A new perspective for nutrition: the health connection.

The science of nutrition has undergone a major transformation in its objectives and approaches because of the influence of new understanding in epidemiology of oral diseases in technically developed countries, as well as in developing countries with different environmental circumstances. Recent findings of biochemical, immunological, and molecular biology investigations related to oral tissues have also added a new health dimension to this understanding. The major challenge ahead is not only to continue to expand the available scientific information, but to recognize the role that nutrition has for oral tissues, which is no different than the one it has for other tissues and organ systems.

Mechanisms of defibrillation. Critical points and the upper limit of vulnerability.

The upper limit of vulnerability hypothesis for defibrillation states that a successful defibrillation shock must both stop the fibrillation wave fronts on the heart at the time that the shock is delivered and not start new wave fronts that will lead to reentrant circuits being formed, causing the heart to refibrillate. Mapping studies have demonstrated that defibrillation shocks can halt all wave fronts on the heart but fibrillation will begin again with an initial activation pattern that is different from the activation pattern on the heart just before the shock is delivered. In a fashion similar to the reinitiation of fibrillation following a failed defibrillation shock, properly sized and timed shocks can be delivered to the heart during paced rhythm to induce functional reentry that will initiate fibrillation.

Molecular biophysics of elastin structure, function and pathology.

Owing to the presence of the recurring sequence XPGX' (where X and X' are hydrophobic residues), the molecular structure of the sequences between cross-links in elastin is viewed primarily as a series of beta-turns which become helically ordered by hydrophobic folding into beta-spirals, which in turn assemble hydrophobically into twisted filaments. Both hydrophobic folding and assembly occur when the temperature is raised above Tt, the onset of an inverse temperature transition. Using poly[fv(VPGVG),fx(VPGXG)] (where fv and fx are mole fractions with fv + fx = 1 and X is now any of the naturally occurring amino acid residues), plots of fx versus Tt result in a new hydrophobicity scale based directly on the hydrophobic folding and assembly processes of interest.

Neonatal genistein chemoprevents mammary cancer.

We have investigated the potential of genistein, an estrogenic component of soy, when administered neonatally, to manifest a protective effect against chemically induced mammary cancer. Female Sprague-Dawley rats were treated on Day 2, 4, and 6 postpartum with genistein or dimethylsulfoxide (vehicle). To induce mammary carcinogenesis, all animals were subsequently exposed on Day 50 postpartum to dimethylbenz(a)anthracene.

Effects of speaking rate changes on native and nonnative speech production.

Twenty monolingual English speakers and 40 native Spanish speakers, who were either relatively proficient or nonproficient in English, produced English /p/ at self-selected normal and fast speaking rates. The native English (NE) subjects showed much the same rate effect on voice onset time (VOT) seen in earlier studies. Native Spanish (NS) subjects who were relatively proficient in pronouncing English used fewer short-lag stops and showed an English-like rate effect on VOT.

Insulin delivery in nosedrops: new formulations containing alkylglycosides.

Insulin was administered to rats via nosedrops in the presence or absence of various alkylglycosides; systemic insulin absorption was measured as a fall in blood D-glucose concentration in animals made hyperglycemic by xylazine/ketamine anesthesia. Nosedrops (0.04 ml) containing alkylglycosides or regular porcine insulin alone were without effect.

Liver, renal and subcutaneous histopathology in PEPCK-bGH transgenic pigs.

Transgenic pigs were created that harboured a phosphoenolpyruvate carboxykinase-bovine growth hormone construct (PEPCK-bGH). Four founder animals and two transgenic offspring from one line were evaluated between 6 1/2 and 12 months of age. There was no evidence of severe hepatic or renal lesions in these pigs, which characterised transgenic PEPCK-bGH mice previously described.

Inhibition of smooth muscle cell growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP.

Recent studies indicate that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cGMP) may inhibit the proliferation of vascular smooth muscle cells (SMC) in vitro. The purpose of this study was to investigate the mechanism of NO- and cGMP-dependent inhibition of cultured rat aortic SMC. The cytokine interleukin-1 beta (IL-1 beta) inhibited serum- and platelet-derived growth factor-stimulated [3H]thymidine incorporation into DNA in subcultured rat aortic SMC.

Increased protein kinase C and isozyme redistribution in pressure-overload cardiac hypertrophy in the rat.

Protein kinase C (PKC) activity and isozyme distribution were evaluated during development of pressure-overload-induced cardiac hypertrophy. Three-week-old rats were loosely banded on the ascending aorta (left ventricular hypertrophy [LVH] group). Two weeks later, when left ventricular mass was 50% greater than in the sham-operated control group and cardiac mass was still rapidly increasing beyond that of normal growth, PKC activity and [3H]phorbol 12,13-dibutyrate (PDBu) binding capacity were determined.

Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a chemically defined system.

Transforming growth factor-beta (TGF-beta) is a potent growth regulatory protein normally secreted by cells in a latent form. Primary regulation of TGF-beta activity occurs through factors which control the processing of the latent to the biologically active molecule. Thrombospondin (TSP), a platelet alpha-granule and extracellular matrix protein, forms specific complexes with active TGF-beta in platelet releasate and activates endogenous latent TGF-beta secreted by endothelial cells via a cell- and protease-independent mechanism.

Electromechanical transduction: reduction-driven hydrophobic folding demonstrated in a model protein to perform mechanical work.

It has long been appreciated that hydrophobic folding is an important element of protein structure formation. Here it is demonstrated for the first time that the electrochemical or chemical reduction of a nicotinamide in a model protein, which increases hydrophobicity, can drive hydrophobic folding and assembly in such a way as to lift a weight or otherwise contract against a constant tensional force. The model protein, poly[0.

Molecular cloning and characterization of the mouse medium-chain acyl-CoA dehydrogenase cDNA.

Medium-chain acyl-CoA dehydrogenase (MCAD) is one of the three straight-chain length-specific dehydrogenases involved in the first step of fatty acid oxidation. Inherited defects of acyl-CoA dehydrogenases occur in humans, and MCAD deficiency is the most common. We have cloned the coding and 3' untranslated sequence of mouse MCAD cDNA.

Nanometric design of extraordinary hydrophobic-induced pKa shifts for aspartic acid: relevance to protein mechanisms.

Commonly a key element enabling proteins to function is an amino acid residue or residues with functional side chains having shifted pKa values. This article reports the results on a set of protein-based polymers (model proteins) that exhibit hydrophobic folding and assembly transitions, and that have been designed for the purpose of achieving large hydrophobic-induced pKa shifts by selectively replacing Val residues by Phe residues. The high molecular weight polypentapeptides, actually poly(tricosapeptides) with six varied pentamers in fixed sequence, were designed and synthesized to have the same amino acid compositions but different proximities between a single aspartic acid residue and 5 Phe residues per 30 residues.

Fibrillin and elastin networks in extrafusal tissue and muscle spindles of bovine extraocular muscles.

Purpose: Bovine extraocular rectus muscles were examined to map the distribution of elastin and fibrillin in extrafusal tissue and muscle spindles.

Methods: Immunohistochemical techniques and immunolocalization were employed to pin-point the placement of molecules relative to muscle fibers.

Results: Strands containing elastin and fibrillin surrounded all extrafusal fibers.

Salt-induced hypertension in normotensive spontaneously hypertensive rats.

Lifetime treatment with oral captopril prevents the development of hypertension in spontaneously hypertensive rats (SHR). We tested the hypothesis that this treatment also prevents the hypertensive response that occurs when untreated NaCl-sensitive SHR are placed on a high NaCl diet. Female SHR were continuously treated with oral captopril before conception and throughout lactation, and the offspring were similarly treated with oral captopril throughout life.

Ultrastructure of developing kidney glomerular basement membranes: temporal changes in binding of anti-laminin IgG and cationized ferritin.

In vivo labeling of infant rat and mouse glomerular basement membranes (GBMs) with polyclonal anti-laminin IgGs results in binding across the full widths of GBMs at all stages of development. These stages include the pre-fusion, double basement membranes found beneath endothelial cells and podocytes in early glomeruli, and the subepithelial matrix outpockets where newly synthesized GBM is spliced into fused basement membrane during glomerular maturation. Identical binding results are obtained either with peroxidase or post-embedding immunogold techniques.

Assessing adherence to asthma medication and inhaler regimens: a psychometric analysis of adult self-report scales.

Poor adherence to recommended regimens is a substantial problem in the clinical management of adults with asthma and other chronic diseases. Research on adherence assessment is complicated by methodological difficulties including limitations associated with the use of self-report measures. In this study, psychometric techniques were used to analyze two self-report scales for assessing adherence to recommended medication and inhaler use regimens in adults with asthma.

Neurologic consequences of hypertension and antihypertensive drug therapy.

Untreated essential hypertension leads to cardiovascular and renal disease and stroke, but antihypertensive drug therapy effectively reduces these consequences of hypertension. Several studies indicate that hypertension can negatively impact on cognitive function, especially on learning and memory, but the ability of antihypertensive drugs to ameliorate these cognitive dysfunctions is less clear. None of the recent studies convincingly demonstrates that any of the antihypertensive drugs currently in use has a major deleterious effect on cognition in hypertensive patients, but some of the drugs more reliably benefit cognitive function in the hypertensive patient.

Basement membrane chondroitin sulfate proteoglycan alterations in a rat model of polycystic kidney disease.

Alterations in basement membrane components, notably proteoglycans, in a rat model of polycystic kidney disease have been investigated. Rats were fed phenol II (2-amino-4-hydroxyphenyl-5-phenyl thiazole) for 4 days and then changed to normal diet for a 7-day recovery period. Marked dilation of distal tubules and collecting ducts was observed by 4 days with phenol II treatment, but the morphology returned to normal after 7 days of subsequent normal diet.

Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component.

Focal adhesion formation in fibroblasts results from complex transmembrane signaling processes initiated by extracellular matrix molecules. Although a role for integrins with attendant tyrosine kinases has been established, there is evidence that cell surface heparan sulfate proteoglycans (HSPGs) are also involved with an associated role of protein kinase C. The identity of the proteoglycan has remained elusive, but we now report that syndecan 4 (ryudocan/amphiglycan) is present in focal adhesions of a number of cell types.

Is there a "dolichol recognition sequence" in enzymes that interact with dolichols and other polyisoprenoid substrates?

Yeast dolichyl-P-mannose synthase and a number of other enzymes that interact with dolichol or dolichyl-P as substrates contain a highly conserved amino-acid sequence that has been proposed as a potential dolichol recognition sequence [Albright, C.F., Orlean, P.

Development of chicken intrafusal muscle fibers.

The first sign of developing intrafusal fibers in chicken leg muscles appeared on embryonic day (E) 13 when sensory axons contacted undifferentiated myotubes. In sections incubated with monoclonal antibodies against myosin heavy chains (MHC) diverse immunostaining was observed within the developing intrafusal fiber bundle. Large primary intrafusal myotubes immunostained moderately to strongly for embryonic and neonatal MHC, but they were unreactive or reacted only weakly with antibodies against slow MHC.

Argatroban and inhibition of the vasomotor actions of thrombin.

We investigated the effects of the thrombin inhibitor, argatroban ((2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid) on the endothelium-derived relaxing factor-nitric oxide (EDRF-NO)-dependent relaxant, and the endothelial cell-independent constrictor actions of thrombin. Experiments were performed in isolated rings of canine coronary arteries. Argatroban inhibited thrombin-induced relaxation (range of thrombin activity 0.

Receptor mechanism of thrombin-induced endothelium-dependent and endothelium-independent coronary vascular effects in dogs.

We previously reported that thrombin produces endothelium-dependent relaxation and endothelium-independent constrictions in canine coronary arteries. To determine whether these opposing vascular effects of thrombin are mediated by the same receptor mechanism, but at different cell types, we investigated the effects of thrombin receptor agonist peptide (TRAP) on isolated canine coronary arteries with and without intact endothelium. In coronary arteries with intact endothelium, addition of 0.

Elastomeric polytetrapeptide matrices: hydrophobicity dependence of cell attachment from adhesive (GGIP)n to nonadhesive (GGAP)n even in serum.

The cross-linked polytetrapeptide matrices based on the repeating amino acid sequences, GGAP, GGVP and GGIP, were prepared and tested for cell adhesion promoting activity in both the absence and presence of fetal bovine serum. For comparison, X20-poly(GVGVP), a matrix previously shown to be a poor support for cell attachment and spreading, was included. In the absence of serum, all three polytetrapeptide-based matrices and the polypentapeptide-based matrix were negative for the adhesion of fibroblasts and endothelial cells.