Robert H. Notter

Bio: Robert H. Notter is an academic researcher from University of Rochester. The author has contributed to research in topics: Pulmonary surfactant & Lung injury. The author has an hindex of 57, co-authored 179 publications receiving 8895 citations. Previous affiliations of Robert H. Notter include University of Rochester Medical Center & Boston Children's Hospital.

Lung surfactants : basic science and clinical applications

Abstract: Introduction Introduction to Surface Tension and Surfactants Phospholipids: Introduction to Structure and Biophysics Physicochemical Methods for Studying Lung Surfactants Lung Surfactant Materials, Research Complexities, and Interdisciplinary Correlations Discovery of Endogenous Lung Surfactant and Overview of Its Metabolism and Actions Analyses of Surfactant Activity and Its Contribution to Lung Mechanics and Stability Functional Composition and Component Biophysics of Endogenous Lung Surfactant Lung Surfactant Dysfunction Diseases of Lung Surfactant Deficiency or Dysfunction Lung Surfactant Replacement in Animal Models Clinical Surfactant Replacement Therapy for Neonatal RDS Surfactant and Combined-Modality Therapies for Clinical ARDS and Acute Lung Injury Exogenous Lung Surfactants: Current and Future Glossary of Common Terms and Abbreviations References

Hydrophobic Surfactant-Associated Protein in Whole Lung Surfactant and Its Importance for Biophysical Activity in Lung Surfactant Extracts Used for Replacement Therapy

Abstract: . Hydrophobic protein of 6,000 and 14,000 daltons was isolated from mammalian pulmonary surfactant obtained from canine, human, and bovine alveolar lavage material. Low molecular weight, hydrophobic, surfactant- associated protein (SAP), herein referred to as SAP 6-14, was distinguished from SAP-35, the major glycoprotein in mammalian surfactants (the 35,000 dalton glycoprotein A or apolipoprotein A) by amino acid composition, peptide mapping, and by resistance of SAP 6-14 to digestion by endoglycosidase F, collagenase, trypsin, and other proteases. The amino acid composition of SAP 6-14 was found to be highly enriched in leucine and other hydrophobic amino acids. The characteristics of protein isolated from bovine replacement surfactant extracts utilized for the treatment of hyaline membrane disease in humans were also studied. SAP 6-14 isolated from calf lung surfactant replacement extracts (CLSE) and surfactant- TA were found to be identical to SAP 6-14 isolated from ether/ethanol extracts of various mammalian surfactants. By contrast, SAP-35, the major surfactant-associated glycoprotein of molecular weight=35,000, and other higher molecular weight proteins were not detected in significant quantities in the CLSE or surfactant-TA replacement surfactants, either by highly sensitive silver stain analysis or by immunoblot using monospecific antisera generated against bovine SAP-35. Biophysical studies of the CLSE replacement surfactant containing only SAP 6-14 and native phospholipids demonstrated full surface activity compared to natural lung surfactant. Dynamic surface tension lowering and adsorption properties of CLSE were essentially identical to those of freshly isolated bovine whole surfactant. Thus, hydrophobic SAP 6-14 is the only protein detected in bovine lung extract surfactants with full biophysical activity. The major surfactant associated protein, SAP-35, was not a significant component of either the CLSE or surfactant-TA replacement preparations.

Surfactant treatment of full-term newborns with respiratory failure.

Abstract: Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns. Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses. The group mean fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O. Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01 before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours. The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/- 1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6 hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation.

Abstract: Background. Exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it. In a randomized, multicenter trial, we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant. Methods. Before birth, 479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract at the time of delivery, whereas the infants in the rescue-therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if ...

Hydrodynamic and heat transfer study of dispersed fluids with submicron metallic oxide particles

Abstract: Turbulent friction and heat transfer behaviors of dispersed fluids (i.e., uttrafine metallic oxide particles suspended in water) in a circular pipe were investigated experimentally. Viscosity measurements were also conducted using a Brookfield rotating viscometer. Two different metallic oxide particles, γ-alumina (Al2O3) and titanium dioxide (TiO2), with mean diameters of 13 and 27 nm, respectively, were used as suspended particles. The Reynolds and Prandtl numbers varied in the ranges l04-I05 and 6.5-12.3, respectively. The viscosities of the dispersed fluids with γ-Al2O3 and TiO2 particles at a 10% volume concentration were approximately 200 and 3 times greater than that of water, respectively. These viscosity results were significantly larger than the predictions from the classical theory of suspension rheology. Darcy friction factors for the dispersed fluids of the volume concentration ranging from 1% to 3% coincided well with Kays' correlation for turbulent flow of a single-phase fluid. The Nusselt n...

Matrix metalloproteinases and their inhibitors in connective tissue remodeling.

Abstract: Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.

Matrix Metalloproteinases: A Review

Abstract: Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn(++)-endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.

Animal models of acute lung injury.

Abstract: Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.