Biomedical subjects

S Pan

Publications and source records attributed to S Pan.

At least 19 recordsLinked to original sources

PubMed2004

Gene transfer of interleukin-4 delays acute rejection of splenic allografts in rats.

Spleen transplantation is the treatment of choice for some diseases, such as hemophilia A. However, the risk and intensity of rejection after spleen transplantation is greater and more difficult to control than other types of transplant. In the present study, we demonstrated that perfusion of IL-4 expression plasmids into donor spleens pretransplantation led to overexpression of IL-4 and downregulation of IFN-gamma in situ, associated with delayed acute rejection of the allograft. Gene transfer of IL-4 may represent a potential therapeutic approach to induce tolerance to splenic allografts.

Animals↗

PubMed2004

Administration of tolerogenic dendritic cells induced by interleukin-10 prolongs rat splenic allograft survival.

The risk and intensity in splenic graft rejection are greater than in other types of transplants, because the spleen is the largest peripheral lymphoid organ and the immunosuppressive drugs administered can cause splenic dysfunction. In this study, we demonstrate that intravenous injection of interleukin-10-treated donor-type dendritic cells into recipient rats prolongs the survival of splenic allografts. Although the mechanisms are not clear, the induction of tolerance to grafted spleens seems to rely mainly on blockage of expression of the costimulatory molecule CD86, by interleukin-10, leading to enhanced apoptosis of allospecific T cells by immature and tolerogenic dendritic cells. Administration of tolerogenic cells induced by interleukin-10 may thus represent a useful approach for protection of splenic allografts. Further study is required to investigate the operative pathways and to optimize the strategy targeting dendritic cells to induce tolerance in splenic allografts.

Animals↗

PubMed2004

Identification of a novel HLA-DQA1 null allele, DQA1*0403N, from an East African woman.

We report a novel DQA1 allele (DQA1*0403N) identified during sequence-based HLA-DQA1 typing of a Kenyan population. The new allele is identical to DQA1*0401 at exon 2 except for a single-nucleotide substitution at codon 53, changing it from lysine to a stop codon (CAA-->TAA). The substitution at codon 53 was confirmed by sequencing two separate polymerase chain reaction products and by sequencing multiple clones obtained following TOPO-TA cloning. The resulting stop codon at position of codon 53 in exon 2 is predicted to produce a non-functional DQA1 alpha-chain. The new allele has been named by the WHO nomenclature committee as DQA1*0403N. This is the first report of a null allele detected in the DQA1 gene.

Adult↗

PubMed2004

The effect of hydraulic retention time on the stability of aerobically grown microbial granules.

AIMS: The aim of this study is to evaluate the effect of hydraulic retention time (HRT) on the development of aerobically grown microbial granules. METHODS AND RESULTS: Five column-shaped sequential aerobic sludge blanket reactors (SASBRs) were seeded with aerobically grown microbial granules and operated in a cyclic mode at different HRTs. At the shortest HRT of 1 h, the strong hydraulic pressure triggered biomass washout and led to reactor failure. At the longest HRT of 24 h, which represented the weakest hydraulic selection in this study, aerobic granules were gradually substituted by bioflocs because of the lower frequency of volumetric exchange. Within the optimum range of HRTs from 2 to 12 h, however, aerobic granules became stabilized in the presence of adequate hydraulic selection in the reactors, with good mixed liquor volatile suspended solids (MLVSS) retention, high volumetric chemical oxygen demand (COD) removal, low sludge volume index (SVI) values, good effluent quality, low sludge production rate, stronger and more compact structures, high cell hydrophobicity and high ratios of extracellular polysaccharides (PS) to extracellular proteins (PN). CONCLUSIONS: HRTs between 2 and 12 h provided the hydraulic selection pressures favourable for the formation and maintenance of stable aerobic granules with good settleability and activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first systematic study on the effect of HRT on heterotrophic aerobic granules. The results of the investigation are useful in understanding how aerobic granules can be applied for wastewater treatment.

Aerobiosis↗

PubMed2003

Biomass and porosity profiles in microbial granules used for aerobic wastewater treatment.

AIMS: To obtain biomass and porosity profiles for aerobically grown granules of different diameters and to determine a suitable range of granule diameters for application in wastewater treatment. METHODS AND RESULTS: Microbial granules were cultivated in an aerobic granulated sludge reactor with model wastewaters containing acetate, or ethanol plus acetate, or glucose as the main carbon source. Granules were formed by retaining microbial aggregates using a settling time of 2 min. Sampled granules had diameters ranging from 0.45 to 3 mm. Microbial biomass in the granules was detected with the nucleic acid stain SYTO 9 and confocal laser scanning microscopy. The thickness of the microbial biomass layer was proportional to the granule diameter, and had a maximum value of 0.8 mm. The thickness of the microbial biomass layer correlated with the penetration depth of 0.1 microm fluorescent beads into the granule. CONCLUSIONS: The microbial biomass and porosity studies suggest that aerobically grown microbial granules should have diameters less than a critical diameter of 0.5 mm, if deployed for wastewater treatment applications. This critical diameter is based on the assumption that whole granules should have a porous biomass-filled matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: This work could contribute to the development of aerobic granulation technology for effective biological wastewater treatment.

Aerobiosis↗

PubMed2003

The effect of organic loading rate on the aerobic granulation: the development of shear force theory.

The effect of organic loading rate (OLR) on aerobic granulation was studied by adopting three column-shaped, sequential aerobic sludge blanket reactors (SASBR). The reactors had been fed with laboratory prepared, synthetic dextrose-nutrient broth substrate. Experimental results showed clearly that the formation, characteristics and stability of aerobic granules had a close relationship with the strength of OLR applied. Aerobic granules appeared firstly under the OLR of 4 kg COD x (m3 x day)(-1). The system stabilization was demonstrated by its little-changed amount and morphology of granules. The characteristics of the stabilized granules were: 5.4 mm in mean diameter, 1.29 in roundness, 118 mg O2 x (mg VSS x hr)(-1) in SPOUR. The respective biomass SVI was 50 mL x (g MLVSS)(-1) and the averaged COD removal rate was 95%. Under the OLR of 8 kg COD x (m3 x day)(-1), granules appeared two days later than those for 4 kg COD x (m3 x day)(-1) and they always coexisted with flocs. The formed granule bed was not as compact as that under 4 kg COD x (m3 x day)(-1). There were no granules formed under the OLR of 1 kg COD x (m3 x day)(-1). Instead, flocs with rather loose structure dominated reactor mixed-liquor. The respective SVI's were 65 and 138 mL x (g MLVSS)(-1) under OLR of 8 and 1 kg COD x (m3 x day)(-1). It was proposed that the growth and maintenance of aerobic granules follow the shear force balance theory. Under the OLR of 4 kg COD x (m3 x day)(-1), a balance was reached between the aeration shear force and organic loading rate. Under this favored condition aerobic granules formed quickly and, became stabilized with the experimental parameters remained unchanged.

Bacteria, Aerobic↗

PubMed2002

HLA-A and HLA-B in Kenya, Africa: allele frequencies and identification of HLA-B1567 and HLA-B4426.

HLA-A and HLA-B alleles of a population from Kenya, Africa were examined by sequencing exon 2 and exon 3 DNA and typing using a Taxonomy-based Sequence-analysis (TBSA) method. Extensive diversities were observed at both HLA-A and HLA-B loci in this population. Forty-one HLA-A alleles were identified from 159 unrelated individuals. The most frequently observed alleles were A*6802 (11.64%), A*02011/09 (9.75%), A*7401/02 (9.43%), A*3001 (7.86%), A*3002 (7.23%) and A*3601 (6.6%). Forty-nine HLA-B alleles were identified in 161 unrelated individuals, including two novel alleles, B*1567 and B*4426. The most frequently observed HLA-B alleles were B*5301 (9.01%), B*5801 (8.38%), B*4201 (7.76%), B*1503 (7.14%), B*1801 (6.21%), and B*5802 (5.90%). The most frequently observed HLA-A-B haplotypes were A*3601-B*5301 (3.55%) and A*3001-B*4201 (3.19%), followed by A*7401/02-B*5801 (2.84%), A*7401/02-B*5802 (2.84%) and A*02011/09-B*1503 (2.13%). Linkage disequilibrium and chi2 analysis showed the association of these HLA-A-B haplotypes at the antigen level to be significant. The frequencies of HLA-A and HLA-B alleles from the Kenyan population were compared with that of a population from Cameroon. The difference in allele and haplotype frequency distributions partly reflected the different ethnic composition of these two African populations.

Adult↗

PubMed2002

Specific layers in aerobically grown microbial granules.

AIMS: To determine the optimal size of aerobically grown granules for wastewater treatment by measuring specific layers within the granules. METHODS AND RESULTS: A variety of biological layers were detected by oligonucleotide probes, specific fluorochromes, and fluorescent microspheres. The channels in the granule matrix penetrated to depths of 900 microm. A layer of obligate anaerobic bacteria was detected at a depth of 800 microm below the granule surface. Dead cells were also observed in the granule interior. CONCLUSIONS: Aerobically grown granules contained layers of aerobic and anaerobic micro-organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: The optimal diameter of the aerobic granule is less than 1600 microm. This is twice the distance from the granule surface to the anaerobic layer. This approach can be used to optimize the thickness of other microbial aggregates such as flocs, colonies and biofilms.

Aerobiosis↗

PubMed2002

Risk factors for male breast cancer in Canada, 1994-1998.

Relatively little attention has been paid to the aetiology of male breast cancer and the current understanding of female breast cancer, primarily related to reproductive events, cannot be readily transferred to understanding the cancer in males. However, since male breast cancer occurs in the absence of factors related to childbearing and menstruation, its aetiology may provide special insights into the causes of breast cancer in women. We examined lifestyle risk factors for male breast cancer as part of a Canadian, multi-site, population-based, case-control study. Eighty-one newly diagnosed, histologically confirmed cases and 1905 male controls aged 42-74 were analysed using unconditional logistic regression. Increased risks were found for men with a mother or sister with breast cancer (adjusted odds ratio (OR) 3.65, 95% confidence interval (95% CI) 1.62-8.19). Higher physical activity levels (moderate, and strenuous recreational plus occupational) were associated with a decreased risk of male breast cancer (highest quartile, adjusted OR 0.48, 95% CI 0.26-0.91). Similarly, higher risks were associated with higher weight 2 years before interview (2.19, 95% CI 1.08-4.43), maximum weight (OR 2.66) and higher body mass index (OR 1.60). Higher vegetable consumption and coffee consumption were associated with decreased risk, whereas higher beta-carotene, vitamin E and calcium supplementation were associated with statistically significant increased risk. The small number of cases and multiple comparisons preclude strong conclusions, but our study is consistent with studies suggesting obesity and family history increase risk, and physical activity decreases risk of breast cancer.

Adult↗

PubMed2001

Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites.

The gene for the major angiogenic factor, vascular endothelial growth factor (VEGF), encodes several spliced isoforms. We reported previously that overexpression of two VEGF isoforms, VEGF(121) and VEGF(165), by human glioma U87 MG cells induced tumor-associated intracerebral hemorrhage, whereas expression of a third form, VEGF(189), did not cause vessel rupture. Here, we test whether these VEGF isoforms have distinct activities for enhancing vascularization and growth of gliomas in mice. U87 MG cells that overexpressed VEGF(165) or VEGF(189) grew more rapidly than the parental cells in both s.c. and intracranial (i.c.) locations. However, cells that overexpressed VEGF(121) only showed enhancement of i.c. tumor growth but had a minimal effect on s.c. glioma progression. At both anatomical sties, VEGF(165) and VEGF(189) strongly augmented neovascularization, whereas VEGF(121) only increased vessel density in brain tumors. In each type of glioma, expression of VEGF receptors -1 and -2 largely phenocopied the tumor vasculature, because increased VEGF/VEGF receptor-activated microvessel densities were strongly correlated with the angiogenicity and tumorigenicity elicited by the VEGF isoforms at both anatomical sites. One notable difference between the sites was the expression of vitronectin, a prototypic ligand of alpha(v)beta(3) and alpha(v)beta(5) integrins, detected in i.c. but not in s.c., gliomas. Endothelial cell migration stimulated by VEGF(121) was potentiated by vitronectin to a greater extent than that stimulated by VEGF(165). This data demonstrates that VEGF isoforms have distinct activities at different anatomical sites and suggest that the microenvironment of different tissues affects the function of VEGF isoforms.

Animals↗

PubMed2001

Role for tissue factor pathway in murine model of vascular remodeling.

Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay between TF and TFPI and the regulation of vascular thrombogenicity in a model of vascular remodeling. To determine the levels and pattern of vascular expression of TF and TFPI associated with vascular remodeling, a murine model of flow cessation was studied. TF activity of the arteries increased after ligation (P<0.05). Quantitative analysis of homogenates of remodeled carotid arteries revealed increased TF expression but unchanged TFPI expression compared with normal carotid arteries, resulting in enhanced TF activity. To determine the potential therapeutic role of TFPI in this thrombogenic state, mice were treated with intravascular adenoviral delivery of either murine TFPI (Ad-mTFPImyc) or a control adenovirus (Ad-DeltaE1). Overexpression of TFPI decreased vascular TF activity compared with viral control (P<0.01). Overexpression of TFPI inhibited neointimal formation (P=0.038), resulting in enhanced luminal area (P=0.001) 4 weeks after flow cessation. In this murine model of vascular remodeling, an imbalance between TF and TFPI expression is generated, resulting in increased TF activity. Overexpression of TFPI in this model inhibits vascular TF activity and results in attenuation of vascular remodeling associated with flow interruption.

Animals↗

PubMed2001

Factors influencing the induction of DT-diaphorase activity by 1,2-dithiole-3-thione in human tumor cell lines.

NAD(P)H:(quinone acceptor)oxidoreductase (DT-diaphorase) is a two-electron reducing enzyme that activates bioreductive antitumor agents and is induced by a wide variety of compounds including 1,2-dithiole-3-thione (D3T). We investigated factors influencing DT-diaphorase induction in fourteen human tumor cell lines. Four cell lines had basal DT-diaphorase activity that was increased by D3T treatment (group A), six cell lines had basal DT-diaphorase activity but the activity was not increased by D3T (group B), and four cell lines had low enzyme activity without, or with, D3T (group C). Two cell lines in group A and two cell lines in group B had a C to T polymorphism at base 609 in the NQO(1), DT-diaphorase gene, in one allele, while all four cell lines in group C were homozygous mutants. The base 609 mutant NQO(1) gene produces a protein with little enzyme activity. In group A, D3T increased NQO(1) mRNA and wild-type protein, and also increased mutant protein in the two heterozygous cell lines. In group B, the inducer slightly increased NQO(1) mRNA, did not increase the wild-type protein, but did increase the mutant protein in the two heterozygous cell lines. In group C, D3T increased NQO(1) mRNA as well as its mutant enzyme product. Transfection of the mutant NQO(1) gene into cells with two wild-type alleles did not alter DT-diaphorase activity. The results suggest that the lack of induction of DT-diaphorase activity is transcriptional in nature, that basal and induced expression of DT-diaphorase are regulated independently, and that mutant NQO(1) does not act as a dominant-negative to suppress DT-diaphorase activity.

Antineoplastic Agents↗

PubMed2001

Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase.

3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1. It was found that several compounds were potent inhibitors of HIV-1 with the most potent compound 24 exhibiting an IC90 = 32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC90s against several clinically meaningful mutant virus strains.

Anti-HIV Agents↗

PubMed2001

3,3a-Dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones are potent non-nucleoside reverse transcriptase inhibitors.

A series of unique 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones and a 2a,5-dihydro-2H-thieno[4,3,2-de]quinazo-line-4(3H)-thione were found to be HIV-1 non-nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed an IC90 = 4.6 nM against wild-type virus in a whole cell antiviral assay and had an IC90 = 76 and 897 nM against the clinically significant K103N and K103N/L100I mutant viruses, respectively.

Binding Sites↗

PubMed2001

Early colonic carcinoma with extensive lymph node metastases: case report and review of literature.

An 81-year-old woman had an early carcinoma invading focally into the upper submucosa of the middle-transverse colon, which was accompanied by extensive lymph node metastases and resulted in a poor prognosis. Although her tumor was small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor enabled its earlier detection. To further study the exceptional lymph node metastases we studied the expression of intestinal trefoil factor and sialyl Tn antigen immunohistochemically on the resected specimen. Their simultaneous expression in lymph node metastasis further supports the aggressive nature of this tumor.

Adenocarcinoma↗

PubMed2001

Mining time dependency patterns in clinical pathways.

Clinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length of hospital stay of each patient. The development of clinical pathways is a lengthy process, and may require the collaboration among physicians, nurses, and staffs in a hospital. However, the individual differences cause great variances in the execution of clinical pathways. It calls for a more dynamic and adaptive process to improve the performance of clinical pathways. This paper reports a data mining technique we have developed to discover the time dependency pattern of clinical pathways for managing brain stroke. The mining of time dependency pattern is to discover patterns of process execution sequences and to identify the dependent relation between activities in a majority of cases. By obtaining the time dependency patterns, we can predict the paths for new patients when he/she is admitted into a hospital; in turn, the health care procedure will be more effective and efficient.

Algorithms↗

PubMed2001

Overexpression of Hp95 induces G1 phase arrest in confluent HeLa cells.

Xp95, a protein recently identified in Xenopus laevis, is potentially involved in progesterone-induced Xenopus oocyte maturation. In this study, we cloned a human homologue of Xp95, designated Hp95, and examined the effect of its overexpression on the growth properties of human malignant HeLa cells which have lost the contact inhibition of cell proliferation. We observed that although HeLa cells did not undergo G1 phase arrest at any stage after confluence, they were able to downregulate their G1 phase CDK activities in response to confluence. When Hp95 was overexpressed in HeLa cells by transfection with a constitutive or an inducible expression vector containing a full-length Hp95 transgene, HeLa cells became able to undergo G1 phase arrest and form a monolayer culture after confluence. However, the G1 phase CDK activities in these Hp95 overexpressing cells were not inhibited further as compared to control cells after confluence. These results indicate that the defects in HeLa cells that cause the loss of contact inhibition of cell proliferation are in components downstream of the G1 phase CDKs and that overexpression of Hp95 counteracts some of these defects.

Amino Acid Sequence↗

PubMed2001

Investigation of the extent of gastric metaplasia in the duodenal bulb by using methylene blue staining.

BACKGROUND AND AIMS: The existence of gastric metaplasia (GM) of the duodenal mucosa has been considered to be highly related to the recurrence of duodenal ulcers (DU). The aims of this study are to evaluate the usefulness of methylene blue staining in the detection of GM, and to clarify the relationship between GM and the deformity of the duodenal bulb. METHODS: Fifteen patients with healed DU and four patients with symptoms of dyspepsia without evidence of ulcers were enrolled into this endoscopic study. During each endoscopy, methylene blue was sprayed evenly on the duodenal bulb, and biopsies were taken from blue-stained and unstained areas. The existence and extent of GM were assessed histologically and grossly. The correlation between duodenal bulb deformity and the extent of GM was also studied. RESULTS: The mean score of methylene blue non-staining (MBNS) was 0, 1.30 +/- 0.15, and 3.00 +/- 0.00 in group A (non-ulcer patients), group B (patients with healed DU and with normal-shaped bulb) and C (patients with healed DU and with deformed duodenal bulb), respectively; showing significant differences among the groups (P < 0.05 in each). Both the existence and the grading of GM were higher in unstained specimens than in blue-stained specimens (100 vs 16.6%, P < 0.0001 and 3.62 +/- 0.09 vs 0.19 +/- 0.06, P < 0.001, respectively). CONCLUSIONS: Methylene blue non-staining can be applied to investigate the existence and extent of GM in the duodenal bulb accurately. The incidence of GM in the duodenal bulb was higher in patients with healed ulcers than in non-ulcer patients. Patients with deformed duodenal bulbs have a higher extent of GM than those without deformed duodenal bulbs.

Adult↗