Olfactory Receptor Database: a database of the largest eukaryotic gene family.

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that stores data on Olfactory Receptor-like molecules (ORs) and has been open to the public since June 1996. It contains a public and a private area. The public area includes published DNA and protein sequence data for ORs, links to OR models and data on their expression, chromosomal localization and source organism, as well as (i) links to bibliography through PubMed and (ii) interactive WWW-based tools, such as BLAST homology searching. The private area functions as a service to laboratories that are actively cloning receptors. Source laboratories enter the sequences of the receptor clones they have characterized to the private database and can search for identical or near identical OR sequences in both public and private databases. If another laboratory has cloned and deposited an identical or closely matching sequence there are means for communication between the laboratories to help avoid duplication of work. ORDB is available via the WWW at http://crepe.med.yale.edu/ORDB/HTML

The Human Brain Project: neuroinformatics tools for integrating, searching and modeling multidisciplinary neuroscience data.

What is neuroinformatics? What is the Human Brain Project? Why should you care? Supported by a consortium of US funding agencies, the Human Brain Project aims to bring to the analysis of brain function the same advantages of Internet-accessible databases and database tools that have been crucial to the development of molecular biology and the Human Genome Project. The much greater complexity of neural data, however, makes this a far more challenging task. As a pilot project in this new initiative, we review some of the progress that has been made and indicate some of the problems, challenges and opportunities that lie ahead.

Database tools for integrating and searching membrane property data correlated with neuronal morphology.

A critical problem in neuroscience is the lack of database tools for integrating neuronal property data. We report here the development of a combined object oriented-relational database (NeuronDB, http://senselab.med.yale.edu/neurondb) that meets these needs by providing tools for integrating data within neurons and comparing data across neurons. It focuses on three types of neuronal properties voltage-gated channels, neurotransmitter receptors, and neurotransmitters. The data are organized in relation to different regions of neurons as represented in canonical forms; using simple canonical models of complex cells as a vehicle for indexing information permits the database to be searchable across different neurons. Using these multidimensional search tools, users can locate specific properties in specific regions of a neuron; obtain integrated summaries of all properties within a region; and carry out searches to compare properties across equivalent compartments in different neurons. These tools thus permit searches of the multidimensional neuron property space equivalent to homology searches of sequence databases. NeuronDB is accessible over the Internet; it provides immediate links to citation indexes and abstracts supporting the deposited data, and annotations that indicate the state of acceptance of the data. Users are encouraged to contribute data. The ability to input the data from NeuronDB directly to NEURON and GENESIS is being developed. As a shared Web resource, NeuronDB should enhance the efforts of neuroscientists and neuronal modellers to analyze and compare the functional operations of different types of neurons.

Olfactory receptor database (ORDB): a resource for sharing and analyzing published and unpublished data.

An olfactory receptor database (ORDB) is being developed to facilitate analysis of this large gene family. ORDB currently contains over 400 olfactory receptor sequences and related information, and is available via the World Wide Web. We plan to incorporate functional data, structural models, spatial localization and other categories of information, toward an integrated model of olfactory receptor function.

Incidence and significance of noncytomegalovirus viral respiratory infection after adult lung transplantation.

Lower respiratory tract infection is a major cause of morbidity and death after lung transplantation. The incidence and significance of noncytomegalovirus viral respiratory tract infections has not been reported to date. We report our center's experience with these infections.

ModelDB: an environment for running and storing computational models and their results applied to neuroscience.

Research groups within the Human Brain Project are developing technologies to help organize and make accessible the vast quantities of information being accumulated in the neurosciences. The goal of this work is to provide systems that enable this complex information from many diverse sources to be synthesized into a coherent theory of nervous system function. Our initial approach to this problem has been to create several small databases. While addressing the issues of each individual database, we are also considering how each might be incorporated into an integrated cluster of databases. In this paper, we describe a pilot project in which we construct a database of computational models of neuronal function. This database allows models to be created and run and their results reviewed through a World Wide Web interface. Because models encapsulate knowledge in a formal manner about how neuronal systems function, we also discuss how this database forms a natural center for our initial attempts at creating a cluster of related databases. General issues of database development in the context of the Web are also discussed.

Drug-mineral interactions: a new responsibility for the hospital dietitian.

Recent hospital accreditation guidelines encourage hospital dietitians to monitor patient drug therapy and provide education regarding drug-food interactions. However, information concerning these interactions is lacking, even though they can occur frequently. Minerals in foods can complex with drugs and/or alter the gastrointestinal environment to affect the normal absorption processes of drugs and minerals. There are three types of drug-mineral interactions: (a) malabsorption of the mineral and/or drug; (b) mineral depletion and retention; and (c) drug-mineral interactions induced by simultaneous antacid ingestion. It is recommended that oral drugs be administered on an empty stomach 1 hour before or 2 hours after a meal and at least 2 hours before or after antacid use. A small snack of refined carbohydrates with low nutrient density can be consumed with drugs that cause gastric upset when given on an empty stomach.

Inhibition of calcium by magnesium in the contraction of rat aortic smooth muscle. I. Mathematical model of calcium and magnesium binding.

A mathematical model of the effect of calcium and magnesium binding on muscle tension was developed. The model was tested on aortic smooth muscle tissue obtained from rats fed magnesium-sufficient (Mg: 650 ppm) and magnesium-deficient (Mg: 4.5 ppm) diets. Ca2+ binding constants of 2.51 X 10(3) and 2.3 X 10(3) M-1 were obtained for aortae from magnesium-sufficient and magnesium-deficient rats, respectively. The corresponding Mg2+ binding constants were 0.6 X 10(3) and 0.4 X 10(3) M-1. The data indicate that Mg2+ is a competitive inhibitor of Ca2+ in tension development in rat aortic smooth muscle tissue.

Effects of long-term therapy with calcitriol in patients with moderate renal failure.

Since abnormalities in divalent ion metabolism occur early in renal insufficiency, treatment of patients with moderate renal failure with calcitriol could halt and/or reverse these disturbances. The effects of long-term treatment with calcitriol (0.5 microgram/day) in three such patients were evaluated. Serum calcium level rose from 0.3 to 0.7 mg/dL. Blood parathyroid hormone levels were mildly elevated and fell to normal. Intestinal absorption of calcium increased. The patients had hypocalciuria and the urinary calcium level increased. Creatinine clearance remained stable in all patients. Iliac crest biopsy specimens obtained after double tetracycline hydrochloride labeling revealed mild osteomalacia and hyperparathyroid bone disease that healed after therapy. The data show that a small dose of calcitriol is safe and effective for the management of the derangements of divalent ion metabolism in patients with moderate renal failure.

Total parenteral nutrition in the management of acute renal failure.

Malnutrition is frequently present in patients with acute renal failure and may affect morbidity and mortality in this condition. When adequate nourishment cannot be given through the gastrointestinal tract, total parental nutrition with amino acids and hypertonic glucose may have beneficial results. Total parenteral nutrition has been reported to stabilize or reduce serum urea nitrogen, potassium and phosphorus levels, improve wound healing, enhance survival from acute renal failure, and possibly increase the rate of recovery of renal function. The optimal composition of the total parenteral nutrition infusate is unknown. Preliminary results of a double-blind study are reported in which one man received hypertonic glucose alone, two received glucose with essential amino acids (21 g/day), and three received glucose with essential (21 g/day) and nonessential (21 g/day) amino acids. All infusates were isocaloric. No differences were observed in serum urea nitrogen levels, serum urea nitrogen/creatinine ratios or urea appearance rates. Nitrogen balance was negative in all patients. The ratio of essential amino acids/nonessential amino acids were higher and the tyrosine/phenylalanine ratios were lower in plasma in the two patients receiving glucose with essential amino acids. No patient survived the hospitalization. In view of the markedly negative nitrogen balance frequently observed in these and earlier studies, the use of a different composition or quantity of amino acids, a higher energy intake, and anabolic hormones deserve further investigation.

The influence of reserpine on the responsiveness to norepinephrine and electrolyte contents of rabbit atria.

This study was designed to investigate the relationships between reserpine-induced supersensitivity and electrolyte levels in isolated rabbit atria. Atria from reserpine-treated (1, 3 or 4 mg/kg 24 hr before) and untreated rabbits were placed in an isolated organ bath for determination of dose-response relationships for norepinephrine, or were used for electrolyte assay. Reserpine-treated atria had greater resting and maximum rates of beat than did untreated atria. However, the ED50 concentrations of norepinephrine producing a rate response were similar. Atria pretreated with 1 or 3 mg/kg reserpine were supersensitive to the inotropic effect of norepinephrine. 4 mg/kg reserpine did not induce inotropic supersensitivity. Atrial sodium contents were significantly increased by 3 mg/kg reserpine. Potassium contents were increased by 1 and 4 mg/kg reserpine. Calcium contents were significantly decreased by 4 mg/kg reserpine, while magnesium contents were increased by 1 and 4 mg/kg. Reserpine induced supersensitivity to the inotropic effects of norepinephrine but did not alter the sensitivity to the chronotropic effect of the drug. This supersensitivity may be linked to alterations in the tissue's homeostatic mechanisms for calcium.