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Biomedical subjects

Y Jin

Publications and source records attributed to Y Jin.

At least 55 records · Page 3Linked to original sources

Quantum partition noise of photon-created electron-hole pairs.

We show experimentally that even when no bias voltage is applied to a quantum conductor, the electronic quantum partition noise can be investigated with GHz radio frequency excitation. Using a quantum point contact configuration as the ballistic conductor we are able to make an accurate determination of the partition noise Fano factor resulting from the photon-assisted shot noise. Applying both voltage bias and rf irradiation we are able to make a definitive quantitative test of the scattering theory of photon-assisted shot noise.

Journal Article↗

Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato.

Epitopes often require co-delivery with an adjuvant or targeting protein to enable recognition by the immune system. This paper reports the ability of transgenic tomato plants to express a fusion protein consisting of the B subunit of the Escherichia coli heat-labile enterotoxin (LTB) and an immunocontraceptive epitope. The fusion protein was found to assemble into pentamers, as evidenced by its ability to bind to gangliosides, and had an average expression level of 37.8 microg g(-1) in freeze-dried transgenic tissues. Processing of selected transgenic fruit resulted in a 16-fold increase in concentration of the antigen with minimal loss in detectable antigen. The species-specific nature of this epitope was shown by the inability of antibodies raised against non-target species to detect the LTB fusion protein. The immunocontraceptive ability of this vaccine will be tested in future pilot mice studies.

Amino Acid Sequence↗

Recombinant matrix metalloproteinase-14 catalytic domain induces apoptosis in human osteoblastic SaOS-2 cells.

Our study previously showed that estrogen and progesterone stimulated the production of matrix metalloproteinase-14 [MMP-14, or also named membrane type matrix metalloproteinses-1 (MT1-MMP)] in osteoblastic cells. MMP-14 was implied to regulate the function of osteoblasts by degrading bone matrix or growth factors, but the mechanism is unclear. Since MMP-14 plays a role primarily through the catalytic domain, and truncated MMP-14 containing the catalytic domain and lacking transmembrane domain can be secreted into medium by cultured cells, our present study was performed to observe the direct effects of recombinant MMP-14 catalytic domain on cultured human osteoblastic osteogenic sarcoma (SaOS)-2 cells. Our data showed that recombinant MMP-14 catalytic domain activated proMMP-2 secreted into media by SaOS-2 cells, and this process was blocked by ethylenediamine tetraacetic acid (EDTA) treatment. Recombinant MMP-14 catalytic domain inhibited the adhesion of SaOS-2 cells to immobilized type I collagen or fibronectin in a dose-dependent manner, and these effects on SaOS-2 cells were abolished by EDTA. Recombinant MMP-14 catalytic domain induced SaOS-2 cells apoptosis in a dose-dependent manner, and apoptosis-inducing activity of MMP-14 catalytic domain was blocked if it was treated with EDTA. In conclusion, we revealed that recombinant MMP-14 catalytic domain induced SaOS-2 cells apoptosis. We also indirectly showed the activity of MMP-14 catalytic domain to degrade extracellular matrix (ECM) in cultures of SaOS-2 cells through Gelatin Zymograms and adhesion assay. This suggests that since adhesion of cells to ECM serves as a survival mechanism in osteoblasts, the catalytic activity of recombinant MMP-14 catalytic domain on matrix proteins contributes to its apoptosis-inducing activity.

Apoptosis↗

Variation in management of community-acquired pneumonia requiring admission to Alberta, Canada hospitals.

Previous studies have shown small area variation in the rate of admission to hospital for patients with community-acquired pneumonia. We determined the rates of admission and length of stay for patients with community-acquired pneumonia in Alberta and the factors influencing admission rates and length of stay. Using hospital abstracts, hospital admissions for community-acquired pneumonia from 1 April 1994 to 31 March 1999 were compared. We classified Alberta hospitals according to geographical regions, by the number of beds, and by number of community-acquired pneumonia cases. There were 12,000 annual hospital discharges for community-acquired pneumonia costing over $40 million per year. The overall in-hospital mortality rate was 12% and the 1 year mortality rate was 26%. Compared with rural hospitals, regional and metropolitan hospitals admitted patients with greater severity of illness as demonstrated by greater in-hospital mortality, cost per case and comorbidity. Age-sex adjusted hospital discharge rates were significantly below the provincial average in both urban regions. Hospital discharge rates for residents in all rural regions and 4 of 5 regions with a regional hospital were significantly higher than the provincial average. After adjusting for comorbidity, the relative risk for a longer length of stay was 22% greater in regional hospitals and about 30% greater in urban hospitals compared to rural hospitals. Seasonal variation in the admission rate was evident, with higher rates in the winter of each year. We conclude that rural hospitals would be likely to benefit from a protocol to help with the admission decision and urban hospitals from a programme to reduce length of stay.

Adolescent↗

D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine.

A goal of pharmacogenetics is to clarify associations between allelic variation and risk factors in psychiatric illness. We report changes in regional brain metabolism based on dopamine alleles. Treatment-resistant schizophrenic subjects were positron emission tomography scanned with 18F-fluorodeoxyglucose after 5 weeks each of placebo and clozapine treatment. Significant regional brain metabolic effects were found for the D1 receptor genotypes (P < 0.05), adjusted for multiple comparisons. Metabolic decreases for the 2,2 genotype but not the 1,2 genotype were observed in all major sectors of the brain, with the exception of the ventral parts of the caudate and putamen. Frontal, temporal, parietal, and occipital neocortices showed decreased metabolism as did the cingulate juxta-allocortex and the parahippocampal allocortex. Decreases were also observed in the thalamus, amygdala, and cerebellum bilaterally. No significant metabolic differences by genotype were observed for D3, 5HT(2A), and 5HT(2C) polymorphisms. In terms of clinical response, the DRD1 2,2 genotype significantly improved with clozapine treatment, demonstrating a 30% decrease in the Brief Psychiatric Rating Scale positive symptoms in contrast to a 7% worsening for the 1,2 genotype (P < 0.05). In this preliminary study, brain metabolic and clinical response to clozapine are related to the D1 receptor genotype.

Adult↗

Biofilm-forming ability of Candida albicans is unlikely to contribute to high levels of oral yeast carriage in cases of human immunodeficiency virus infection.

An increased prevalence of candidal carriage and oral candidiasis is common in cases of human immunodeficiency virus (HIV) infection, and the reasons for this may include the enhanced ability of colonizing yeasts to produce biofilms on mucosal surfaces. The aim of the present study was therefore to examine the differences, if any, in the biofilm-forming abilities of 26 Candida albicans yeast isolates from HIV-infected individuals and 20 isolates from HIV-free individuals, as this attribute of yeast isolates from patients with HIV disease has not been examined before. Biofilm formation in microtiter plate wells was quantitatively determined by both the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) reduction method and the crystal violet method. Although candidal biofilm formation could be quantitatively evaluated by either technique, the better reproducibility (P < 0.05) of the XTT reduction assay compared with that of the crystal violet method led us to conclude that the former is more reliable. There were no significant quantitative differences in biofilm formation between C. albicans isolates from HIV-infected patients and isolates from HIV-free individuals during in vitro incubation in a multiwell culture system over a period of 66 h. Three of eight host factors in the HIV-infected group were found to be associated with candidal biofilm formation. Thus, yeasts isolated from older individuals and those with higher CD4-cell counts exhibited decreased biofilm formation, while the findings for yeasts from individuals receiving zidovudine showed the reverse (P < 0.05 for all comparison). Our data indicate that attributes other than biofilm formation may contribute to the increased oral yeast carriage rates in cases of HIV infection.

AIDS-Related Opportunistic Infections↗

Mortality during hospitalisation for pneumonia in Alberta, Canada, is associated with physician volume.

The association of mortality with patient factors (severity of illness, comorbidity), physician factors (specialty training, prehospitalisation visit, in-hospital consultation, volume of patients seen per physician) and healthcare organisation factors (patient-travel distances, regional beds per capita, admitting hospital-bed occupancy, admitting hospital-bed turnover, hospital location, volume of pneumonia cases per hospital) after hospital admission with community-acquired pneumonia was investigated using administrative data from Alberta, Canada from April 1, 1994-March 31, 1999. During the 5-yr study period there were 43,642 pneumonia hospitalisations, with an 11% in-hospital and 26% 1-yr mortality. Patient severity of illness and comorbidity were the strongest predictors of increased mortality. Physicians with the highest in-hospital pneumonia patient volume (>27 patients x yr(-1)) cared for patients with greater severity/comorbidity, but with decreased odds of in-hospital mortality, compared with the lowest volume physicians (less than seven patients per year). The effects of internal medicine specialist or subspecialist care were mixed, with a reduction in deaths for the first 72 h and an increase in in-hospital deaths. Prehospitalisation visit by a physician was associated with decreased mortality. Healthcare organisation factors were the least strong predictor of mortality, demonstrating an effect only for 1-yr mortality in those discharged alive from hospital. Admissions to larger volume or metropolitan hospitals were associated with a decrease in mortality. Severity of illness and comorbidity had the strongest association with mortality. The first association of high-volume physician and pre-hospital care with decreased in-hospital mortality for community-acquired pneumonia is reported.

Adolescent↗

The transmembrane domain of vesicular stomatitis virus glycoprotein suffices to anchor HIV-1 envelope gp120 expressed by a recombinant vaccinia virus.

The shedding of HIV-1 glycoprotein gp120 results from the proteolytic cleavage of its precursor gp160 into gp120 and an anchoring gp41, to which gp120 is non-covalently attached. This report is directed toward the anchorage of gp120 expressed by three recombinant vaccinia virus (rvv): vPE16 expresses wild-type gp160; vvE13 the gp120-vesicular stomatitis virus G transmembrane and cytoplasmic tail (VSVGTMCT) fusion protein; and vvE14 the gp120 with 52 amino acids (aa) from the vector. In order to convert gp120 into an integral membrane protein, a gp120- VSVGTMCT chimerical gene fragment has been constructed and expressed in mammalian cells. This gp120 fusion protein expressed by an rvv, vvE13, has been shown to elicit better immunogenicity and protection against a gp160-expressing tumor cell line than the full-length envelope (env) glycoprotein gp160 in mice. The results show that gp120-VSVGTMCT expressed by vvE13 is not shed because it is membrane associated. The hydrophobic fragment of vesicular stomatitis virus G (VSVG) furnishes an anchor of the chimeric protein just as it does in the native VSVG.

Genetic Vectors↗

Cross-linking mechanisms of calcium and zinc in production of alginate microspheres.

Calcium chloride and zinc sulphate were used to cross-link alginate microspheres prepared by an emulsification method. The microspheres cross-linked by a combination of these two salts showed different morphology and slower drug release compared with those cross-linked by the calcium salt alone. From viscosity study, it was found that zinc cations interacted with the alginate molecules to a greater extent than calcium cations. The varying effects of the salts on the properties of the microspheres were largely attributed to their ability to interact with the alginate molecules.

Alginates↗

Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres.

Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant, mitotically unstable tumours expressed the reverse transcriptase subunit of telomerase. These data indicate that some of the genomic instability in head and neck tumours is initiated by telomere dysfunction, leading to the formation of dicentric chromosomes. These form chromosome bridges at mitosis that could prevent the normal anaphase-telophase transition. In turn, this may cause an accumulation of centrosomes and mitotic multipolarity. Telomerase expression does not confer total stability to the tumour genome but could be crucial for moderating the rate of chromosomal evolution.

Adenoma, Pleomorphic↗

Genomic-scale analysis of gene expression profiles in TNF-alpha treated human umbilical vein endothelial cells.

OBJECTIVE AND DESIGN: TNF-alpha is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, and in the control of cell proliferation, differentiation and programmed cell death. However, it is known that TNF-alpha is also the founding member of a still growing family of cytokines with diverse bioregulative functions. Its detailed molecular mechanisms on endothelial activation and injury remain to be elucidated. This study was aimed at determining genomic-scale gene expression profiles in TNF-alpha treated human endothelial cells. MATERIALS AND METHODS: In this study cultured human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (10 ng/ml) for 2 and 16 h, respectively, and the gene expression pattern was profiled using a cDNA array representing 14,000 gene/cDNA clusters. RESULTS: In total, 72 known human genes were identified the expression levels of which altered over 2-fold in response to TNF-a stimulation. Such alteration was confirmed for IL-8 and MCP-1, with an independent quantitative mRNA assay. It was observed that genes with related biological functions were often temporally co-regulated. CONCLUSIONS: These results indicate the transcriptional pathways mediated by TNF-alpha inside the HUVECs. Expression profiling in HUVECs responding to TNF-alpha stimulation should give an understanding of the molecular mechanisms involved in vascular inflammation.

Cells, Cultured↗

Accumulation of ammonia in the body and NH(3) volatilization from alkaline regions of the body surface during ammonia loading and exposure to air in the weather loach Misgurnus anguillicaudatus.

The weather loach Misgurnus anguillicaudatus inhabits rice fields that experience drought in summer and ammonia loading during agricultural fertilisation. Exposure of specimens to ammonia led to the accumulation of ammonia in muscle, liver and blood. The level of ammonia reached in the plasma was the highest reported among fishes. Ammonia was not detoxified to urea, and urea excretion rate was unaffected by ammonia exposure. Fish acidified the water to reduce ammonia loading. Ammonia loading, unlike aerial exposure, did not induce glutamine synthesis, and there was no accumulation of glutamine. This is a unique observation different from those reported for other fishes in the literature. An initial switch to partial amino acid catabolism led to the accumulation of alanine and was probably associated with a decreased rate of ammonia production. Aerial exposure led to decreases in rates of ammonia and urea excretion, as well as the accumulation of tissue ammonia. As the internal ammonia levels increased, M. anguillicaudatus was able to excrete some ammonia in the gaseous form (NH(3)). The percentage of ammonia excreted as NH(3) increased with time of exposure and with increasing temperature. It appears that air-breathing through the gut is involved, with the anterior portion of the digestive tract playing a central role: it became significantly more alkaline in fish exposed to air or to environmental ammonia. The skin, which also became more alkaline during air exposure, may also be involved in ammonia volatilization in air-exposed fish. This represents the first report of a fish using volatilization of NH(3) as part of a defence against ammonia toxicity. It can be concluded that the main strategy adopted by M. anguillicaudatus confronted with ammonia loading or air exposure is to tolerate high ammonia levels in the tissues. During periods of elevated tissue ammonia levels, some ammonia is lost by volatilization via air-breathing using the gut. In addition, some ammonia may be lost across the skin during air exposure.

Air↗

UNC-16, a JNK-signaling scaffold protein, regulates vesicle transport in C. elegans.

Transport of synaptic components is a regulated process. Loss-of-function mutations in the C. elegans unc-16 gene result in the mislocalization of synaptic vesicle and glutamate receptor markers. unc-16 encodes a homolog of mouse JSAP1/JIP3 and Drosophila Sunday Driver. Like JSAP1/JIP3, UNC-16 physically interacts with JNK and JNK kinases. Deletion mutations in Caenorhabditis elegans JNK and JNK kinases result in similar mislocalization of synaptic vesicle markers and enhance weak unc-16 mutant phenotypes. unc-116 kinesin heavy chain mutants also mislocalize synaptic vesicle markers, as well as a functional UNC-16::GFP. Intriguingly, unc-16 mutations partially suppress the vesicle retention defect in unc-104 KIF1A kinesin mutants. Our results suggest that UNC-16 may regulate the localization of vesicular cargo by integrating JNK signaling and kinesin-1 transport.

Adaptor Proteins, Signal Transducing↗

Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage.

The effect of over-expressing neuronal calcium sensor 1 (NCS-1) upon stimulated adrenocorticotrophin (ACTH) secretion was studied in AtT-20 cells. Stably-transfected AtT-20 cell lines over-expressing NCS-1 were obtained and compared to wild type AtT-20 cells. Corticotrophin releasing factor (CRF-41)-stimulated ACTH secretion from NCS-1 over-expressing cells was significantly reduced from that obtained in wild type AtT-20 cells. The effects of other stimulants of ACTH secretion from wild type AtT-20 cells were not attenuated in NCS-1 over-expressing cells. Calcium, guanosine 5'-O-(3'-thiotriphosphate) (GTP-gamma-S) and mastoparan stimulated ACTH secretion from permeabilised wild type AtT-20 and NCS-1 over-expressing AtT-20 cells with significantly greater ACTH secretion obtained in NCS-1 over-expressing cells. This study shows that in intact cells over-expression of NCS-1 reduces exocytotic ACTH release, while in permeabilised cells increases ACTH release. NCS-1 has multiple cellular targets and that directly and indirectly via these targets acts to increase the releasable ACTH pool while inhibiting CRF-41 stimulus-secretion coupling.

Adrenocorticotropic Hormone↗

Immature granules are not major sites for segregation of constitutively secreted granule content proteins in NIT-1 insulinoma cells.

Immature secretory granules (ISG's) are sites of segregation of proteins destined for secretion by unregulated pathways from those stored in mature secretory granules in endocrine cells. To determine whether significant soluble protein sorting occurs in ISG's, the secretion of soluble versions of the pancreatic protein GP2 (GP2-GPI(-)) and placental alkaline phosphatase (SEAP) was analyzed in NIT-1 cells. By immunofluorescence microscopy, neither protein localized to SG's in transfected cells. Their secretion was secretagogue-independent in pulse-chase radiolabeling experiments even at early times of chase, while a small increase in the secretion of amylase, which is known to enter ISG's, could be detected. Finally, in sucrose gradient fractionation experiments, SEAP was present in light density fractions. We conclude that while some proteins, such as amylase, have a limited intrinsic capacity to enter ISG's, the segregation of proteins secreted via the constitutive pathway from SG content proteins occurs primarily in the trans Golgi network.

Alkaline Phosphatase↗

A genomewide search for quantitative-trait loci underlying asthma.

A genomewide screen for quantitative-trait loci (QTLs) that underlie asthma was performed on 533 Chinese families with asthma, by the unified Haseman-Elston method. Nine asthma-related phenotypes were studied, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), airway responsiveness as indicated by methacholine (MTCH)-challenge test, serum total immunoglobulin E (TIgE), serum-specific immunoglobulin E, eosinophil count in peripheral blood, and skin-prick tests with three different allergens (cockroach, Dermatophagoides pteronyssinus, and D. farinae). Our study showed significant linkage between airway responsiveness to MTCH and D2S1780 on chromosome 2 (P<.00002) and provided suggestive evidence (P<.002) for six additional possible QTLs: D10S1435 and D22S685, for FEV1; D16S412, for FVC; D19S433, for airway responsiveness to MTCH; D1S518, for TIgE; and D4S1647, for skin reactivity to cockroach. No significant or suggestive evidence of linkage for the other four traits was found.

Adult↗

Cytogenetic and fluorescence in situ hybridization characterization of chromosome 8 rearrangements in head and neck squamous cell carcinomas.

Structural rearrangements of chromosome 8 are frequently encountered in squamous cell carcinomas of the head and neck (HNSCC). These aberrations often affect the centromeric region, resulting in the formation of isochromosome i(8q) and whole arm translocations. Some tumors may display structural rearrangements of 8p23. To characterize further the localization of the breakpoints in such rearrangements, 12 HNSCC known to carry pericentromeric rearrangements of chromosome 8 and 8p23 abnormalities were investigated with fluorescence in situ hybridization (FISH) by the use of 15 YAC clones spanning 8p23 and 8p11 to 8q11. FISH confirmed that all, except one, aberrations cytogenetically interpreted to be i(8q) were true, monocentric i(8q). Similarly, all whole-arm translocations appeared as centric fusions. It could thus be concluded that the essential outcome of these rearrangements is genomic imbalances and not rearrangement of genes in the pericentromeric region. By the use of five YAC clones mapping to 8p23, different breakpoints at the molecular level were disclosed in cases with cytogenetically identical 8p23 rearrangements. An evaluation of the genomic imbalances detected in the present series revealed that overrepresentation of 8q material was present in 11 of the 12 tumors. The most commonly gained segment was 8q22 approximately qter, found in all cases with 8q overrepresentation. Loss of parts of or the entire 8p was seen in 10 tumors. The smallest overlapping deleted region was localized to the subtelomeric region of 8p.

Aged↗