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Biomedical subjects

L R Brown

Publications and source records attributed to L R Brown.

At least 37 records · Page 2Linked to original sources
PubMed1997

Concentrations of chlorinated organic compounds in biota and bed sediment in streams of the San Joaquin Valley, California.

Samples of resident biota and bed sediments were collected in 1992 from 18 sites on or near the floor of the San Joaquin Valley, California, for analysis of 33 organochlorine compounds. The sites were divided into five groups on the basis of physiographic region and land use. Ten compounds were detected in tissue, and 15 compounds were detected in bed sediment. The most frequently detected compound in both media was p,p'-DDE. Concentrations of SigmaDDT (sum of o,p'- and p, p' forms of DDD, DDE, and DDT) were statistically different among groups of sites for both tissue and sediment (Kruskal-Wallis, p < 0.05). Concentrations in both media were highest in streams draining the west side of the valley. Concentrations of SigmaDDT in tissue were significantly correlated with specific conductance, pH, and total alkalinity (p < 0.05), which are indicators of the proportion of irrigation return flows in stream discharge. Concentrations in sediment on a dry-weight basis were not correlated with these water-quality parameters, but total organic carbon (TOC) normalized concentrations were significantly correlated with specific conductance and pH (p < 0.05). Regressions of the concentration of SigmaDDT in tissue, as a function of SigmaDDT in bed sediment, were significant and explained up to 76% of the variance in the data. The concentration of SigmaDDT in sediment may be related to mechanisms of soil transport to surface water with bioavailability of compounds related to the concentration of TOC in sediment. The results of this study did not indicate any clear advantage to using either bed sediment or tissues in studies of organochlorine chemicals in the environment. Some guidelines for protection of fish and wildlife were exceeded. Concentrations of organochlorine chemicals in biota, and perhaps sediment, have declined from concentrations measured in the 1970s and 1980s, but remain high compared to other regions of the United States.

Animals↗
PubMed1997

NMR secondary structure of the plasminogen activator protein staphylokinase.

Staphylokinase (Sak) is a 15.5 kDa protein secreted by several strains of Staphylococcus aureus. Due to its ability to convert plasminogen, the inactive proenzyme of the fibrinolytic system, into plasmin, Sak is presently undergoing clinical trials for blood clot lysis in the treatment of thrombovascular disorders. With a view to developing a better understanding of the mode of action of Sak, we have initiated a structural investigation of Sak via multidimensional heteronuclear NMR spectroscopy employing uniformly 15N- and 15N, 13C-labelled Sak. Sequence-specific resonance assignments have been made employing 15N-edited TOCSY and NOE experiments and from HNCACB, CBCA(CO)NH, HBHA-(CBCACO) NH and CC(CO)NH sets of experiments. From an analysis of the chemical shifts, 3JHNH alpha scalar coupling constants, NOEs and HN exchange data, the secondary structural elements of Sak have been characterized.

Amino Acid Sequence↗
PubMed1997

NMR investigations of recombinant 15N/13C/2H-labeled bradykinin bound to a Fab mimic of the B2 receptor.

NMR spectroscopy has been used to obtain structural information on the bioactive conformation of the nonapeptide hormone bradykinin (Arg-Pro-Pro-Gly-Ser-Pro-Phe-Arg, BK) bound to the Fab-fragment of an antibody that mimics the hormone binding site of the natural bradykinin B2-receptor. Using 15N or 15N,13C, 60% 2H isotope labelled bradykinin, complete 1H, 13C and 15N assignments for bradykinin bound to the Fab-fragment have been obtained. Preliminary interpretation of 15N edited NOE spectra indicates that the conformation of bradykinin bound to the model receptor differs substantially from previous computer models of the bioactive conformation of bradykinin.

Bradykinin↗
PubMed1996

Detection of multiple conformations of the E-domain of 5S rRNA from Escherichia coli in solution and in crystals by NMR spectroscopy.

NMR spectroscopy of the E-domain fragment of Escherichia coli 5S rRNA indicates that this molecule exists in solution as either a stem-loop or as a duplex with two U-U base pairs in the bulge region. At temperatures below 27 degrees C, interconversion between the monomeric and dimeric forms in solution occurs on a time scale of weeks and allows the preparation of samples on which NMR structure determinations can be carried out on predominantly monomeric or dimeric species. The NMR results obtained provide comparison data for the distinction between A- and B-form E.coli 5S rRNA and for the possible kinetics of conversion between these forms. NMR evidence is presented that the duplex form also exists in crystals and suggestions are made for means to obtain stem-loop conformations of E-domain and other small RNA stem-loop sequences in crystals.

Base Sequence↗
PubMed1996

Initial analysis of 750 MHz NMR spectra of selective 15N-G,U labelled E. coli 5S rRNA.

The overall folding of an RNA molecule is reflected in its base pairing pattern. The identification of that pattern provides a first step towards the determination of the structure of an RNA molecule. We show that the application of heteronuclear NMR methods at 750 MHz to E. coli 5S rRNA (120 nucleotides) selectively labelled with 15N in guanine and uridine allows observation of base pairing patterns for a larger RNA molecule. We also present evidence that the fold of the E-domain of the 5S rRNA (nt 79-97) as a contiguous part of the 5S rRNA and as an isolated molecule is virtually the same.

Base Composition↗
PubMed1996

Sequential assignments in uniformly 13C- and 15N-labelled RNAs: the HC(N,P) and HC(N,P)-CCH-TOCSY experiments.

An approach for the simultaneous acquisition of HCN and HCP as well as HCN-CCH-TOCSY and HCP-CCH-TOCSY triple resonance data sets for 13C-/15N-labelled RNAs is presented. The new HCN-CCH-TOCSY scheme unambiguously links all sugar resonances to the base nitrogen. In addition, simultaneous acquisition of HCN-CCH-TOCSY and HCP-CCH-TOCSY data sets provides sequential and base-type information in a single experiment, thereby saving data acquisition time as well as providing complementary data sets that are useful in clarifying ambiguous assignments. Virtually complete sequence-specific phosphate-ribose 1H, 31P, and base 15N1,9, assignments as well as partial 13C assignments could be obtained in a single experiment for a 0.5-mM sample of a 19-mer ribonucleotide.

Base Sequence↗
PubMed1996

Characterization of glucose-mediated insulin release from implantable polymers.

We characterized a glucose-sensitive, controlled-release insulin delivery system. Insulin release rates increased when glucose was perfused in the release media surrounding the matrix. The system was composed of solid, particulate insulin, incorporated into an ethylene-vinyl acetate copolymer (EVAc) matrix. Feedback control was mediated by the glucose oxidase enzyme immobilized to Sepharose beads, which were incorporated along with insulin into the EVAc matrix. When glucose in solution entered the insulin delivery system, gluconic acid was produced, causing a drop in the microenvironmental pH of the matrix. This fall in pH resulted in a rise in insulin solubility and consequently a rise in the insulin release rate from the matrix. Insulin concentrations increased in vitro and in vivo in response to glucose infusion. The increased insulin release was shown to consist of a finite pulse of insulin that required an optimal recovery period of 1 h to achieve a maximal repeated response to a glucose stimulus. Repeated pulses were demonstrated over a 4 h period. An optimum enzyme ratio was also determined.

Animals↗
PubMed1996

Lung nodule enhancement at CT: prospective findings.

PURPOSE: To determine if lung nodule enhancement measured with computed tomography (CT) is directly related to the likelihood of malignancy and to nodule vascularity. MATERIALS AND METHODS: Radiologically indeterminate 7-30-mm pulmonary nodules were studied in 107 patients with malignant neoplasms (n = 52), granulomas (n = 51), and benign neoplasms (n = 4). Attenuation was recorded from serial thin-section CT scans before and after injection of contrast material. Twenty-four histologic specimens were graded after immunoperoxidase vascular staining with antibody to factor VIII-associated antigen. RESULTS: Malignant neoplasms were enhanced (median, 46.5 HU; range, 11-110 HU) statistically significantly more than granulomas and benign neoplasms (median, 8 HU; range, -10 to 94 HU) (P < .001). With 20 HU as the threshold for a positive test result, the sensitivity was 98%, specificity was 73%, and accuracy was 85% (prevalence of malignancy, 49% ¿52 of 107 nodules]). The degree of enhancement was statistically significantly related to the amount of central vascular staining (P < .001). CONCLUSION: Enhancement appears to be an indicator of malignancy and vascularity. These prospective findings corroborate previously reported results.

Adult↗
PubMed1995

Cross-sectional follow-up of a flu-like respiratory illness among fiberglass manufacturing employees: endotoxin exposure associated with two distinct sequelae.

Over a period of 10 years, employees in a manufacturing plant experienced sporadic flu-like episodes after work in a basement containing a recirculated washwater mist. We report a cross-sectional study to define the flu-like illness and bioaerosol exposures. High concentrations of gram-negative bacteria (GNB) (> 10(7) cfu/ml) and endotoxin (range 34-46 micrograms/ml) were found in the water. Mist contained > 10(3) cfu/m3 of GNB, and endotoxin up to 13,900 to 27,800 ng/m3. Few fungi and thermotolerant Bacillus species and no Actinomycetes, Legionella species, or amoeba were found in washwater. Airborne levels of fungi were of the same species and magnitudes as outdoor samples. Subjects volunteered (n = 28) because of a history of flu-like symptoms or were randomly selected (n = 102) from workers with and without current exposure to the basement. No acute cases were examined. Cases did not fulfill criteria for hypersensitivity pneumonitis (HP) and high levels of IgG antibodies to water-borne antigens were not observed. However, among 20 subjects indicating a history of severe flu-like episodes (severe basement flu, SBF), diffusion capacity (DLCO) was significantly lower (p = 0.015) than among other workers. The prevalence of SBF was independent of smoking. Cases occurred in clusters, and SBF was more common among workers with intermittent exposure to the basement (19 cases) than with daily exposure (1 case). These findings suggest that SBF and associated chronically depressed DLCO resulted from toxic injury following high-level endotoxin exposure. Asthma was prevalent in the study population, particularly among employees with daily, rather than intermittent, exposure to endotoxin-containing mist (odds ratio 6.7, p = 0.02). Thus, endotoxin exposure in this study was associated with two distinct sequelae depending on the temporal pattern of exposure.

Adult↗
PubMed1995

Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material.

PURPOSE: To determine if the degree of enhancement of pulmonary nodules is directly related to the likelihood of malignancy and to the vascularity of the nodule. MATERIALS AND METHODS: Uncalcified 6-40-mm-diameter pulmonary nodules were studied in 163 patients with malignant neoplasm (n = 111), granuloma (n = 43), and benign neoplasm (n = 9). Serial thin-section computed tomography (CT) was performed before and after injection of 100 mL of nonionic contrast material at 2 mL/sec. The maximum level of enhancement was recorded. Eighteen histologic specimens were graded after vascular staining. RESULTS: Malignant neoplasms enhanced (median, 40.0 HU; range, 20-108 HU) significantly more than granulomas and benign neoplasms (median, 12.0 HU; range, -4 to 58 HU) (P < .001). With 20 HU as the threshold for a positive test, sensitivity was 100%; specificity, 76.9%; positive predictive value, 90.2%; negative predictive value, 100%; and accuracy, 92.6% (prevalence of malignancy, 68.1%). Degree of enhancement was significantly related to amount of central vascular staining (P = .003). CONCLUSION: Enhancement is an indicator of malignancy and vascularity.

Adult↗
PubMed1994

The NMR solution structure of the pheromone Er-1 from the ciliated protozoan Euplotes raikovi.

The 3-dimensional structure of the pheromone Er-1 isolated from the ciliated protozoan Euplotes raikovi has been determined in aqueous solution by 1H NMR spectroscopy. The structure of this 40-residue protein was calculated with the distance geometry program DIANA on the basis of 503 upper distance constraints derived from nuclear Overhauser effects and 77 dihedral angle constraints derived from spin-spin coupling constants, and refined by restrained energy minimization with the program OPAL. The Er-1 solution structure is represented by a group of 20 conformers with an average RMS deviation relative to the mean structure of 0.55 A for the backbone atoms N, C alpha, and C', and 0.93 A for all heavy atoms of the complete polypeptide chain, residues 1-40. The molecular architecture is dominated by an up-down-up bundle of 3 alpha-helices formed by residues 2-9, 12-19, and 24-33. Although this core part coincides closely with the previously determined structure of the homologous pheromone Er-10, the C-terminal peptide segment adopts a novel conformation. This is of interest in view of previous suggestions, based on sequence comparisons, that this molecular region may be important for the different specificity of receptor recognition by different pheromones.

Amino Acid Sequence↗
PubMed1994

The radiographic findings of fibrosing mediastinitis.

We retrospectively reviewed the radiographic findings of fibrosing mediastinitis (FM) in 33 patients. Imaging studies included chest radiographs, computed tomographic scans, magnetic resonance imaging examinations, esophograms, ventilation perfusion scans, angiograms, and venograms. Findings include bronchial narrowing in 11 patients (33 percent), pulmonary artery obstruction/narrowing in 6 patients (18 percent), esophageal narrowing in 3 patients (9 percent), and superior vena cava obstruction/narrowing in 13 patients (39 percent). Two distinctly different radiographic patterns were identified: a localized pattern seen in 27 patients (82 percent) that frequently contained calcification and a diffuse pattern seen in 6 patients (18 percent) that did not contain calcification. The localized pattern is most likely due to histoplasmosis and does not show radiographic evidence of improvement with steroid therapy. The diffuse pattern may more likely be truly idiopathic or of a noninfectious etiology. Several patients with the diffuse pattern showed radiographic evidence of improvement with steroid therapy.

Adolescent↗
PubMed1993

Nuclear magnetic resonance solution structure of the pheromone Er-10 from the ciliated protozoan Euplotes raikovi.

The three-dimensional structure in solution of the pheromone Er-10 from the ciliated protozoan Euplotes raikovi has been determined by nuclear magnetic resonance spectroscopy. The structure of this 38-residue protein was obtained from 384 nuclear Overhauser enhancement distance constraints and 78 dihedral angle constraints using the distance geometry program DIANA for the structure calculation and the program AMBER for energy minimization. For a group of 20 conformers used to characterize the solution conformation, the average root-mean-square distance calculated for the backbone heavy atoms relative to the mean structure was 0.33 A. The structure includes three short helices of residues 2 to 8, 12 to 19 and 24 to 33, and a turn in the carboxy-terminal region of residues 34 to 38. These structural elements are held together by three disulfide bridges. The structure is quite stable relative to heat denaturation, since at both pH 4.6 and pH 6.0 only minor changes in the circular dichroism and nuclear magnetic resonance spectra were observed over the temperature range 20 to 80 degrees C. The surface of the Er-10 structure shows an asymmetric charge distribution that results in a predominantly apolar surface on one side of the molecule. There is also a deep cleft in the structure with an asymmetric distribution of charged and apolar residues on the two walls. These surface features may be important for the homologous (autocrine) and heterologous binding of the pheromone to receptors.

Amino Acid Sequence↗
PubMed1993

Presentation of newly synthesized glycoproteins to CD4+ T lymphocytes. An analysis using influenza hemagglutinin transport mutants.

Human lymphoblastoid cells transiently expressing the hemagglutinin (HA) glycoprotein of influenza virus are rapidly and efficiently recognized by CD4+ HA-specific T lymphocytes. This endogenous presentation pathway is sensitive to chloroquine and is therefore likely related to the classical class II major histocompatibility complex (MHC) exogenous pathway of antigen presentation. In this study we have examined a series of transport-defective HA mutants. We correlate the intracellular fate of the native antigen with its presentation characteristics. We have found that the native antigen must enter the secretory pathway since a cytosolic form is not presented. However, surface expression and normal trafficking through the Golgi apparatus are not required for efficient presentation. Instead, escape of native antigen from the endoplasmic reticulum appears to be both necessary and sufficient for gaining access to a compartment where antigen is processed and binds class II MHC molecules.

Amino Acid Sequence↗
PubMed1993

Primary mediastinal neoplasms (other than thymoma).

Primary mediastinal neoplasms encompass a long list of histologically diverse lesions that can arise from a wide variety of mediastinal structures. Recent advances in diagnostic techniques have considerably enhanced the evaluation of the mediastinum with use of noninvasive or minimally invasive procedures. In adults, most primary mediastinal neoplasms can be classified in one of four categories: thymus-derived neoplasms, neurogenic tumors, lymphomas, or germ cell neoplasms. In children, neurogenic tumors (especially neuroblastomas) and lymphomas are most frequently encountered. Because of the presence of many vital structures in the confined thoracic cavity, even benign mediastinal neoplasms can cause severe symptoms from the mass effect and therefore warrant a carefully planned management strategy. With modern therapeutic and surgical interventions, associated morbidity and mortality can often be substantially decreased.

Endocrine Gland Neoplasms↗