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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 793 records · Page 44Linked to original sources

Reduction of latex aeroallergens and latex-specific IgE antibodies in sensitized workers after removal of powdered natural rubber latex gloves in a hospital.

BACKGROUND: Respiratory symptoms of natural rubber latex (NRL) allergy in health care workers (HCWs) have been reported in rooms with a detectable allergen load. Preventive measures have been proposed to reduce the risk of NRL sensitization. OBJECTIVES: Eliminating powdered NRL gloves from the workplace and giving NRL-free material to sensitized workers has been among proposed preventive measures. To appraise the success of such procedures among HCWs, a prospective study was carried out. METHODS: Sensitization of HCWs to NRL was determined by skin prick tests and measurements of specific IgE antibodies. NRL allergen concentrations in room air were measured before and after substitution of powdered NRL gloves with powder-free or synthetic gloves in different departments of a hospital and determined by a competitive inhibition immunoassay. RESULTS: The prevalence of HCWs with positive skin prick test responses and NRL-specific IgE-positive HCWs was 8% (n = 7) among the 90 examined staff members before the intervention started. All 7 reported glove-related allergic symptoms. Six of 7 sensitized subjects had a significant decrease of latex-specific IgE antibody concentrations during follow-up examinations in April and September 1997 (P <.003). Within 24 hours after substitution took place, NRL aeroallergen levels (up to 49.9 ng/m3) fell below the detection limit in areas with synthetic gloves or powder-free NRL gloves alike. Use of asthma medication and antiallergic drugs could be discontinued by 2 HCWs with NRL-related respiratory tract symptoms. CONCLUSIONS: Our results demonstrate that elimination of powdered NRL gloves is a useful device in reducing aerogen NRL allergen loads below the detection limit and permitting sensitized or allergic personnel to remain on the job.

Adult↗

Identification of hevein (Hev b 6.02) in Hevea latex as a major cross-reacting allergen with avocado fruit in patients with latex allergy.

BACKGROUND: Recent studies demonstrated that allergy to natural rubber latex is frequently associated with hypersensitivity to avocado fruit. The responsible cross-sensitizing allergen has not been identified. OBJECTIVE: The purpose of this study was to investigate the cross-reactivity of a latex major allergen, hevein, with avocado proteins. METHODS: Serum samples from 118 health care workers (HCWs) allergic to latex (HCW group) and 78 patients with spina bifida (SB) allergic to latex (SB group) were included in this study. Anti-hevein and anti-avocado IgE antibodies were measured by enzyme-linked allergosorbent assay. Cross-reactivity of hevein to avocado proteins was assessed by inhibition of the IgE binding in individual patients' sera containing IgE antibodies to both hevein and avocado. RESULTS: The prevalence of seropositive IgE antibodies to avocado was found to be strongly associated with the presence of hevein-specific IgE antibodies in subjects of both groups (P < .001). Sixty-seven of 91 (73%) subjects from the HCW group and all 19 subjects in the SB group with positive IgE antibodies to hevein also had elevated IgE values to avocado. Competitive RAST inhibition with 42 sera showed that IgE binding to avocado could be completely inhibited in 27 (64%) sera by preincubation with hevein. By contrast, the degrees of inhibition of IgE to hevein by avocado extract ranged from 0% to 36% (n = 16). These results indicate that sensitization to avocado in most patients allergic to latex is caused exclusively by IgE-binding epitopes present in hevein. Results of immunoblots and immunoblot inhibition with 11 serum samples confirmed that a 30-kd protein in avocado was the major IgE-binding component; the IgE-binding reactivity to this protein could be inhibited by hevein in all sera tested. CONCLUSION: Hevein is the major cross-reacting allergen with avocado in subjects with latex allergy.

Adolescent↗

Can a threshold limit value for natural rubber latex airborne allergens be defined?

BACKGROUND: Recent studies have shown that systemic or respiratory occupational responses to latex can be induced by inhalation of latex aeroallergens. OBJECTIVE: Our objectives were to study the relationship between exposure to different latex aeroallergen levels and type I allergic reactions in subjects with occupational contact with latex and to assess a threshold value for latex airborne allergens required for sensitization and symptom elicitation. METHODS: We screened 145 subjects working in 32 hospitals or operating rooms with different latex aeroallergen levels. The quantified latex aeroallergen concentrations in the 32 rooms were compared with latex-related allergic symptoms. RESULTS: Different latex aeroallergen concentrations could be detected in rooms where powdered latex gloves were used and no effective ventilation systems were installed. In environments with latex aeroallergen levels of 0.6 ng/m3 or greater, the reported workplace-related symptoms were significantly increased (p < 0.02). All 22 subjects with latex-specific IgE antibodies worked in rooms contaminated with latex aeroallergens (p < 0.05). CONCLUSIONS: Our results demonstrate that symptoms and presence of latex-specific IgE antibodies in subjects are significantly associated with measurable levels of latex aeroallergens. A latex aeroallergen level of 0.6 ng/m3 is a critical threshold, especially for health care workers who are sensitized to natural rubber latex.

Air Pollutants, Occupational↗

TCR diversity in gammadeltaTCR+ hybridomas derived from mice given portal vein donor-specific pre-immunization and skin allografts.

Portal venous (p.v.) immunization with multiple minor histoincompatible cells leads to antigen-specific increased skin allograft survival. GammadeltaTCR+ hybridoma cells, prepared from mesenteric lymphocytes of p.v. immunized animals, can adoptively transfer this increased graft survival to naive animals. We have analyzed VgammaVdelta gene usage, and TCR gamma-chain junctional diversity in gammadeltaTCR+ hybridomas from mice immunized with different antigen combinations by p.v. or conventional lateral tail vein (i.v.) immunization. Following p.v. immunization two independent sets of hybridoma cells were derived, one expressing a common gamma-chain junctional sequence which was also found in > 85% of the hybridomas derived following i.v. immunization, while the other set showed remarkable gamma-chain junctional sequence diversity. The diversity seen in these latter hybridomas was associated with the antigen specificity of the hybridoma cells. Cells expressing these 'unique' TCR junctional sequences were stimulated to produce cytokines both by hsp and by minor-histocompatibility-specific irradiated peritoneal cells. Cells expressing TCR with a common gamma-chain junctional sequence were stimulated to cytokine production by MHC-matched but minor-histocompatibility mismatched (as well as matched) peritoneal cells, but not by hsp. We suggest that p.v. immunization results in stimulation of both antigen-specific and non-specific regulatory gammadeltaTCR+ cells, which can be distinguished by gamma-chain TCR sequence diversity.

Adoptive Transfer↗

The Philadelphia chromosome as a secondary change in leukemia: three case reports and an overview of the literature.

Three cases of acute nonlymphocytic leukemia with a Philadelphia chromosome (Ph) as a secondary abnormality are reported. The Ph was late-appearing in one patient and appeared as an additional anomaly in the other two patients. Fluorescence in situ hybridization studies of the first patient identified the presence of a minor BCR/ABL rearrangement. The findings of these cases support the conclusion that the Ph plays a role not only in leukemogenesis, but also in disease progression. An overview of the literature dealing with similar cases is also presented.

Adolescent↗

Detection of chromosome over- and underrepresentations in hyperdiploid acute lymphoblastic leukemia by comparative genomic hybridization.

Chromosomal analysis of acute lymphoblastic leukemia (ALL) is often difficult because of the suboptimal in vitro growth of the immature lymphoid cell and the poor morphology obtained. In this study, we describe the application of comparative genomic hybridization (CGH) to investigate the genomic abnormalities in 14 patients with ALL, all of whom had cytogenetically identified numerical aberrations or gross chromosomal structural alteration. With the use of CGH, regional or whole chromosome overrepresentation or both were found to be more frequent than underrepresentation (52 gains vs. 6 losses), the most common gains being chromosomes 21 and X. The results of the comparison between CGH and conventional R-banding analysis could be classified into three categories: (1) in three cases, including two with trisomy, CGH and banding analysis gave identical results; (2) in six cases with hyperdiploidy and two cases presenting chromosome structural abnormalities, the results were consistent but with minor discrepancies; (3) in three cases, including two with triploidy and tetraploidy and one with chimeric karyotype together with +22, the data from CGH and cytogenetical analysis were discrepant. CGH could not find the triploidy and tetraploidy. Our results suggest that CGH has certain value in the detection of gains or losses of chromosome materials in hyperdiploid ALL. Nevertheless, the combination of CGH and conventional karyotyping provides more precise information on the genomic imbalance in ALL.

Adolescent↗

Differential expression of the murine Ly-6A/E antigen homolog of human squamous cell carcinoma antigen E48 during malignant transformation and tumor progression of squamous cell carcinoma line Pam 212.

The mRNA differential display method detected increased expression of the mRNA of an immune recognition antigen known as Ly-6A/E after malignant transformation of the murine squamous cell carcinoma line Pam 212. Subsequent loss of expression of Ly-6A/E occurred with metastatic tumor progression of Pam in vivo. Ly-6 molecules have been implicated in immune cell recognition and signal transduction and are homologous to the human E48 SCC antigen that has been shown to be involved in cell-cell recognition. These observations suggest that loss of Ly-6A/E antigen may contribute to tumor progression and metastasis of squamous cell carcinoma through decreased tumor-lymphocyte or tumor-tumor recognition.

Animals↗

Comparison of the ability of viral protein-expressing plasmid DNAs to protect against influenza.

The ability of plasmid DNA encoding various influenza viral proteins from the A/PR/8/34 (H1N1) virus to protect against influenza was compared in BALB/c mice. The plasmid DNA encoded hemagglutinin (HA), neuraminidase (NA), matrix protein (M1), nucleoprotein (NP) or nonstructural protein (NS1) in a chicken beta-actin-based expression vector (pCAGGS). Each DNA was inoculated twice 3 weeks apart at a dose of 1 microgram per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after a second immunization, mice were challenged with the homologous virus and the ability of each DNA to protect mice from influenza was evaluated by decreased lung virus titers and increased survival. Mice, given HA- or NA-expressing DNA, induced a high level of specific antibody response and protected well against the challenge virus. On the other hand, mice given M1-, NP-, or NS1-DNA failed to provide protection, although M1- and NP-DNAs did induce detectable antibody responses. These results indicate that both HA- and NA-expressing DNAs for the surface glycoproteins are most protective against influenza from among the various viral protein-expressing DNAs used here.

Animals↗

neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia.

The NEUROGENINS (NGNs) are neural-specific basic helix-loop-helix (bHLH) transcription factors. Mouse embryos lacking ngn1 fail to generate the proximal subset of cranial sensory neurons. ngn1 is required for the activation of a cascade of downstream bHLH factors, including NeuroD, MATH3, and NSCL1. ngn1 is expressed by placodal ectodermal cells and acts prior to neuroblast delamination. Moreover, NGN1 positively regulates the Delta homolog DLL1 and can be negatively regulated by Notch signaling. Thus, ngn1 functions similarly to the proneural genes in Drosophila. However, the initial pattern of ngn1 expression appears to be Notch independent. Taken together with the fact that ectopic ngn1 expression can convert ectodermal cells to neurons in Xenopus (Ma et al., 1996), these data and those of Fode et al. (1998 [this issue of Neuron]) identify ngns as vertebrate neuronal determination genes, analogous to myoD and myf5 in myogenesis.

Animals↗

Differential expression of MAM-subfamily protein tyrosine phosphatases during mouse development.

The MAM-subfamily of type II transmembrane protein tyrosine phosphatases (PTPases) currently comprises the enzymes PTPkappa, PTPmu and PCP2. In an effort to elucidate the individual physiological roles of these closely related proteins we performed a detailed analysis of their mRNA transcript distributions at different stages of mouse embryogenesis and postnatal brain development. Our in situ hybridization studies revealed distinct and complementary expression patterns of PTPkappa, PTPmu and PCP2 transcripts. Based on our results and previous reports we discuss MAM-PTPases as a new class of morphoregulatory molecules.

Amino Acid Sequence↗

Molecular characterization of the Notch homologue from the Australian sheep blowfly, Lucilia cuprina.

The Drosophila melanogaster Notch gene product as a receptor of intercellular signals and is central to cell fate specification. The Scalloped wings (Scl) gene is the homologue of Notch in the Australian sheep blowfly, Lucilia cuprina. An allele of Scl is thought to be involved in the modification of Darwinian fitness and bristle asymmetry in flies resistant to organophosphorous chemicals (OPs). As a first step towards the testing of this hypothesis we cloned and sequenced Scl. A full-length cDNA segment representing the mRNA of Scl is 8503 bp and encodes a protein of 2653 amino acids, which shares 73.6% identity with Notch. All functional motifs including EGF-like repeats, LNR repeats, cdc 10/ankyrin repeats, opa and PEST elements are present in the same order as in Notch and the sequence identities peak in these motifs. With respect to genomic structure, intron/exon boundaries are conserved but, in most cases, the Scl introns are larger. Sequence analysis of the upstream genomic region reveals that the gene has a TATA-less promoter. Consistent with a central role in embryogenesis and imaginal development, high levels of Scl expression were detected in the early embryonic and pupal stages.

Animals↗

Molecular modeling studies of the binding modes of aldose reductase inhibitors at the active site of human aldose reductase.

Molecular modeling studies using the CHARMM method have been conducted to study the binding modes of aldose reductase inhibitors at the active site of aldose reductase. The energy minimized structures of aldose reductase with six structurally diverse inhibitors (spirofluorene-9,5'-imidazolidine-2',4'-dione (1), 9-fluoreneacetic acid (2), AL1576 (3), 2,7-difluoro-9-fluoreneacetic acid (4), FK366 (5), and Epalrestat (9)) indicate that the side chains of Tyr48, His110, and Trp111 can form numerous hydrogen bonds with either the carboxylate or the hydantoin group of the inhibitors while the side chains of Trp20, Trp111, and Phe122 are positioned to form aromatic-aromatic interactions. Of the three residues (Tyr 48, His 110, and Trp 111) that can form hydrogen bonds with the ionized portion of aldose reductase inhibitors, protonated His110 appears to play an important role in directing charged inhibitors to bind at the active site through charge interaction. Based on the binding mode of the inhibitors and their observed inhibitory activities, pharmacophore requirements for aldose reductase inhibitors are discussed.

Acetates↗

Nonsense and missense translational suppression in plant cells mediated by tRNA(Lys).

A nuclear tRNA(Lys) gene from Arabidopsis thaliana was cloned and mutated so as to express tRNAs with altered anticodons which bind to a UAG nonsense (amber) codon and to the Arg (AGG), Asn (AAC,AAT), Gln (CAG) or Glu (GAG) codons. Concomitantly, a codon in the firefly luciferase gene for a functionally important Lys was altered to an amber codon, or to Arg, Asn, Gln, Glu, Thr and Trp codons, so as to construct reporter genes reliant upon incorporation of Lys. The altered tRNA(Lys) and luciferase genes were introduced into Nicotiana benthamiana protoplasts and expression of the mutated tRNAs was verified by translational suppression of the mutant firefly luciferase genes. Expression of the amber suppressor tRNA(LysCUA) from non-replicative vectors promoted 10-40% suppression of the luciferase nonsense reporters while expression of the amber and missense tRNA(Lys) suppressor genes from a geminivirus vector capable of replication promoted 30-80% suppression of the luciferase nonsense reporter and up to 10% suppression of the luciferase missense reporters with Arg, Asn, Gln and Glu codons.

Amino Acid Sequence↗

The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and KC.

Human and murine squamous cell carcinomas (SCC) have been reported to produce proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and IL-8 or KC. Production of individual members of the proinflammatory cytokine family has been associated with increased tumor growth or metastasis in a variety of neoplasms. In this study, we determined whether the expression of these cytokines occurs as a result of the events of cellular transformation or culture, or is promoted by interaction of neoplastic cells with factors or cells in the host environment. We compared the expression of proinflammatory cytokines following the spontaneous transformation of murine keratinocytes in vitro, and following the formation of tumors and metastases from these transformed keratinocytes in syngeneic recipients in vivo. Using sensitive ELISA assays, we found that cultures of the in vitro transformed Balb/c SCC line Pam 212 do not produce elevated levels of proinflammatory cytokines IL-1alpha, IL-6, GM-CSF and KC, indicating that transformation or culture alone is insufficient to account for the level of cytokine expression detected in patient and experimental tumors. In contrast, Pam reisolates from primary and metastatic tumors were obtained which constitutively produce markedly elevated levels of cytokines IL-1alpha, IL-6, KC and GM-CSF. The increase in the expression of these cytokines by SCC in vivo occurred independent of T and B lymphocyte-mediated immunity, since increases in expression of the cytokines was observed in lines reisolated from immunodeficient athymic nude and SCID Balb/c congenic mice. The increased expression of cytokines appeared to result from additional events in vivo, rather than due to selection of a pre-existing cytokine-producing subpopulation, since clones of the parental cell line expressed lower cytokine levels than cloned reisolates, and clones of the non-secreting parental cell line that formed tumors in vivo secreted elevated levels of cytokines following reisolation. We conclude that the development of SCC that express proinflammatory cytokines is promoted by tumor-host interaction(s) that are independent of specific T and B cell immunity.

Animals↗

Wave propagation mediated by GABAB synapse and rebound excitation in an inhibitory network: a reduced model approach.

A reduction method is used to analyze a spatially structured network model of inhibitory neurons. This network model displays wave propagation of postinhibitory rebound activity, which depends on GABAB synaptic interactions among the neurons. The reduced model allows explicit solutions for the wavefronts and their velocity as a function of various parameters, such as the synaptic coupling strength. These predictions are shown to agree well with the numerical simulations of the conductance-based biophysical model.

Electric Conductivity↗

Methylation of CpG island is not a ubiquitous mechanism for the loss of oestrogen receptor in breast cancer cells.

Methylation has been shown to play an important role in the down-regulation of oestrogen receptors (ER) in breast cancer cells. One critical question that remains unclear is whether methylation can account for the loss of ER expression in cells derived from an ER-positive cell line. This laboratory has established an in vitro cell system using long-term growth of human ER-positive breast cancer cell line T47D in oestrogen-free medium. A clonal cell line, T47D:C4:2 (C4:2), has been characterized. Unlike T47D:A18 (A18), which is a T47D line maintained in oestrogen medium, C4:2 has lost the expression of ER and hormone responsiveness. DNA fingerprinting and restriction fragment length polymorphism (RFLP) analysis results confirmed that C4:2 was of the same lineage as A18. These cell lines provide an invaluable system to study the mechanism of ER expression and regulatory pathways leading to hormone-independent growth. The results here clearly demonstrate that the ER CpG island in C4:2 cells remains unmethylated. The loss of ER in the cell line must be due to mechanisms other than methylation. We also evaluated the ER CpG island in the MDA-MB-231:10A (10A) cell line, which is a clone from the MDA-MB-231 line obtained from ATCC and the DNA from the MDA-MB-231 cell line used in the original report. Unlike the cell line from the report, which showed a full methylation pattern in the island, the 10A line only showed a partial methylation pattern in the CpG island. Possible mechanisms pertaining to the heterogeneous methylation pattern of the ER CpG island in the breast cancer cells are discussed.

Breast Neoplasms↗

Latex allergens.

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Allergens↗