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Biomedical subjects

Mei Chen

Publications and source records attributed to Mei Chen.

At least 37 records · Page 2Linked to original sources

Wound-healing perspectives.

Wound-healing in the skin is a complex orchestration of cellular processes, which has been perfected throughout the eons of phylogeny. It has so many coordinated biologic processes invoked both simultaneously and in a regulated orderly fashion that it has been likened to a recapitulation of gestation. Part of the problem with studying wound healing is in analyzing the processes independently and then seeing how they fit together and influence each other. This article discusses selected and recent scientific observations that have given insight into the biology of human skin wound healing. The article then discusses selected clinical advances that are based less on evidence-based observation and more on what works in practice and promotes wound healing.

Bandages↗

National evaluation of the US Department of Housing and Urban Development Lead-Based Paint Hazard Control Grant Program: study methods.

The US Department of Housing and Urban Development (HUD) undertook an evaluation of its Lead Hazard Control Grant Program between 1994 and 1999. The Evaluation is the largest study ever done on the effectiveness of lead hazard controls implemented in residential dwellings. The Evaluation had several major objectives: determining the effectiveness of various lead hazard controls in reducing residential dust lead levels and children's blood lead levels, establishing the costs of doing lead hazard control work and factors that influence those costs, determining the rate of clearance testing failures and their causes, and identifying possible negative effects of lead hazard control work on children's blood lead levels. This paper reports the overall research design and data collection methods of the Evaluation. The large number of dwelling units enrolled in the Evaluation was possible only by the innovative partnership among HUD, the Evaluators, and the grantees. HUD and the Evaluators relied on the grantees for essentially all of the data collection. The 14 participating HUD Lead Hazard Control Grantees were responsible for implementing the lead hazard control programs in their communities and collecting the study data. This paper describes the methods for recruiting and enrolling dwellings and families, collecting environmental and housing data, interviewing participating families, and collecting data on lead hazard control work performed and its costs. The paper also describes the basic quality control and quality assurance procedures used. The principal outcome measures were lead in dust collected using wipes from floors, window sills, and window troughs and lead in blood collected from children who were 6 years old or younger at enrollment. Data collection was conducted before intervention, immediately postintervention, and 6 and 12 months postintervention. For a subset of dwellings undergoing an extended follow-up data were also collected at 24 and 36 months postintervention. This paper provides the context for subsequent reports that will describe such findings as the influence of lead hazard control work on serial dust lead levels, the influence of lead hazard control work on serial blood lead levels in children, the nature and costs of the lead hazard control work done at the dwellings, and the experience of the grantees in meeting clearance testing requirements.

Environmental Exposure↗

Effectiveness of lead-hazard control interventions on dust lead loadings: findings from the evaluation of the HUD Lead-Based Paint Hazard Control Grant Program.

From 1994 to 1999, the Evaluation of the US Department of Housing and Urban Development Lead-Based Paint Hazard Control Grant Program studied the intervention experiences of over 2800 homes in 11 states in the USA. Each interior intervention was categorized as (in order of increasing intensity) (a) cleaning/spot painting; (b) complete repainting; (c) complete repainting plus window treatments; (d) window abatement plus treatments to other components; (e) abatement of all lead-based paint hazards; or (f) abatement of all lead-based paint. Complete dust testing and environmental data were available for 1034 and 278 dwellings through 12 and 36 months postintervention, respectively. Strategies ranging from complete repainting to window abatement plus other treatments reduced geometric mean preintervention windowsill and floor dust lead loadings up to 36 months postintervention (reductions for complete repainting, from 16 to 5 microg/ft2 on floors and 182 to 88 microg/ft2 on sills; for window abatement plus other treatments, 27-8 microg/ft2 on floors and 570-124 microg/ft2 on sills). Full abatement reduced windowsill and floor loadings from baseline to 12 months postintervention [95-6 microg/ft2 on floors and 518-30 microg/ft2 on sills (data were not available for this strategy at 36 months)]. Window lead-hazard abatement was the most effective measure to reduce dust lead loadings on windows, but this treatment would need to be performed in conjunction with treatments to floors as well as exterior and soil treatments for the most effective control of dust lead on floors.

Dust↗

The influence of common area lead hazards and lead hazard control on dust lead loadings in multiunit buildings.

Owners of multiunit buildings built before 1978 that have interior common areas, and who receive certain forms of federal assistance are generally required to address lead-based paint hazards in those common areas. This study examines the relationships between common area paint and dust lead levels and the floor dust lead loadings in associated dwelling units, as well as the effects of lead hazard control treatments in common areas. This article presents data from common areas in 145 low-income, mostly pre-1940, multiunit buildings with 342 associated dwellings in the U.S. Department of Housing and Urban Development Lead Hazard Control Grant Program at preintervention, clearance, and 1-year postintervention. Interior common areas in these multiunit buildings were not as well maintained as the dwellings in the buildings. At preintervention, a higher percent of the interior common areas had non-intact, lead-based paint on windows, doors and trim, and other interior components than in associated dwellings (95% versus 85%; 78% versus 67%; and 85% versus 62%). Common areas had preintervention entry and interior (i.e., nonentry) floor dust lead loadings more than four times higher than in dwelling units (128 versus 30 micro g/ft(2); 130 versus 28 micro g/ft(2)) while 1-year postintervention common area dust lead loadings are four to six times that of dwelling dust lead loadings (41 versus 11 micro g/ft(2); 44 versus 8 micro g/ft(2)). Windowsill dust lead loadings in common areas were twice the loadings in dwelling units at preintervention and 1-year postintervention (756 versus 383 mu g/ft(2); 154 versus 68 micro g/ft(2)). Interior common area treatments reduced geometric mean common entry dust lead loadings 71% from preintervention to clearance, and maintained those reduced levels from clearance to 1-year postintervention. Higher level interventions were not more effective than low-level interventions in reducing preintervention levels to clearance or 1-year postintervention. This study demonstrates that interior common areas in the multiunit buildings examined contain substantial amounts of deteriorated lead-based paint and dust. Remediation of common areas can effectively reduce those hazards.

Air Pollution, Indoor↗

Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease characterized by autoantibodies to type VII (anchoring fibril) collagen. Therefore, it is a prototypic autoimmune disease defined by a well-known autoantigen and autoantibody. In this study, we injected hairless immune competent mice with purified immunoglobulin G (IgG) fraction of serum from rabbits immunized with the non-collagenous amino-terminal domain (NC1) of human type VII collagen, the domain known to contain immunodominant epitopes. As a control, identical mice were injected with the IgG fraction of serum from non-immunized rabbits. Mice injected with immune IgG developed subepidermal skin blisters and erosions, IgG deposits at the epidermal-dermal junction of their skin, and circulating anti-NC1 antibodies in their serum-all features reminiscent of patients with EBA. Similar concentrations of control IgG purified from normal rabbits did not induce disease in the mice. These findings strongly suggest that autoantibodies that recognize human type VII collagen in EBA are pathogenic. This murine model, with features similar to the clinical, histological, and immunological features of EBA, will be useful for the fine dissection of immunopathogenic mechanisms in EBA and for the development of new therapeutic interventions.

Animals↗

[Clinical study on electroacupuncture combined with manual acupuncture for treatment of simple obesity].

OBJECTIVE: To compare therapeutic effects of electroacupuncture combined with manual acupuncture and simple electroacupuncture on simple obesity. METHODS: One hundred and twenty cases were randomly divided into an electroacupuncture plus manual acupuncture group (observation group, n = 63) and a simple electroacupuncture group (electroacupuncture group, n = 57). Their clinical therapeutic effects and the time starting the therapeutic effect were compared. RESULTS: In the observation group 57 cases (90.5%) were cured and the total effective rate was 100.0%, and in the electroacupuncture group 42 cases (73.7%) were cured and the total effective rate was 96.5%, with significant difference in the cured rate between the two groups (P < 0.05); and the time starting the therapeutic effect in the observation group was superior to the electroacupuncture group. CONCLUSION: Electroacupuncture combined with manual acupuncture is superior to the simple electroacupuncture in the cured rate and the time starting the effect in treatment of simple obesity.

Acupuncture Therapy↗

[Effect of acupuncture on plasma peptide YY in the patient of simple obesity].

OBJECTIVE: To observe changes of plasma peptide YY (PYY) in acupuncture for slimming. METHODS: Thirty-four cases of simple obesity were treated with acupuncture for 3 courses. Body mass index (BMI), and fat percent (F%), and insulin, PYY, blood fat, and blood sugar levels before and after treatment were determined, with 20 normal persons used as controls. RESULTS: The clinical total effective rate was 88.23%. Acupuncture could increase the decreased insulin sensitive index and PYY level (both P < 0.01), with no correlativity between them (P > 0.05). CONCLUSION: Regulation of PYY is possibly one of the mechanisms of acupuncture in slimming, but the relation of PPY with insulin resistance remains to be studied.

Body Mass Index↗

Using DSP, a reversible cross-linker, to fix tissue sections for immunostaining, microdissection and expression profiling.

Mammalian organs are typically comprised of several cell populations. Some (e.g. brain) are very heterogeneous, and this cellular complexity makes it difficult, if not impossible, to interpret expression profiles obtained with microarrays. Instruments, such as those manufactured by Leica or Arcturus, that permit laser capture microdissection of specific cells or cell groups from tissues were developed to solve this problem. To take full advantage of these instruments, however, one must be able to recognize cell populations of interest and, after they are harvested, to extract intact, unmodified RNA from them. Here we describe a novel, fast and simple method to fix and immunostain tissue sections that permits this to be done.

Animals↗

Identification of genes expressed in primate primordial oocytes.

BACKGROUND: The factors involved in oocyte survival and transition from quiescence to the growing phenotype remain unknown. Herein we report genes that are differentially expressed in the primordial oocyte revealed by DNA arrays. METHODS: Primordial oocytes were captured selectively in rhesus monkey ovary sections using laser capture microdissection. The RNA was extracted and amplified in two rounds by T7-based linear RNA amplification, fluorescence labelled and then hybridized to human cDNA arrays containing 7680 elements. RNA from human placenta served as a reference sample. RESULTS: Ninety-five genes were found to be consistently expressed at a higher level in primordial oocytes. Expression of several of these genes in the oocyte has been reported before, e.g. deleted in azoospermia (DAZ), prohibitin and transglutaminase 2. Oocyte expression of several novel transcripts revealed on array hybridization, such as gene 33, ubiquitin-conjugating enzyme E2A, G1 to S phase transition 1, growth arrest and DNA damage-inducible (GADD), and dendritic cell-derived ubiquitin-like protein (DC-UbP) was confirmed by in situ hybridization. Some array-identified gene products [integrin beta3, alpha-tubulin, regulatory telomere elongation protein (RAP1) and cellular repressor of EIA-stimulated genes (CREG protein)] were detected in human oocytes by immunofluorescence. Bioinformatic analysis of the oocyte-enriched transcripts reveals a functional profile summarized as follows: cell cycle (14%); transporter (13%); signal transduction (10%); cytoskeletal (7%); transcription factor (5%); immune response (5%); apoptosis-related (5%); RNA processing (5%); and the remainder of miscellaneous categories. CONCLUSIONS: These observations may contribute to the elucidation of molecular pathways involved in oocyte survival and maturation.

Animals↗

Autocrine erythropoietin signaling inhibits hypoxia-induced apoptosis in human breast carcinoma cells.

Disordered perfusion and the resulting hypoxia are important features conferring tumor heterogeneity, which may contribute to relapse. Hypoxic tumor cells have been associated with resistance both to radiation and to cytotoxic drugs. Hypoxia may also serve as a selection pressure in tumors by promoting apoptosis of some cells and expanding variants with decreased apoptotic potential, and thus play a role in the development of a more aggressive phenotype. Erythropoietin (Epo), induced by hypoxia, controls erythropoiesis and plays a role in protection of neurons from hypoxic damage. We have recently demonstrated hypoxia-stimulated expression of Epo and Epo receptor (EpoR) in human breast and cervix cancers, suggesting a role for autocrine Epo signaling in the hypoxic adaptations of carcinomas. In the current study we provide evidence that increased autocrine Epo signaling induced by moderate levels of hypoxia inhibits hypoxia-induced apoptosis and promotes survival in MCF-7 human breast cancer cells. The anti-apoptotic effect of Epo correlates with upregulation of bcl-2 and bcl-XL, suggesting a mechanism similar to those described in hematopoietic cells. The resulting decreased apoptotic potential of hypoxic tumor cells may contribute to increased aggressiveness and therapy resistance of breast cancers.

Apoptosis↗

Occurrence of antimicrobials in the final effluents of wastewater treatment plants in Canada.

To investigate the occurrence of antimicrobials in the final effluents from wastewater treatment plants (WWTPs) in Canada, analytical methods were developed or modified from previously described methods using solid-phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry. Thirty-one antimicrobials from the macrolide, quinolone, quinoxaline dioxide, sulfonamide, and tetracycline classes were investigated in the final (treated) effluents from eight WWTPs, located in five Canadian cities. Ciprofloxacin, clarithromycin, erythromycin-H20, ofloxacin, sulfamethoxazole, sulfapyridine, and tetracycline were frequently detected in the effluents. The detection of sulfapyridine in effluents is the first report of this compound in environmental samples. Antimicrobials used exclusively for veterinary applications or treatment of livestock, such as carbadox, olaquindox, and chlortetracycline were not detected in the WWTP final effluents. There appear to be differences in the relative concentrations of antimicrobials detected in WWTP final effluents in Canada relative to concentrations reported previously in northern Europe, particularly for quinolone and sulfonamide compounds. These data may reflect differences in prescription patterns in Canada and northern Europe. The antimicrobials frequently detected in WWTP effluents appear to be those prescribed heavily in Canada for medical applications, and these compounds should be considered priority compounds for monitoring in surface water near WWTP discharges. The concentrations of antimicrobials detected in WWTP final effluents did not exceed 1 microg/L; levels that are unlikely to affect the growth and survival of aquatic organisms.

Anti-Bacterial Agents↗

Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders that are caused by mutations in the type VII collagen gene and for which ex vivo gene therapy has been considered. To develop a simpler approach for treating DEB, we evaluated the feasibility of protein-based therapy by intradermally injecting human recombinant type VII collagen into mouse skin and a DEB human skin equivalent transplanted onto mice. The injected collagen localized to the basement membrane zone of both types of tissues, was organized into human anchoring fibril structures and reversed the features of DEB disease in the DEB skin equivalent.

Animals↗

Toxoplasma gondii infection inhibits the development of lupus-like syndrome in autoimmune (New Zealand Black x New Zealand White) F1 mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. In the present study using New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZBW F1) mice, we planned to investigate the effects of Toxoplasma gondii infection on the progress of lupus nephritis. Female NZBW F1 mice at the age of 2 months were perorally infected with T. gondii. The T. gondii infection reduced the number of mice developing proteinuria and immune complex deposits in their kidneys and prolonged their life span. A marked decrease in the levels of IgM and IgG anti-DNA antibodies, especially IgG2a and IgG3 subclasses, was observed in T. gondii-infected NZBW F1 mice at 9 months of age. The level of anti-HSP70 IgG autoantibody in the sera of NZBW F1 mice was significantly higher than that in control mice at 9 weeks after T. gondii infection. Moreover, NZBW F1 mice treated with anti-self heat shock protein 70 (HSP70) monoclonal antibody were substantially protected against the onset of glomerulonephritis. Further, down-regulation of intracellular expression of IFN-gamma and IL-10 was shown in spleen cells of T. gondii-infected NZBW F1 mice. This was consistent with the previous data indicating the involvement of Th1-type and Th2-type cytokines in the development of lupus-like nephritis. These results suggest that T. gondii infection is capable of preventing the development of autoimmune renal disorder in NZBW F1 mice.

Animals↗

Occurrence and determinants of increases in blood lead levels in children shortly after lead hazard control activities.

This study is an examination of the effect of lead hazard control strategies on children's blood lead levels immediately after an intervention was conducted as part of the US Department of Housing and Urban Development's Lead-Based Paint Hazard Control Grant Program. Fourteen state and local government grantees participated in the evaluation. The findings indicated an overall average reduction in the blood lead levels of 869 children soon after the implementation of lead hazard controls. However, 9.3% of these children (n = 81) had blood lead increases of 5 microg/dL or more. Data routinely collected as part of the evaluation, as well as additional information supplied by the individual programs, were used to determine potential reasons for these observed increases in blood lead. A logistic regression analysis indicated that three principal factors were associated with the blood lead increases: the number of exterior deteriorations present in the child's home (prior to intervention), the educational level of the female parent or guardian of the child, and the child's age. The statistical analysis did not find evidence that children living in households that either did not relocate or relocated for less than the full work period were significantly more likely to have a blood lead increase equal to or greater than 5 microg/dL than children living in households that fully relocated. Statistical analyses also did not reveal any single interior strategy to be more or less likely than others to be associated with a blood lead increase of 5 microg/dL or more.

Child↗

A patient with both bullous pemphigoid and epidermolysis bullosa acquisita: an example of intermolecular epitope spreading.

Bullous pemphigoid (BP) and epidermolysis bullosa acquisita are distinct autoimmune blistering disorders. BP is characterized by autoantibodies directed against the NC16A domain of collagen XVII, whereas patients with epidermolysis bullosa acquisita have autoantibodies against the NC1 domain of type VII collagen. We followed up a patient with BP for 9 years. During that time his clinical disease took on several features suggestive of epidermolysis bullosa acquisita. The objective of this study was to determine if the patient's autoantibody profile reflected the change in his clinical picture. Enzyme-linked immunosorbent assay and immunoblotting for detection and subclass determination of autoantibodies to type XVII and type VII collagen were performed on banked patient sera from the 9-year period. The patient's initial autoantibodies were exclusively IgG1 directed against collagen XVII. During the course of his illness, the subclass specificity of the patient's type XVII collagen autoantibodies shifted to the IgG4 subclass and during the same time interval the patient developed IgG2 autoantibodies directed against type VII collagen. This patient with BP exhibited both subclass shifting and development of a second autoantibody system that correlated with a change in the clinical appearance of the disease. The analysis of the patient's autoantibodies provides strong evidence for the involvement of epitope spreading in the evolution of his autoimmune disease.

Autoantibodies↗

A quantitative assay method of Toxoplasma gondii HSP70 mRNA by quantitative competitive-reverse transcriptase-PCR.

Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) has been identified as a virulent molecule expressing only in T. gondii tachyzoites during lethal acute infection. Therefore, it is of importance to determine the expression of T.g.HSP70 mRNA in a quantitative manner for analysis of virulence of T. gondii in tissues. We have constructed a competitor T.g.HSP70 and have successfully established a quantitative competitive-reverse transcriptase-polymerase chain reaction (QC-RT-PCR) targeting T.g.HSP70 gene. By using the established QC-RT-PCR method, we have demonstrated that the copy number of T.g.HSP70 mRNA per T. gondii tachyzoite was highest in the lung among the organs examined in interferon-gamma knockout (GKO) mice.

Animals↗