Faculty Bibliography

Oral health care professionals could drastically improve the quality of life for patients with potentially malignant oral lesions by using a noninvasive test that could be used to detect cancer using saliva. Promoter DNA hypermethylation is a critical step in oral carcinogenesis and has a number of significant advantages over genetic and protein diagnostic markers. Methylight is a recently developed assay that rapidly quantifies promoter hypermethylation and could potentially be applied into a clinical setting

Neurons in posterior parietal cortex (PPC) may serve both proprioceptive and exteroceptive functions during prehension, signaling hand actions and object properties. To assess these roles, we used digital video recordings to analyze responses of 83 hand-manipulation neurons in area 5 as monkeys grasped and lifted objects that differed in shape (round and rectangular), size (large and small spheres), and location (identical rectangular blocks placed lateral and medial to the shoulder). The task contained seven stages -- approach, contact, grasp, lift, hold, lower, relax -- plus a pretrial interval. The four test objects evoked similar spike trains and mean rate profiles that rose significantly above baseline from approach through lift, with peak activity at contact. Although representation by the spike train of specific hand actions was stronger than distinctions between grasped objects, 34% of these neurons showed statistically significant effects of object properties or hand postures on firing rates. Somatosensory input from the hand played an important role as firing rates diverged most prominently on contact as grasp was secured. The small sphere -- grasped with the most flexed hand posture -- evoked the highest firing rates in 43% of the population. Twenty-one percent distinguished spheres that differed in size and weight, and 14% discriminated spheres from rectangular blocks. Location in the workspace modulated response amplitude as objects placed across the midline evoked higher firing rates than positions lateral to the shoulder. We conclude that area 5 neurons, like those in area AIP, integrate object features, hand actions, and grasp postures during prehension

The aim of this study was to validate the published University of California San Francisco (UCSF) Oral Cancer Pain Questionnaire. To test for validity of the questionnaire, 16 patients with oral cancer completed the 8-item questionnaire immediately before and after treatment (surgical resection) of their oral cancer. For all 8 questions, the difference between mean preoperative and mean postoperative responses were statistically significant (P < .05), confirming the validity of the questionnaire to measure oral cancer pain. Internal consistency of the questionnaire was evaluated by using Cronbach's alpha, which provides an estimate of reliability based on all correlations between the items (questions) of the instrument (questionnaire). In the oral cancer pain questionnaire, questions 1, 3, and 5 evaluate the intensity, sharpness, and throbbing nature of pain when the patient is not engaged in oral function (talking, eating, and drinking). Questions 2, 4, and 6 measure the intensity, sharpness, and throbbing nature of pain during oral function. Cronbach's alpha for questions 1, 3, and 5 is 0.87 and Cronbach's alpha for questions 2, 4, and 6 is 0.94; values greater than 0.7 indicate reliability. In this study, we have validated the UCSF Oral Cancer Pain Questionnaire as an effective tool in quantifying pain from oral cancer. PERSPECTIVE: The study validates an oral cancer pain questionnaire. The questionnaire can be used to reliably measure pain levels before and after surgical resection in patients with oral cancer

BACKGROUND: Dysfunction of basocortical cholinergic projection neurons of the nucleus basalis (NB) correlates with cognitive deficits in Alzheimer disease (AD). Nucleus basalis neurons receive cholinergic inputs and express nicotinic acetylcholine receptors (nAChRs) and muscarinic AChRs (mAChRs), which may regulate NB neuron activity in AD. Although alterations in these AChRs occur in the AD cortex, there is little information detailing whether defects in nAChR and mAChR gene expression occur in cholinergic NB neurons during disease progression. OBJECTIVE: To determine whether nAChR and mAChR gene expression is altered in cholinergic NB neurons during the progression of AD. DESIGN: Individual NB neurons from subjects diagnosed ante mortem as having no cognitive impairment (NCI), mild cognitive impairment (MCI), or mild to moderate AD were analyzed by single-cell AChR expression profiling via custom-designed microarrays. SETTING: Academic research. PARTICIPANTS: Participants were members of the Rush Religious Orders Study cohort. MAIN OUTCOME MEASURES: Real-time quantitative polymerase chain reaction was performed to validate microarray findings. RESULTS: Cholinergic NB neurons displayed a statistically significant up-regulation of alpha7 nAChR messenger RNA expression in subjects with mild to moderate AD compared with those with NCI and MCI (P<.001). No differences were found for other nAChR and mAChR subtypes across the cohort. Expression levels of alpha7 nAChRs were inversely associated with Global Cognitive Score and with Mini-Mental State Examination performance. CONCLUSIONS: Up-regulation of alpha7 nAChRs may signal a compensatory response to maintain basocortical cholinergic activity during AD progression. Alternatively, putative competitive interactions of this receptor with beta-amyloid may provide a pathogenic mechanism for NB dysfunction. Increasing NB alpha7 nAChR expression may serve as a marker for the progression of AD.

This review focuses on the current findings regarding interaction between amyloid beta peptide (Abeta) and receptor for advanced glycation endproducts (RAGE) and its roles in the pathogenesis of Alzheimer's disease (AD). As a ubiquitously expressed cell surface receptor, RAGE mediates the effects of Abeta on microglia, blood-brain barrier (BBB) and neurons through activating different signaling pathways. Data from autopsy brain tissues, in vitro cell cultures and transgenic mouse models suggest that Abeta-RAGE interaction exaggerates neuronal stress, accumulation of Abeta, impaired learning memory, and neuroinflammation. Blockade of RAGE protects against Abeta-mediated cellular perturbation. These findings may have an important therapeutic implication for neurodegenerative disorders relevant to AD.

OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) has been increasingly used to examine striatal neurochemistry in adult major depressive disorder. This study extends the use of this modality to pediatric major depression to test the hypothesis that adolescents with major depression have elevated concentrations of striatal choline and creatine and lower concentrations of N-acetylaspartate. METHOD: Fourteen adolescents (ages 12-19 years, eight female) who had major depressive disorder for at least 8 weeks and a severity score of 40 or higher on the Children's Depression Rating Scale-Revised and 10 healthy comparison adolescents (six female) group-matched for gender, age, and handedness were enrolled. All underwent three-dimensional 3-T (1)H-MRS at high spatial resolution (0.75-cm(3) voxels). Relative levels of choline, creatine, and N-acetylaspartate in the left and right caudate, putamen, and thalamus were scaled into concentrations using phantom replacement, and levels were compared for the two cohorts. RESULTS: Relative to comparison subjects, adolescents with major depressive disorder had significantly elevated concentrations of choline (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left caudate. No other neurochemical differences were observed between the groups. CONCLUSIONS: These findings most likely reflect accelerated membrane turnover and impaired metabolism in the left caudate. The results are consistent with prior imaging reports of focal and lateralized abnormalities in the caudate in adult major depression

Using functional magnetic resonance imaging and an experimental paradigm of instructed fear, we observed a striking pattern of decreased activity in primary motor cortex with increased activity in dorsal basal ganglia during anticipation of aversive electrodermal stimulation in 42 healthy participants. We interpret this pattern of activity in motor neurocircuitry in response to cognitively-induced fear in relation to evolutionarily-conserved responses to threat that may be relevant to understanding normal and pathological fear in humans