[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
B Chen
Publications and source records attributed to B Chen.
Priority among air pollution factors for preventing chronic obstructive pulmonary disease in Shanghai.
The problems that city environmental protection planners face are how important the air pollution exposures are in relation to chronic obstructive pulmonary disease (COPD) in local residents and which factor should be controlled most urgently. The purpose of our study is to determine the control priority among ambient sulphur dioxide (SO2) inhalable particulates (IP) and indoor use of coal to prevent COPD in residents of the city. Ambient air pollution is mainly from SO2 and IP(< 10 nm). Indoor air pollution is mainly from the use of coal for heating and/or cooking. Distribution of ambient SO2, and IP concentrations were described using a quartic trend surface simulation. When stratified by two extreme levels of ambient SO2 and IP and types of fuel used indoors, eight local area populations in four communities with different combinations of exposure levels were selected. In each community a local area population mostly using coal and one mostly burning gas was chosen. Chronic obstructive pulmonary diseases (COPD, ICD 490-493) including chronic bronchitis, asthma and emphysema, are a major cause of death in residents of Shanghai. The relationship between the three air pollution factors and their health effects were analyzed at the level of mortality (1978-1987, 232,459 person-years), prevalence of symptoms (12,037 persons) of COPD, lung function and non-specific immunologic function (514 women). The results show that indoor use of coal has stronger associations with health than estimated exposure to ambient SO2 or IP.
Adult↗
Transforming growth factor-beta 1 bifunctionally regulates murine macrophage proliferation.
Transforming growth factor-beta (TGF-beta) is a family of polypeptide growth factors with multiple functional activities. Recent studies suggest that TGF-beta is a selective inhibitor of hematopoietic cells. In this report, we study the effect of TGF-beta 1 on the proliferation of murine peritoneal exudate macrophages (PEM) in response to purified murine recombinant granulocyte-macrophage colony-stimulating factor (rMuGM-CSF) and human recombinant M-CSF (rHuM-CSF). In mice, PEM and other types of tissue macrophages display multiple types of receptors for CSFs and respond to them, either alone or in combination, to undergo extensive proliferation in vitro. Recombinant human TGF-beta 1 (rHuTGF-beta 1) (0.1 to 1.0 ng/mL) markedly enhanced the growth of PEM in response to rMuGM-CSF but inhibited their responsiveness to rHuM-CSF. Similar effects of rHuTGF-beta 1 were also detected using murine pulmonary alveolar macrophages (PAM) and bone marrow-derived macrophages (BMDM). Receptor binding assays using iodinated rMuGM-CSF and rHuM-CSF showed that rHuTGF-beta 1 treatment greatly enhanced the expression of GM-CSF receptors in PEM, in a time- and dose-dependent manner, suggesting a possible mechanism for the synergistic effect of TGF-beta 1. On the other hand, the expression of M-CSF receptors was not affected by TGF-beta 1 treatment. Analysis by mRNA PCR showed that the synergistic effect of TGF-beta 1 is not due to autocrine CSFs produced by treated cells. Our results suggest that TGF-beta 1 is an important regulator of macrophage proliferation. Depending on the types of CSFs present, TGF-beta 1 may act either as a growth promoter or inhibitor.
Animals↗
Mesenchymal cells isolated after acute lung injury manifest an enhanced proliferative phenotype.
After acute lung injury, mesenchymal cells migrate into the alveolar airspace where they proliferate and deposit connective tissue macromolecules. Early in the disease process, inflammatory cell-derived trophic factors modulate these mesenchymal cell functions. However, in those patients who die, even as the inflammatory response abates, the fibroproliferative response continues, resulting in extensive intraalveolar fibrosis. We therefore hypothesized that lung mesenchymal cells obtained from individuals dying with acute alveolar fibrosis would manifest an enhanced proliferative capacity that was independent of persistent exogenous signals. To examine this hypothesis, the in vitro growth properties of mesenchymal cells prepared from patients dying with acute lung injury (n = 3) were analyzed in defined medium and compared with those of mesenchymal cells similarly prepared from patients dying with histologically normal lungs (n = 3). Isolates were characterized as mesenchymal cells by using morphological and immunohistochemical criteria. In accord with the hypothesis, mesenchymal cells isolated from lung-injured patients doubled within 3 d in the complete absence of exogenous peptide growth factors, reaching a saturation density of approximately 15 x 10(3) cells/cm2. As expected, lung mesenchymal cells from normal individuals failed to significantly increase in number. Consistent with this proliferative phenotype, the immediate early cell division cycle genes c-fos and c-jun were constitutively expressed in each cell strain prepared from injured lungs, but not in those from control lungs. The observed proliferative phenotype was stable through the fifth subcultivation of the cells. Despite these proliferative properties, three separate criteria indicated the mesenchymal cells from injured lungs were not transformed: normal karyotype; finite lifespan in vitro (9-10 subcultivations); and inability to disseminate in mice with severe combined immunodeficiency. These data support the hypothesis that mesenchymal cells manifest an enhanced proliferative state after acute lung injury.
Acute Disease↗
Phospholipase C-induced monocytic differentiation in a human monocytic leukemia cell line THP-1.
Previous studies showed that the human monocytic leukemia cell line THP-1 can be induced to undergo monocytic differentiation by tumor promoting phorbol esters (TPA), suggesting that protein kinase C (PK-C), the primary binding site of TPA, may play a role in the control of monocytic differentiation: The effect of exogenous phospholipase C (PLC) on THP-1 cells was investigated. Within 24-48 hr, PLC induced over 40% of THP-1 cells to undergo monocytic differentiation as manifested by adherence, growth arrest, functional expression, morphological changes and expression of c-fms gene which encode for M-CSF receptors. Compared to TPA, however, the inducing activity of PLC was weaker, slower and not as effective. PLC treatment also induced a transient expression of c-fos proto-oncogene prior to c-fms expression. On the contrary, the level of c-myc RNA, which is constitutively expressed in THP-1 cells, was down-regulated 48 hr after PLC treatment. The PLC-induced monocytic differentiation in THP-1 cells was inhibited by staurosporine, a potent PK-C inhibitor, further suggesting that direct activation of the PK-C is one of the metabolic events essential for monocytic differentiation. It is postulated that in THP-1 cells the metabolic pathway transducing PK-C activation has been permanently blocked, thereby leading to uncontrolled proliferation without differentiation.
Cell Differentiation↗
[Use of glutaraldehyde preserved allogeneic and xenogeneic cartilage in plastic surgery].
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Adolescent↗
[Survey and treatment of the blind in Xinhui, Guangdong, China].
Co-operating with Helen Keller International (HKI) in 1987 and 1988, Zhongshan Ophthalmic Center made a large scale prevalent survey of the blind in Xinhui, Guangdong, China. Three screening methods were used in the project. The first was a house-to-house visit by ophthalmologists. The second was performed initially by trained country health workers and then checked by ophthalmologists. In the third one, the blind people were asked to come together to be examined by ophthalmologists. The second method was found to be the most effective. The survey revealed that the prevalent rate of blindness was 0.24% in the county. Of all the blind, 89% were over 50 years old, 73% were females. Cataract accounted for 47% of the blindness. Thirty percent of the blind from cataract received surgical treatment. The postoperative re-examination half a year later showed that the corrected visual acuity in 86% of the patients was more than 0.05.
Aged↗
[Effect of concentration of nutrients solution on the growth of Salvia miltiorrhiza Bge].
The experiment on the effect of various concentrations of nutrient solution on sand culture of Salvia miltiorrhiza was carried out. The results show that Salvia miltiorrhiza is a fertilizer tolerant plant. It can grow well and give high yield when the total concentration of nutrient reaches 0.37%.
Fertilizers↗
[Restenosis after balloon angioplasty: role of platelets, thrombosis and smooth muscle cells proliferation].
Iliac atherosclerosis was produced in 50 New Zealand rabbits and followed by balloon angioplasty (BA) for the study of the mechanism of restenosis after BA. 41 rabbits undergoing successful dilatation were randomly grouped and killed at 30 min, 24 h, one and four weeks after BA, respectively. Histomorphological results showed that platelets adhered to the angioplastic areas 30 min after BA. At 24 h, a large quantity of platelets adhered to or aggregated at the areas to form a dense carpet of platelets and large or small thrombi, even a totally obstructive luman. At the 4th week, organized mural thrombi in lumen produced restenosis. There were plenty of foam cells and less smooth muscle cells (SMCs) in the vessel wall of atherosclerotic rabbits before BA. One week after BA, SMCs proliferated increasingly and migrated into the intima from the media at the second week. At the fourth week, SMCs proliferated markedly in the intima, forming new atherosclerotic plaque, which resulted in thickening of vessel wall and restenosis of originally angioplastic sites.
Angioplasty, Balloon↗
Effect of CD4+ cell count measurement variability on staging HIV-1 infection.
A single CD4+ cell count (CD4) measurement is often used to stage HIV-1 infection, decide when to initiate prophylactic therapy and inform patients, and may soon even define AIDS onset. Documentation of the reliability and validity of employing CD4 for the above purposes in a population-based setting is needed. We utilized data from 4,954 homosexual/bisexual men followed over 6 years, with CD4 testing at 6 month intervals, to study the timing of CD4-based staging of HIV-1 disease and quantify and evaluate the potential impact of CD4 measurement error. The median time from seroconversion to first CD4 test below 500 x 10(6)/L or clinical AIDS was 1.70 years, and the first CD4 test below 200 x 10(6)/L or clinical AIDs was 5.29 years. The time from first testing less than 500 x 10(6)/L to clinical AIDS in untreated men was 5.55 years. With confirmatory retesting, these times were significantly lengthened. The 95% confidence ranges for the true CD4 state in individuals with measured CD4 of 500 and 200 x 10(6)/L are at least (297 x 10(6), 841 x 10(6)/L) and (118 x 10(6), 337 x 10(6)/L), respectively. Without confirmatory retesting, individuals with true CD4 remaining at 700 x 10(6) and 280 x 10(6)/L have at least a 40% chance for one of five CD4 measurements to fall below guideline limits of 500 x 10(6) and 200 x 10(6)/L, respectively. Confirmatory retesting can reduce these probabilities to as low as 4%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Study of quantitative diagnosis of cerebral arteriosclerosis].
On the basis of clinical diagnostic criterion of cerebral arteriosclerosis, we selected, 72 patients with cerebral arteriosclerosis, 72 patients with suspected cerebral arteriosclerosis and 70 healthy individuals and screened 42 variables obtained from clinical and accessory examination with a stepwise discriminant analysis and a stepwise regression analysis. Finally we performed a logistic discriminant analysis of 15 selected variables in order to establish diagnostic discriminant formulas, Ya and Yc. It was found that a diagnostic coincidence rate for rediscriminant analysis of 212 individuals with the formulas was 100%. Very high sensitivity (96.7%), specificity (100%), positive predicted value (100%), negative predicted value (83.3%) and accuracy (97.1%) were noted in a prospective double-blind test on 34 subjects. The authors suggest that the discriminant formulas Ya and Yc established for diagnosis of cerebral arteriosclerosis be widely applicated.
Aged↗
[Screening and distinguishing heavy chain variable region genes of McAb against encephalitis type B virus].
In order to prepare human-mouse chimeric antibody against encephalitis type B virus, hybridoma 51-8 cells secreting monoclonal antibody against the virus were used as material for isolating heavy-chain variable region gene of the McAb. High molecular weight DNA of the hybridoma cell was partially digested by BamHI, and then constructed a gene library containing 2 x 10(7) pfu with lambda EMBL-3 as vector. With cDNA of heavy-chain variable region of the monoclonal antibody as probe, nine positive plaques were screened from 360,000 plaques, which have been proven that they contained a fragment of heavy-chain variable region genes by dot hybridization and Southern hybridization. Four recombinants among the nine positive plaques were further distinguished with J11 probe containing J3, J4 and heavy-chain enhancer. After cutting by EcoR1, there was a 3.8 kb fragment in three recombinants as similar to that in liver cell and Sp2/0 cell, but not in the fourth recombinant (lambda 8a4) which contained a 4.5 kb fragment that did not present in liver cell and Sp2/0 cell. The results showed that the inserts in former 3 recombinants were non-rearranged fragment of heavy-chain variable region genes, but the insert in lambda 8a4 contained a rearranged functional variable region gene. The 4.5 kb fragment could not be hybridized with a probe containing J1 and J2, but contained VH, J3 or/and J4 and enhancer, that further proved it was a functional variable region gene. Therefore, the 4.5 kb fragment was isolated and subcloned in pUC 19, and its physical map was made.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Thermal unfolding pathway for the thermostable P22 tailspike endorhamnosidase.
The conditions in which protein stability is biologically or industrially relevant frequently differ from those in which reversible denaturation is studied. The trimeric tailspike endorhamnosidase of phage P22 is a viral structural protein which exhibits high stability to heat, proteases, and detergents under a range of environmental conditions. Its intracellular folding pathway includes monomeric and trimeric folding intermediates and has been the subject of detailed genetic analysis. To understand the basis of tailspike thermostability, we have examined the kinetics of thermal and detergent unfolding. During thermal unfolding of the tailspike, a metastable unfolding intermediate accumulates which can be trapped in the cold or in the presence of SDS. This species is still trimeric, but has lost the ability to bind to virus capsids and, unlike the native trimer, is partially susceptible to protease digestion. Its N-terminal regions, containing about 110 residues, are unfolded whereas the central regions and the C-termini of the polypeptide chains are still in the folded state. Thus, the initiation step in thermal denaturation is the unfolding of the N-termini, but melting of the intermediate represents a second kinetic barrier in the denaturation process. This two-step unfolding is unusually slow at elevated temperature; for instance, in 2% SDS at 65 degrees C, the unfolding rate constant is 1.1 x 10(-3) s-1 for the transition from the native to the unfolding intermediate and 4.0 x 10(-5) s-1 for the transition from the intermediate to the unfolded chains. The sequential unfolding pathway explains the insensitivity of the apparent Tm to the presence of temperature-sensitive folding mutations [Sturtevant, J. M., Yu, M.-H., Haase-Pettingell, C., & King, J. (1989) J. Biol. Chem. 264, 10693-10698] which are located in the central region of the chain. The metastable unfolding intermediate has not been detected in the forward folding pathway occurring at lower temperatures. The early stage of the high-temperature thermal unfolding pathway is not the reverse of the late stage of the low-temperature folding pathway.
Binding Sites↗
Cadherin mRNAs during rat embryo development in vivo and in vitro.
Whole rat embryo cultures are being used in increasing numbers of laboratories to study the mechanisms by which teratogens disturb development. The development of early somite stage embryos in vitro is very similar morphologically to that in vivo, yet few biochemical comparisons have been made. The purpose of this study was to determine the steady-state mRNA concentrations of a family of Ca(2+)-dependent cell adhesion molecules, the cadherins, during rat embryonic development in vivo and in vitro. Embryos and yolk sacs were collected on days 10, 11, and 12 of gestation (in vivo); they were also obtained from day 10 embryos after growth in culture for 24 hr (day 11 in vitro) or 45 hr (day 12 in vitro). Total RNAs isolated from embryos and yolk sacs were studied by Northern blot analysis using specific cDNA probes for three cadherins, E-cadherin, N-cadherin, and P-cadherin. Although E-cadherin mRNA was detected in embryos, it was present at much higher concentrations in yolk sacs. In addition, multiple species of E-cadherin mRNA ranging from 3.0 to 13 kb were detected. Interestingly, the concentration of the major 4.5-kb E-cadherin mRNA species in yolk sac after 45 hr in culture was increased 2.8-fold over that on day 12 of gestation in vivo. Second, two species (4.3 and 3.5 kb) of N-cadherin mRNA were detected, almost exclusively in embryos. In yolk sac, N-cadherin mRNA was detected only after 45 hr in culture. Third, P-cadherin mRNA was detected as a single 3.5-kb species, mainly in embryos. P-cadherin mRNA concentrations in yolk sac after 45 hr in culture were 5.6-fold higher than in vivo. Thus, these results demonstrate that there is a differential distribution of cadherin mRNAs in rat embryos and yolk sacs. Further, there appear to be multiple species of mRNAs for E-cadherin and N-cadherin. Finally, while whole embryo culture in vitro did not significantly alter the steady-state concentrations of cadherin mRNAs in the embryo, these concentrations were dramatically increased in the yolk sac.
Animals↗
Modelling approach for separating blood time-activity curves in positron emission tomographic studies.
A modelling approach is developed to generate the full time course of an injected radiotracer and its labelled metabolites in plasma/blood, based on measurements of the total radioactivities in withdrawn plasma/blood samples. A compartmental model is used to describe the conversion of an injected tracer to its metabolites in the body. The model equation is formulated with the total radioactivity concentration curve as the input function. The utility and characteristics of the approach in quantitative positron emission tomographic (PET) studies are shown with two examples. In the first example, using the tracer 6-[18F]fluoro-L-dopa (FDOPA), the approach is shown to derive the full time course of plasma FDOPA and its metabolites. In the second example of dynamic 15O oxygen PET, the approach is used to solve a deconvolution problem to give separated time-activity curves of 15O oxygen and 15O water in blood. The modelling approach improves the separation of blood/plasma time-activity curves and leads to better quantitative interpretation of PET results.
Dihydroxyphenylalanine↗
Preferential utilization of lactate in neonatal dog brain: in vivo and in vitro proton NMR study.
In vivo proton nuclear magnetic resonance spectroscopy was utilized to determine whether lactate is preferentially utilized as metabolic fuel by the neonatal dog brain. The data showed that during lactate influx, metabolism of lactate could account for most of the fuel needed for oxidative metabolism. The in vivo nuclear magnetic resonance measurements were corroborated by conventional arteriovenous determinations which showed steep decline of arteriovenous difference of glucose and sharp increase in arteriovenous difference of lactate during lactate infusion.
Animals↗
Acute lung injury. Pathogenesis of intraalveolar fibrosis.
In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication.
Adolescent↗
Brain energy state and lactate metabolism during status epilepticus in the neonatal dog: in vivo 31P and 1H nuclear magnetic resonance study.
The purpose of these experiments was to determine whether flurothyl-induced status epilepticus causes progressive decline of brain high-energy phosphates and progressive increase in brain lactate in neonatal dogs who are paralyzed and oxygenated. In vivo 31P nuclear magnetic resonance spectroscopic measurements showed that the fall in brain pH occurred early in the course of seizure. The decline in phosphocreatine was more gradual, i.e. 50% reduction, during the 1st h of seizure. There was no reduction in ATP during the 3 h of status epilepticus. In vivo 1H nuclear magnetic resonance measurement of brain lactate disclosed a steep rise that stabilized by 60 min. Brain and blood lactate were closely related during the initial phase of seizure, suggesting rapid efflux of lactate from brain or systemic production of lactate. Blood lactate exceeded brain lactate after 1 h of status epilepticus. The new steady state for cerebral phosphocreatine and lactate during status epilepticus was achieved much more slowly during neonatal status epilepticus than has been reported during status epilepticus in the adult experimental animal. The lack of change in ATP during 3 h of seizure indicates that brain energy state is not radically altered during prolonged seizure if oxygenation is maintained.
Adenine Nucleotides↗