Faculty Bibliography

The Ig cell adhesion molecules (CAM) neurofascin (NF) and Nr-CAM are localized at developing nodes of Ranvier in peripheral myelinated axons prior to clustering of Na(+) channels. Different isoforms of NF are expressed on neurons and glia, and NF binding on both cells has been suggested to play roles in node and paranode formation. To clarify the role of NF further, we analyzed effects of NF-Fc fusion proteins in Schwann cell-DRG neuron myelinating cocultures. NF-Fc significantly inhibited nodal clustering of Na(+) channels, ankyrin(G), and betaIV spectrin, and modestly reduced Caspr clustering at paranodal junctions; it did not significantly affect lengths or numbers of myelin-positive segments, axon initial segments, or accumulations of phosphorylated-ERM proteins in Schwann cell nodal microvilli. NF-Fc binds to Schwann cells but little or no binding to DRG neurons was detected. The results suggest a critical early role for axonal NF in clustering of Na(+) channels at nodes of Ranvier via interactions with receptors on Schwann cells

Adenoid cystic carcinoma is an indolent, slow-growing tumor that may first cause low-grade pain in the affected region. This article describes a case involving adenoid cystic carcinoma of the maxilla that was present for approximately nine years. Prior to diagnosis, five dentists reported that the patient had anisocoria, migraine headaches, and low-to-moderate upper jaw pain that was refractory to conventional therapy. A surgical resection was performed; after a period of soft tissue healing, radiation therapy was initiated. The surgical defect was obturated using an interim removable prosthesis while awaiting final reconstruction by a maxillofacial prosthodontist. This article examines possible reasons why this lesion was not diagnosed sooner and discusses how this case should raise the general dentist's awareness of such lesions

Sensory information is encoded by populations of neurons. The responses of individual neurons are inherently noisy, so the brain must interpret this information as reliably as possible. In most situations, the optimal strategy for decoding the population signal is to compute the likelihoods of the stimuli that are consistent with an observed neural response. But it has not been clear how the brain can directly compute likelihoods. Here we present a simple and biologically plausible model that can realize the likelihood function by computing a weighted sum of sensory neuron responses. The model provides the basis for an optimal decoding of sensory information. It explains a variety of psychophysical observations on detection, discrimination and identification, and it also directly predicts the relative contributions that different sensory neurons make to perceptual judgments

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development

OBJECTIVE: We optimized a time-resolved 3D contrast-enhanced MR angiography sequence with integrated parallel imaging technique that can provide a large field of view with high temporal and spatial resolution, by which the hemodialysis access and the entire course of the inflow and outflow vessels can be imaged at a single anatomic station. Our objective was to evaluate the feasibility and usefulness of this method in the evaluation of patients referred for possible abnormalities in hemodialysis access. CONCLUSION: Time-resolved contrast-enhanced 3D MR angiography with parallel imaging has the potential to provide a rapid and comprehensive evaluation for the surveillance and diagnosis of hemodialysis access malfunctions. This technique may function as an important complement to conventional digital subtraction angiography and may be able to help guide medical management. The MR angiography protocol we present is a noninvasive, versatile, and time-efficient technique, without the need of direct graft puncture or flow interruption, and can be performed using a single injection of contrast material at a single station

Mutations in eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, childhood ataxia with CNS hypomyelination/vanishing white matter disease or CACH/VWM. Patients may develop a wide spectrum of neurological abnormalities from prenatal-onset white matter disease to juvenile or adult-onset ataxia and dementia, sometimes with ovarian insufficiency. The pattern of diffuse white matter abnormalities on MRI of the head is often diagnostic. Neuropathological abnormalities indicate a unique and selective disruption of oligodendrocytes and astrocytes with sparing of neurons. Marked decrease of asialo-transferrin in cerebrospinal fluid is the only biochemical abnormality identified thus far. Eukaryotic translation initiation factor 2B (eIF2B) mutations cause a decrease in guanine nucleotide exchange activity on eIF2-GDP, resulting in increased susceptibility to stress and enhanced ATF4 expression during endoplasmic reticulum stress. eIF2B mutations are speculated to lead to increased susceptibility to various physiological stress conditions. Future research will be directed towards understanding why abnormal control of protein translation predominantly affects brain glial cells.

Acute hypercapnia may develop during periodic breathing from an imbalance between abnormal ventilatory patterns during apnea and/or hypopnea and compensatory ventilatory response in the interevent periods. However, transition of this acute hypercapnia into chronic sustained hypercapnia during wakefulness remains unexplained. We hypothesized that respiratory-renal interactions would play a critical role in this transition. Because this transition cannot be readily addressed clinically, we modified a previously published model of whole-body CO2 kinetics by adding respiratory control and renal bicarbonate kinetics. We enforced a pattern of 8 h of periodic breathing (sleep) and 16 h of regular ventilation (wakefulness) repeated for 20 days. Interventions included varying the initial awake respiratory CO2 response and varying the rate of renal bicarbonate excretion within the physiological range. The results showed that acute hypercapnia during periodic breathing could transition into chronic sustained hypercapnia during wakefulness. Although acute hypercapnia could be attributed to periodic breathing alone, transition from acute to chronic hypercapnia required either slowing of renal bicarbonate kinetics, reduction of ventilatory CO2 responsiveness, or both. Thus the model showed that the interaction between the time constant for bicarbonate excretion and respiratory control results in both failure of bicarbonate concentration to fully normalize before the next period of sleep and persistence of hypercapnia through blunting of ventilatory drive. These respiratory-renal interactions create a cumulative effect over subsequent periods of sleep that eventually results in a self-perpetuating state of chronic hypercapnia.

PURPOSE: To retrospectively assess the usefulness of contrast material-enhanced T1-weighted magnetic resonance (MR) imaging alone and with T2-weighted MR imaging in the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A waiver of informed consent and institutional review board approval for this retrospective study were granted. The study was HIPAA compliant. Twenty-eight men (mean age, 49 years; range, 23-70 years) and 10 women (mean age, 53 years; range, 42-72 years) with cirrhosis underwent T2-weighted and contrast-enhanced T1-weighted MR imaging at 1.5 T within 90 days of liver transplantation. Three readers reviewed the T1-weighted images alone and then the T2-weighted and T1-weighted images together. Lesion detection, characterization, and reader confidence levels were recorded. RESULTS: At liver explantation, 57 lesions were present in 18 patients: 19 HCCs, 33 dysplastic nodules, and five cysts. Contrast-enhanced T1-weighted imaging depicted 13 of 19 HCCs with an overall sensitivity of 68.4% (13 of 19) and specificity of 65.7% (23 of 35). The sensitivity and specificity for detection of dysplastic nodules (sensitivity, 9%; specificity, 68.4%) and HCCs (sensitivity, 68.4%; specificity, 65.7%) were nearly identical for T1-weighted images read alone or read with T2-weighted images. The only difference was the specificity for T1-weighted images read alone (65.7%) and read with T2-weighted images (62.9%). The addition of T2-weighted images altered the diagnosis in one of 90 (1.1%) cases and provided an increase in diagnostic confidence in four of 258 (1.6%) cases for independent readers and three of 90 (3.3%) cases at consensus reading. CONCLUSION: Contrast-enhanced T1-weighted imaging can be used as a stand-alone sequence for the diagnosis of HCC in patients with cirrhosis prior to liver transplantation

A lightweight 32-element MRI receiver-coil array was designed and built for cardiac imaging. It comprises an anterior array of 21 copper rings (75 mm diameter) and a posterior array of 11 rings (107 mm diameter) that are arranged in hexagonal lattices so as to decouple nearest neighbors, and curved around the left side of the torso. Imaging experiments on phantoms and human volunteers show that it yields superior performance relative to an eight-element cardiac array as well as a 32-element whole-torso array for both traditional nonaccelerated cardiac imaging and 3D parallel imaging with acceleration factors as high as 16