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Biomedical subjects

Y Shi

Publications and source records attributed to Y Shi.

At least 55 records · Page 3Linked to original sources
PubMed2003

Air bag effectiveness as function of impact speed.

An investigation was conducted to estimate the effectiveness of air bags as a function of velocity. The study consisted of three parts: a theoretical idealization, an analysis of National Automotive Sampling System/Crashworthiness Data System (NASS/CDS), and a reanalysis of previously published Fatality Analysis Reporting System (FARS) data. The theoretical analysis looked at idealized risk curves as a function of velocity; assuming that the air bag offers a benefit for both belted and unbelted occupants. Analysis of the NASS/CDS data looked at the effectiveness of air bags as a function of velocity for Maximum Abbreviated Injury Scale (MAIS) 3+ injuries. The reanalysis of the previously published FARS data looked at the effectiveness of the air bag as a function of velocity for fatalities. The theoretical analysis indicates that the air bag effectiveness should be greatest at the low velocities. The field data analysis of both NASS/CDS and FARS were consistent with the theoretical analysis, indicating that air bags are most effective at the lower velocities, below 40 kph (25 mph), for both belted and unbelted occupants. Although it was not possible to estimate a different effect for belted and unbelted for fatalities using FARS, it was possible for MAIS 3+ using NASS/CDS. For unbelted occupants the effectiveness goes to zero or becomes negative above 40 kph (25 mph) for MAIS 3+, and for belted occupants the effectiveness stays positive but with significantly lower magnitude for speeds above 40 kph (25 mph).

Abbreviated Injury Scale↗
PubMed2003

Carbon monoxide concentrations in paediatric sepsis syndrome.

Plasma carbon monoxide (CO) concentrations were measured in 12 patients with sepsis syndrome. CO concentrations were found to be significantly increased in patients compared with those in 30 normal controls. Patients with septic shock had significantly higher plasma CO concentrations than those without shock. Results suggest that CO might play an important role in paediatric sepsis syndrome.

Carbon Monoxide↗
PubMed2003

Microwave-induced thermal imaging of tissue dielectric properties.

A new imaging method, microwave-induced thermal imaging (MITI), was developed to differentiate tissue based on thermal and dielectric properties. Image contrast depends on temporal strain in tissue, which was determined by one-dimensional speckle tracking using a phase-sensitive, correlation-based technique. The underlying mechanisms were analyzed and experimental results on biologic tissue agreed well with theoretical predictions. Because of its strong contrast between water-bearing and lipid-bearing tissue, the technique may enhance existing intravascular ultrasound (IVUS) imaging systems to identify vulnerable arterial plaque.

Adipose Tissue↗
PubMed2002

A new cell line-based neutralization assay for primary HIV type 1 isolates.

Simple and standardized assays for detection and quantification of neutralizing antibodies to primary HIV-1 isolates are needed in research on HIV-1 vaccines and pathogenesis. Here we describe a new HIV-1 neutralization assay that is based on plaque formation in U87.CD4-CCR5 and U87.CD4-CXCR4 cells, which is an attractive alternative to peripheral blood mononuclear cell-based assays. Infected cells form syncytia, that is, plaques, that can be stained with hematoxylin and enumerated by light microscopy. Neutralization is determined by the ability of a serum to reduce the number of plaque-forming units (PFU) relative to controls exposed to medium or negative serum. The intraassay variation of the plaque-forming unit determinations was tested with 15 serum-virus combinations and showed good reproducibility. The differences ranged from -19 to +27% and had a standard deviation of +/- 9.1%. On the basis of these data the cutoff for neutralization (i.e., plaque reduction) was set to 30% (3.3 standard deviations). Virus titration experiments showed that neutralization results were dependent on virus dose and therefore the neutralization assays should be performed with a virus dose of 10-100 PFU/well. The reproducibility of the new neutralization assay was tested with 4 primary viruses and 9 sera for a total of 20 virus-serum combinations. The mean difference in neutralization (i.e. plaque reduction) determinations performed on different days was as small as 11%. None of 10 Swedish sera and 1 Ugandan plasma pool from HIV-1-uninfected subjects were positive for neutralization, indicating that the assay has high specificity. In summary, the new U87.CD4 cell line-based neutralization assay for primary HIV-1 isolates is a highly reproducible, sensitive, and high-throughput assay that is well suited for large-scale HIV-1 neutralization studies.

CD4-Positive T-Lymphocytes↗
PubMed2002

Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor.

We report the isolation and functional characterization of the gene encoding MGr1-Ag, a multidrug-resistance-associated protein. A lambdagt11 cDNA library derived from colorectal carcinoma SW480 cells was screened with monoclonal antibody MGr1. DNA homology analysis of 22 positive clones (designated R1-R22) suggested human 37-kDa laminin receptor precursor (37LRP, R7/R9/R15/R16/R19/R20) and a novel gene (R22) as candidate genes encoding MGr1-Ag. Western blot analysis showed that anti-R20 serum reacted with a unique protein band that was consistent with MGr1-Ag, while anti-R22 serum could not react with MGr1-Ag. The coding gene for MGr1-Ag was amplified using reverse transcription-PCR. Sequence analysis revealed that the MGr1-Ag and 37LRP genes shared the same coding sequence. An in vitro drug sensitivity assay indicated that down-regulation of 37LRP by an antisense technique could significantly enhance the cytotoxicity of anticancer drugs to gastric cancer cells. Thus we draw the conclusion that MGr1-Ag is identical to 37LRP.

Carcinoma↗
PubMed2002

Interventional study of high dose folic acid in gastric carcinogenesis in beagles.

BACKGROUND: A decrease in folic acid and subsequent DNA hypomethylation may be involved in gastric carcinogenesis. Epidemiological and nutritional studies have indicated that folate status modulates the risk of developing cancers. AIMS: To investigate whether folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by N-ethyl-N-nitrosoguanidine (ENNG) in beagles. METHODS: Sixteen male beagles were randomly divided into two groups: folic acid treated group and control group. In both groups beagles were fed ENNG 75 mg per day for eight months and in the treated group 20 mg folic acid was given to beagles for 15 months. Gastroscopy and biopsies were performed before and every 2-3 months after administration of ENNG until the end of the experiment. Histopathological lesions were diagnosed with regard to the criteria for human gastric mucosal biopsies. Serum and gastric mucosal tissue folic acid concentrations were measured. RESULTS: In the control group, all beagles developed gastric cancer (8/8) compared with only 3/8 in the folic acid treated group (p<0.05). Moreover, serum and gastric mucosal tissue folic acid concentrations were markedly elevated 15 months after folic acid administration. The difference was statistically significant between the two groups (p<0.05). CONCLUSIONS: Our results indicate that high dose folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by a chemical carcinogen ENNG in beagles.

Animals↗
PubMed2002

Helicobacter pylori associated gastric diseases and lymphoid tissue hyperplasia in gastric antral mucosa.

AIM: To investigate the relation between Helicobacter pylori associated gastroduodenal diseases and lymphoid tissue hyperplasia in the antral mucosa and to pursue its evolution after eradication of H pylori. METHODS: Gastric antral biopsy specimens were obtained from 438 patients with H pylori positive gastroduodenal diseases (185 chronic gastritis, 69 gastric ulcer, and 184 duodenal ulcer) and 50 H pylori negative healthy controls. Lymphoid follicles and aggregates were counted and other pathological features were scored according to the updated Sydney system for classification of chronic gastritis. After a course of anti-H pylori treatment, biopsy specimens were obtained at four to six weeks, 12 months, and 24 months in the chronic gastritis patient group. RESULTS: The total prevalence of lymphoid follicles and aggregates in the biopsies was 79.9% (350 of 438; 95% confidence intervals (CI), 0.76 to 0.84). The prevalence and density of lymphoid follicles and aggregates were significantly different in the various gastroduodenal diseases. The highest prevalence (89.9%; 95% CI, 0.83 to 0.97) and density (0.82) of lymphoid follicles and aggregates occurred in patients with gastric ulcers. The lowest prevalence of lymphoid follicles and aggregates was found in patients with chronic gastritis (74.6%; 95% CI, 0.68 to 0.81), and the lowest density of lymphoid follicles and aggregates (0.56) was seen in patients with duodenal ulcers. The prevalence and density of lymphoid follicles and aggregates correlated strongly with the activity and severity of gastric antral mucosal inflammation. The eradication of H pylori resulted in a decrease in the prevalence and density of lymphoid follicles and aggregates. CONCLUSION: The prevalence and density of lymphoid follicles and aggregates in gastric antral mucosal biopsies correlated closely with H pylori infection.

Adolescent↗
PubMed2001

A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis.

In Caenorhabditis elegans, histone acetyltransferase CBP-1 counteracts the repressive activity of the histone deacetylase HDA-1 to allow endoderm differentiation, which is specified by the E cell. In the sister MS cell, the endoderm fate is prevented by the action of an HMG box-containing protein, POP-1, through an unknown mechanism. In this study, we show that CBP-1, HDA-1 and POP-1 converge on end-1, an initial endoderm-determining gene. In the E lineage, an essential function of CBP-1 appears to be the activation of end-1 transcription. We further identify a molecular mechanism for the endoderm-suppressive effect of POP-1 in the MS lineage by demonstrating that POP-1 functions as a transcriptional repressor that inhibits inappropriate end-1 transcription. We provide evidence that POP-1 represses transcription via the recruitment of HDA-1 and UNC-37, the C.elegans homolog of the co-repressor Groucho. These findings demonstrate the importance of the interplay between acetyltransferases and deacetylases in the regulation of a critical cell fate-determining gene during development. Furthermore, they identify a strategy by which concerted actions of histone deacetylases and other co-repressors ensure maximal repression of inappropriate cell type-specific gene transcription.

Animals↗
PubMed2001

Role of cyclin-dependent kinase inhibitors in the growth arrest at senescence in human prostate epithelial and uroepithelial cells.

Cellular senescence has been proposed to be an in vitro and in vivo block that cells must overcome in order to immortalize and become tumorigenic. To characterize these pathways, we focused on changes in the cyclin-dependent kinase inhibitors and their binding partners that underlie the cell cycle arrest at senescence. As a model, we utilized normal human prostate epithelial cell (HPEC) and human uroepithelial cell (HUC) cultures. After 30-40 population doublings cells became growth-arrested in G0/1 with a threefold decrease in Cdk2-associated activity, a point defined as pre-senescence. Temporally following this growth arrest, the cells develop a senescence morphology and express senescence-associated beta-galactosidase (SA-beta-gal). Levels of p16(INK4a) and p57(KIP2) rise in HUCs during progressive passages, whereas only p16 increases in HPEC cultures. The induced expression of p57, similar to p16, produces a senescent-like phenotype. pRB, cyclin D, p19(INK4d) and p27(KIP1) decrease in both cell types. We find that p53, p21(CIP1) and p15(INK4b) are transiently elevated in HPECs and HUCs at the pre-senescent growth arrest, then return to low proliferating levels at terminal senescence. Analysis of p53, p21(CIP1), p15(INK4b), p16(INK4a), and p57(KIP2) reveals altered expression in immortalized, non-tumorigenic HPV16 E6 and E7 prostate lines and in tumorigenic prostate cancer cells. These results indicate: (i) the existence of a subset of growth inhibiting genes elevated at the onset of the senescence, (ii) a distinct class of genes involved in the maintenance of senescence, and (iii) the frequent inactivation of these pathways during immortalization.

Adult↗
PubMed2001

Cloning and characterization of a novel gene encoding keratin-like protein from nematode Nippostrongylus brasiliensis.

Nippostrongylus brasiliensis (Nb) is one of the most important parasites in studying Th2 immune response of the host, but little is known about its antigenic structures of the excretory-secretory or structural proteins of the parasite. Here we report cloning and characterization of a novel antigenic gene from cDNA library of Nb adult worm by immunoscreening. The positive clone, KLP-Nb, had an open reading frame of 612 bp that encodes a 203-amino-acid protein and was homologous to 'similar to keratins in a glycine-rich region' of Caenorhabditis elegans. Its expression was confirmed by Northern blotting and IgG enzyme-linked immunosorbent assay. This protein seems to be one of the components of cuticle that covers the nematode body.

Amino Acid Sequence↗
PubMed2001

Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding.

Apoptosis is primarily executed by active caspases, which are derived from the inactive procaspase zymogens through proteolytic cleavage. Here we report the crystal structures of a caspase zymogen, procaspase-7, and an active caspase-7 without any bound inhibitors. Compared to the inhibitor-bound caspase-7, procaspase-7 zymogen exhibits significant structural differences surrounding the catalytic cleft, which precludes the formation of a productive conformation. Proteolytic cleavage between the large and small subunits allows rearrangement of essential loops in the active site, priming active caspase-7 for inhibitor/substrate binding. Strikingly, binding by inhibitors causes a 180 degrees flipping of the N terminus in the small subunit, which interacts with and stabilizes the catalytic cleft. These analyses reveal the structural mechanisms of caspase activation and demonstrate that the inhibitor/substrate binding is a process of induced fit.

Amino Acid Sequence↗
PubMed2001

The AKT kinase is activated in multiple myeloma tumor cells.

Immunohistochemistry (IHC) was performed on archived bone marrow (BM) with a phosphospecific anti-AKT antibody. IHC on 26 BM biopsies from patients with multiple myeloma (MM) demonstrated phospho-AKT staining of malignant plasma cells in a cell membrane-specific pattern, whereas nonmalignant hematopoietic cells did not stain. Preabsorption of the antibody with phosphorylated AKT peptide, but not nonphosphorylated peptide, abrogated staining. Frequency of plasma cell staining in BMs of patients with stage I or smoldering MM was significantly less than that of stage III MM marrows. Plasma cells in 10 patients with monoclonal gammopathy of undetermined significance were not stained by the antibody. To investigate the significance of AKT activation, 2 cell lines initiated from cultures of primary MM cells were also studied. Both demonstrated constitutive AKT activation. Interruption of AKT activation and activity, achieved by either exposure to wortmannin or by ectopic expression of a dominant negative AKT mutant, resulted in inhibition of MM cell growth in vitro. These results indicate that activation of the AKT kinase is a characteristic of MM cells and suggest that AKT activity is important for MM cell expansion.

Androstadienes↗
PubMed2001

Change in the degree of adsorption of proteins by aluminum-containing adjuvants following exposure to interstitial fluid: freshly prepared and aged model vaccines.

The ability of interstitial fluid to change the degree of adsorption of ovalbumin to aluminum hydroxide adjuvant or lysozyme to aluminum phosphate adjuvant was studied. Ovalbumin and lysozyme were almost completely eluted after exposure at 37 degrees C to sheep lymph fluid for 4h or 15 min, respectively. The ability of sheep lymph fluid to elute lysozyme from aluminum phosphate adjuvant did not change as the model vaccine aged. However, only 60% of the ovalbumin adsorbed to aluminum hydroxide adjuvant was eluted during exposure to sheep lymph fluid for 24h after the model vaccine aged for 11 weeks at 4 degrees C.

Adjuvants, Immunologic↗
PubMed2001

Molecular genetics and the evolution of ultraviolet vision in vertebrates.

Despite the biological importance of UV vision, its molecular bases are not well understood. Here, we present evidence that UV vision in vertebrates is determined by eight specific amino acids in the UV pigments. Amino acid sequence analyses show that contemporary UV pigments inherited their UV sensitivities from the vertebrate ancestor by retaining most of these eight amino acids. In the avian lineage, the ancestral pigment lost UV sensitivity, but some descendants regained it by one amino acid change. Our results also strongly support the hypothesis that UV pigments have an unprotonated Schiff base-linked chromophore.

Amino Acid Sequence↗
PubMed2001

A novel[2 + 3]cycloaddition reaction: singlet oxygen mediated formation of 1,3-dipole from iminodiacetic acid dimethyl ester and its addition to maleimides.

Sensitized photolysis of iminodiacetic acid methyl ester and maleimides follows a [2 + 3] cycloaddition pathway yielding pyrrolidine derivatives. This is similar to the photochemical reaction between C(60) and amines. A series of pyrrolidine derivatives are prepared by the method including multipyrrolidines from bis- and tris-maleimide starting materials. The yields range from 13% to 85%. The reaction is highly stereoselective. All the isolated products have the 1,3-dimethoxycarbonyl groups in the cis configuration. Various sensitizers may be used with slightly different yields. A plausible mechanism is proposed that involves the singlet oxygen abstraction of two alpha hydrogen atoms from the iminodiacetate and formation of a 1,3-dipole with a structure similar to the classical thermally generated 1,3-dipole.

Journal Article↗
PubMed2001

Distinct requirements for C.elegans TAF(II)s in early embryonic transcription.

TAF(II)s are conserved components of the TFIID, TFTC and SAGA-related mRNA transcription complexes. In yeast (y), yTAF(II)17 is required broadly for transcription, but various other TAF(II)s appear to have more specialized functions. It is important to determine how TAF(II)s contribute to transcription in metazoans, which have larger and more diverse genomes. We have examined TAF(II) functions in early Caenorhabditis elegans embryos, which can survive without transcription for several cell generations. We show that taf-10 (yTAF(II)17) and taf-11 (yTAF(II)25) are required for a significant fraction of transcription, but apparently are not needed for expression of multiple developmental and other metazoan-specific genes. In contrast, taf-5 (yTAF(II)48; human TAF(II)130) seems to be required for essentially all early embryonic mRNA transcription. We conclude that TAF-10 and TAF-11 have modular functions in metazoans, and can be bypassed at many metazoan-specific genes. The broad involvement of TAF-5 in mRNA transcription in vivo suggests a requirement for either TFIID or a TFTC-like complex.

Animals↗