Showing papers by "Research Triangle Park published in 1991"

Coordinate Gene Activity in Response to Agents That Induce Systemic Acquired Resistance.

Abstract: In a variety of plant species, the development of necrotic lesions in response to pathogen infection leads to induction of generalized disease resistance in uninfected tissues. A well-studied example of this "immunity" reaction is systemic acquired resistance (SAR) in tobacco. SAR is characterized by the development of a disease-resistant state in plants that have reacted hypersensitively to previous infection by tobacco mosaic virus. Here, we show that the onset of SAR correlates with the coordinate induction of nine classes of mRNAs. Salicylic acid, a candidate for the endogenous signal that activates the resistant state, induces expression of the same "SAR genes." A novel synthetic immunization compound, methyl-2,6-dichloroisonicotinic acid, also induces both resistance and SAR gene expression. These observations are consistent with the hypothesis that induced resistance results at least partially from coordinate expression of these SAR genes. A model is presented that ties pathogen-induced necrosis to the biosynthesis of salicylic acid and the induction of SAR.

DNA deaminating ability and genotoxicity of nitric oxide and its progenitors

Abstract: Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were greater than 99% C----T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer.

Better speech recognition with cochlear implants.

Abstract: HIGH levels of speech recognition have been achieved with a new sound processing strategy for multielectrode cochlear implants. A cochlear implant system consists of one or more implanted electrodes for direct electrical activation of the auditory nerve, an external speech processor that transforms a microphone input into stimuli for each electrode, and a transcutaneous (rf-link) or percutaneous (direct) connection between the processor and the electrodes. We report here the comparison of the new strategy and a standard clinical processor. The standard compressed analogue (CA) processor presented analogue waveforms simultaneously to all electrodes, whereas the new continuous interleaved sampling (CIS) strategy presented brief pulses to each electrode in a nonoverlapping sequence. Seven experienced implant users, selected for their excellent performance with the CA processor, participated as subjects. The new strategy produced large improvements in the scores of speech reception tests for all subjects. These results have important implications for the treatment of deafness and for minimal representations of speech at the auditory periphery.

Resistance to ddI and Sensitivity to AZT Induced by a Mutation in HIV-1 Reverse Transcriptase

Abstract: Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.

Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung.

Abstract: An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.

Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: an innovative approach for cancer therapy.

Abstract: An approach involving retroviral-mediated gene therapy for the treatment of neoplastic disease is described. This therapeutic approach is called "virus-directed enzyme/prodrug therapy" (VDEPT). The VDEPT approach exploits the transcriptional differences between normal and neoplastic cells to achieve selective killing of neoplastic cells. We now describe development of the VDEPT approach for the treatment of hepatocellular carcinoma. Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated alpha-fetoprotein or liver-associated albumin transcriptional regulatory sequences. Subsequent to retroviral infection, expression of VZV TK was limited to either alpha-fetoprotein- or albumin-positive cells, respectively. VZV TK metabolically activated the nontoxic prodrug 6-methoxypurine arabinonucleoside (araM), ultimately leading to the formation of the cytotoxic anabolite adenine arabinonucleoside triphosphate (araATP). Cells that selectively expressed VZV TK became selectively sensitive to araM due to the VZV TK-dependent anabolism of araM to araATP. Hence, these retroviral-delivered chimeric genes generated tissue-specific expression of VZV TK, tissue-specific anabolism of araM to araATP, and tissue-specific cytotoxicity due to araM exposure. By utilizing such retroviral vectors, araM was anabolized to araATP in hepatoma cells, producing a selective cytotoxic effect.

Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs.

Abstract: Numerous cannabinoids have been synthesized that are extremely potent in all of the behavioral assays conducted in our laboratory. An important feature in increasing potency has been the substitution of a dimethylheptyl (DMH) side chain for the pentyl side chain. Our previous studies have shown that (−)-11-OH-Δ8-THC-dimethylheptyl was 80–1150 times more potent than Δ9-THC. Stereospecificity was demonstrated by its (+)- enantiomer which was more than 1400–7500 times less potent. A related series of DMH cannabinoid analogs has recently been synthesized and preliminary evaluations reported here. (−)-11-OH-Δ9-THC-DMH was found to be equipotent with (−)-11-OH-Δ8-THC-DMH. The aldehyde (−)-11-oxo-Δ9-THC-DMH was 15–50 times more potent than Δ9-THC. Surprisingly, (−)-11-carboxy-Δ9-THC-DMH was also active, being slightly more potent than Δ9-THC. In the bicyclic cannabinoid series, the length and bulk of the side chain were found to be equally important. Aminoalkylindoles, which are structurally dissimilar from classical cannabinoids, have been found to exhibit a pharmacological profile similar to Δ9-THC. Though not extremely potent in vivo, they appear to represent an entirely new approach to studying the actions of the cannabinoids. The structural diversity and wide-ranging potencies of the analogs described herein provide the opportunity to develop a pharmacophore for the cannabinoids using molecular modeling techniques.

Fourier transform infrared spectroscopic study of the carbonate ions in bone mineral during aging

Abstract: The environment of CO32− ions in the bone mineral of chickens of different ages and in bone fractions of different density have been investigated by resolution-enhanced Fourier Transform Infrared (FTIR) Spectroscopy Three carbonate bands appear in thev2 CO3 domain at 878, 871, and 866 cm−1, which may be assigned to three different locations of the ion in the mineral: in monovalent anionic sites of the apatitic structure (878 cm−1), in trivalent anionic sites (871 cm−1), and in unstable location (866 cm−1) probably in perturbed regions of the crystals The distribution of the carbonate ions among these locations was estimated by comparing the intensities of the corresponding FTIR spectral bands The intensity ratio of the 878 and 871 cm−1 bands remains remarkably constant in whole bone as well as in the fractions obtained by density centrifugation On the contrary, the intensity ratio of the 866 cm−1 to the 871 cm−1 band was found to vary directly and decreased with the age of the animal In bone of the same age, the relative content of the unstable carbonate ion was found to be highest in the most abundant density centrifugation fraction A resolution factor of the CO32− band (CO3 RF) was calculated from the FTIR spectra which was shown to be very sensitive to the degree of crystallinity of the mineral The crystallinity was found to improve rapidly with the age of the animal The CO3 RF in the bone samples obtained by density centrifugation from bone of the same animal was found to be essentially constant This indicates a fairly homogeneous, crystalline state of the mineral phase A comparison of the maturation characteristics of synthetic carbonated apatites with bone mineral indicates that a simple, passive, physicochemical maturation process cannot explain the changes observed in the mineral phase of whole bone tissue or in the density centrifugation fractions of bone during aging and maturation

Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta.

Abstract: Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), a widespread environmental contaminant, may elicit its effects by altering gene expression in susceptible cells. Five TCDD-responsive complementary DNA clones were isolated from a human keratinocyte cell line. One of these clones encodes plasminogen activator inhibitor-2, a factor that influences growth and differentiation by regulating proteolysis of the extracellular matrix. Another encodes the cytokine interleukin-1 beta. Thus, TCDD alters the expression of growth regulatory genes and has effects similar to those of other tumor-promoting agents that affect both inflammation and differentiation.

Prediction of insecticidal activity of Bacillus thuringiensis strains by polymerase chain reaction product profiles.

Abstract: A rapid analysis of Bacillus thuringiensis strains predictive of insecticidal activity was established by using polymerase chain reaction (PCR) technology. Primers specific to regions of high homology within genes encoding three major classes of B. thuringiensis crystal proteins were used to generate a PCR product profile characteristic of each insecticidal class. Predictions of insecticidal activity were made on the basis of the electrophoretic patterns of the PCR products. Included in the screen were PCR primers specific for cryI, cryIII, and cryIV genes, which are insecticidal for lepidopterans, coleopterans, and dipterans, respectively. Known B. thuringiensis strains as well as unidentified strains isolated from soil and insect cadavers were analyzed by PCR. Small amounts of crude sample lysates were assayed in a single PCR reaction containing 12 to 20 primers capable of distinguishing between the different insecticidal genes. Insecticidal activity predicted by the PCR screen was found to correspond with the insecticidal activity of insect bioassays. In addition to identifying strains with known insecticidal genes, the PCR screen can identify strains with altered electrophoretic patterns containing potentially novel genes. Images

Use of Four-Dimensional Data Assimilation in a Limited-Area Mesoscale Model Part II: Effects of Data Assimilation within the Planetary Boundary Layer

Abstract: A four-dimensional data assimilation (FDDA) scheme based on Newtonian relaxation or nudging has been developed and evaluated in the Pennsylvania State University/National Center for Atmospheric Research (PSU/NCAR) Limited-Area Mesoscale Model. It was shown in Part I of this study that continuous assimilation of standard-resolution rawinsonde observations throughout a model integration, rather than at only the initial time, can successfully limit large model error growth (amplitude and phase errors) while the model maintains intervariable consistency and generates realistic mesoscale structures not resolved by the data. The purpose of this paper is to further refine the previously reported FDDA strategy used to produce “dynamic analyses” of the atmosphere by investigating the effects of data assimilation within the planetary boundary layer (PBL). The data used for assimilation include conventional synoptic-scale rawinsonde data and mesoalpha-scale surface data. The main objective of this study is ...

Medical capsule device actuated by radio-frequency (RF) signal

Abstract: A medical capsule device for releasing a substance at a defined location in the gastrointestinal tract. The device has a capsule body defining one or more apertures in the circumferential wall thereof and a sleeve valve rotatably positioned therein having one or more corresponding apertures in the circumferential wall thereof. The sleeve valve comprises a coil and electrically connected heatable resistor which are operatively associated with an actuator member formed of a shape memory alloy responsive to heat and which will move from a non-heated first shape to a heated second shape. Actuator stop means are provided in the capsule body for being engaged by the actuator member during movement from the non-heated first shape to the heated second shape so that the actuator member movement will serve to rotate the sleeve valve to an open position.

Lifetime and Current Prevalence of Specific Psychiatric Disorders Among Vietnam Veterans and Controls

Abstract: • To determine if Vietnam theater veterans were more likely than controls to have a specific psychiatric disorder other than posttraumatic stress disorder, the rates of specific psychiatric disorders were estimated using the Diagnostic Interview Schedule for national samples of veterans who served in Vietnam, other veterans of the Vietnam era, and matched civilian controls. Overall, there were few differences in rates of disorder between theater and other veterans; there were somewhat more differences between theater veterans and civilians. There were striking differences, however, in rates for most disorders, both lifetime and current, between male theater veterans with high levels of exposure to war zone stress and other male veterans or civilians. Female veterans exposed to high levels of war zone stress also had higher rates than other female respondents for several disorders.

A microgel electrophoresis technique for the direct quantitation of DNA damage and repair in individual fibroblasts cultured on microscope slides

Abstract: We demonstrate by single-cell microgel electrophoresis that the 2 main techniques, trypsinization and scraping, used to collect normal diploid mammalian cells cultured in monolayer induce DNA damage. To minimize this potential interference with studies on DNA damage and repair, we have standardized the single-cell gel electrophoretic (SCG) technique for the in situ quantitation of DNA single-strand breaks and alkali-labile sites in cultured human-fibroblasts. To demonstrate the utility of this technique, human neonatal foreskin-derived fibroblasts were allowed to attach to frosted microscope slides and then either irradiated with X-rays (25-200 rad) or treated for 1 h with hydrogen peroxide (2.2-140.8 mumoles). Treatment with either agent induced a dose-dependent increase in DNA migration. At equal levels of DNA damage, cell-to-cell variability in DNA migration was more heterogeneous for hydrogen peroxide-treated cells than for X-irradiated cells. A time course study to evaluate the kinetics of DNA repair for X-ray (200 rad)-induced damage indicated that the damage was completely repaired within 2 h. Applications of this technique for in vitro toxicology are discussed.

Development of a recombinant baculovirus expressing an insect-selective neurotoxin: potential for pest control.

Abstract: Recombinant nuclear polyhedrosis viruses (NPVs) expressing insect-selective toxins, hormones, or enzymes could enhance their insecticidal properties. We have constructed a recombinant, polyhedrin-positive Autographa californica NPV (AcNPV) that is orally infectious and expresses an insect-selective toxin (AalT), isolated from the scorpion Androctonus australis, under the control of the p10 promoter. Bioassays with the recombinant baculovirus on 2nd instar larvae of Heliothis virescens demonstrated a significant decrease in the time to kill (LT50 88.0 hours) compared to wild-type AcNPV (LT50 125 hours). Production of AalT was confirmed by western blot analysis of larval hemolymph from infected H. virescens, and bioassays with larvae of Sarcophaga falculata.

The Application of the Principle of Intention–to–Treat to the Analysis of Clinical Trials:

Abstract: A chronology of populations of patients eligible for analysis in clinical trials is discussed. A practical definition of the intention–to–treat population is given and its role relative to the efficacy analyzable population discussed for both parallel groups and crossover trials. Sensitivity analyses are proposed to address dilemmas as to which population of patients is appropriate for the final analysis of the trial. Associated issues regarding multiple comparisons, exclusion analyses, and post hoc analyses are discussed in the context of the intention–to–treat approach to statistical analysis. Examples for analgesia, intermittent claudication, anxiety or depression, and duodenal ulcers are given to illustrate the points discussed.

The single cell gel (SCG) assay: an electrophoretic technique for the detection of DNA damage in individual cells.

Abstract: Techniques which permit the sensitive detection of DNA damage are needed to evaluate the genotoxic potential of biologically reactive intermediates. Since the effects of many reactive intermediates are tissue and cell-type specific, it is important to utilize techniques which can directly detect DNA damage in individual cells. Cytogenetic techniques, while providing information at the level of the individual cell, are largely limited to proliferating cell populations. Furthermore, these techniques require the processing of DNA damage into microscopically visible lesions. Biochemical techniques, such as alkaline elution and nucleoid sedimentation, circumvent these difficulties in that DNA damage can be evaluated directly in almost any cell population. However, the resulting data do not provide any information about the distribution of damage or repair among individual cells. Recently, an electrophoretic technique capable of detecting DNA single-strand breaks and alkali labile sites in individual cells was developed (Singh et al., 1988). Eukaryote cells are embedded in an agarose gel on a microscope slide, lysed by detergents and high salt at pH 10, and then electrophoresed for a short time under alkaline conditions. Cells with increased DNA damage display increased migration of the DNA from the nucleus towards the anode. The importance of this technique lies in its ability to detect intercellular differences in DNA damage in virtually any eukaryote cell population, and in its requirement for extremely small cell samples (from 1 to 10,000 cells). Data from three recent pilot studies, involving (i) the exposure of human lymphocytes to hydrogen peroxide, (ii) the incubation of isolated mouse hepatocytes with cyclophosphamide, and (iii) the treatment of mice with acrylamide, will be used to demonstrate the sensitivity and utility of this technique for evaluating intercellular differences in DNA damage.

Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate.

Abstract: The pathogenic yeast, Candida albicans, is insensitive to the anti-mitotic drug, benomyl, and to the dihydrofolate reductase inhibitor, methotrexate. Genes responsible for the intrinsic drug resistance were sought by transforming Saccharomyces cerevisiae, a yeast sensitive to both drugs, with genomic C. albicans libraries and screening on benomyl or methotrexate. Restriction analysis of plasmids isolated from benomyl- and methotrexate-resistant colonies indicated that both phenotypes were encoded by the same DNA fragment. Sequence analysis showed that the fragments were nearly identical and contained a long open reading frame of 1694 bp (ORF1) and a small ORF of 446 bp (ORF2) within ORF1 on the opposite strand. By site-directed mutagenesis, it was shown that ORF1 encoded both phenotypes. The protein had no sequence similarity to any known proteins, including β-tubulin, dihydrofolate reductase, and the P-glycoprotein of the multi-drug resistance family. The resistance gene was detected in several C. albicans strains and in C. stellatoidea by DNA hybridization and by the polymerase chain reaction.

Nuclear and axonal localization of Ca2+/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex.

Abstract: The granule cell-enriched Ca2+/calmodulin-dependent protein kinase (CaM kinase-Gr) is a recently discovered neuron-specific enzyme. The kinase avidly phosphorylates synapsin I and contains a polyglutamate sequence, which suggests an association with chromatin as well. A possible role in synapsin I phosphorylation and in nuclear Ca2+ signaling was supported by immunochemical and ultrastructural examination of CaM kinase-Gr distribution. CaM kinase-Gr immunoreactivity was present in the molecular and granule cell layers of the rat cerebellum. This pattern corresponded to the occurrence of the enzyme in the granule cell axons and nuclei, respectively. Immunoblots confirmed these findings. Thus, CaM kinase-Gr may mediate and coordinate Ca2(+)-signaling within different subcellular compartments.

A resolution-enhanced Fourier transform infrared spectroscopic study of the environment of the CO3(2-) ion in the mineral phase of enamel during its formation and maturation.

Abstract: A resolution-enhanced Fourier Transform Infrared (FTIR) Spectroscopic study of the CO32− ion in pig enamel of increasing age and maturity has demonstrated the existence of four different, main carbonate locations. The major CO32− site arises as a result of the substitution of CO32− ions in the positions occupied by PO43− ions in the apatitic lattice. In addition, two minor locations have been identified in positions in which the CO32− ions substitute for OH− ions. The fourth carbonate group appears to be in an unstable location. Its concentration has been found to decrease with aging and maturation, during which there is a progressive increase in the amount of mineral deposited in the enamel. The distribution of the carbonate ions in the different apatitic sites varies randomly during the formation of the mineral phase in enamel and during its maturation. Although these changes have been shown to be related to changes in the composition of the mineral phase, a comparison of the parameters assessing the degree of crystallinity of the mineral phase from υ2CO32− and υ4PO32− infrared absorption data reveals a significant discrepancy related to the nonhomogeneous partition of the CO32− ion in the mineral phase. After maximum mineralization is reached, the composition of the mature mineral phase is decidedly different than that of the initial mineral deposited; the changes affect principally the concentrations of Ca2+, OH−, and HPO42− ions, but not the CO32− ions.

Design, synthesis, and pharmacological evaluation of ultrashort- to long-acting opioid analgetics.

Abstract: In an effort to discover a potent ultrashort-acting mu opioid analgetic that is capable of metabolizing to an inactive species independent of hepatic function, several classes of 4-anilidopiperidine analgetics were synthesized and evaluated. One series of compounds displayed potent mu opioid agonist activity with a high degree of analgesic efficacy and an ultrashort to long duration of action. These analgetics, 4-(methoxycarbonyl)-4-[(1-oxopropyl)phenylamino]-1-piperidinepropanoi c acid alkyl esters, were evaluated in vitro in the guinea pig ileum for mu opioid activity, in vivo in the rat tail withdrawal assay for analgesic efficacy and duration of action, and in vitro in human whole blood for their ability to be metabolized in blood. Compounds in this series were all shown to be potent mu agonists in vitro, but depending upon the alkyl ester substitution the potency and duration of action in vivo varied substantially. The discrepancies between the in vitro and in vivo activities and variations in duration of action are probably due to different rates of ester hydrolysis by blood esterase(s). The SAR with respect to analgesic activity and duration of action as a function of the various esters synthesized is discussed. It was also demonstrated that the duration of action for the ultrashort-acting analgetic, 8, does not change upon prolonged infusion or administration of multiple bolus injections.

Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line.

Abstract: Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of 1 cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well-characterized human malignant melanomas (A375 and MeWo) with differing metastatic traits, properties presumed to be involved in metastatic propensity were examined. C8161 showed a 2- to 14-fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type-IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM-1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto-oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis. c-myc expression was 6-fold greater than both A375 variants; c-fos expression was 3.4-fold less than A375P and 1.7-fold less than A375M; c-jun in C8161 cells was 2.5-fold and 2.1-fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.

The Interaction of Vapour Phase Organic Compounds with Indoor Sinks

Abstract: The interaction of indoor air pollutants with interior surfaces (i.e., sinks) is a well known, but poorly understood, phenomenon. Studies have shown that re-emissions of adsorbed organic vapours can contribute to elevated concentrations of organics in indoor environments. Research is being conducted in small environmental test chambers to develop data for predicting sink behaviour. This paper reports on the development of sink models based on fundamental mass transfer theory. The results of experiments conducted to determine the magnitude and rate of adsorption and desorption of vapour phase organic compounds for several materials are presented. Five materials were evaluated: carpet, painted wallboard, ceiling tile, window glass, and upholstery. Two organic compounds were tested with each material: tetrachloroethylene (a common cleaning solvent) and ethylbenzene (a common constituent of petroleum-based solvents widely used in consumer products). The results of the experimental work are presented showing the relevant sink effect parameters for each material tested and comparing the sorptive behaviour of the two organic compounds evaluated. An indoor air quality (IAQ) model was modified to incorporate adsorption and desorption sink rates. The model was used to predict the temporal history of the concentration of total vapour phase organics in a test house after application of a wood finishing product. The predicted results are presented and compared to measured values. Suggestions for further research on indoor sinks are presented.

A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

Abstract: Background Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants. Methods We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo. Results Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055). Conclusions In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.

Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir.

Abstract: Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart All nine of the ganciclovir-resistant strains were susceptible to foscarnet Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(29-deoxy-29-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance Images