Faculty Bibliography

Taste and smell are fundamental sensory systems essential in nutrition and food selection, for the hedonic and sensory experience of food, for efficient metabolism, and, in general, for the maintenance of a good quality of life. The gustatory and olfactory systems demonstrate a diversity of transduction mechanisms, and during the last decade, considerable progress has been made toward our understanding of the basic mechanisms of taste and smell. Understanding normal chemosensory function helps clarify the molecular events that underlie taste and smell disorders. At least 2,000,000 Americans suffer from chemosensory disorders--a number that is likely to grow as the aging segment of the population increases. Smell disorders are more frequent than taste disturbances, due to the vulnerability and anatomical distinctiveness of the olfactory system, and because a decline in olfactory function is part of the normal aging process. Common gustatory and olfactory complaints are due to a number of medications, to upper respiratory infections, to nasal and paranasal sinus diseases, and to damage to peripheral nerves supplying taste and smell. Most chemosensory complaints have an identifiable cause. Although diagnosis of taste and smell disorders has improved considerably over the last two decades, treatment of these disorders is still limited to conditions with discernible and reversible causes. Future research is needed for a better understanding of chemosensory mechanisms, establishing improved diagnostic procedures, and disseminating knowledge on chemosensory disorders among practitioners and the general public

Protein kinase A- (PKA-) catalyzed phosphorylation of phospholamban (PLN), the protein regulator of the cardiac Ca pump, mediates abbreviation of systole in response to beta-adrenergic agonists. Investigators previously, however, have been unsuccessful in demonstrating an effect of PLN phosphorylation or anti-PLN monoclonal antibody (mAb), which is considered to mimic phosphorylation's well-known effect on Km(Ca), on microsomal Ca uptake at the (high) Ca2+ concentrations found intracellularly at peak systole. We therefore compared the effects of the catalytic subunit of PKA and anti-PLN mAb on the kinetics of Ca uptake in sucrose gradient-purified cardiac microsomes. Both treatments produced a 33-44% increase in Vmax(Ca) at 25 and 37 degrees C, and an 11-31% decrease in Km(Ca) with comparable changes in Ca2+-ATPase activity. An acceleration of E2P decomposition upon PLN phosphorylation may contribute to the increased Vmax(Ca) of Ca uptake at 25 degrees C but not at 37 degrees C, based on measurement of the kinetics of E2P decomposition and steady-state E2P formation from Pi at different temperatures. Our data document almost identical increases in Vmax(Ca) of microsomal Ca uptake with PLN phosphorylation or addition of anti-PLN mAb and hence provide insight into the kinetic mechanism of PLN's regulation of the cardiac sarcoplasmic reticulum Ca pump protein

The widespread use of actigraphy has led to the recognition that a number of methodological issues have to be addressed to facilitate an increased acceptability of this relatively new method. These methodological issues include actigraph placement, reliability, and sensitivity, and the phenomenon known as the "first night effect." Our findings have demonstrated that actigraphy is a reliable instrument for assessment of sleep and wakefulness. In addition, actigraph placement and reliability do not constitute a significant methodological problem as no differences were found in all of these studies. We have also observed no first-night effects associated with sleep-wake monitoring with actigraphy.

Decades of empirical observations have established the validity of actigraphy primarily in individuals without sleep disorders. Methodological problems encountered thus far coupled with the widespread use of actigraphy signal the need for concentrated efforts to establish a consensus regarding scoring procedures. Currently available scoring methods show less reliability in clinical populations. To address these issues two validation studies were conducted: one for individuals without sleep disorders and the other for patients diagnosed with insomnia. The results of these two studies using the Actigraph Data Analysis Software as the scoring method have shown that the described system is fairly precise. It can be used for actigraphs with different features and mode of operation and is applicable to individuals with insomnia. These findings corroborate previous research showing that actigraphy is a valid instrument for assessment of sleep and wakefulness.

Regulation of the calcium pump of the cardiac sarcoplasmic reticulum by phosphorylation/dephosphorylation of phospholamban is central to the inotropic and lusitropic effects of beta-adrenergic agonists on the heart. In order to study the mechanism of this regulation, we first obtained purified ruthenium red-insensitive microsomes enriched in sarcoplasmic reticulum membranes. The kinetics of microsomal Ca2+ uptake after phospholamban phosphorylation or trypsin treatment, which cleaves the inhibitory cytoplasmic domain of phospholamban, were then compared with those in the presence of jasmone, whose effects on the kinetics of fast skeletal muscle Ca2+-ATPase are largely known. All three treatments increased Vmax (Ca) at 25 degrees C and millimolar ATP; phosphorylation and trypsin decreased the Km (Ca), while jasmone increased it. Trypsin and jasmone increased the rate of E2P decomposition 1.8- and 3. 0-fold, respectively. The effects of phospholamban phosphorylation and jasmone on the Ca2+-ATPase activity paralleled their effects on Ca2+ uptake. Our data demonstrate that phospholamban regulates E2P decomposition in addition to the known increase in the rate of a conformational change in the Ca2+-ATPase upon binding the first of two Ca2+. These steps in the catalytic cycle of the Ca2+-ATPase may contribute to or account for phospholamban's effects on both Vmax (Ca) and Km (Ca), whose relative magnitude may vary under different experimental and, presumably, physiological conditions

Halitosis is caused primarily by bacterial putrefaction and the generation of volatile sulfur compounds. Ninety percent of patients suffering from halitosis have oral causes, such as poor oral hygiene, periodontal disease, tongue coat, food impaction, unclean dentures, faulty restorations, oral carcinomas, and throat infections. The remaining 10 percent of halitosis sufferers have systemic causes that include renal or hepatic failure, carcinomas, diabetes or trimethylaminuria. Modern analytical and microbiological techniques permit diagnosis of bad breath. Management of halitosis involves maintaining proper oral hygiene, and periodontal treatment, including tongue brushing

To address the glaring problems of disparity in oral health and representation in the manpower pool of oral health researchers, the National Institute for Dental Research (NIDR) of the National Institutes of Health established Regional Research Centers for Minority Oral Health. The Minority Oral Health Research Center at New York University College of Dentistry, a collaboration between the college and the Fosyth Dental Center, is one of four centers established by the NIDR in the United States to improve oral health for all Americans and to enhance accessibility of research careers for minority individuals. This article describes the center's progress to date, expected outcomes and its call for partners to improve minority oral health.

Current evidence has shown that, overall, actigraphy is an excellent tool for unobtrusive documentation of sleep/wake activity in normal individuals. However, a number of methodological issues remain to be resolved to warrant its use in clinical research. In this paper, we report the results of a study aimed at the development of a new scoring software that can accurately identify sleep and wakefulness. Using total sleep time as an index of comparison, the software was optimized on a calibration sample and prospectively tested on a validation sample. A strong correlation coefficient (r = 0.93, p < 0.008), with an average discrepancy value of 10 minutes, was observed for the calibration sample. The application of the optimal software to the validation sample revealed an even higher correlation coefficient (r = 0.97, p < 0.0001), with an average discrepancy value of 12 minutes.

Certain eukaryotic cells can sense changes in their extracellular Ca2+ concentration through molecular structures termed Ca(2+)-sensing receptors (CaRs). We have shown recently that in the bone-resorbing osteoclast, a unique cell surface-expressed ryanodine receptor (RyR), functions as the CaR. The present study demonstrates that the sensitivity of this receptor is modulated by physiological femtomolar concentrations of the bone-conserving hormone, calcitonin. Calcitonin was found to inhibit cytosolic Ca2+ responses to both Ca2+ and Ni2+. The latter inhibition was mimicked by amylin (10(-12) M), calcitonin gene-related peptide (10(-12) M), cholera toxin (5 micrograms/l) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (2.5 x 10(-4) or 5 x 10(-4) M) and was reversed by the protein kinase A phosphorylation inhibitor, IP-20. Finally, using a quench flow module, we showed that cellular cAMP levels rise to a peak within 25 ms of calcitonin application; this is consistent with the peptide's rapid effect on CaR activation. We conclude, therefore, that cAMP plays a critical role in the control of CaR function by calcitonin