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Biomedical subjects

A S Lee

Publications and source records attributed to A S Lee.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of the structure and properties of authentic and counterfeit polypropylene surgical meshes.

A counterfeit version of the Ethicon Prolene polypropylene mesh was distributed to hospitals and clinics and unintentionally implanted into patients undergoing tension-free hernia repair. On December 19, 2003, the Food and Drug Administration (FDA) issued a public health web notification indicating that the counterfeit mesh was not sterile or safe to use. To develop safety recommendations for patients with the counterfeit mesh implant, we compared the counterfeit's structural, physical, chemical and mechanical properties with polypropylene meshes previously cleared by FDA. The mesh fibers for all the products tested were found to have similar chemical and physical properties. The mechanical properties were directly related to the knitted structure (loop size, repeat distance, fabric tightness) and the porosity. Extracts from the counterfeit mesh passed cytotoxicity screening tests. The FDA further recommended that if the mesh had been inadvertently implanted, then those patients should be monitored as would be the practice for any patient with an implanted surgical mesh.

Herniorrhaphy↗
PubMed2006

The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases.

The mechanism by which glucocorticoids govern antiproteinuric effect in nephrotic syndrome remains unknown. Present study examined the protective role of dexamethasone (DEX) in the intracellular trafficking of nephrin under endoplasmic reticulum (ER) stress. Human embryonic kidney-293 cell line expressing a full-length human nephrin was cultured in mediums containing 5.5 or 25 mM glucose with or without DEX. The result revealed that glucose starvation evoked a rapid ER stress leading to formation of underglycosylated nephrin that was remained in the ER as a complex with calreticulin/calnexin. DEX rescued this interfered trafficking through binding to its receptor and stimulating the mitochondrial transcripts and adenosine 5' triphosphate (ATP) production, leading to synthesis of fully glycosylated nephrin. These results suggest that ER-stress in podocytes may cause alteration of nephrin N-glycosylation, which may be an underlying factor in the pathomechanism of the proteinuria in nephrotic syndrome. DEX may restore this imbalance by stimulating expression of mitochondrial genes, resulted in the production of ATP that is essential factor for proper folding machinery aided by the ER chaperones.

Adenosine Triphosphate↗
PubMed2006

Agreement of anti-neutrophil cytoplasmic antibody measurements obtained from serum and plasma.

Serum and plasma are used interchangeably to measure anti-neutrophil cytoplasmic antibodies (ANCA), even though the release of ANCA target antigens during the preparation of serum could affect ANCA assays and cause discrepancies between the results obtained from serum and plasma. To what extent ANCA test results obtained from serum agree and correlate with results from plasma remains unknown. Therefore, a comprehensive comparison was performed using serum and plasma samples which were collected in 175 patients with active Wegener's granulomatosis at enrollment of a recent randomized trial. These paired serum and plasma samples were subjected to parallel ANCA testing by standard indirect immunofluorescence on ethanol-fixed neutrophils, a direct enzyme-linked immunoassay (ELISA) for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, and two different capture ELISAs for PR3-ANCA. The concordance of categorical serum and plasma ANCA results was assessed using kappa-coefficients. These were > 0.8 for all assays, indicating a very good concordance between positive and negative serum and plasma results. Spearman's correlation coefficients for serum and plasma PR3-ANCA values obtained by direct ELISA and both capture ELISAs were > or = 0.95 (P < 0.0001). Our study shows that serum and plasma samples can be used interchangeably for measuring ANCA.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2003

Brachiocephalic-superior vena cava metallic stenting in malignant superior vena cava obstruction.

INTRODUCTION: We studied the effectiveness of unilateral brachiocephalic (BC)-superior vena cava (SVC) metallic stent therapy in malignant SVC obstruction. MATERIALS AND METHODS: From November 1998 to February 2002, SVC stenting was performed in 11 patients with symptomatic malignant SVC obstruction. There were 10 males and 1 female, with a mean age of 64.2 years (range, 37 to 78 years). The computed tomography (CT) scan and superior vena cavogram findings of all patients showed malignant SVC obstruction. Both internal jugular veins were patent in all patients by ultrasound. SVC stenting was performed with Wallstent (Boston Scientific, Minneapolis, MN, USA) in 10 patients and Memotherm stent (Bard angiomed, Wachhausstrasse, Germany) in 1 patient. Pressure gradient, duration of the procedure, peri-procedural morbidity and mortality and the general well-being of the patients were reviewed. RESULTS: SVC stenting was performed at a mean duration of 9.6 days (range, 3 to 30 days) after presentation. All were technically successful with 10 across the right BC-SVC and 1 across the left BC-SVC. There was no peri-procedural morbidity or mortality. The entire procedure was completed at a mean duration of 115 minutes (range, 75 to 225 minutes) with good angiographic and pressure results. Immediate symptomatic relief of SVC syndrome was achieved in 10 patients who had received prompt work-up and stenting 3 to 18 days after presentation. The remaining patient, who received work-up and stenting 30 days after presentation, remained dyspnoeic and died of pneumonia 7 days after the procedure. CONCLUSION: Unilateral BC-SVC metallic stenting is an effective measure in malignant SVC obstruction. Prompt pre-stenting work-up and stenting are recommended to achieve a longer symptomatic relief period.

Adult↗
PubMed2001

YY1 as a regulator of replication-dependent hamster histone H3.2 promoter and an interactive partner of AP-2.

In analyzing cis-regulatory elements important for cell cycle control of the replication-dependent hamster histone H3.2 gene, we discovered a binding site for the transcription factor YY1 embedded within GC-rich sequences between the two tandem CCAAT repeats proximal to the TATA element. Base mutations that specifically eliminated YY1 binding resulted in suppression of the S phase induction of the H3.2 promoter. In addition, we discovered that YY1 is an interactive partner of AP-2, which also binds the H3.2 promoter and regulates its cell cycle-dependent expression. The critical domains for YY1 and AP-2A interaction are mapped, revealing that the N-terminal portion of YY1 (amino acids 1-300) and the DNA-binding/dimerization region of AP-2A are required. Our results suggest that YY1, acting as a transcription factor binding to its site on the promoter, or through protein-protein interaction with AP-2, may be part of a regulatory network including key cell cycle regulators such as c-Myc and Rb in controlling growth- and differentiation-regulated gene expression.

Animals↗
PubMed2001

Vitrectomy for pars planitis complicated by vitreous hemorrhage: visual outcome and long-term follow-up.

PURPOSE: To characterize the visual results of vitrectomy for nonclearing vitreous hemorrhage in pars planitis. METHODS: Case series. RESULTS: All six eyes (100%) had a visual acuity of 20/200 or less preoperatively. Postoperatively, five eyes (83%) improved to a final visual acuity of better than 20/30, and one eye improved to 20/100. The poorer vision of the latter patient was attributed to cystoid macular edema. Postoperative follow-up range was from 1.3 to 9 years (mean, 4.2 years). CONCLUSION: A substantial long-term benefit is seen in patients with pars planitis treated with vitrectomy for nonclearing vitreous hemorrhage. A larger case series will be needed to confirm whether such excellent outcomes can be expected.

Adolescent↗
PubMed2001

Patellar tendon length following opening wedge high tibial osteotomy using an external fixator with particular reference to later total knee replacement.

The aim of this retrospective study was to examine a cohort of patients who had undergone high tibial osteotomy (HTO) using the method of opening wedge hemicallotasis, and who later required conversion to total knee replacement (TKR). The incidence of patella infra and any technical difficulties encountered during TKR operation were examined. A consecutive series of 76 valgus osteotomies in 65 patients were carried out by one surgeon using a dynamic axial fixator (DAF). Later conversion to TKR, required for the progression of symptoms, was carried out in nine knees (seven patients) at a mean time from the initial osteotomy of 7 years (1.5-11). All of those patients who underwent HTO and subsequently required conversion to TKR were followed up. The patellar height was assessed by one observer in all knees pre- and post-HTO using the Insall and Salvati and Blackburne and Peel ratios. Using these criteria, only one case of patella infra occurred. There were no added technical difficulties in performing TKR as a result of the previous osteotomy and clinical outcomes using the Oxford knee score were satisfactory (34 where 48 is maximum).

Adult↗
PubMed2001

The glucose-regulated proteins: stress induction and clinical applications.

A protective mechanism used by cells to adapt to stress of the endoplasmic reticulum (ER) is the induction of members of the glucose-regulated protein (Grp) family. The induction of mammalian Grp proteins in response to ER stress involves a complex network of regulators and novel mechanisms. The elucidation of Grp function and regulation opens up new therapeutic approaches to diseases associated with ER stress and cancer.

Animals↗
PubMed2001

High tibial osteotomy using a dynamic axial external fixator.

High tibial osteotomy is an accepted treatment for unicompartmental osteoarthritis of the knee. Conventional osteotomy can be a demanding procedure with potential for complications. Opening wedge high tibial osteotomy using an external fixator is an alternative that may have advantages in comparison with classic methods. The aims of the current study were to determine if opening wedge osteotomy using hemicallotasis techniques is safer than, and the outcome comparable with that of, conventional techniques. Seventy-six high tibial osteotomies were performed in 65 patients for primary osteoarthritis. The mean age of the patients was 54.8 years (range, 36-70 years). The mean followup was 6 years. The only serious complication occurred in one patient, who had chronic osteomyelitis develop 2 years after surgery. There were no neurologic or vascular complications. The authors think this technique is safer than conventional techniques. Survivorship at 5 and 10 years was 89% and 63%, respectively. The mean knee score in osteotomies was 26.6 (maximum possible score, 48). The outcome is comparable with, or better than, that of other techniques for osteotomy. Subsequent knee replacement, in cases requiring conversion, was straightforward. The mean score in knees that had osteotomies that were converted to total knee replacements was 33.7.

Activities of Daily Living↗
PubMed2001

Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates.

Novel mutations in NADH dehydrogenase (ndh) were detected in 8 of 84 (9.5%) isoniazid (INH)-resistant isolates (T110A [n = 1], R268H [n = 7]), but not in 22 INH-susceptible isolates of Mycobacterium tuberculosis. Significantly, all eight isolates with mutations at ndh did not have mutations at katG, kasA, or the promoter regions of inhA or ahpC, except for one isolate. Mutations in ndh appear to be an additional molecular mechanism for isoniazid resistance in M. tuberculosis.

Amino Acid Sequence↗
PubMed2001

Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6.

When mammalian cells are subjected to stress targeted to the endoplasmic reticulum (ER), such as depletion of the ER Ca(2+) store, the transcription of a family of glucose-regulated protein (GRP) genes encoding ER chaperones is induced. The GRP promoters contain multiple copies of the ER stress response element (ERSE), consisting of a unique tripartite structure, CCAAT(N(9))CCACG. Within a subset of mammalian ERSEs, N(9) represents a GC-rich sequence of 9 bp that is conserved across species. A novel complex (termed ERSF) exhibits enhanced binding to the ERSE of the grp78 and ERp72 promoters using HeLa nuclear extracts prepared from ER-stressed cells. Optimal binding of ERSF to ERSE and maximal ERSE-mediated stress inducibility require the conserved GGC motif within the 9-bp region. Through chromatographic purification and subsequent microsequencing, we have identified ERSF as TFII-I. Whereas TFII-I remains predominantly nuclear in both nontreated NIH 3T3 cells and cells treated with thapsigargin (Tg), a potent inducer of the GRP stress response through depletion of the ER Ca(2+) store, the level of TFII-I transcript was elevated in Tg-stressed cells, correlating with an increase in TFII-I protein level in the nuclei of Tg-stressed cells. Purified recombinant TFII-I isoforms bind directly to the ERSEs of grp78 and ERp72 promoters. The stimulation of ERSE-mediated transcription by TFII-I requires the consensus tyrosine phosphorylation site of TFII-I and the GGC sequence motif of the ERSE. We further discovered that TFII-I is an interactive protein partner of ATF6 and that optimal stimulation of ERSE by ATF6 requires TFII-I.

3T3 Cells↗
PubMed2000

Heterogeneous nuclear ribonucleoproteins as regulators of gene expression through interactions with the human thymidine kinase promoter.

In search for nuclear proteins that interact with the human thymidine kinase (htk) promoter, we discovered that p37AUF, a hnRNP C-like protein, and hnRNP A1, both members of the heterogeneous ribonucleoprotein family, can bind with high affinity to an ATTT sequence motif contained within the cell cycle regulatory unit (CCRU). We report here that over-expression of p37AUF stimulates gene expression mediated by the htk promoter in a promoter-sequence specific manner, whereas hnRNP A1 suppresses it. Both recombinant p37AUF and hnRNP A1 can bind the htk CCRU, suggesting that their binding to the DNA target does not require additional cellular components. We further discovered that hnRNP K is a potent suppressor of htk mediated gene activity. However, its mechanism of action is mediated through protein-protein interaction, since hnRNP K itself cannot bind the htk CCRU but can competitively inhibit the binding of other hnRNPs. The binding site for the hnRNPs on the htk CCRU is not required for S-phase induction of the htk promoter. However, in stable but not transient transfectants, the mutation of the hnRNP binding site results in 5- to 10-fold reduction of htk mediated gene activity in synchronized and exponentially growing cells. Collectively, these findings support emerging evidence that hnRNPs, in addition to their traditional role in RNA biogenesis, could be regulators of gene expression through direct DNA binding or interaction with other proteins.

Amino Acid Sequence↗
PubMed2000

Low-level doxorubicin resistance in benzo[a]pyrene-treated KB-3-1 cells is associated with increased LRP expression and altered subcellular drug distribution.

The P-glycoprotein (P-gp)-negative epidermoid pharyngeal carcinoma cells KB-3-1 were grown in 0.25 mM benzo[a]pyrene (BaP) for 3 months and increased resistance to doxorubicin, but not to vinblastine, colchicine, or cisplatin, was found. Doxorubicin resistance was not altered by cyclosporin, the P-gp inhibitor. Intracellular accumulation of BaP or calcein, a substrate for P-gp and multidrug resistance protein (MRP), was not altered by inhibitors of the P-gp and MRP. The expression of cytochrome P450 (CYP) 1A1, lung-resistance-related protein (LRP), P-gp, and MRP was investigated. Overexpression of CYP1A and LRP, on the mRNA and protein levels, was found. BaP-treated KB-3-1 cells remained P-gp negative while the level of MRP was not altered. Subcellular accumulation of BaP was found to be localized in the cytoplasm and minimal in the nuclei in BaP treated cells. In contrast, even penetration of BaP to the nuclei and cytoplasm was found in untreated cells. Subcellular distribution of doxorubicin was altered following BaP treatment with localized accumulation of the cancer drug in cytoplasmic organelles but not in the nuclei. Our data suggested that LRP might play a protective role against toxic compounds. The correlation of increased expression of LRP, but not P-gp nor MRP, with decreased doxorubicin accumulation in the nuclear target suggests a pivotal role of this perinuclear transporter in the MDR phenotype of P-gp-negative cancer cells. These results also propose an alternative mechanism of cancer drug resistance emergence, namely, induction of LRP activity following treatment with BaP, an environmental toxicant and a carcinogen.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Improvement in macular function after retinal translocation surgery in a patient with age-related macular degeneration.

PURPOSE: To assess focal electroretinographic findings before and after retinal translocation surgery in a patient with age-related macular degeneration. METHOD: Case report. A 79-year-old man with a well-defined subfoveal choroidal neovascular membrane from age-related macular degeneration underwent preoperative and postoperative focal electroretinography. RESULTS: After retinal translocation surgery, best-corrected Snellen visual acuity improved from 9/200 to 20/60. A significant increase in mean foveal amplitude, from 0.08 microV to 0.16 microV (P = 0.008) was recorded. CONCLUSION: Age-related macular degenerative changes in visual acuity and foveal electroretinogram amplitude may be reversible after retinal translocation surgery.

Aged↗
PubMed2000

Eradication of murine mammary adenocarcinoma through HSVtk expression directed by the glucose-starvation inducible grp78 promoter.

Gene therapy strategies employing the HSVtk/ganciclovir (GCV) suicide gene offer promising approaches towards the treatment of metastatic breast cancer. These include bystander effects on non-transduced tumor cells, lower systemic toxicity, and the possibility of inducing immunity against the tumor. Previously we have demonstrated the ability of the grp78 stress-inducible promoter to stimulate expression of reporter genes within the tumor microenvironment. However, experimental evidence demonstrating the ability of this promoter to activate therapeutic agents within the breast cancer environment causing tumor eradication is needed prior to clinical trials. In this report, we test the efficacy of the grp78 promoter in a retroviral system to drive the expression of the HSVtk suicide gene in a murine mammary adenocarcinoma cell line (TSA) in syngeneic, immune-competent hosts. Our results show that under glucose-starvation conditions in vitro, the expression of HSVtk and GCV induced cell death are enhanced in tumor cells in which the HSVtk gene is driven by the internal grp78 promoter compared to cells in which the Moloney murine leukemia virus LTR drives HSVtk. In in vivo studies, in tumors in which the HSVtk gene is driven by the grp78 promoter, GCV treatment causes complete tumor eradication, whereas tumors persist when the HSVtk gene is driven by the retroviral LTR. Our study suggests that the grp78 promoter may be useful to enhance the effectivity of therapeutic agents within a breast tumor. In addition, it is shown that immune memory is induced in syngeneic, immune-competent hosts. This new retroviral vector might therefore be useful for breast cancer gene therapy.

Adenocarcinoma↗
PubMed2000

Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression.

Presenilin 1 (PS1), a polytopic membrane protein, has a critical role in the trafficking and proteolysis of a selected set of transmembrane proteins. The vast majority of individuals affected with early onset familial Alzheimer's disease (FAD) carry missense mutations in PS1. Two studies have suggested that loss of PS1 function, or expression of FAD-linked PS1 variants, compromises the mammalian unfolded-protein response (UPR), and we sought to evaluate the potential role of PS1 in the mammalian UPR. Here we show that that neither the endoplasmic reticulum (ER) stress-induced accumulation of BiP and CHOP messenger RNA, nor the activation of ER stress kinases IRE1alpha and PERK, is compromised in cells lacking both PS1 and PS2 or in cells expressing FAD-linked PS1 variants. We also show that the levels of BiP are not significantly different in the brains of individuals with sporadic Alzheimer's disease or PS1-mediated FAD to levels in control brains. Our findings provide evidence that neither loss of PS1 and PS2 function, nor expression of PS1 variants, has a discernable impact on ER stress-mediated induction of the several established 'readouts' of the UPR pathway.

Alzheimer Disease↗
PubMed2000

Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma.

Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22-q23 in several types of tumours of diverse cell origin. Previous investigations of LOH at this chromosomal region in colorectal carcinoma have been contradictory in their findings, and have only included between 1-4 loci. In order to define any regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the highest frequencies of LOH at D11S1340 (41.0%), located between 105.13-111.97 Mb from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located approximately 113 Mb from the centromere. No statistically significant associations between LOH and age-of-presentation or Dukes' stage were found. LOH was observed in colorectal tumours of all Dukes' stages, including Dukes' stages A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23 occurs in the early stages of colorectal carcinoma. These results confirm the presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in the carcinogenesis of colorectal carcinoma, and will facilitate future identification of candidate genes.

Adenocarcinoma↗