) images of the brain are of immense clinical and research utility. At the atomic and subatomic levels, the sources of MR signals are well understood. However, we lack a comprehensive understanding of the macromolecular correlates of MR signal contrast. To address this gap, we used genome-wide measurements to correlate gene expression with MR signal intensity across the cerebral cortex in the Allen Human Brain Atlas (AHBA). We focused on the ratio of T1-weighted and T2-weighted intensities (T1-w/T2-w ratio image), which is considered to be a useful proxy for myelin content. As expected, we found enrichment of positive correlations between myelin-associated genes and the ratio image, supporting its use as a myelin marker. Genome-wide, there was an association with protein mass, with genes coding for heavier proteins expressed in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly correlated with the T1-w/T2-w ratio, but this was not driven by myelin-associated genes. Mitochondrial genes exhibit the strongest relationship, showing higher expression in regions with low T1-w/T2-w ratio. This may be due to the pH gradient in mitochondria as genes up-regulated by pH in the brain were also highly correlated with the ratio. While we corroborate associations with myelin and synaptic plasticity, differences in the T1-w/T2-w ratio across the cortex are more strongly linked to molecule size, oligodendrocyte markers, mitochondria, and pH. We evaluate correlations between AHBA transcriptomic measurements and a group averaged T1-w/T2-w ratio image, showing agreement with in-sample results. Expanding our analysis to the whole brain results in strong positive T1-w/T2-w correlations for immune system, inflammatory disease, and microglia marker genes. Genes with negative correlations were enriched for neuron markers and synaptic plasticity genes. Lastly, our findings are similar when performed on T1-w or inverted T2-w intensities alone

  19. S1PR1 is crucial for accumulation of regulatory T cells in tumors via STAT3

    PubMed Central

    Priceman, Saul J.; Shen, Shudan; Wang, Lin; Deng, Jiehui; Yue, Chanyu; Kujawski, Maciej; Yu, Hua

    2014-01-01

    Summary S1PR1 signaling has been shown to restrain the number and function of Tregs in the periphery under physiological conditions and in colitis models, but its role in regulating tumor-associated T cells is unknown. Here, we show that S1PR1 signaling in T cells drives Treg accumulation in tumors, limits CD8+ T cell recruitment and activation, and promotes tumor growth. S1PR1 intrinsic in T cells affects Tregs, but not CD8+ T cells, as demonstrated by adoptive transfer models and transient pharmacological S1PR1 modulation. We further investigated the molecular mechanism(s) underlying S1PR1-mediated Treg accumulation in tumors, showing that increasing S1PR1 in CD4+ T cells promotes STAT3 activation and JAK/STAT3-dependent Treg tumor migration. Furthermore functionally ablating STAT3 in T cells diminishes tumor-associated Treg accumulation and tumor growth. Our study demonstrates a stark contrast of the consequences by the same signaling receptor, namely S1PR1, in regulating Tregs in the periphery and in tumors. PMID:24630990

  20. T1 weighted Brain Images at 7 Tesla Unbiased for Proton Density, T2* contrast and RF Coil Receive B1 Sensitivity with Simultaneous Vessel Visualization

    PubMed Central

    Van de Moortele, Pierre-François; Auerbach, Edwards J.; Olman, Cheryl; Yacoub, Essa; Uğurbil, Kâmil; Moeller, Steen

    2009-01-01

    At high magnetic field, MR images exhibit large, undesirable signal intensity variations commonly referred to as “intensity field bias”. Such inhomogeneities mostly originate from heterogeneous RF coil B1 profiles and, with no appropriate correction, are further pronounced when utilizing rooted sum of square reconstruction with receive coil arrays. These artifacts can significantly alter whole brain high resolution T1-weighted (T1w) images that are extensively utilized for clinical diagnosis, for gray/white matter segmentation as well as for coregistration with functional time series. In T1 weighted 3D-MPRAGE sequences, it is possible to preserve a bulk amount of T1 contrast through space by using adiabatic inversion RF pulses that are insensitive to transmit B1 variations above a minimum threshold. However, large intensity variations persist in the images, which are significantly more difficult to address at very high field where RF coil B1 profiles become more heterogeneous. Another characteristic of T1w MPRAGE sequences is their intrinsic sensitivity to Proton Density and T2* contrast, which cannot be removed with post-processing algorithms utilized to correct for receive coil sensitivity. In this paper, we demonstrate a simple technique capable of producing normalized, high resolution T1w 3D-MPRAGE images that are devoid of receive coil sensitivity, Proton Density and T2* contrast. These images, which are suitable for routinely obtaining whole brain tissue segmentation at 7 Tesla, provide higher T1 contrast specificity than standard MPRAGE acquisitions. Our results show that removing the Proton Density component can help identifying small brain structures and that T2* induced artifacts can be removed from the images. The resulting unbiased T1w images can also be used to generate Maximum Intensity Projection angiograms, without additional data acquisition, that are inherently registered with T1w structural images. In addition, we introduce a simple technique

  1. 1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients.

    PubMed

    Gutierrez-Rubio, S A; Quintero-Ramos, A; Durán-Cárdenas, A; Franco-Topete, R A; Castro-Cervantes, J M; Oceguera-Villanueva, A; Jiménez-Pérez, L M; Balderas-Peña, L M A; Morgan-Villela, G; Del-Toro-Arreola, A; Daneri-Navarro, A

    2015-02-13

    MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

  2. Hydrogels incorporating GdDOTA: towards highly efficient dual T1/T2 MRI contrast agents.

    PubMed

    Courant, Thomas; Roullin, Valérie Gaëlle; Cadiou, Cyril; Callewaert, Maïté; Andry, Marie Christine; Portefaix, Christophe; Hoeffel, Christine; de Goltstein, Marie Christine; Port, Marc; Laurent, Sophie; Elst, Luce Vander; Muller, Robert; Molinari, Michaël; Chuburu, Françoise

    2012-09-03

    Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles (GdDOTA NPs) exhibited high relaxivity (r(1) =101.7 s(-1) mM(-1) per Gd(3+) ion at 37 °C and 20 MHz). This high relaxation rate is due to efficient Gd loading, reduced tumbling of the Gd complex, and the hydrogel nature of the nanoparticles. The efficacy of the nanoparticles as a T(1)/T(2) dual-mode contrast agent was studied in C6 cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. T1 mapping and survival in systemic light-chain amyloidosis

    PubMed Central

    Banypersad, Sanjay M.; Fontana, Marianna; Maestrini, Viviana; Sado, Daniel M.; Captur, Gabriella; Petrie, Aviva; Piechnik, Stefan K.; Whelan, Carol J.; Herrey, Anna S.; Gillmore, Julian D.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Hawkins, Philip N.; Moon, James C.

    2015-01-01

    Aims To assess the prognostic value of myocardial pre-contrast T1 and extracellular volume (ECV) in systemic amyloid light-chain (AL) amyloidosis using cardiovascular magnetic resonance (CMR) T1 mapping. Methods and results One hundred patients underwent CMR and T1 mapping pre- and post-contrast. Myocardial ECV was calculated at contrast equilibrium (ECVi) and 15 min post-bolus (ECVb). Fifty-four healthy volunteers served as controls. Patients were followed up for a median duration of 23 months and survival analyses were performed. Mean ECVi was raised in amyloid (0.44 ± 0.12) as was ECVb (mean 0.44 ± 0.12) compared with healthy volunteers (0.25 ± 0.02), P < 0.001. Native pre-contrast T1 was raised in amyloid (mean 1080 ± 87 ms vs. 954 ± 34 ms, P < 0.001). All three correlated with pre-test probability of cardiac involvement, cardiac biomarkers, and systolic and diastolic dysfunction. During follow-up, 25 deaths occurred. An ECVi of >0.45 carried a hazard ratio (HR) for death of 3.84 [95% confidence interval (CI): 1.53–9.61], P = 0.004 and pre-contrast T1 of >1044 ms = HR 5.39 (95% CI: 1.24–23.4), P = 0.02. Extracellular volume after primed infusion and ECVb performed similarly. Isolated post-contrast T1 was non-predictive. In Cox regression models, ECVi was independently predictive of mortality (HR = 4.41, 95% CI: 1.35–14.4) after adjusting for E:E′, ejection fraction, diastolic dysfunction grade, and NT-proBNP. Conclusion Myocardial ECV (bolus or infusion technique) and pre-contrast T1 are biomarkers for cardiac AL amyloid and they predict mortality in systemic amyloidosis. PMID:25411195

  4. Does rehabilitation of cervical lordosis influence sagittal cervical spine flexion extension kinematics in cervical spondylotic radiculopathy subjects?

    PubMed

    Moustafa, Ibrahim Moustafa; Diab, Aliaa Attiah Mohamed; Hegazy, Fatma A; Harrison, Deed E

    2017-01-01

    To test the hypothesis that improvement of cervical lordosis in cervical spondylotic radiculopathy (CSR) will improve cervical spine flexion and extension end range of motion kinematics in a population suffering from CSR. Thirty chronic lower CSR patients with cervical lordosis < 25° were included. IRB approval and informed consent were obtained. Patients were assigned randomly into two equal groups, study (SG) and control (CG). Both groups received stretching exercises and infrared; the SG received 3-point bending cervical extension traction. Treatments were applied 3 × per week for 10 weeks, care was terminated and subjects were evaluated at 3 intervals: baseline, 30 visits, and 3-month follow-up. Radiographic neutral lateral cervical absolute rotation angle (ARA C2-C7) and cervical segmental (C2-C7 segments) rotational and translational flexion-extension kinematics analysis were measured for all patients at the three intervals. The outcome were analyzed using repeated measures one-way ANOVA. Tukey's post-hoc multiple comparisons was implemented when necessary. Pearson correlation between ARA and segmental translational and rotational displacements was determined. Both groups demonstrated statistically significant increases in segmental motion at the 10-week follow up; but only the SG group showed a statistically significant increase in cervical lordosis (p < 0.0001). At 3-month follow up, only the SG improvements in segmental rotation and translation were maintained. Improved lordosis in the study group was associated with significant improvement in the translational and rotational motions of the lower cervical spine. This finding provides objective evidence that cervical flexion/extension is partially dependent on the posture and sagittal curve orientation. These findings are in agreement with several other reports in the literature; whereas ours is the first post treatment analysis identifying this relationship.

  5. Conserved region C functions to regulate PD-1 expression and subsequent CD8 T cell memory1

    PubMed Central

    Bally, Alexander P. R.; Tang, Yan; Lee, Joshua T.; Barwick, Benjamin G.; Martinez, Ryan; Evavold, Brian D.; Boss, Jeremy M.

    2016-01-01

    Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic antigen exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved Region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse (CRC−) was established to determine its role on PD-1 expression and corresponding effects on T cell function in vivo. Deletion of CR-C decreased PD-1 expression on CD4 T cells and antigen-specific CD8 T cells during acute and chronic lymphocytic choriomeningitis virus (LCMV) challenges, but did not affect the ability to clear an infection. Following acute LCMV infection, memory CD8 T cells in the CRC− mouse were formed in greater numbers, were more functional, and were more effective at responding to a melanoma tumor than wild-type memory cells. These data implicate a critical role for CR-C in governing PD-1 expression, and a subsequent role in guiding CD8 T cell differentiation. The data suggest the possibility that titrating PD-1 expression during CD8 T cell activation could have important ramifications in vaccine development and clinical care. PMID:27895178

  6. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells

    PubMed Central

    Weiss, Jonathan M.; Bilate, Angelina M.; Gobert, Michael; Ding, Yi; Curotto de Lafaille, Maria A.; Parkhurst, Christopher N.; Xiong, Huizhong; Dolpady, Jayashree; Frey, Alan B.; Ruocco, Maria Grazia; Yang, Yi; Floess, Stefan; Huehn, Jochen; Oh, Soyoung; Li, Ming O.; Niec, Rachel E.; Rudensky, Alexander Y.; Dustin, Michael L.; Littman, Dan R.

    2012-01-01

    Foxp3 activity is essential for the normal function of the immune system. Two types of regulatory T (T reg) cells express Foxp3, thymus-generated natural T reg (nT reg) cells, and peripherally generated adaptive T reg (iT reg) cells. These cell types have complementary functions. Until now, it has not been possible to distinguish iT reg from nT reg cells in vivo based solely on surface markers. We report here that Neuropilin 1 (Nrp1) is expressed at high levels by most nT reg cells; in contrast, mucosa-generated iT reg and other noninflammatory iT reg cells express low levels of Nrp1. We found that Nrp1 expression is under the control of TGF-β. By tracing nT reg and iT reg cells, we could establish that some tumors have a very large proportion of infiltrating iT reg cells. iT reg cells obtained from highly inflammatory environments, such as the spinal cords of mice with spontaneous autoimmune encephalomyelitis (EAE) and the lungs of mice with chronic asthma, express Nrp1. In the same animals, iT reg cells in secondary lymphoid organs remain Nrp1low. We also determined that, in spontaneous EAE, iT reg cells help to establish a chronic phase of the disease. PMID:22966001

  7. Optimized efficient liver T1ρ mapping using limited spin lock times

    NASA Astrophysics Data System (ADS)

    Yuan, Jing; Zhao, Feng; Griffith, James F.; Chan, Queenie; Wang, Yi-Xiang J.

    2012-03-01

    T1ρ relaxation has recently been found to be sensitive to liver fibrosis and has potential to be used for early detection of liver fibrosis and grading. Liver T1ρ imaging and accurate mapping are challenging because of the long scan time, respiration motion and high specific absorption rate. Reduction and optimization of spin lock times (TSLs) are an efficient way to reduce scan time and radiofrequency energy deposition of T1ρ imaging, but maintain the near-optimal precision of T1ρ mapping. This work analyzes the precision in T1ρ estimation with limited, in particular two, spin lock times, and explores the feasibility of using two specific operator-selected TSLs for efficient and accurate liver T1ρ mapping. Two optimized TSLs were derived by theoretical analysis and numerical simulations first, and tested experimentally by in vivo rat liver T1ρ imaging at 3 T. The simulation showed that the TSLs of 1 and 50 ms gave optimal T1ρ estimation in a range of 10-100 ms. In the experiment, no significant statistical difference was found between the T1ρ maps generated using the optimized two-TSL combination and the maps generated using the six TSLs of [1, 10, 20, 30, 40, 50] ms according to one-way ANOVA analysis (p = 0.1364 for liver and p = 0.8708 for muscle).

  8. 26 CFR 1.904(g)-0T - Outline of regulation provisions (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....904(g)-0T Section 1.904(g)-0T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Income from Sources Without the United States § 1.904(g)-0T Outline of regulation provisions (temporary). This section lists the headings for §§ 1.904(g)-1T through 1...

  9. The association between MR T1ρ and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction.

    PubMed

    Su, F; Pedoia, V; Teng, H-L; Kretzschmar, M; Lau, B C; McCulloch, C E; Link, T M; Ma, C B; Li, X

    2016-07-01

    To determine if cartilage T1ρ and T2 relaxation time measures after ACL injury and prior to reconstruction (baseline) are associated with patient-reported outcomes at baseline, 6-months, and 1-year after surgery. Fifty-four ACL-injured participants were scanned in both knees at baseline using 3T MR T1ρ and T2 mapping. Participants also completed Knee-injury and Osteoarthritis Outcome Score (KOOS) and Marx activity level questionnaires at baseline, 6-months, and 1-year after reconstruction. The difference between cartilage T1ρ or T2 of the injured and contralateral knee (side-to-side difference, SSD) was calculated to account for physiological variations among patients. Linear regression models were built to evaluate the association between the baseline SSD T1ρ or T2 and KOOS or Marx at all time points. Higher baseline SSD T1ρ posterolateral tibia (pLT) was associated with worse KOOS in all subscales except symptoms at baseline, worse KOOS pain at 6-months, and worse KOOS in all subscales except sports function at 1-year. Higher baseline SSD T2 femoral trochlea (TrF) was associated with worse KOOS activities of daily living (ADL) at 1-year. Higher baseline SSD T1ρ pLT was associated with lower Marx activity level at 1-year. More severe cartilage lesions, as assessed by Whole-Organ MRI Scoring (WORMS), was significantly associated with worse KOOS pain at 6-months and 1-year. T1ρ and T2 of cartilage after ACL injury were associated with KOOS after injury and both KOOS and Marx after reconstruction. Such associations may help clinicians stratify outcomes post-injury, and thus, improve patient management. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. 26 CFR 31.3402(p)-1T - Voluntary Withholding Agreements (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...). 31.3402(p)-1T Section 31.3402(p)-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... COLLECTION OF INCOME TAX AT SOURCE Collection of Income Tax at Source § 31.3402(p)-1T Voluntary Withholding Agreements (temporary). (a)-(b) [Reserved] For further guidance, see § 31.3402(p)-1(a) and (b). (c) Other...

  11. Shp1 regulates T cell homeostasis by limiting IL-4 signals

    PubMed Central

    Johnson, Dylan J.; Pao, Lily I.; Dhanji, Salim; Murakami, Kiichi

    2013-01-01

    The protein-tyrosine phosphatase Shp1 is expressed ubiquitously in hematopoietic cells and is generally viewed as a negative regulatory molecule. Mutations in Ptpn6, which encodes Shp1, result in widespread inflammation and premature death, known as the motheaten (me) phenotype. Previous studies identified Shp1 as a negative regulator of TCR signaling, but the severe systemic inflammation in me mice may have confounded our understanding of Shp1 function in T cell biology. To define the T cell–intrinsic role of Shp1, we characterized mice with a T cell–specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1fl/fl CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4+ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. After IL-4 stimulation of Shp1-deficient T cells, Stat 6 activation was sustained, leading to enhanced Th2 skewing. Accordingly, we observed elevated serum IgE in the steady state. Blocking or genetic deletion of IL-4 in the absence of Shp1 resulted in a marked reduction of the CD44hi population. Therefore, Shp1 is an essential negative regulator of IL-4 signaling in T lymphocytes. PMID:23797092

  12. 26 CFR 1.163-9T - Personal interest (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... computing income or loss from a passive activity of the taxpayer, (iv) Any qualified residence interest (within the meaning of section 163(h)(3) and § 1.163-10T), and (v) Any interest payable under section 6601...-10T for rules concerning qualified residence interest. (c) Effective date—(1) In general. The...

  13. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing.

    PubMed

    Jones, Christopher P; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-02-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.

  14. Neurogenic muscle hypertrophy in a 12-year-old girl.

    PubMed

    Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip

    2017-01-01

    Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

    PubMed Central

    Cobb, Dustin A.; Bhadra, Rajarshi

    2016-01-01

    CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

  16. A patient with thoracic intradural disc herniation.

    PubMed

    Whitmore, Robert G; Williams, Brian J; Lega, Bradley C; Sanborn, Matthew R; Marcotte, Paul

    2011-12-01

    Intradural disc herniation is a rare disease that occurs most commonly in the lumbar region, while fewer than 5% occur in the thoracic and cervical regions. We report a patient with thoracic intradural disc herniation at T12-L1 who presented with radiculopathy and motor weakness. The preoperative MRI did not demonstrate an intradural lesion, and it was identified intraoperatively by inspection and palpation of the thecal sac. The disc was removed, and the patient experienced good neurological recovery and remains pain free 1 year after surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Role of T-bet, the master regulator of Th1 cells, in the cytotoxicity of murine CD4+ T cells.

    PubMed

    Eshima, Koji; Misawa, Kana; Ohashi, Chihiro; Iwabuchi, Kazuya

    2018-05-01

    Although CD4 + T cells are generally regarded as helper T cells, some activated CD4 + T cells have cytotoxic properties. Given that CD4 + cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4 + T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to expression of IFN-γ has been well-documented, it remains unclear whether T-bet is involved in CD4 + T cell-mediated cytotoxicity. In this study, to investigate the ability of T-bet to confer cytolytic activity on CD4 + T cells, the T-bet gene (Tbx21) was introduced into non-cytocidal CD4 + T cell lines and their cytolytic function analyzed. Up-regulation of FasL (CD178), which provided the transfectant with cytotoxicity, was observed in Tbx21transfected CD4 + T cells but not in untransfected parental cells. In one cell line, T-bet transduction also induced perforin gene (Prf1) expression and Tbx21 transfectants efficiently killed Fas - target cells. Although T-bet was found to repress up-regulation of CD40L (CD154), which controls FasL-mediated cytolysis, the extent of CD40L up-regulation on in vitro-differentiated Th1 cells was similar to that on Th2 cells, suggesting the existence of a compensatory mechanism. These results collectively indicate that T-bet may be involved in the expression of genes, such as FasL and Prf1, which confer cytotoxicity on Th1 cells. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

  18. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells

    PubMed Central

    Spolski, Rosanne; Robertson, Avril A. B.; Klos, Andreas; Rheinheimer, Claudia; Dutow, Pavel; Woodruff, Trent M.; Yu, Zu Xi; O'Neill, Luke A.; Coll, Rebecca C.; Sher, Alan; Leonard, Warren J.; Köhl, Jörg; Monk, Pete; Cooper, Matthew A.; Arno, Matthew; Afzali, Behdad; Lachmann, Helen J.; Cope, Andrew P.; Mayer-Barber, Katrin D.; Kemper, Claudia

    2016-01-01

    The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4+ T cells and initiates caspase-1–dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is an integral component of normal adaptive TH1 responses. PMID:27313051

  19. Blockade of PD-1/PD-L1 Promotes Adoptive T-Cell Immunotherapy in a Tolerogenic Environment

    PubMed Central

    Kenna, Tony J.; Galea, Ryan; Large, Justin; Yagita, Hideo; Steptoe, Raymond J.

    2015-01-01

    Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells. PMID:25741704

  20. Blockade of PD-1/PD-L1 promotes adoptive T-cell immunotherapy in a tolerogenic environment.

    PubMed

    Blake, Stephen J P; Ching, Alan L H; Kenna, Tony J; Galea, Ryan; Large, Justin; Yagita, Hideo; Steptoe, Raymond J

    2015-01-01

    Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells.

  1. Temperature- and Phase-Dependent Phonon Renormalization in 1T'-MoS2.

    PubMed

    Tan, Sherman Jun Rong; Sarkar, Soumya; Zhao, Xiaoxu; Luo, Xin; Luo, Yong Zheng; Poh, Sock Mui; Abdelwahab, Ibrahim; Zhou, Wu; Venkatesan, Thirumalai; Chen, Wei; Quek, Su Ying; Loh, Kian Ping

    2018-05-22

    Polymorph engineering of 2H-MoS 2 , which can be achieved by alkali metal intercalation to obtain either the mixed 2H/1T' phases or a homogeneous 1T' phase, has received wide interest recently, since this serves as an effective route to tune the electrical and catalytic properties of MoS 2 . As opposed to an idealized single crystal-to-single crystal phase conversion, the 2H to 1T' phase conversion results in crystal domain size reduction as well as strained lattices, although how these develop with composition is not well understood. Herein, the evolution of the phonon modes in Li-intercalated 1T'-MoS 2 (Li x MoS 2 ) are investigated as a function of different 1T'-2H compositions. We observed that the strain evolution in the mixed phases is revealed by the softening of four Raman modes, B g ( J 1 ), A g ( J 3 ), E 1 2g , and A 1g , with increasing 1T' phase composition. Additionally, the first-order temperature coefficients of the 1T' phonon mode vary linearly with increasing 1T' composition, which is explained by increased electron-phonon and strain-phonon coupling.

  2. The importance of the presence of a 5'-ribonucleotide and the contribution of the T1R1 + T1R3 heterodimer and an additional low-affinity receptor in the taste detection of L-glutamate as assessed psychophysically.

    PubMed

    Smith, Kimberly R; Spector, Alan C

    2014-09-24

    The molecular receptors underlying the purported "umami" taste quality commonly associated with l-glutamate have been controversial. Evidence supports the involvement of the T1R1 + T1R3 heterodimer, a GPCR broadly tuned to l-amino acids, but variants of two mGluRs expressed in taste buds have also been implicated. Using a rigorous psychophysical taste-testing paradigm, we demonstrated impaired, if not eliminated, detection of MSG in WT and T1R1, T1R2, T1R3, and T1R2 + T1R3 KO mice when the contribution of sodium was minimized by the epithelial sodium channel blocker amiloride. When inosine 5'-monophosphate (IMP), a ribonucleotide that potentiates the l-glutamate signal through the T1R1 + T1R3 heterodimer, was added, the WT and T1R2 KO mice were able to detect the compound stimulus across all MSG (+amiloride) concentrations due, in part, to the taste of IMP. In contrast, mice lacking T1R1 or T1R3 could not detect IMP alone, yet some were able to detect MSG + amiloride + IMP, but only at the higher MSG concentrations. Interestingly, the sensitivity of T1R1 KO mice to another l-amino acid, lysine, was unimpaired, suggesting that some l-amino acids can be detected through T1R1 + T1R3-independent receptors without sensitivity loss. Given that IMP is not thought to affect mGluRs, behavioral detection of l-glutamate appears to require the contribution of the T1R1 + T1R3 receptor. However, the partial competence observed in some T1R1 and T1R3 KO mice when MSG + amiloride + IMP was tested suggests that a T1R1 or T1R3 homodimer or an unidentified protein, perhaps in conjunction with T1R1 or T1R3, can serve as a low-affinity taste receptor for l-glutamate in the presence of IMP. Copyright © 2014 the authors 0270-6474/14/3413234-12$15.00/0.

  3. 26 CFR 1.103(n)-6T - Determinations of population (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...(n)-6T Section 1.103(n)-6T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....103(n)-6T Determinations of population (temporary). Q-1: What is the proper method for determining...(n)-6T: Example. County Q is located within State R. There are no constitutional home rule cities in...

  4. Quantitative DLA-based compressed sensing for T1-weighted acquisitions

    NASA Astrophysics Data System (ADS)

    Svehla, Pavel; Nguyen, Khieu-Van; Li, Jing-Rebecca; Ciobanu, Luisa

    2017-08-01

    High resolution Manganese Enhanced Magnetic Resonance Imaging (MEMRI), which uses manganese as a T1 contrast agent, has great potential for functional imaging of live neuronal tissue at single neuron scale. However, reaching high resolutions often requires long acquisition times which can lead to reduced image quality due to sample deterioration and hardware instability. Compressed Sensing (CS) techniques offer the opportunity to significantly reduce the imaging time. The purpose of this work is to test the feasibility of CS acquisitions based on Diffusion Limited Aggregation (DLA) sampling patterns for high resolution quantitative T1-weighted imaging. Fully encoded and DLA-CS T1-weighted images of Aplysia californica neural tissue were acquired on a 17.2T MRI system. The MR signal corresponding to single, identified neurons was quantified for both versions of the T1 weighted images. For a 50% undersampling, DLA-CS can accurately quantify signal intensities in T1-weighted acquisitions leading to only 1.37% differences when compared to the fully encoded data, with minimal impact on image spatial resolution. In addition, we compared the conventional polynomial undersampling scheme with the DLA and showed that, for the data at hand, the latter performs better. Depending on the image signal to noise ratio, higher undersampling ratios can be used to further reduce the acquisition time in MEMRI based functional studies of living tissues.

  5. 26 CFR 1.41-0T - Table of contents (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Table of contents (temporary). 1.41-0T Section 1... Credits Against Tax § 1.41-0T Table of contents (temporary). This section lists the table of contents for...) Election. (1) In general. (2) Time and manner of election. (3) Revocation. (4) Special rules for controlled...

  6. Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2

    PubMed Central

    Crouthamel, Matthew H.; Lau, Wei Ling; Leaf, Elizabeth M.; Chavkin, Nick; Wallingford, Mary C.; Peterson, Danielle F.; Li, Xianwu; Liu, Yonggang; Chin, Michael T.; Levi, Moshe; Giachelli, Cecilia M.

    2014-01-01

    Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells. PMID:23968976

  7. Hyperpolarized (129)Xe T (1) in oxygenated and deoxygenated blood

    NASA Technical Reports Server (NTRS)

    Albert, M. S.; Balamore, D.; Kacher, D. F.; Venkatesh, A. K.; Jolesz, F. A.

    2000-01-01

    The viability of the new technique of hyperpolarized (129)Xe MRI (HypX-MRI) for imaging organs other than the lungs depends on whether the spin-lattice relaxation time, T(1), of (129)Xe is sufficiently long in the blood. In previous experiments by the authors, the T(1) was found to be strongly dependent upon the oxygenation of the blood, with T(1) increasing from about 3 s in deoxygenated samples to about 10 s in oxygenated samples. Contrarily, Tseng et al. (J. Magn. Reson. 1997; 126: 79-86) reported extremely long T(1) values deduced from an indirect experiment in which hyperpolarized (129)Xe was used to create a 'blood-foam'. They found that oxygenation decreased T(1). Pivotal to their experiment is the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles); this necessitated a complicated analysis to extract the T(1) of (129)Xe in blood. In the present study, the experimental design minimizes gas exchange after the initial bolus of hyperpolarized (129)Xe has been bubbled through the sample. This study confirms that oxygenation increases the T(1) of (129)Xe in blood, from about 4 s in freshly drawn venous blood, to about 13 s in blood oxygenated to arterial levels, and also shifts the red blood cell resonance to higher frequency. Copyright 2000 John Wiley & Sons, Ltd. Abbreviations used BOLD blood oxygen level dependent NOE nuclear overhouses effect PO(2) oxygen partial pressure RBC red blood cells RF radio frequency SNR signal-to-noise ratio.

  8. Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

    PubMed Central

    Huang, Hongbin; Peng, Cong; Liu, Yong; Liu, Xu; Chen, Qicong; Huang, Zunnan

    2016-01-01

    Abstract Background: Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results. Methods: Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association. Results: The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09–1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32–2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26–2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02–1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66–0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03–1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility. Conclusion: The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility. PMID

  9. Two unusual anatomic variations create a diagnostic dilemma in distal ulnar nerve compression.

    PubMed

    Kiehn, Mark W; Derrick, Allison J; Iskandar, Bermans J

    2008-09-01

    Diagnosis of peripheral neuropathies is based upon patterns of functional deficits and electrodiagnostic testing. However, anatomic variations can lead to confounding patterns of physical and electrodiagnostic findings. Authors present a case of ulnar nerve compression due to a rare combination of anatomic variations, aberrant branching pattern, and FCU insertion at the wrist, which posed a diagnostic and therapeutic dilemma. The literature related to isolated distal ulnar motor neuropathy and anatomic variations of the ulnar nerve and adjacent structures is also reviewed. This case demonstrates how anatomic variations can complicate the interpretation of clinical and electrodiagnostic findings and underscores the importance of thorough exploration of the nerve in consideration for possible variations. (c) 2008 Wiley-Liss, Inc.

  10. New approaches to design HIV-1 T-cell vaccines.

    PubMed

    Perrin, Hélène; Canderan, Glenda; Sékaly, Rafick-Pierre; Trautmann, Lydie

    2010-09-01

    Following the evidence that T-cell responses are crucial in the control of HIV-1 infection, vaccines targeting T-cell responses were tested in recent clinical trials. However, these vaccines showed a lack of efficacy. This review attempts to define the qualitative and quantitative features that are desirable for T-cell-induced responses by vaccines. We also describe strategies that could lead to achievement of this goal. Using the yellow fever vaccine as a benchmark of an efficient vaccine, recent studies identified factors of immune protection and more importantly innate immune pathways needed for the establishment of long-term protective adaptive immunity. To prevent or control HIV-1 infection, a vaccine must induce efficient and persistent antigen-specific T cells endowed with mucosal homing capacity. Such cells should have the capability to counteract HIV-1 diversity and its rapid spread from the initial site of infection. To achieve this goal, the activation of a diversified innate immune response is critical. New systems biology approaches will provide more precise correlates of immune protection that will pave the way for new approaches in T-cell-based vaccines.

  11. PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.

    PubMed

    Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying

    2018-04-01

    The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined. We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls. Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-γ-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Diagnostic value of T1 and T2 * relaxation times and off-resonance saturation effects in the evaluation of Achilles tendinopathy by MRI at 3T.

    PubMed

    Grosse, Ulrich; Syha, Roland; Hein, Tobias; Gatidis, Sergios; Grözinger, Gerd; Schabel, Christoph; Martirosian, Petros; Schick, Fritz; Springer, Fabian

    2015-04-01

    To evaluate and compare the diagnostic value of T1 , T2 * relaxation times and off-resonance saturation ratios (OSR) in healthy controls and patients with different clinical and morphological stages of Achilles tendinopathy. Forty-two healthy Achilles tendons and 34 tendons of 17 patients with symptomatic and asymptomatic tendinopathy were investigated clinically with conventional magnetic resonance imaging (MRI) sequences on a 3T whole-body MR scanner and a dynamic ultrasound examination. In addition, T1 and T2 * relaxation times were assessed using an ultrashort echo time (UTE) imaging sequence with flip angle and echo time variation. For the calculation of OSR values a Gaussian off-resonance saturation pulse (frequency offset: 750-5000 Hz) was used. The diagnostic value of the derived MR values was assessed and compared using receiver operating characteristic (ROC) curves. ROC curves demonstrate the highest overall test performance for OSR values at 2000 Hz off-resonance in differentiating slightly (OSR-2000 [AUC: 0.930] > T2 * [AUC: 0.884] > T1 [AUC: 0.737]) and more severe pathologically altered tendon areas (OSR-2000 [AUC: 0.964] > T2 * [AUC: 0.917] > T1 [AUC: 0.819]) from healthy ones. OSR values at a frequency offset of 2000 Hz demonstrated a better sensitivity and specificity for detecting mild and severe stages of tendinopathy compared to T2 * and particularly when compared to T1 relaxation times. © 2014 Wiley Periodicals, Inc.

  13. Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression.

    PubMed

    Li, Jin-Lian; Xiong, Kang-Hui; Dong, Yu-Lin; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

    2003-08-18

    Vesicular glutamate transporters are responsible for glutamate transport into synaptic vesicles. In the present study, we examined immunohistochemically the expression of vesicular glutamate transporters, VGluT1 and VGluT2, in trigeminal ganglion neurons of the rat. Immunohistochemistry for VGluT1 and VGluT2 indicated that more than 80% of trigeminal ganglion neurons express VGluT1 and/or VGluT2 in their cell bodies. It also indicated that large and small trigeminal ganglion neurons express VGluT2 more frequently than VGluT1. Dual immunofluorescence histochemistry for VGluT1 and VGluT2 indicated that trigeminal ganglion neurons express VGluT2 more frequently than VGluT1 and that more than 80% of VGluT-expressing trigeminal ganglion neurons express VGluT1 and VGluT2. Many axon terminals in the superficial layers of the medullary dorsal horn also showed VGluT1 and VGluT2 immunoreactivities. Some of these axon terminals were confirmed to form the central core of the synaptic glomerulus. These results indicated that VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most trigeminal ganglion neurons. Copyright 2003 Wiley-Liss, Inc.

  14. Functional characterization of a human cyclin T1 mutant reveals a different binding surface for Tat and HEXIM1.

    PubMed

    Kuzmina, Alona; Hadad, Uzi; Fujinaga, Koh; Taube, Ran

    2012-05-10

    HIV transcription is regulated at the step of elongation by the viral Tat protein and the cellular positive transcription elongation factor b (P-TEFb; Cdk9/cyclin T1). Herein, a human cyclin T1 mutant, cyclin T1-U7, which contains four substitutions and one deletion in the N-terminal cyclin box, was stably expressed in HeLa cells. HIV transcription was efficiently inhibited in HeLa-HA-CycT1-U7 stable cells. Cyclin T1-U7 bound Tat but did not modulate its expression levels, which remained high. Importantly cyclin T1-U7 failed to interact with Cdk9 or HEXIM1 and did not interfere with endogenous P-TEFb activity to stimulate MEF2C or NFkB mediated transcription. In a T cell line and primary CD4+ cells, cyclin T1-U7 also inhibited HIV transcription. We conclude that cyclin T1-U7 sequesters Tat from P-TEFb and inhibits HIV transcription. Importantly, N-terminal residues in cyclin T1 are specifically involved in the binding of cyclin T1 to HEXIM1 but not to Tat. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. 46 CFR 34.05-1 - Fire main system-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Fire main system-T/ALL. 34.05-1 Section 34.05-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Firefighting Equipment, Where Required § 34.05-1 Fire main system—T/ALL. (a) Fire pumps, piping, hydrants, hose and nozzles...

  16. 46 CFR 32.02-1 - Means of escape-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Means of escape-T/ALL. 32.02-1 Section 32.02-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS SPECIAL EQUIPMENT, MACHINERY, AND HULL REQUIREMENTS Safety Requirements § 32.02-1 Means of escape—T/ALL. On all tankships where the plans and...

  17. 46 CFR 32.02-1 - Means of escape-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Means of escape-T/ALL. 32.02-1 Section 32.02-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS SPECIAL EQUIPMENT, MACHINERY, AND HULL REQUIREMENTS Safety Requirements § 32.02-1 Means of escape—T/ALL. On all tankships where the plans and...

  18. 46 CFR 34.05-1 - Fire main system-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Fire main system-T/ALL. 34.05-1 Section 34.05-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS FIREFIGHTING EQUIPMENT Firefighting Equipment, Where Required § 34.05-1 Fire main system—T/ALL. (a) Fire pumps, piping, hydrants, hose and nozzles...

  19. 26 CFR 1.181-6T - Effective/applicability dates (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... paragraph (b) of this section, § 1.181-1T applies to productions, the first day of principal photography for... animation” in place of “principal photography.” Productions involving both animation and live-action photography may use either standard. (2) The applicability of § 1.181-1T expires on October 17, 2014. (b...

  20. Loss of DNAM-1 contributes to CD8+ T cell exhaustion in chronic HIV-1 infection

    PubMed Central

    Cella, Marina; Presti, Rachel; Vermi, William; Lavender, Kerry; Turnbull, Emma; Ochsenbauer-Jambor, Christina; Kappes, John C.; Ferrari, Guido; Kessels, Lisa; Williams, Ian; McMichael, Andrew J.; Haynes, Barton F.; Borrow, Persephone; Colonna, Marco

    2011-01-01

    Summary The hallmark of chronic viral infections is a progressive exhaustion of antigen specific CD8+ T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8+ T cells that makes them dysfunctional. Here we show that during human chronic HIV-1 infection a CD8+ T cell positive costimulatory pathway mediated by DNAM-1 is also disrupted. Thus, DNAM-1 downregulation on CD8+ T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection. PMID:20201043

  1. Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material.

    PubMed Central

    Nagai, H; Kuroda, A; Morioka, Y

    1986-01-01

    Eight autopsy cases of pancreatic cancer (duct cell adenocarcinoma) with T1 and T2 primary tumors were studied histologically to examine the exact extent of lymphatic and local spread. Six of them had microscopic metastasis in grossly negative lymph nodes near the primary tumor. In addition, four of them had a few metastatic nodes in the para-aortic region. In cases with lymphatic metastases, the extent of cancer infiltration within lymphatic vessels, nerves, and/or connective tissues was almost the same as that of lymph node metastasis. Major vascular involvement was found in four cases. There was no case in which multicentricity or marked intraductal spread of cancer cells was observed in the pancreas. It has been suggested that most of T1 and T2 pancreatic cancers have a fairly widespread microscopic extension, although extremely small T1 cancers have a very limited extension. Images FIG. 2. FIGS. 4a-c. FIGS. 5a-c. PMID:3015059

  2. Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsui, Keiji; Oda, Kasumi; Mizuta, Shumpei

    2013-10-11

    Highlights: •MED1 is a bona fide T3-dependent coactivator on TSHB promoter. •Mice with LxxLL-mutant MED1 have attenuated TSHβ mRNA and thyroid hormone levels. •MED1 activates TSHB promoter T3-dependently in cultured cells. •T3-dependent MED1 action is enhanced when SRC1/SRC2 or HDAC2 is downregulated. •MED1 is also a T3-independent GATA2/Pit1 coactivator on TSHB promoter. -- Abstract: The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor β (TRβ) on the TSHβmore » gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHβ gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHβ gene promoter.« less

  3. Spiral MR fingerprinting at 7T with simultaneous B1 estimation.

    PubMed

    Buonincontri, Guido; Schulte, Rolf F; Cosottini, Mirco; Tosetti, Michela

    2017-09-01

    Magnetic resonance fingerprinting is an efficient, new approach for quantitative imaging with MR. We aimed to extend this technique to cases with B1+ inhomogeneities within the imaging volume. Previous approaches have used abrupt changes in flip angles to estimate the B1+ field simultaneously with T1 and T2, using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated whether a similar approach would be suitable for imaging human brains using spiral readouts with a 7T scanner. We found that our modified scheme could significantly reduce the adverse effects of B1+ inhomogeneities even in extreme cases, reducing both the bias and the variance in T2 estimations by an order of magnitude when compared to literature methods. Acquisitions used less than 1.5W/kg SAR and could be performed in 12s per slice. In conclusion, our approach can be used to perform quantitative imaging of the brain at 7T in a short time, simultaneously estimating the B1+ profile. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Tuning the relaxation rates of dual-mode T1/T2 nanoparticle contrast agents: a study into the ideal system

    NASA Astrophysics Data System (ADS)

    Keasberry, Natasha A.; Bañobre-López, Manuel; Wood, Christopher; Stasiuk, Graeme. J.; Gallo, Juan; Long, Nicholas. J.

    2015-09-01

    Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in

  5. Synovial T cell hyporesponsiveness to myeloid dendritic cells is reversed by preventing PD-1/PD-L1 interactions.

    PubMed

    Moret, Frederique M; van der Wurff-Jacobs, Kim M G; Bijlsma, Johannes W J; Lafeber, Floris P J G; van Roon, Joel A G

    2014-11-30

    The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)-primed CD1c myeloid dendritic cells (mDCs). Expression of PD-1 on naïve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression. PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation. SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation.

  6. T cell virological synapses and HIV-1 pathogenesis.

    PubMed

    Chen, Benjamin K

    2012-12-01

    Human immunodeficiency virus type 1 is the cause of a modern global pandemic associated with progressive acquired immune deficiency. The infection is characterized by the loss of the primary target of viral infection, the CD4+ T cell. The measurement of plasma viremia in patients can predict the rate of CD4+ cell decline; however, it is not clear whether this cell-free plasma virus represents the engine that drives viral spread. Active viral replication is mainly observed within lymphoid tissues that are hotbeds of cell-cell interactions that initiate and organize immune responses. It is well established that cell-cell interactions enhance viral spread in vitro. Dendritic cell-T cell interactions, which lie at the heart of adaptive immune responses, enhance viral infection in vitro. Interactions between infected and uninfected CD4+ T cells are a dominant route of viral spread in vitro and are likely to play a central role in viral dissemination in vivo. Future studies will test existing paradigms of HIV-1 dissemination to determine whether virus-transmitting contacts between infected and uninfected T cells called virological synapses are the dominant mode of viral spread in vivo. Here, we review the status of our understanding of this mode of infection with a focus on T cell-T cell interactions and examine how it may explain resistance to neutralizing antibodies and or the generation of genetic diversity of HIV.

  7. Engineered contrast agents in a single structure for T1-T2 dual magnetic resonance imaging.

    PubMed

    Cabrera-García, Alejandro; Checa-Chavarria, Elisa; Pacheco-Torres, Jesús; Bernabeu-Sanz, Ángela; Vidal-Moya, Alejandro; Rivero-Buceta, Eva; Sastre, Germán; Fernández, Eduardo; Botella, Pablo

    2018-04-05

    The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

  8. Quantitative evaluation of knee cartilage and meniscus destruction in patients with rheumatoid arthritis using T1ρ and T2 mapping.

    PubMed

    Meng, Xiang Hong; Wang, Zhi; Guo, Li; Liu, Xiu Chan; Zhang, Yu Wei; Zhang, Ze Wei; Ma, Xin Long

    2017-11-01

    To calculate T1ρ and T2 values of articular cartilage and menisci in knee joints of patients with RA, and compare the values between RA patients and healthy volunteers, to gain insight into the pathogenesis of cartilage and meniscus degradation in patients with RA. Nine patients with RA and knee joints symptoms were enrolled in the study, twenty healthy volunteers without knee joint diseases were included as controls. Sagittal fat-saturated T1ρ and T2 mapping images were obtained on a 3T MR scanner (GE750, GE Healthcare, Waukesha, WI), using a dedicated 8-channel knee coil. In the T1rho mapping sequence, the amplitude of the spin-lock pulse was 500Hz, spin lock durations=10/20/30/50ms. In the T2 mapping sequence,TR/TE were 1794/6.5, 13.4, 27, 40.7ms. Both sequences were performed with the following parameters: flip angle (FA)=90°, matrix: 320×256, FOV: 16×16cm 2 , slice thickness: 3mm, bandwidth: 62.5kHZ, and a total scan time of 5:11min. T1ρ- and T2-mapping images were used for the segmentation of the articular cartilage of the patella, femoral trochlea, medial and lateral femoral condyle, medial and lateral tibial plateau. These images were also used for the segmentation of the anterior and posterior horns of the medial and lateral menisci with livewire semi-automatic segmentation algorithm of MATLAB. A Mann-Whitney U test was performed to compare the T1ρ and T2 values of the above mentioned regions between the two groups. T1ρ (Z=-3.913 to -2.121, P=0.000-0.034) and T2 (Z=-3.866 to -2.216, P=0.000-0.026) values of knee cartilage in patients with RA were higher than that in healthy volunteers, except the cartilage of the patella (T1ρ: Z=-1.273, P=0.203,T2: Z=-0.236, P=0.814) and lateral tibial plateau (T1ρ:Z=-1.037, P=0.317). The T1ρ (Z=-1.462 to 0.572, P=0.095-0.908) and T2 (Z=-1.461 to 0.278, P=0.153-0.764) values of medial and lateral menisci showed no difference between the two groups. Patients with RA exhibit diffuse knee cartilage destruction in

  9. α4β7+ CD4+ Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection.

    PubMed

    Cheung, Ka-Wai; Wu, Tongjin; Ho, Sai Fan; Wong, Yik Chun; Liu, Li; Wang, Hui; Chen, Zhiwei

    2018-04-15

    HIV-1 transmission occurs mainly through mucosal tissues. During mucosal transmission, HIV-1 preferentially infects α 4 β 7 + gut-homing CCR7 - CD4 + effector/effector memory T cells (T EM ) and results in massive depletion of these cells and other subsets of T EM in gut-associated lymphoid tissues. However, besides being eliminated by HIV-1, the role of T EM during the early stage of infection remains inconclusive. Here, using in vitro -induced α 4 β 7 + gut-homing T EM (α 4 β 7 + T EM ), we found that α 4 β 7 + T EM differentiated into CCR7 + CD4 + central memory T cells (T CM ). This differentiation was HIV-1 independent but was inhibited by SB431542, a specific transforming growth factor β (TGF-β) receptor I kinase inhibitor. Consistently, T EM -to-T CM differentiation was observed in α 4 β 7 + T EM stimulated with TGF-β1 (TGF-β). The T CM properties of the TGF-β-induced T EM -derived T CM (α 4 β 7 + T CM ) were confirmed by their enhanced CCL19 chemotaxis and the downregulation of surface CCR7 upon T cell activation in vitro Importantly, the effect of TGF-β on T CM differentiation also held in T EM directly isolated from peripheral blood. To investigate the significance of the TGF-β-dependent T EM -to-T CM differentiation in HIV/AIDS pathogenesis, we observed that both productively and latently infected α 4 β 7 + T CM could differentiate from α 4 β 7 + T EM in the presence of TGF-β during HIV-1 infection. Collectively, this study not only provides a new insight for the plasticity of T EM but also suggests that the TGF-β-dependent T EM -to-T CM differentiation is a previously unrecognized mechanism for the formation of latently infected T CM after HIV-1 infection. IMPORTANCE HIV-1 is the causative agent of HIV/AIDS, which has led to millions of deaths in the past 30 years. Although the implementation of highly active antiretroviral therapy has remarkably reduced the HIV-1-related morbidity and mortality, HIV-1 is not eradicated in

  10. Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain.

    PubMed

    Nakamura, Kouichi; Hioki, Hiroyuki; Fujiyama, Fumino; Kaneko, Takeshi

    2005-11-21

    Vesicular glutamate transporter 1 (VGluT1) and VGluT2 accumulate neurotransmitter glutamate into synaptic vesicles at presynaptic terminals, and their antibodies are thus considered to be a good marker for glutamatergic axon terminals. In the present study, we investigated the postnatal development and maturation of glutamatergic neuronal systems by single- and double-immunolabelings for VGluT1 and VGluT2 in mouse forebrain including the telencephalon and diencephalon. VGluT2 immunoreactivity was widely distributed in the forebrain, particularly in the diencephalon, from postnatal day 0 (P0) to adulthood, suggesting relatively early maturation of VGluT2-loaded glutamatergic axons. In contrast, VGluT1 immunoreactivity was intense only in the limbic regions at P0, and drastically increased in the other telencephalic and diencephalic regions during three postnatal weeks. Interestingly, VGluT1 immunoreactivity was frequently colocalized with VGluT2 immunoreactivity at single axon terminal-like profiles in layer IV of the primary somatosensory area from P5 to P10 and in the ventral posteromedial thalamic nucleus from P0 to P14. This was in sharp contrast to the finding that almost no colocalization was found in glomeruli of the olfactory bulb, patchy regions of the caudate-putamen, and the ventral posterolateral thalamic nucleus, where moderate to intense immunoreactivities for VGluT1 and VGluT2 were intermingled with each other in neuropil during postnatal development. The present results indicate that VGluT2-loaded glutamatergic axons maturate earlier than VGluT1-laden axons in the mouse telencephalic and diencephalic regions, and suggest that VGluT1 plays a transient developmental role in some glutamatergic systems that mainly use VGluT2 in the adulthood. (c) 2005 Wiley-Liss, Inc.

  11. Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) pathway initiated by T cell antigen receptor (TCRγδ) activation is required to overcome inhibition by ubiquitin ligase Cbl-b during γδT cell cytotoxicity.

    PubMed

    Yin, Shanshan; Zhang, Jianmin; Mao, Yujia; Hu, Yu; Cui, Lianxian; Kang, Ning; He, Wei

    2013-09-13

    T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing. However, NKG2D ligation augmented the activation of γδT cell cytotoxicity through the Vav1-phospholipase C-γ1 pathway. Vav1 overexpression or Cbl-b knockdown not only enhanced TCRγδ activation-initiated killing but also enabled NKG2D activation alone to induce γδT cell cytotoxicity. Taken together, our results suggest that the activation of γδT cell cytotoxicity requires a strong activation signal to overcome the inhibitory effect of Cbl-b. Our finding provides new insights into the molecular mechanisms underlying the initiation of γδT cell cytotoxicity and likely implications for optimizing γδT cell-based cancer immunotherapy.

  12. The Importance of the Presence of a 5′-Ribonucleotide and the Contribution of the T1R1 + T1R3 Heterodimer and an Additional Low-Affinity Receptor in the Taste Detection of l-Glutamate as Assessed Psychophysically

    PubMed Central

    Smith, Kimberly R.

    2014-01-01

    The molecular receptors underlying the purported “umami” taste quality commonly associated with l-glutamate have been controversial. Evidence supports the involvement of the T1R1 + T1R3 heterodimer, a GPCR broadly tuned to l-amino acids, but variants of two mGluRs expressed in taste buds have also been implicated. Using a rigorous psychophysical taste-testing paradigm, we demonstrated impaired, if not eliminated, detection of MSG in WT and T1R1, T1R2, T1R3, and T1R2 + T1R3 KO mice when the contribution of sodium was minimized by the epithelial sodium channel blocker amiloride. When inosine 5′-monophosphate (IMP), a ribonucleotide that potentiates the l-glutamate signal through the T1R1 + T1R3 heterodimer, was added, the WT and T1R2 KO mice were able to detect the compound stimulus across all MSG (+amiloride) concentrations due, in part, to the taste of IMP. In contrast, mice lacking T1R1 or T1R3 could not detect IMP alone, yet some were able to detect MSG + amiloride + IMP, but only at the higher MSG concentrations. Interestingly, the sensitivity of T1R1 KO mice to another l-amino acid, lysine, was unimpaired, suggesting that some l-amino acids can be detected through T1R1 + T1R3-independent receptors without sensitivity loss. Given that IMP is not thought to affect mGluRs, behavioral detection of l-glutamate appears to require the contribution of the T1R1 + T1R3 receptor. However, the partial competence observed in some T1R1 and T1R3 KO mice when MSG + amiloride + IMP was tested suggests that a T1R1 or T1R3 homodimer or an unidentified protein, perhaps in conjunction with T1R1 or T1R3, can serve as a low-affinity taste receptor for l-glutamate in the presence of IMP. PMID:25253867

  13. Simian T Lymphotropic Virus 1 Infection of Papio anubis: tax Sequence Heterogeneity and T Cell Recognition.

    PubMed

    Termini, James M; Magnani, Diogo M; Maxwell, Helen S; Lauer, William; Castro, Iris; Pecotte, Jerilyn; Barber, Glen N; Watkins, David I; Desrosiers, Ronald C

    2017-10-15

    Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8 + T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. IMPORTANCE It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A

  14. Myocardial T1 mapping at 3.0 tesla using an inversion recovery spoiled gradient echo readout and bloch equation simulation with slice profile correction (BLESSPC) T1 estimation algorithm.

    PubMed

    Shao, Jiaxin; Rapacchi, Stanislas; Nguyen, Kim-Lien; Hu, Peng

    2016-02-01

    To develop an accurate and precise myocardial T1 mapping technique using an inversion recovery spoiled gradient echo readout at 3.0 Tesla (T). The modified Look-Locker inversion-recovery (MOLLI) sequence was modified to use fast low angle shot (FLASH) readout, incorporating a BLESSPC (Bloch Equation Simulation with Slice Profile Correction) T1 estimation algorithm, for accurate myocardial T1 mapping. The FLASH-MOLLI with BLESSPC fitting was compared with different approaches and sequences with regards to T1 estimation accuracy, precision and image artifact based on simulation, phantom studies, and in vivo studies of 10 healthy volunteers and three patients at 3.0 Tesla. The FLASH-MOLLI with BLESSPC fitting yields accurate T1 estimation (average error = -5.4 ± 15.1 ms, percentage error = -0.5% ± 1.2%) for T1 from 236-1852 ms and heart rate from 40-100 bpm in phantom studies. The FLASH-MOLLI sequence prevented off-resonance artifacts in all 10 healthy volunteers at 3.0T. In vivo, there was no significant difference between FLASH-MOLLI-derived myocardial T1 values and "ShMOLLI+IE" derived values (1458.9 ± 20.9 ms versus 1464.1 ± 6.8 ms, P = 0.50); However, the average precision by FLASH-MOLLI was significantly better than that generated by "ShMOLLI+IE" (1.84 ± 0.36% variance versus 3.57 ± 0.94%, P < 0.001). The FLASH-MOLLI with BLESSPC fitting yields accurate and precise T1 estimation, and eliminates banding artifacts associated with bSSFP at 3.0T. © 2015 Wiley Periodicals, Inc.

  15. Eight new T4.5-T7.5 dwarfs discovered in the UKIDSS Large Area Survey Data Release 1

    NASA Astrophysics Data System (ADS)

    Lodieu, N.; Pinfield, D. J.; Leggett, S. K.; Jameson, R. F.; Mortlock, D. J.; Warren, S. J.; Burningham, B.; Lucas, P. W.; Chiu, K.; Liu, M. C.; Venemans, B. P.; McMahon, R. G.; Allard, F.; Baraffe, I.; Barrado y Navascués, D.; Carraro, G.; Casewell, S. L.; Chabrier, G.; Chappelle, R. J.; Clarke, F.; Day-Jones, A. C.; Deacon, N. R.; Dobbie, P. D.; Folkes, S. L.; Hambly, N. C.; Hewett, P. C.; Hodgkin, S. T.; Jones, H. R. A.; Kendall, T. R.; Magazzù, A.; Martín, E. L.; McCaughrean, M. J.; Nakajima, T.; Pavlenko, Y.; Tamura, M.; Tinney, C. G.; Zapatero Osorio, M. R.

    2007-08-01

    We present eight new T4.5-T7.5 dwarfs identified in the UKIRT (United Kingdom Infrared Telescope) Infrared Deep Sky Survey (UKIDSS) Large Area Survey (LAS) Data Release 1 (DR1). In addition we have recovered the T4.5 dwarf SDSSJ020742.91+000056.2 and the T8.5 dwarf ULASJ003402.77-005206.7. Photometric candidates were picked up in two-colour diagrams over 190deg2 (DR1) and selected in at least two filters. All candidates exhibit near-infrared spectra with strong methane and water absorption bands characteristic of T dwarfs and the derived spectral types follow the unified scheme of Burgasser et al.. We have found six new T4.5-T5.5 dwarfs, one T7 dwarf, one T7.5 dwarf and recovered a T4.5 dwarf and a T8.5 dwarf. We provide distance estimates which lie in the 15-85pc range; the T7.5 and T8.5 dwarfs are probably within 25pc of the Sun. We conclude with a discussion of the number of T dwarfs expected after completion of the LAS, comparing these initial results to theoretical simulations. Based on observations made with the United Kingdom Infrared Telescope, operated by the Joint Astronomy Centre on behalf of the UK Particle Physics and Astronomy Research Council. E-mail: nlodieu@iac.es ‡ Alfred P. Sloan Research Fellow.

  16. Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

    PubMed Central

    Righart, Ruthger; Biberacher, Viola; Jonkman, Laura E.; Klaver, Roel; Schmidt, Paul; Buck, Dorothea; Berthele, Achim; Kirschke, Jan S.; Zimmer, Claus; Hemmer, Bernhard; Geurts, Jeroen J. G.

    2017-01-01

    Objective In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Methods Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Results Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. Interpretation The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529 PMID:28833433

  17. Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.

    PubMed

    Cherkasova, Vera; Maury, Luis Lopez; Bacikova, Dagmar; Pridham, Kevin; Bähler, Jürg; Maraia, Richard J

    2012-02-01

    Deletion of the sla1(+) gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1(+) have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1-like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1(+) (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1(+) regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae.

  18. Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p

    PubMed Central

    Cherkasova, Vera; Lopez Maury, Luis; Bacikova, Dagmar; Pridham, Kevin; Bähler, Jürg; Maraia, Richard J.

    2012-01-01

    Deletion of the sla1+ gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1+ have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1–like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1+ (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1+ regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae. PMID:22160596

  19. Loss of RUNX1/AML1 arginine-methylation impairs in peripheral T cell homeostasis

    PubMed Central

    Mizutani, Shinsuke; Yoshida, Tatsushi; Zhao, Xinyang; Nimer, Stephen D.; Taniwaki, Masafumi; Okuda, Tsukasa

    2016-01-01

    Summary RUNX1 (previously termed AML1) is a frequent target of human leukaemia-associated gene aberrations, and it encodes the DNA-binding subunit of the Core-Binding Factor transcription factor complex. RUNX1 expression is essential for the initiation of definitive haematopoiesis, for steady-state thrombopoiesis, and for normal lymphocytes development. Recent studies revealed that protein arginine methyltransferase 1 (PRMT1), which accounts for the majority of the type I PRMT activity in cells, methylates two arginine residues in RUNX1 (R206 and R210), and these modifications inhibit corepressor-binding to RUNX1 thereby enhancing its transcriptional activity. In order to elucidate the biological significance of these methylations, we established novel knock-in mouse lines with non-methylable, double arginine-to-lysine (RTAMR-to-KTAMK) mutations in RUNX1. Homozygous Runx1KTAMK/KTAMK mice are born alive and appear normal during adulthood. However, Runx1KTAMK/KTAMK mice showed a reduction in CD3+ T lymphoid cells and a decrease in CD4+ T cells in peripheral lymphoid organs, in comparison to their wild-type littermates, leading to a reduction in the CD4+ to CD8+ T-cell ratio. These findings suggest that arginine-methylation of RUNX1 in the RTAMR-motif is dispensable for the development of definitive haematopoiesis and for steady-state platelet production, however this modification affects the role of RUNX1 in the maintenance of the peripheral CD4+ T-cell population. PMID:26010396

  20. T1 vs. T2 weighted magnetic resonance imaging to assess total kidney volume in patients with autosomal dominant polycystic kidney disease.

    PubMed

    van Gastel, Maatje D A; Messchendorp, A Lianne; Kappert, Peter; Kaatee, Merel A; de Jong, Marissa; Renken, Remco J; Ter Horst, Gert J; Mahesh, Shekar V K; Gansevoort, Ron T

    2018-05-01

    In ADPKD patients total kidney volume (TKV) measurement using MRI is performed to predict rate of disease progression. Historically T1 weighted images (T1) were used, but the methodology of T2 weighted imaging (T2) has evolved. We compared the performance of both sequences. 40 ADPKD patients underwent an abdominal MRI at baseline and follow-up. TKV was measured by manual tracing with Analyze Direct 11.0 software. Three readers established intra- and interreader coefficients of variation (CV). T1 and T2 measured kidney volumes and growth rates were compared with ICC and Bland-Altman analyses. Participants were 49.7 ± 7.0 years of age, 55.0% female, with estimated GFR of 50.1 ± 11.5 mL/min/1.73 m 2 . CVs were low and comparable for T2 and T1 (intrareader: 0.83% [0.48-1.79] vs. 1.15% [0.34-1.77], P = 0.9, interreader: 2.18% [1.59-2.61] vs. 1.69% [1.07-3.87], P = 0.9). TKV was clinically similar, but statistically significantly different between T2 and T1: 1867 [1172-2721] vs. 1932 [1180-2551] mL, respectively (P = 0.006), with a bias of only 0.8% and high agreement (ICC 0.997). Percentage kidney growth during 2.2 ± 0.3 years was similar for T2 and T1 (9.3 ± 10.6% vs. 7.8 ± 9.9%, P = 0.1, respectively), with a bias of 1.5% and high agreement (ICC 0.843). T2 was more often of sufficient quality for volume measurement (86.7% vs. 71.1%, P < 0.001). In patients with ADPKD, measurement of kidney volume and growth rate performs similarly when using T2 compared to T1 weighted images, although T2 performs better on secondary outcome parameters; they are more often of sufficient quality for volume measurement and result in slightly lower intra- and interreader variability.

  1. 26 CFR 1.1502-21T - Net operating losses (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Net operating losses (temporary). 1.1502-21T...) INCOME TAX (CONTINUED) INCOME TAXES Computation of Consolidated Items § 1.1502-21T Net operating losses...)(B). (C) Partial waiver of carryback period for 2001 and 2002 losses—(1) Application. The acquiring...

  2. 46 CFR 32.16-1 - Navigation bridge visibility-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Navigation bridge visibility-T/ALL. 32.16-1 Section 32..., AND HULL REQUIREMENTS Navigation Bridge Visibility § 32.16-1 Navigation bridge visibility-T/ALL. Each..., must meet the following requirements: (a) The field of vision from the navigation bridge, whether the...

  3. High-speed multislice T1 mapping using inversion-recovery echo-planar imaging.

    PubMed

    Ordidge, R J; Gibbs, P; Chapman, B; Stehling, M K; Mansfield, P

    1990-11-01

    Tissue contrast in MR images is a strong function of spin-lattice (T1) and spin-spin (T2) relaxation times. However, the T1 relaxation time is rarely quantified because of the long scan time required to produce an accurate T1 map of the subject. In a standard 2D FT technique, this procedure may take up to 30 min. Modifications of the echo-planar imaging (EPI) technique which incorporate the principle of inversion recovery (IR) enable multislice T1 maps to be produced in total scan times varying from a few seconds up to a minute. Using IR-EPI, rapid quantification of T1 values may thus lead to better discrimination between tissue types in an acceptable scan time.

  4. Preteen-parent experiences with PREP-T1 feasibility intervention.

    PubMed

    Hughes, Patricia; Johnson, Kim; Ramchandani, Neesha; Quinn, Diane; D'Alesandro, Bianca; Streisand, Randi; Sullivan-Bolyai, Susan

    2015-08-01

    The purpose of this article is to report the focus group perspectives of preteens' and parents' experiences with a feasibility intervention entitled PREP-T1 (Preteen Re-Education with Parents-Type 1 Diabetes), an interactive education and peer mentoring intervention. The parent and preteen focus groups were conducted by the principal investigator, coinvestigator, and note takers at 2 sites. The preteen-parent groups were conducted concurrently with a total of 11 preteens and 11 parents. Note-based qualitative content analysis was used, resulting in preteen-parent perspectives on reeducation and strategies for families to work more effectively in managing type 1 diabetes (T1DM). The findings suggest that the preteens enjoyed learning about their diabetes management from a teen educator mentor in conjunction with a human patient simulator. They reported this type of peer support would benefit other preteens with T1DM. Parents were overwhelmingly positive about their interactions with the parent educator mentor in conjunction with the psychologist and about focusing on how to better collaborate with their preteens on diabetes management decision making. Further recommendations about the timing and intervention dose were also discussed. Moderated peer mentoring with technology has potential as a means for teaching preteens and their parents shared diabetes management. These data will be used to inform the PREP-T1 fully powered intervention study. © 2015 The Author(s).

  5. Immediate and lasting effects of a thoracic spine manipulation in a patient with signs of cervical radiculopathy and upper extremity hyperalgesia: A case report.

    PubMed

    Deschenes, Beth K; Zafereo, Jason

    2017-01-01

    Patients with cervical radiculopathy (CR) may present with accompanying symptoms of hyperalgesia, allodynia, heaviness in the arm, and non-segmental pain that do not appear to be related to a peripheral spinal nerve. These findings may suggest the presence of central or autonomic nervous system involvement, requiring a modified management approach. The purpose of this case report is to describe the treatment of a patient with signs of CR and upper extremity (UE) hyperalgesia who had a significant decrease in her UE pain and hypersensitivity after a single thoracic spine manipulation (TSM). A 48-year-old female presented to physical therapy with acute neck pain radiating into her left UE that significantly limited her ability to sleep and work. After a single TSM, the patient demonstrated immediate and lasting reduction in hyperalgesia, hypersensitivity to touch, elimination of perceived heaviness and coldness in her left UE, and improved strength in the C6-8 myotome, allowing for improved functional activity capacity and tolerance to a multi-modal PT program. Based on these results, clinicians should consider the early application of TSM in patients with CR who have atypical, widespread, or severe neurological symptoms that limit early mobilization and tolerance to treatment at the painful region.

  6. 26 CFR 1.6041-1T - Return of information as to payments of $600 or more (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Return of information as to payments of $600 or more (temporary). 1.6041-1T Section 1.6041-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF.... The applicability of this section expires on February 28, 2017. [T.D. 9658, 79 FR 12793, Mar. 6, 2014] ...

  7. Early T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors

    PubMed Central

    Wang, Shu-Fang; Fouquet, Stéphane; Chapon, Maxime; Salmon, Hélène; Regnier, Fabienne; Labroquère, Karine; Badoual, Cécile; Damotte, Diane; Validire, Pierre; Maubec, Eve; Delongchamps, Nicolas B.; Cazes, Aurélie; Gibault, Laure; Garcette, Marylène; Dieu-Nosjean, Marie-Caroline; Zerbib, Marc; Avril, Marie-Françoise; Prévost-Blondel, Armelle; Randriamampita, Clotilde; Trautmann, Alain; Bercovici, Nadège

    2011-01-01

    To improve cancer immunotherapy, a better understanding of the weak efficiency of tumor-infiltrating T lymphocytes (TIL) is necessary. We have analyzed the functional state of human TIL immediately after resection of three types of tumors (NSCLC, melanoma and RCC). Several signalling pathways (calcium, phosphorylation of ERK and Akt) and cytokine secretion are affected to different extents in TIL, and show a partial spontaneous recovery within a few hours in culture. The global result is an anergy that is quite distinct from clonal anergy induced in vitro, and closer to adaptive tolerance in mice. PD-1 (programmed death -1) is systematically expressed by TIL and may contribute to their anergy by its mere expression, and not only when it interacts with its ligands PD-L1 or PD-L2, which are not expressed by every tumor. Indeed, the TCR-induced calcium and ERK responses were reduced in peripheral blood T cells transfected with PD-1. Inhibition by sodium stibogluconate of the SHP-1 and SHP-2 phosphatases that associate with several inhibitory receptors including PD-1, relieves part of the anergy apparent in TIL or in PD-1-transfected T cells. This work highlights some of the molecular modifications contributing to functional defects of human TIL. PMID:21408177

  8. SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain

    PubMed Central

    Yan, Wenjun; Fang, Zongping; Yang, Qianzi; Dong, Hailong; Lu, Yan; Lei, Chong; Xiong, Lize

    2013-01-01

    Our previous studies have shown that hyperbaric oxygen preconditioning (HBO-PC) induces tolerance to cerebral ischemia/reperfusion (I/R). This study aimed to investigate whether SirT1, a class III histone deacetylase, is involved in neuroprotection elicited by HBO-PC in animal and cell culture models of ischemia. Rats were subjected to middle cerebral artery occlusion for 120 minutes after HBO-PC (once a day for 5 days). Primary cultured cortical neurons were exposed to 2 hours of HBO-PC after 2 hours of oxygen–glucose deprivation (OGD). We showed that HBO-PC increased SirT1 protein and mRNA expression, promoted neurobehavioral score, reduced infarct volume, and improved morphology at 24 hours and 7 days after cerebral I/R. Neuroprotection of HBO-PC was attenuated by SirT1 inhibitor EX527 and SirT1 knockdown by short interfering RNA (siRNA), whereas it was mimicked by SirT1 activator resveratrol. Furthermore, HBO-PC enhanced SirT1 expression and cell viability and reduced lactate dehydrogenase release 24 hours after OGD/re-oxygenation. The neuroprotective effect of HBO-PC was emulated through upregulating SirT1 and, reversely, attenuated through downregulating SirT1. The modulation of SirT1 was made by adenovirus infection carrying SirT1 or SirT1 siRNA. Besides, SirT1 increased B-cell lymphoma 2 (Bcl-2) expression and decrease cleaved caspase 3. These results indicate that SirT1 mediates HBO-PC-induced tolerance to cerebral I/R through inhibition of apoptosis. PMID:23299244

  9. T1 bright appendix sign to exclude acute appendicitis in pregnant women.

    PubMed

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun

    2017-08-01

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. • Magnetic resonance imaging is increasingly used in emergency settings. • Acute appendicitis is the most common cause of acute abdomen. • Magnetic resonance imaging is widely used in pregnant population. • T1 bright appendix sign can be a specific sign representing normal appendix.

  10. Physics reach of the XENON1T dark matter experiment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aprile, E.; Anthony, M.; Aalbers, J.

    2016-04-01

    The XENON1T experiment is currently in the commissioning phase at the Laboratori Nazionali del Gran Sasso, Italy. In this article we study the experiment's expected sensitivity to the spin-independent WIMP-nucleon interaction cross section, based on Monte Carlo predictions of the electronic and nuclear recoil backgrounds. The total electronic recoil background in 1 tonne fiducial volume and (1, 12) keV electronic recoil equivalent energy region, before applying any selection to discriminate between electronic and nuclear recoils, is (1.80 ± 0.15) · 10{sup −4} (kg·day·keV){sup −1}, mainly due to the decay of {sup 222}Rn daughters inside the xenon target. The nuclear recoil background in the correspondingmore » nuclear recoil equivalent energy region (4, 50) keV, is composed of (0.6 ± 0.1) (t·y){sup −1} from radiogenic neutrons, (1.8 ± 0.3) · 10{sup −2} (t·y){sup −1} from coherent scattering of neutrinos, and less than 0.01 (t·y){sup −1} from muon-induced neutrons. The sensitivity of XENON1T is calculated with the Profile Likelihood Ratio method, after converting the deposited energy of electronic and nuclear recoils into the scintillation and ionization signals seen in the detector. We take into account the systematic uncertainties on the photon and electron emission model, and on the estimation of the backgrounds, treated as nuisance parameters. The main contribution comes from the relative scintillation efficiency L{sub eff}, which affects both the signal from WIMPs and the nuclear recoil backgrounds. After a 2 y measurement in 1 t fiducial volume, the sensitivity reaches a minimum cross section of 1.6 · 10{sup −47} cm{sup 2} at m{sub χ} = 50 GeV/c{sup 2}.« less

  11. Spectroscopic Studies of Perturbed T1 Cu Sites in the Multicopper Oxidases Saccharomyces Cerevisiae Fet3p And Rhus Vernicifera Laccase: Allosteric Coupling Between the T1 And Trinuclear Cu Sites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Augustine, A.J.; Kragh, M.E.; Sarangi, R.

    2009-04-30

    The multicopper oxidases catalyze the 4e{sup -} reduction of O{sub 2} to H{sub 2}O coupled to the 1e{sup -} oxidation of 4 equiv of substrate. This activity requires four Cu atoms, including T1, T2, and coupled binuclear T3 sites. The T2 and T3 sites form a trinuclear cluster (TNC) where O{sub 2} is reduced. The T1 is coupled to the TNC through a T1-Cys-His-T3 electron transfer (ET) pathway. In this study the two T3 Cu coordinating His residues which lie in this pathway in Fet3 have been mutated, H483Q, H483C, H485Q, and H485C, to study how perturbation at the TNCmore » impacts the T1 Cu site. Spectroscopic methods, in particular resonance Raman (rR), show that the change from His to Gln to Cys increases the covalency of the T1 Cu?S Cys bond and decreases its redox potential. This study of T1?TNC interactions is then extended to Rhus vernicifera laccase where a number of well-defined species including the catalytically relevant native intermediate (NI) can be trapped for spectroscopic study. The T1 Cu?S covalency and potential do not change in these species relative to resting oxidized enzyme, but interestingly the differences in the structure of the TNC in these species do lead to changes in the T1 Cu rR spectrum. This helps to confirm that vibrations in the cysteine side chain of the T1 Cu site and the protein backbone couple to the Cu?S vibration. These changes in the side chain and backbone provide a possible mechanism for regulating intramolecular T1 to TNC ET in NI and partially reduced enzyme forms for efficient turnover.« less

  12. Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

    PubMed

    Ishikawa, Tetsuhiro; Watanabe, Atsuya; Kamoda, Hiroto; Miyagi, Masayuki; Inoue, Gen; Takahashi, Kazuhisa; Ohtori, Seiji

    2018-04-01

    An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs ( p <0.05). There was a significant difference between grade 1 and grade 2 IVDs only in terms of T1ρ values ( p <0.05). T1ρ and T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

  13. Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer's disease cortex.

    PubMed

    Sokolow, Sophie; Luu, Sanh H; Nandy, Karabi; Miller, Carol A; Vinters, Harry V; Poon, Wayne W; Gylys, Karen H

    2012-01-01

    Amyloid-beta (Aβ) is thought to play a central role in synaptic dysfunction (e.g. neurotransmitter release) and synapse loss. Glutamatergic dysfunction is involved in the pathology of Alzheimer's disease (AD) and perhaps plays a central role in age-related cognitive impairment. Yet, it is largely unknown whether Aβ accumulates in excitatory boutons. To assess the possibility that glutamatergic terminals are lost in AD patients, control and AD synaptosomes were immunolabeled for the most abundant vesicular glutamate transporters (VGluT1 and VGluT2) and quantified by flow cytometry and immunoblot methods. In post-mortem parietal cortex from aged control subjects, glutamatergic boutons are fairly abundant as approximately 40% were immunoreactive for VGluT1 (37%) and VGluT2 (39%). However, the levels of these specific markers of glutamatergic synapses were not significantly different among control and AD cases. To test the hypothesis that Aβ is associated with excitatory terminals, AD synaptosomes were double-labeled for Aβ and for VGluT1 and VGluT2, and analyzed by flow cytometry and confocal microscopy. Our study demonstrated that Aβ immunoreactivity (IR) was present in glutamatergic terminals of AD patients. Quantification of Aβ and VGluT1 in a large population of glutamatergic nerve terminals was performed by flow cytometry, showing that 42% of VGluT1 synaptosomes were immunoreactive for Aβ compared to 9% of VGluT1 synaptosomes lacking Aβ-IR. Percentage of VGluT2 synaptosomes immunoreactive for Aβ (21%) was significantly higher than VGluT2 synaptosomes lacking Aβ-IR (9%). Moreover, Aβ preferentially affects VGluT1 (42% positive) compared to VGluT2 terminals (21%). These data represent the first evidence of high levels of Aβ in excitatory boutons in AD cortex and support the hypothesis that Aβ may play a role in modulating glutamate transmission in AD terminals. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis.

    PubMed

    Mortaz, Esmaeil; Rezayat, Fatemeh; Amani, Davar; Kiani, Arda; Garssen, Johan; Adcock, Ian M; Velayati, Aliakbar

    2016-08-01

    Sarcoidosis is a systemic granulomatous disorder of unidentified etiology, with a heterogeneous clinical presentation. It is characterized by a reduced delayed-type hypersensitivity to tuberculin and common antigens. The balance between Th1, Th17 and Regulatory T(Treg) cells controls T-cell proliferation and activation.The Th17/Treg ratio in the peripheral blood and bronchoalveolar lavage fluidis increased in patients with active sarcoidosis. Amplified IL-17A expression in granulomas and the presence of IL-17A+, IL-17A+IL-4+ and IL-17A+IFN-γ+ memory T helper cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction and/or maintenance in sarcoidosis. Sarcoidosis should therefore be considered as a Th1/Th17 multisystem disorder and anti-IL-17/Th17 approaches that control and reduce IL-17Amay be an option, therefore, for the treatment of sarcoidosis.Here we provide a short overview as to the role of Th17 cells as critical cells in the pathogenesis of sarcoidosis.

  15. Therapeutic targeting of HES1 transcriptional programs in T-ALL

    PubMed Central

    Schnell, Stephanie A.; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Belver, Laura; Xu, Luyao; Qin, Yue; Kageyama, Ryoichiro

    2015-01-01

    Oncogenic activation of NOTCH1 signaling plays a central role in the pathogenesis of T-cell acute lymphoblastic leukemia, with mutations on this signaling pathway affecting more than 60% of patients at diagnosis. However, the transcriptional regulatory circuitries driving T-cell transformation downstream of NOTCH1 remain incompletely understood. Here we identify Hairy and Enhancer of Split 1 (HES1), a transcriptional repressor controlled by NOTCH1, as a critical mediator of NOTCH1-induced leukemogenesis strictly required for tumor cell survival. Mechanistically, we demonstrate that HES1 directly downregulates the expression of BBC3, the gene encoding the PUMA BH3-only proapoptotic factor in T-cell acute lymphoblastic leukemia. Finally, we identify perhexiline, a small-molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1-induced leukemias in vitro and in vivo. PMID:25784680

  16. 26 CFR 1.181-1T - Deduction for qualified film and television production costs (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Deduction for qualified film and television... and Corporations (continued) § 1.181-1T Deduction for qualified film and television production costs... film or television production (as defined in § 1.181-3T(b)) that the owner reasonably expects will be...

  17. [TNF-α, diabetes type 1 and regulatory T cells].

    PubMed

    Ryba, Monika; Myśliwska, Jolanta

    2010-01-01

    Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

  18. Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma

    PubMed Central

    Ome, Yusuke; Hashida, Kazuki; Yokota, Mitsuru; Nagahisa, Yoshio; Okabe, Michio; Kawamoto, Kazuyuki

    2017-01-01

    AIM To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC). METHODS We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach. RESULTS The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence. CONCLUSION LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results. PMID:28465640

  19. Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma.

    PubMed

    Ome, Yusuke; Hashida, Kazuki; Yokota, Mitsuru; Nagahisa, Yoshio; Okabe, Michio; Kawamoto, Kazuyuki

    2017-04-14

    To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC). We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach. The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence. LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results.

  20. Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

    PubMed Central

    Franco, Christopher B.; Scripture-Adams, Deirdre D.; Proekt, Irina; Taghon, Tom; Weiss, Angela H.; Yui, Mary A.; Adams, Stephanie L.; Diamond, Rochelle A.; Rothenberg, Ellen V.

    2006-01-01

    PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment. PMID:16880393