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J Lee

Publications and source records attributed to J Lee.

At least 721 records · Page 40Linked to original sources
PubMed1999

A prospective randomised study comparing polyethylene glycol and sodium phosphate bowel cleansing solutions for colonoscopy.

Polyethylene glycol (Klean-Prep, Norgine) is widely used for bowel cleansing in the United Kingdom. This study compares the efficacy, acceptability and adverse effects of a polyethylene glycol (PEG) solution with sodium phosphate (Fleet Phospho-soda, De Witt) for bowel preparation prior to colonoscopy. Two hundred and nine consecutive patients were prospectively randomised to either PEG or sodium phosphate (SP) preparation. The endoscopist was blinded to the randomisation process. Fifty patients were excluded from the study because of previous colectomies or incomplete data. Of the remaining 159 patients, 88 had been randomised to the PEG group and 71 to the SP group. There was no difference in sex distribution between the groups. There were no significant differences between groups in terms of patient acceptability, side effects (nausea/vomiting and abdominal cramps), adequacy of bowel preparation and colonoscopy completion rates. 74% of the PEG and 70.4% of the SP group were rated by the endoscopist as having good or excellent bowel preparation. Sodium phosphate is well tolerated without additional side effects when compared with PEG solution. Both solutions were found to be equally effective in bowel cleansing.

Cathartics↗
PubMed1999

Trends in initiation of dialysis in an urban dialysis clinic in the United States: a long way from dialysis outcomes quality initiative guidelines.

The guidelines issued for peritoneal dialysis by the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) suggest initiation of dialysis at a glomerular filtration rate (GFR) of 10.5 mL/min/1.73 m2. We undertook this study to determine trends at a center in Philadelphia. Using the MDRD (Modification of Diet in Renal Disease) formula, we estimated the GFR (mL/min/1.73 m2) at the time of first dialysis for patients starting on dialysis at the center between 1994 and 1996. Data on 72 of the 86 new patients were available. Of the 72, 69 patients (96%) were black and 29 (40%) were diabetic. The estimated GFR at the time of dialysis initiation was 6.3 +/- 0.3 mL/min/1.73 m2. Only 3 patients (4%) had a GFR > 10.5; 25 patients (35%) had GFR < 5.0. Patients with a lower GFR had more severe acidosis (HCO3 15.8 +/- 0.5 mmol/L vs 19.5 +/- 0.9 mmol/L, p = 0.0023) and greater impairment in divalent ion metabolism (PO4: 7.6 +/- 0.2 mg/dL vs 5.6 +/- 0.3 mg/dL, p < 0.0001). Diabetic patients were initiated on dialysis at a higher level of GFR than non diabetic patients (7.2 +/- 0.3 mL/min/1.73 m2 vs 5.7 +/- 0.4 mL/min/1.73 m2, p = 0.0087). Even though diabetic patients had higher GFR and lower serum creatinine (8.6 +/- 0.5 mg/dL vs 11.8 +/- 0.9 mg/dL, p = 0.0021) than non diabetic patients, blood urea nitrogen (BUN) was similar in the two groups (89 +/- 3.7 mg/dL vs 96.8 +/- 5.8 mg/dL, p = 0.73). This difference may indicate that nondiabetic patients had a greater decline in protein intake. Finally, a trend towards initiation of dialysis at higher levels of renal function was seen with time (GFRs 5.5 +/- 0.4 mL/min/1.73 m2, 6.4 +/- 0.4 mL/min/1.73 m2, and 6.9 +/- 0.6 mL/min/1.73 m2 for 1994, 1995, and 1996 respectively; p = 0.058, 1994 vs 1996). The trend was stronger for diabetic patients (GFR 6.3 +/- 0.4 mL/min/1.73 m2 and 8.1 +/- 0.7 mL/min/1.73 m2 for 1994 and 1996 respectively; p = 0.06) than for non diabetic patients (GFR 5.1 +/- 0.5 mL/min/1.73 m2 and 6.2 +/- 0.7 mL/min/1.73 m2 for 1994 and 1996 respectively; p = 0.22). We conclude that initiation of dialysis is delayed in urban centers, particularly in non diabetic patients, and that the current practice is far below the DOQI recommendations.

Diabetes Mellitus↗
PubMed1999

Fibreoptic bronchoscopy in the diagnosis of lung cancer.

A total of 562 patients with lung cancer was evaluated by fibreoptic bronchoscopy (FOB) by three bronchoscopic diagnostic procedures: biopsy, bronchial brushing and bronchial washing. Endoscopically visible tumours (EV) were detected in 264, while 257 had endoscopically nonvisible tumours > or = 2 cm in diameter and FOB was done without fluoroscopy because of limited availability (ENV). Forty-one had small (< 2 cm), endoscopically nonvisible tumours with FOB performed under uniplanar fluoroscopy (ENV + F). The overall diagnostic yield rates of FOB were 98.1%, 61.5% and 58.5% for the EV, ENV and ENV + F cases, respectively. Reviewing the differential yield rates of the three diagnostic techniques and comparing them with the results of previous studies led to the following conclusions. (1) Combinations of biopsy with brushing and biopsy with washing can diagnose more than 95% of all fibreoptic bronchoscopy positive cases with endoscopically visible tumours. Performing either of these combinations may be more cost-effective than doing all three techniques routinely. (2) For cases with endoscopically nonvisible tumours, performance of all three diagnostic techniques is recommended, especially when fibreoptic bronchoscopy is performed without fluoroscopic guidance, as washing and brushing seem to compensate for a lower yield of the biopsy. (3) For tumours < 2 cm in diameter, knowledge on the diagnostic efficacy of fibreoptic bronchoscopy was limited owing to the small size of previous studies. The yield of 58.5% for fibreoptic bronchoscopy in these patients with performance of all three diagnostic procedures was comparatively high. It could be further increased to 75.6% if supplemented by percutaneous needle biopsy when fibreoptic bronchoscopy turned out to be nondiagnostic. If available, the use of transbronchial needle aspiration may also increase the overall diagnostic yield of fibreoptic bronchoscopy in these cases.

Biopsy↗
PubMed1998

Development of an in vitro assay system for screening of gp41 inhibitory compounds.

The transmembrane protein of HIV-1, gp41, mediates fusion between membranes of the virus and target cell. Strong interaction between the helical regions in the ectodomain of gp41 has been exploited to develop a method that can detect a potential inhibitor against gp41. The N-terminus coiled-coil or the C-terminus helical sequences within the ectodomain of gp41 were inserted into the C-terminus of thioredoxin (Trx) or glutathione S-transferase (GST) to generate the fusion proteins, Trx-N and GST-C, respectively. The inserted sequences of GST-C and Trx-N cause the two proteins to interact with each other and to form a complex. Furthermore, GST-C binds specifically to the surface-coated Trx-N, and the amount of attached GST-C is detected by an ELISA assay using anti-GST antibodies. Peptides derived from the helical regions of gp41 compete with GST-C for binding to Trx-N as well as prevent the gp41-mediated cell fusion. This in vitro assay system can be applied to screening compounds that have an inhibitory activity against gp41.

Amino Acid Sequence↗
PubMed1998

Expression of Fas system-related genes in the testis during development and after toxicant exposure.

The Fas system has been identified as a key regulator of testicular germ cell apoptosis. The goal of these experiments was to explore the expression of Fas system-related genes in the testis during development and after toxicant exposure. Both Fas ligand (FasL) and Fas receptor (Fas) were expressed postnatally in rat testis with peak expression associated with the high levels of germ cell apoptosis found during the first wave of spermatogenesis. The testicular expression of RIP and FAP-1, components of the Fas activating complex, increased after exposure to mono-(2-ethylhexyl)phthalate (MEHP), a Sertoli cell toxicant which induces massive germ cell death. Finally, the expression of additional apoptosis-inducing genes, including tumor necrosis factor receptor (TNFR), FADD, TRAIL, and DR5, was detected in mammalian testis. These results provide additional support for the following concepts: (1) Sertoli-germ cell interactions are important in the control of germ cell apoptosis; and (2) the Fas system and similar paracrine systems are important modulators of testicular homeostasis.

Animals↗
PubMed1998

Methionine analogues as inhibitors of methionyl-tRNA synthetase.

A series of methionine analogues have been synthesized as inhibitors of methionyl-tRNA synthetase and evaluated for their inhibitory activities of E. coli methionyl-tRNA synthetase and bacterial growth. Among them, L-methionine hydroxamate 20 has proved to be the best inhibitor of the enzyme with Ki = 19 microM and showed a growth inhibition against E.coli JM 109, P. vulganis 6059 and C. freundii 8090.

Bacteria↗
PubMed1998

WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.

Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis.

Amino Acid Sequence↗
PubMed1998

Interaction of yeast Rvs167 and Pho85 cyclin-dependent kinase complexes may link the cell cycle to the actin cytoskeleton.

BACKGROUND: . PHO85 encodes the catalytic subunit of a cyclin-dependent kinase (Cdk) in budding yeast and functions in phosphate and glycogen metabolism. Pho85 associated with the G1 cyclins Pcl1 and Pcl2 is also required for cell cycle progression in the absence of the Cdc28 cyclins Cln1 and Cln2. Loss of Pcl1, Pcl2 and related Pho85 cyclins results in budding defects, suggesting that Pcl-Pho85 complexes function in cell morphogenesis early in the cell cycle; their precise role is not clear, however. RESULTS: . To identify targets for Pcl-Pho85 kinases, we performed yeast two-hybrid interaction screens using Pcl2 and the related cyclin Pcl9. We identified RVS167, a gene involved in endocytosis, organization of the actin cytoskeleton, and cell survival after starvation. Like rvs167Delta mutants, pho85 mutants or strains deleted for the Pcl1,2-type Pho85 cyclins showed abnormal cell morphology on starvation, sensitivity to salt, random budding in diploids, and defects in endocytosis and in the actin cytoskeleton. Overexpression of Rvs167 in wild-type cells caused morphological abnormalities and growth arrest at high temperatures; these phenotypes were exacerbated by deleting PHO85. Rvs167 has a Src homology 3 (SH3) domain and five potential Pho85 phosphorylation sites; recombinant Rvs167 was phosphorylated by the Pcl2-Pho85 kinase in vitro. Maximal phosphorylation of Rvs167 in vivo required Pho85 and the Pcl1,2-type cyclins. CONCLUSIONS: . Rvs167 interacts with Pho85 cyclins and is implicated as a target of Pho85 kinases in vivo. Our results identify a connection between Cdks and the actin cytoskeleton; interaction of Rvs167 and Pcl-Pho85 Cdks might contribute to actin cytoskeleton regulation in response to stresses such as starvation.

Actins↗
PubMed1998

Demonstration of IgM antibodies of high affinity within the anti-Galalpha1-3Gal antibody repertoire.

BACKGROUND: Human anti-Galalpha1-3Gal IgG and IgM xenoantibodies can distinguish between very similar epitopes with a high degree of selectivity. METHODS: Anti-Galalpha1-3Gal antibodies were affinity isolated using two separate Galalpha1-3Gal-based immunoadsorbents, Galalpha1-3Gal itself and Galalpha1-3Galbeta1-4Glc. IgG and IgM were separated using a protein G column. Antibody purity was achieved by serial adsorption/elutions from the columns. By this means, different antibody fractions were prepared that contained either IgG or IgM, reactive with either Galalpha1-3Gal, Galalpha1-3Galbeta1-4Glc, or both. The dissociation equilibrium constants (Kd) of these antibodies were then measured using an IAsys biosensor. RESULTS AND CONCLUSIONS: Sera from two individuals were used and Kd values for one IgG (fraction 1A) and two IgM (fractions 1B and 2A) fractions were obtained. The Kd for the IgG was 4.85 x 10(-7) M (fraction 1A). For IgM, the Kd values were higher at 7.8x10(-10) M (fraction 1B) and 1.07x10(-10) M (fraction 2A). Natural anti-pig antibodies include high affinity IgM that continue to be produced without class switch. The B cell mechanism behind this is not known. It may be possible to exploit this mechanism in future xenotransplantation strategies.

Antibodies↗
PubMed1998

IL-10 impacts autoimmune diabetes via a CD8+ T cell pathway circumventing the requirement for CD4+ T and B lymphocytes.

IL-10 is essential for an early phase of diabetes in nonobese diabetic (NOD) mice, but later becomes protective against its development. The mechanism by which IL-10 mediates the pathway to diabetes in these mice is unknown. Herein, we dissected the cellular and costimulation requirements for diabetes in transgenic (tg) NOD mice that expressed IL-10 in their pancreatic islets (IL-10-NOD mice). We found that IL-10 alone did not cause diabetes because the offspring (IL-10-NOD-scid mice) from back-crosses of IL-10-NOD mice with NOD-scid mice had no diabetes. Moreover, these IL-10-NOD-scid mice were free of lymphocytic infiltration. Treatment of IL-10-NOD mice with depleting anti-CD4 mAb or control mAb had no effect on diabetes. Surprisingly, depletion of CD8+ T cells by treatment with the corresponding mAb inhibited diabetes without attenuating insulitis, demonstrating a critical role for CD8+ T cells in the disease process. Interestingly, B cell-deficient IL-10-NOD mice readily developed diabetes with kinetics and incidence similar to those observed in wild-type mice, demonstrating that B lymphocytes as APCs were not required in the disease process. Administration of anti-CD40 ligand (CD40L) mAb did not prevent disease, indicating that CD40/CD40L costimulation is not required for diabetes in IL-10-NOD mice. Immunization of IL-10-NOD mice with CFA or heat-shock protein 65, known to block diabetes in NOD mice, had no effect on their diabetes. We demonstrate that IL-10 contributes early to the pathology of diabetes via a CD8+ T cell pathway, eliminating the requirement for B lymphocytes and CD40-CD40L costimulation. Our findings provide a mechanism for the participation of IL-10 in the early development of diabetes.

Animals↗
PubMed1998

Repair of DNA strand gaps and nicks containing 3'-phosphate and 5'-hydroxyl termini by purified mammalian enzymes.

A putative role for mammalian polynucleotide kinases that possess both 5'-phosphotransferase and 3'-phosphatase activity is the restoration of DNA strand breaks with 5'-hydroxyl termini or 3'-phosphate termini, or both, to a form that supports the subsequent action of DNA repair polymerases and DNA ligases, i.e. 5'-phosphate and 3'-hydroxyl termini. To further assess this possibility, we compared the activity of the 3'-phosphatase of purified calf thymus polynucleotide kinase towards a variety of substrates. The rate of removal of 3'-phosphate groups from nicked or short (1 nt) gapped sites in double-stranded DNA was observed to be similar to that of 3'-phosphate groups from single-stranded substrates. Thus this activity of polynucleotide kinase does not appear to be influenced by steric accessibility of the phosphate group. We subsequently demonstrated that the concerted reactions of polynucleotide kinase and purified human DNA ligase I could efficiently repair DNA nicks possessing 3'-phosphate and 5'-hydroxyl termini, and similarly the combination of these two enzymes together with purified rat DNA polymerase beta could seal a strand break with a 1 nt gap. With a substrate containing a nick bounded by 3'- and 5'-OH termini, the rate of gap filling by polymerase beta was significantly enhanced in the presence of polynucleotide kinase and ATP, indicating the positive influence of 5'-phosphorylation. The reaction was further enhanced by addition of DNA ligase I to the reaction mixture. This is due, at least in part, to an enhancement by DNA ligase I of the rate of 5'-phosphorylation catalyzed by polynucleotide kinase.

Animals↗
PubMed1998

The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

Animals↗
PubMed1998

Polymorphism in the human anti-pig natural antibody repertoire: implications for antigen-specific immunoadsorption.

BACKGROUND: Anti-Galalpha1-3Gal antibodies cause hyperacute rejection (HAR) in pig-to-primate xenotransplantation. Long-term graft survival has not been achieved despite abrogation of HAR using transgenic pigs. IgG and IgM anti-Galalpha1-3Gal also play a role in the events following abrogation of HAR. Characterizing these antibodies and developing a system for their removal is therefore crucial to future success in xenotransplantation. METHODS AND RESULTS: We have developed a neoglycoprotein enzyme-linked immunosorbent assay to probe the precise antigenic requirements for the binding of anti-Galalpha1-3Gal and have analyzed 77 normal sera. Sixty-six percent of individuals have IgG that recognizes the Galalpha1-3Gal di-, tri-, and pentasaccharides (D, T, and P, respectively), termed DTP phenotype. The frequency of other phenotypes was - -P, 13%; -TP, 12%; D-P, 8%; and DT-, 1%. The IgG subclasses found were IgG2 (95%), IgG3 (34%), IgG1 (31%), and IgG4 (17%). IgM in 91% of individuals recognized all three antigens. Further antibody heterogeneity was demonstrated when immunoadsorbents derived from Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc (PENTA) were tested. Galalpha1-3Galbeta1-4Glc (TRI 6) or PENTA agarose were effective for IgG removal in all individuals. For IgM removal, two deoxy derivatives were completely successful in 73% of individuals. Combining the Galalpha1-3Gal (DI) and TRI 6 agarose produced an adsorbent that completely removed anti-Galalpha1-3Gal IgG and IgM in all individuals tested. CONCLUSIONS: Although the polymorphism in the anti-Galalpha1-3Gal repertoire, which we have demonstrated, represents a major obstacle to the development of an effective immunoadsorbent, the combination of DI and TRI 6 agarose appears sufficient for pig-to-human xenotransplantation.

Animals↗
PubMed1998

The Th2 cytokine IL-4 is not required for the progression of antibody-dependent autoimmune myasthenia gravis.

Experimental autoimmune myasthenia gravis (EAMG), a disorder of the neuromuscular junction, is mediated by autoantibodies against muscle nicotinic acetylcholine receptor (AChR). The roles of IFN-gamma (Th1) and IL-4 (Th2) cytokines in the initiation and progression of this disease are not fully understood. Recently, we have demonstrated that IFN-gamma is necessary for the initiation of tAChR-induced EAMG in mice. However, the role of IL-4 in the progression of clinical EAMG remained undetermined. In this study we have addressed the contribution of IL-4 in the disease progression in IL-4(-/-) C57BL/6j mice whose IL-4 gene has been disrupted. Following immunization with Torpedo (t) AChR, the IL-4(-/-) mice readily developed signs of muscle weakness and succumbed to clinical EAMG with kinetics similar to the susceptibility of IL-4(+/+) mice. The tAChR-primed lymph node cells from IL-4(-/-) mice vigorously proliferated to tAChR and to its dominant alpha146-162 sequence associated with disease pathogenesis. However, these T cells secreted higher levels of IFN-gamma and IL-2, suggesting the development of a Th1 default pathway in these mice. Nevertheless, the IL-4 mutation had no effect on the recruitment of CD4+ Vbeta6+ T cells specific to the dominant tAChR alpha146-162 sequence in vivo. Immune sera from IL-4(-/-) mice showed a dramatic increase in mouse AChR-specific IgG2a levels followed by a concomitant decrease in IgG1 levels, but these mice did not exhibit an accelerated disease. In conclusion, we have demonstrated for the first time that IL-4 is not required either for the generation of a pathogenic anti-AChR humoral immune response or for progression of clinical EAMG in mice.

Amino Acid Sequence↗