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Biomedical subjects

X Shen

Publications and source records attributed to X Shen.

At least 55 records · Page 3Linked to original sources

Impacts of low-level lead exposure on development of children: recent studies in China.

BACKGROUND: In China, comprehensive epidemiological data relating to the prevalence of childhood lead poisoning are not available. However, existing data suggest that this disease may be widely pervasive as a result of rapid industrialization and the extensive use of leaded gasoline. About twenty publications have reported elevated blood lead levels (BPb) in children from different areas of the country. For the past 5 years, several prospective and retrospective studies have been added to evaluate the harmful health effects of lead at the current degrees of exposure in different places in China. The link between low-level lead exposure and deficits in IQ, neurobehavioral development and physical growth is remarkably consistent without exception. CONCLUSIONS: The harmful health effects of childhood lead poisoning in limited studies of exposed and "unexposed" children demonstrate that this totally preventable disease warrants considerable public health attention in China.

Child↗

Brain iron transport and neurodegeneration.

Despite years of investigation, it is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders. Also, it is not clear whether iron accumulation in the brain is an initial event that causes neuronal death or is a consequence of the disease process. Here, we propose that iron and iron-induced oxidative stress constitute a common mechanism that is involved in the development of neurodegeneration. Also, we suggest that, at least in some neurodegenerative disorders, brain iron misregulation is an initial cause of neuronal death and that this misregulation might be the result of either genetic or non-genetic factors.

Animals↗

Redescription of Steinernema longicaudum Shen & Wang (Nematoda: Steinernematidae); geographic distribution and phenotypic variation between allopatric populations.

Steinernema longicaudum Shen & Wang is redescribed based on a comparative morphological study of specimens from the type isolate from China, and two other isolates recovered from Korea and the USA. For the first and second generation female, the location of the vulva, shape of the vulval lips, and shape and length of the tail were newly observed diagnostic characters. A more detailed description of the morphology of the male spicules and gubernaculum, and the arrangement of the genital papillae is included. A description, based on scanning electron microscopy observations, of the lateral field pattern of the third-stage infective juveniles is also provided. Additionally, restriction fragment length polymorphism profiles based on the internal transcribed spacer region, and cross-breeding tests supplement the description of this species.

Animals↗

Seroetiology of acute lower respiratory infections among hospitalized children in Beijing.

BACKGROUND: Little is known of the etiology of childhood acute lower respiratory infections in China, where the use of antimicrobials is indiscriminate. Trials to change such a policy require etiologic data, especially on the bacteria most relevant to these common diseases. METHODS: One hundred consecutive infants and children from 3 months to 14 years of age with symptoms and signs compatible with acute lower respiratory infections were studied prospectively in the largest pediatric hospital in Beijing from February to May, 1997. Blood culture, thorax radiography and paired sera for 20 microbiologic assays were taken, and the course of illness was monitored uniformly. Disease severity was graded. RESULTS: In 24 cases there was evidence only of bacterial etiology, and in 5 solely viral agents were found; 3 children probably had a mixed bacterial-viral infection. Surprisingly no pneumococcal infection was detected, Mycoplasma pneumoniae (n = 21), Haemophilus influenzae type b (n = 8) and Chlamydia pneumoniae (n = 7) being the dominant bacteria. All children recovered. CONCLUSIONS: Routine use of antimicrobials for these patients seems unjustified. Serologic evidence for the H. influenzae type b etiology is encouraging in terms of vaccination, but confirmatory studies are needed.

Adolescent↗

Group B Streptococcus capsular polysaccharide-cholera toxin B subunit conjugate vaccines prepared by different methods for intranasal immunization.

Group B Streptococcus (GBS) type III capsular polysaccharide (CPS III) was conjugated to recombinant cholera toxin B subunit (rCTB) using three different methods which employed (i) cystamine and N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), (ii) carbodiimide with adipic acid dihydrazide (ADH) as a spacer, or (iii) reductive amination (RA). The CPS III-rCTB conjugates were divided into large- and small-molecular-weight (M(r)) fractions, and the immunogenicities of the different preparations after intranasal (i.n.) immunization were studied in mice. Both large- and small-M(r) conjugates of CPS III-rCTB(RA) or CPS III-rCTB(ADH) induced high, almost comparable levels of CPS-specific immunoglobulin G (IgG) in serum, lungs, and vagina that were generally superior to those obtained with CPS III-rCTB(SPDP) conjugates or a CPS III and rCTB mixture. However, the smaller-M(r) conjugates of CPS III-rCTB(RA) or CPS III-rCTB(ADH) in most cases elicited a lower anti-CPS IgA immune response than the large-M(r) conjugates, and the highest anti-CPS IgA titers in both tissues and serum were obtained with the large-M(r) CPS III-rCTB(RA) conjugate. Serum IgG anti-CPS titers induced by the CPS III-rCTB(RA) conjugate had high levels of specific IgG1, IgG2a, IgG2b, and IgG3 antibodies. Based on the effectiveness of RA for coupling CPS III to rCTB, RA was also tested for conjugating GBS CPS Ia with rCTB. As for the CPS III-rCTB conjugates, the immunogenicity of CPS Ia was greatly increased by conjugation to rCTB. Intranasal immunization with a combination of CPS Ia-rCTB and CPS III-rCTB conjugates was shown to induce anti-CPS Ia and III immune responses in serum and lungs that were fully comparable with the responses to immunization with the monovalent CPS Ia-rCTB or CPS III-rCTB conjugates. These results suggest that the GBS CPS III-rCTB and CPS Ia-rCTB conjugates prepared by the RA method may be used in bivalent and possibly also in multivalent mucosal GBS conjugate vaccines.

Administration, Intranasal↗

The human immunodeficiency virus type 1 gag gene encodes an internal ribosome entry site.

Several retroviruses have recently been shown to promote translation of their gag gene products by internal ribosome entry. In this report, we show that mRNAs containing the human immunodeficiency virus type 1 (HIV-1) gag open reading frame (ORF) exhibit internal ribosome entry site (IRES) activity that can promote translational initiation of Pr55(gag). Remarkably, this IRES activity is driven by sequences within the gag ORF itself and is not dependent on the native gag 5'-untranslated region (UTR). This cap-independent mechanism for Pr55(gag) translation may help explain the high levels of translation of this protein in the face of major RNA structural barriers to scanning ribosomes found in the gag 5' UTR. The gag IRES activity described here also drives translation of a novel 40-kDa Gag isoform through translational initiation at an internal AUG codon found near the amino terminus of the Pr55(gag) capsid domain. Our findings suggest that this low-abundance Gag isoform may be important for wild-type replication of HIV-1 in cultured cells. The activities of the HIV-1 gag IRES may be an important feature of the HIV-1 life cycle and could serve as a novel target for antiretroviral therapeutic strategies.

5' Untranslated Regions↗

Airway branching morphology of mature and immature rabbit lungs.

The scheme of Horsfield et al. for describing the pulmonary airway tree (J Appl Physiol 52: 21-26, 1982) catalogs each airway according to its order and the difference in order of its two daughters (denoted Delta). Although this scheme captures the natural asymmetry in the airway tree, it is still deterministic, because it assumes that all airways of a given order are the same; yet such variability is extremely important in determining the overall behavior of the lungs. We therefore analyzed complete lung lobes from three mature and two immature rabbits and determined the Horsfield order and Delta of every airway down to the terminal bronchioles. We also measured the diameter of each airway. This allowed us to determine the average structure of the rabbit airway tree, the variation about this average, and also how the structures of mature and immature airway trees compare. We found some variation in branching asymmetry and airway diameter at a given order between animals but no evidence of systematic differences in structure between mature and immature lungs. We found evidence of a difference in the branching structure of the peripheral vs. the central part of the airway tree (the break point being around order 20). We also determined the nature of the variation in Delta and diameter as a function of order, which should be valuable for the development of computer models seeking to encapsulate the naturally occurring regional variation in airway geometry in the normal rabbit lung.

Animals↗

Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge.

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.

Aging↗

Comparison of piezo-assisted micromanipulation with conventional micromanipulation for intracytoplasmic sperm injection into human oocytes.

OBJECTIVE: To compare the efficacy of piezo-assisted micromanipulation with conventional micromanipulation for intracytoplasmic sperm injection (ICSI) into oocytes in patients with impaired semen parameters and no success with in vitro fertilization (IVF). STUDY DESIGN: A retrospective randomized study was conducted on 204 cycles for 104 couples with piezo-assisted ICSI and 122 cycles for 96 couples with conventional ICSI. Piezo-assisted ICSI consists of two steps, namely penetration of the zona pellucida alone with a piezo-pulse and then puncturing of the oolemma with a light negative pressure without piezo, as with conventional ICSI. The tips of injection pipettes were prepared after pulling by breakage with a scalpel under a microscope, so that the inner diameter at and near the tip was 5 microm, as for conventional ICSI. RESULTS: Piezo-assisted ICSI demonstrated significantly more favorable results, with a fertilization rate of 90.3% (conventional ICSI: 83.1%, p < 0.01) and a cleavage rate of 88.1% (conventional ICSI: 84.6%, p < 0.01). CONCLUSION: Piezo-assisted ICSI is easy to incorporate a spermatozoa exactly into the ooplasm with little deformation of the oocyte during insertion. Piezo-assisted ICSI can be used effectively for human oocytes to improve the fertilization, cleavage rates.

Adult↗

Role of AMP-activated protein kinase in mechanism of metformin action.

Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.

AMP-Activated Protein Kinases↗

Structural and thermodynamic behavior of eukaryotic initiation factor 4E in supramolecular formation with 4E-binding protein 1 and mRNA cap analogue, studied by spectroscopic methods.

The structural and thermodynamic behavior of the complex formation of eIF4E with either or both mRNA cap analogue (m7GTP, m7GpppA, or m7GpppG) and 4EBP1 has been investigated by spectroscopic measurements. Although the circular dichroism (CD) spectrum of eIF4E was little affected by the association with any cap analogue, the association constant of eIF4E with m7GpppA/G, estimated from the fluorescence quenching, was about 10 times larger than that with m7GTP. The van't Hoff analyses showed that the m7GpppA/G binding is enthalpy-driven with a large negative deltaH(o), and this is in contrast with the entropy-driven binding of m7GTP, where the positive deltaS(o) is large enough to overcome an increase of deltaH(o). This different behavior obviously originates in the interaction of the second nucleotide in m7GpppA with eIF4E, suggesting the importance of the nucleotide sequence linked to the m7Gppp terminal moiety, in addition to the specific interaction with the m7G base, for the recognition of mRNA cap structure by eIF4E. On the other hand, the CD spectra indicated that the binding of 4EBP1, an endogenous eIF4E-regulatory protein without having any defined secondary structure, shifted the m7GTP- or m7GpppA/G-bound eIF4E to an irregular structure, although such a structural change was not observed for eIF4E alone. The association constant of 4EBP1 with m7GTP- or m7GpppA/G-bound eIF4E was by two orders of magnitude larger than that with eIF4E alone. These results suggest the close interrelation in the supramolecular formation of 4EBP-eIF4E-mRNA cap structure.

Adaptor Proteins, Signal Transducing↗

Detection of oligoclonal immunoglobulins in the cerebrospinal fluid by immunofixation electrophoresis.

Many disorders of the central nervous system are associated with increased concentration of cerebrospinal fluid protein due to either an increase in the permeability of blood-brain barrier or the synthesis of immunoglobulins within the central nervous system. Immunofixation electrophoresis was used to detect the immunoglobulins in sera and cerebrospinal fluid in patients with different central nervous system disorders. A strong oligoclonal band, or a single weak monoclonal band, observed in the cerebrospinal fluid but not in the serum, indicates the endogenous immunoglobulin synthesis. In 17 cases of non-infectious central nervous system diseases, we diagnosed one case of progressive multifocal leukoencephalopathy, one case of multiple sclerosis, one case of Guillain-Barre syndrome, and one case of epilepsy. A weak band was observed in both serum and cerebrospinal fluid samples in two cases of cerebral trauma. Out of 25 cases of infectious central nervous system diseases, two cases of nervous system syphilis were positive only in cerebrospinal fluid samples, and 23 cases were negative in both samples. Compared with the standard immunofixation, the application of an enzyme-labeled antibody can significantly increase the sensitivity of the method.

Adult↗

Post-thymic selection of peripheral CD4+ T-lymphocytes on class II major histocompatibility antigen-bearing cells.

Following positive and negative selection in the thymus, mature CD4+ T-cells emigrate into peripheral lymphoid organs. Whether resting T-cells require periodic stimulation to remain viable in the absence of antigen is important for understanding peripheral T-cell homeostasis. A prerequisite for T-cell receptor (TCR)-mediated signals in maintaining peripheral CD4+ T-cell longevity has been demonstrated. Here, we show in mice expressing a mutant I-Abeta transgene on an I-Abeta knockout background that naïve CD4+ T-cells also require engagement of their CD4 coreceptors by peripheral, class II MHC-bearing cells for their survival. The transgene's product combines with endogenous Aalpha, but this mutant AalphaAbeta heterodimer cannot interact with CD4 molecules, although it efficiently presents antigens to TCRs. Resting CD4+ T-lymphocytes from mutant Abeta transgenic mice die by apoptosis at a much higher rate than do CD4+ T-cells from normal mice. Apoptosis of CD4+ T-cells in mutant Abeta transgenic mice is partially mediated by Fas. Adoptive transfer experiments revealed that the increase in apoptosis is due to a lack of interactions with mutant MHC class II rather than to an intrinsic defect in the CD4+ T-cells selected on mutant Abeta-expressing thymic epithelial cells. Thus, interactions between CD4 and MHC class II molecules contribute to the regulation of homeostasis in the peripheral immune system. Our results further suggest that thymic emigrant cells are continuously retested in the periphery for appropriate coreceptor interactions. Peripheral selection may be important in eliminating potentially autoreactive T-cells.

Animals↗

[The survey of polycyclic aromatic hydrocarbons in a habitation air in Hangzhou].

The twelve polycyclic aromatic hydrocarbons(PAHs) were detected in a habitation air air of Hangzhou. The results indicated that the concentrations of PAHs in the habitation air were between 8.237 micrograms/m3 and 14.234 micrograms/m3. The habitation air was seriously polluted by PAHs. The main source of PAHs in the habitation air was from cooking and burning. And the waste gases from vehicular will contribute to it also.

Air Pollutants↗

Spatial learning deficits in amyloid precursor protein 770 transgenic mice.

OBJECTIVE: To determine whether learning deficits could be seen in transgenic mice expressing human amyloid precursor protein 770 (APP770). METHODS: Female heterozygous transgenic and nontransgenic mice aged 3, 6 and 9 months at the start of testing were used, with eight mice in each age group. All mice were subjected to various behavioral tasks including the Y-maze task and the Morris water maze. After behavioral testing, the mice were sacrificed, and their brain tissues were used for measuring the choline acetyltransferase (ChAT) activity. RESULTS: Nine-month-old transgenic mice exhibited spatial learning deficits in the Morris water maze and in spontaneous alternation in the Y-maze, compared with those of the age-matched non-transgenic mice. The behavioral changes accompanied a reduction of ChAT activity in the cortical and hippocampal regions of transgenic mice. On the other hand, these behavioral deficits were not observed in transgenic mice either at 3 or at 6 months of age, in which ChAT activity remained unchanged. CONCLUSIONS: The present results show that the learning impairment observed in 9-month-old APP770 transgenic mice are accompanied by a decrease in cortical and hippocampal ChAT activities. This suggests that cholinergic deficits may be involved in the learning impairment observed in these APP770 mice. This model will be a useful tool in advancing our understanding of the relationship between the cholinergic system and the cognitive deficits observed in Alzheimer's disease (AD).

Amyloid beta-Protein Precursor↗

[Changes of serum transferrin receptor in children with iron deficiency and its response to iron supplementation].

OBJECTIVES: To study the level of serum transferrin receptor (sTfR) in children with different stages of iron deficiency, as well as in the normal children, to observe its response to iron supplementation, and to explore the role of sTfR in surveillance of iron status and assessment of iron supplementation in population. METHODS: By determining iron status index, 1,006 children aged 6-14 years in Fangshan District, Beijing were divided into four groups, control group, iron depletion (ID) group, iron deficiency erythropoiesis (IDE) group and iron deficiency anemia (IDA) group, and 239 of them were measured for sTfR with Quintikine enzyme immunoassay (R&D system, Minneapolis, MN) and sTfR/logserum ferratin (SF) was estimated. Iron supplementation (NaFeEDTA capsules, containing 60 mg iron element per capsule) was administered for the children with ID and IDE per capsule once weekly and for the children with IDA per capsule thrice weekly for nine weeks. Iron status index and sTfR were measured before and after iron supplementation. RESULTS: The levels of sTfR and sTfR/log SF in children with ID, IDE and IDA were (20.03 +/- 2.33) nmol/L, (24.52 +/- 1.07) nmol/L, (33.28 +/- 6.09) nmol/L and (18.15 +/- 5.31), (20.98 +/- 8.88), (29.08 +/- 8.57), respectively, significantly higher than those in the control group [sTfR(18.74 +/- 3.06) nmol/L and sTfR/log SF(9.89 +/- 1.74)]. Statistical analysis showed that sTfR correlated to free erythrocyte protoporphyrin and hemoglobin. sTfR levels in normal children was (12.5-23.5) nmol/L. After iron supplementation, sTfR levels in children with ID was (16.37 +/- 3.10) nmol/L, significantly decreased than those before iron supplementation, but no change in sTfR was observed in children with IDE and IDA. sTfR/log SF were decreased significantly in all children with ID group(11.42 +/- 3.12), IDE (16.54 +/- 4.70) and IDA (23.59 +/- 9.93). CONCLUSION: sTfR is a specific indicator for identifying IDE and IDA, and sTfR/log SF is a sensitive index for assessing the effects of iron supplementation.

Adolescent↗

[Sources analysis and contribution identification of polycyclic aromatic hydrocarbons in indoor and outdoor air of Hangzhou].

Twelve polycyclic aromatic hydrocarbons (PAHs) were measured in eight homes in Hangzhou during the summer and autumn in 1999. The sources of PAHs and the contributions of the sources to the total concentration of PAHs in the indoor air were identified by the combination of correlation analysis, factor analysis and multiple regression, and the equations between the concentrations of PAHs in indoor and outdoor air and factors were got. It was indicated that the factors of PAHs in the indoor air were domestic cuisine, the volatility of the mothball, cigarette smoke and heating, the waste gas from vehicles. In the smokers' home, cigarette smoke was the most important factor, and it contributed 25.8% of BaP to the indoor air of smokers' home.

Air Pollutants↗

[A study on the epidemiological characteristics and the preventive measures of rabies in Shanghai].

OBJECTIVE: To analyze the epidemiological characteristics and the preventive measures of rabies in Shanghai from 1950 to 2000. METHODS: Suspected cases of rabies were investigated epidemiologically and collection of samples to isolate the virus. RESULTS: The most highest morbidity of rabies was 1.98/100,000 in 1950. There had been neither case of rabies, nor the rabies virus positive identified in dogs between 1958 and 1988. The morbidity of rabies was 0 - 0.03/100,000 from 1989 to 2000. According to the data of 20 reported cases from 1985 to Sept. 2000, the mean incubation was 66.37 days, except one case of 14 years. The mean course of diseases was 4.55 days. Seventy percent of the cases did not receive any preventive measure. A hundred and ninety-four persons who were bitten by rabies virus positive dogs were timely treated and all of them survived. In recent years, there has been more than 50,000 persons bitten by dogs every year in Shanghai. The rate of rabies vaccine immunization was over 95%. The rate of anti-rabies serum immunization was over 20%. CONCLUSION: Rabies is a preventable disease even when persons were bitten by dogs with rabies virus positive. The important measure is to treat the wound timely, giving vaccine and anti-rabies serum injection. According to the regulation of dog control in Shanghai, the number of dogs be kept at the lowest level, immunizing all the registration dogs, and destroying the none-registration dogs are the most essential measures to be taken.

Animals↗