Search PubMed⌕ Search

Biomedical subjects

D Chung

Publications and source records attributed to D Chung.

At least 19 recordsLinked to original sources
PubMed2006

Bell-shaped nuclei dividing by symmetrical and asymmetrical nuclear fission have qualities of stem cells in human colonic embryogenesis and carcinogenesis.

Large cell nuclei with at least eight distinct morphologies have been discovered throughout the fetal gut (5-7 weeks), colonic adenomas, and adenocarcinomas, five of which are not present in the normal adult colon. The most remarkable nuclear forms are hollow bells, approximately 10-15 microns in height and about 7-10 microns in bell mouth diameter. When encased in tubular syncytia, these bell-shaped structures divide symmetrically by an amitotic nuclear fission process resembling the separation of two paper cups. Seven other nuclear morphotypes emerge from the bell-shaped nuclei within the syncytia by asymmetrical amitotic nuclear fission. Cells containing these differentiated nuclear forms subsequently divide extra-syncytially by mitoses that form clonal populations of cells with identical nuclear morphotypes in embryos, adenomas, adenocarcinomas, and metastases. Cells with bell-shaped nuclei thus appear to be responsible for both net growth and differentiation in the embryonic gut, adenomas, and adenocarcinomas, and fulfill the requirements for post-embryonic stem cells in colon organogenesis and carcinogenesis.

Cell Nucleus↗
PubMed2006

Mapping a new genetic locus for X linked retinitis pigmentosa to Xq28.

We have defined a new genetic locus for an X linked form of retinitis pigmentosa (RP) on chromosome Xq28. We examined 15 members of a family in which RP appeared to be transmitted in an X linked manner. Ocular examinations were performed, and fundus photographs and electroretinograms were obtained for selected patients. Blood samples were obtained from all patients and an additional seven family members who were not given examinations. Visual acuity in four affected individuals ranged from 20/40 to 20/80+. Patients described the onset of night blindness and colour vision defects in the second decade of life, with the earliest at 13 years of age. Examined affected individuals had constricted visual fields and retinal findings compatible with RP. Based on full field electroretinography, cone function was more severely reduced than rod function. Female carriers had no ocular signs or symptoms and slightly reduced cone electroretinographic responses. Affected and non-affected family members were genotyped for 20 polymorphic markers on the X-chromosome spaced at 10 cM intervals. Genotyping data were analysed using GeneMapper software. Genotyping and linkage analyses identified significant linkage to markers DXS8061, DXS1073, and DXS1108 with two point LOD scores of 2.06, 2.17, and 2.20, respectively. Haplotype analysis revealed segregation of the disease phenotype with markers at Xq28.

Adolescent↗
PubMed2004

Cell and toxicant specific phosphorylation of conexin43: effects of lindane and TPA on rat myometrial and WB-F344 liver cell gap junctions.

Previous studies showed that the pesticide lindane (gamma-hexachlorocyclohexane) inhibits gap junction intercellular communication in rat myometrial cells. The present study tested the hypothesis that lindane and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit gap junction communication in rat myometrial and liver WBr-F344 cells by the common mechanism of increasing phosphorylation of the gap junction protein connexin43. We evaluated changes of connexin43 phosphorylation using Western blot of standard SDS-PAGE gels and cell immunostaining, and we monitored gap junction communication using microinjection and transfer of Lucifer yellow dye. Exposure of rat myometrial cells to lindane or TPA nearly abolished dye transfer but did not alter the electrophoretic mobility of connexin43, and neither lindane nor TPA increased phosphorylation of connexin43 as assessed by immunoblot with anti-phospho-connexin43 (S368) antibody. However, TPA increased punctate immunofluorescence staining of phospho-connexin43 (S368) in myometrial cells whereas lindane had no such effect. In WBr-F344 cells, lindane and TPA inhibited dye transfer. Lindane increased immunostaining for phospho-connexin43 (S368) in WBr-F344 cells without altering the abundance, electrophoretic mobility or phosphorylation of connexin43 as detected in immunoblots. TPA intensified a slower migrating connexin43 band and increased phospho-connexin43 (S368) in immunoblots, and intensified phospho-connexin43 immunostaining at WBr-F344 cell interfaces and nuclear regions. These results show that phosphorylation of connexin43 at serine 368 occurred in cell and toxicant specific manners and was independent of changes in electrophoretic mobility in standard SDS-PAGE gels. Moreover, lindane inhibited gap junction communication in myometrial cells by a mechanism that was not be explained by changes in phosphorylation of connexin43.

Animals↗
PubMed2003

An assessment of surgeons' abilites to site colostomies accurately.

AIMS: The ability of surgeons to site a colostomy is assessed in a clinical model. In addition, the tuition received by surgical trainees in stoma siting is also reviewed. MATERIALS AND METHODS: Eleven surgeons (trainees--six, colorectal subspeciality interest--two) were asked to site an end colostomy on nine patients using an adhesive disc (diameter--1cm). The position of the stoma was then measured on the 'x' and 'y' axis of a 2cm box grid, (maximum error--1cm) which was placed on the abdomen and centred on the umbilicus. The positions were then compared with that chosen by the stoma nurse who was taken as the gold standard. Results were compared using ANOVA and the Mann Whitney--U test. A telephone questionnaire was then undertaken to review the training of junior surgeons. RESULTS: There was variance present within the group of surgeons studied (p<0.01). Trainees and consultants had a similar accuracy in stoma-siting (p<0.2). Consultants with a colorectal subspeciality interest were better at placing stomas than those with a general interest (p<0.002). Badly placed stomas were three times more likely to be too low than too high (p<0.002). Thirty of 37 trainees reported receiving no undergraduate training from a specialist stoma nurse. Ninety per cent received postgraduate training from another surgeon while a specialist nurse trained only 35%. CONCLUSION: There was no difference between trainees and consultants in their ability to site a colostomy. However, surgeons with a subspeciality interest chose stoma sites that were more consistent with the specialist nurse than general surgeons. Training is haphazard and ability is frequently assumed rather than proven.

Clinical Competence↗
PubMed2002

Simple models for assessing migration from food-packaging films.

Owing to their simplicity, two migration models based on Fick's Second Law have been frequently used for the assessment of migration of additives and contaminants from food-packaging films. While the two models are known to provide accurate estimates of diffusion coefficients for complete migration, they could generate considerable estimation errors for significantly partitioned migration. In this paper, the applicability of the two models to partitioned migration is defined by examining the assumptions and derivations of the two models as well as their errors in estimating diffusion coefficients. Furthermore, a simple migration model, based on more realistic assumptions than the two models, is proposed. The proposed model can provide far better estimates of diffusion coefficients for partitioned migration than the two models.

Diffusion↗
PubMed2001

Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family.

von Willebrand factor (vWF) is synthesized in megakaryocytes and endothelial cells as a very large multimer, but circulates in plasma as a group of multimers ranging from 500 to 10 000 kd. An important mechanism for depolymerization of the large multimers is the limited proteolysis by a vWF-cleaving protease present in plasma. The absence or inactivation of the vWF-cleaving protease results in the accumulation of large multimers, which may cause thrombotic thrombocytopenic purpura. The vWF-cleaving protease was first described as a Ca(++)-dependent proteinase with an apparent molecular weight of approximately 300 kd. Thus far, however, it has not been isolated and characterized. In this study, the purification of human vWF-cleaving protease from a commercial preparation of factor VIII/vWF concentrate by means of several column chromatographic steps, including 2 steps of heparin-Sepharose column, is reported. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the anion exchange and gel filtration column fractions showed that the vWF-cleaving protease activity corresponded to a protein band of 150 kd. After reduction, it migrated with an apparent weight of 190 kd. The amino terminal sequence of the 150-kd band was AAGGIL(H)LE(L)L(D)AXG(P)X(V)XQ (single-letter amino acid codes), with the tentative residues shown in parentheses. A search of the human genome sequence identified the vWF-cleaving protease as a new member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin type I motif) family of metalloproteinase. An active site sequence of HEIGHSFGLEHE (single-letter amino acid codes) was located at 150 residues from the N terminus of the protein.

ADAM Proteins↗
PubMed2001

Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is associated with acquired or congenital deficiency of a plasma von Willebrand factor-cleaving protease (VWFCP). Based on partial amino acid sequence, VWFCP was identified recently as a new member of the ADAMTS family of metalloproteases and designated ADAMTS13. The 4.6-kilobase pair cDNA sequence for VWFCP has now been determined. By Northern blotting, full-length VWFCP mRNA was detected only in liver. VWFCP consists of 1427 amino acid residues and has a signal peptide, a short propeptide terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat, a Cys-rich domain, an ADAMTS spacer, seven additional thrombospondin-1 repeats, and two CUB domains. VWFCP apparently is made as a zymogen that requires proteolytic activation, possibly by furin intracellularly. Sites for Zn(2+) and Ca(2+) ions are conserved in the protease domain. The Cys-rich domain contains an RGDS sequence that could mediate integrin-dependent binding to platelets or other cells. Alternative splicing gives rise to at least seven potential variants that truncate the protein at different positions after the protease domain. Alternative splicing may have functional significance, producing proteins with distinct abilities to interact with cofactors, connective tissue, platelets, and von Willebrand factor.

Amino Acid Sequence↗
PubMed2001

Differences in patterns of activation of MAP kinases induced by oncogenic ras-p21 and insulin in oocytes.

Oncogenic ras (Val 12-containing)-p21 protein induces oocyte maturation by a pathway that is blocked by peptides from effector domains of ras-p21, i.e., residues 35-47 (that block Val 12-p21-activated raf) and 96-110 and 115-126, which do not affect the ability of insulin-activated cellular p21 to induce maturation. Oncogenic p21 binds directly to jun-N-terminal kinase (JNK), which is blocked by the p21 96-110 and 115-126 peptides. This finding predicts that oncogenic p21, but not insulin, induces maturation by early and sustained activation of JNK. We now directly confirm this prediction by showing that oncogenic p21 induces activating phosphorylation of JNK (JNK-P) and of ERK (MAP kinase) (MAPK-P), whose levels correlate with oocyte maturation. p21 peptides 35-47 and 96-110 block formation of JNK-P and MAPK-P, further confirming this correlation and suggesting, unexpectedly, that raf-MEK-MAPK and JNK-jun pathways strongly interact on the oncogenic p21 pathway. In contrast, insulin activates only low levels of JNK-P, and, surprisingly, we find that insulin induces only low levels of MAPK-P, indicating that insulin and activated normal p21 utilize MAP kinase-independent signal transduction pathways.

Animals↗
PubMed2001

Design parameters for an electrochemical cell with porous electrode to treat metal-ion solution.

An electrochemical reactor was designed and operated to treat the solution containing copper ions. Design parameters for the electrochemical reactor using the porous cathode and RuO2/IrO2/Ti anode were investigated. The porous cathode was prepared by the electroless nickel deposition on polyurethane. The apparent current, the gap between cathode and anode, and hydraulic retention time (HRT) were selected as design parameters. The copper removal rate increased with an increase in apparent current. It was not affected by the gap between the cathode and the anode. A reduction in hydraulic retention time stimulated the mass transfer toward the electrode and increased the cathodic current efficiency. Dimensional analysis was conducted to obtain the design equation for scale-up of the electrochemical reactor. The dependence of Sh on Re, Sc, and characteristic lengths, DC/A/L and DW/C/L, was described in the form of a power series. The coefficients were obtained from experimental data.

Cations↗
PubMed2001

Inhibition of Saccharomyces cerevisiae by slow release of propyl paraben from a polymer coating.

The inhibition of Saccharomyces cerevisiae by slow release of propyl paraben from a styrene-acrylate copolymer coating was examined and compared with the inhibition by direct addition of propyl paraben. Under slow release condition, a slow but continuous microbial inhibition was observed, whereas a cell outgrowth was observed under direct addition condition after a sufficient incubation time. S. cerevisiae cells isolated from the culture under direct addition condition were more tolerant of propyl paraben than cells isolated from the culture under slow release condition. The equilibrium propyl paraben concentrations under both conditions were 150 ppm. The release kinetics of propyl paraben from the coating at 30 degrees C was found to be controlled by Fickian diffusion within the coating. The estimated partition and diffusion coefficients were 4.65 x 10(-3) and 2.01 x 10(-10) cm2/s, respectively.

Food Contamination↗
PubMed2000

Phenotypic characteristics associated with the APC gene I1307K mutation in Ashkenazi Jewish patients with colorectal polyps.

CONTEXT: The I1307K mutation of the APC gene is found in approximately 6% of the Ashkenazi Jewish population and is associated with elevated risk of colorectal cancer. The incidence of the mutation in patients with colorectal adenomas is unknown. OBJECTIVES: To determine the carrier rate of the I1307K mutation in Ashkenazi Jewish patients with a history of colorectal polyps but without colorectal cancer and to compare phenotypic characteristics and family history of carriers vs noncarriers. DESIGN, SETTING, AND PATIENTS: A total of 231 patients who had at least 1 large bowel polyp diagnosed between January 1, 1992, and January 31, 1999, at 1 of 5 centers in Boston, Mass, were included, of whom 183 were Ashkenazi Jewish. DNA was isolated from cheek swab samples. MAIN OUTCOME MEASURES: Presence of the I1307K variant in the APC gene. RESULTS: The I1307K variant was identified in 22 (14%) of 161 Ashkenazi Jewish patients with a history of adenomatous polyps and in 1 (5%) of 20 Ashkenazi Jewish patients with hyperplastic polyps. The phenotypic features of adenomas, family history of polyps, colorectal cancer, and other cancers were indistinguishable between I1307K carriers and noncarriers. CONCLUSIONS: The frequency of the APC I1307K mutation is elevated in Ashkenazi Jewish patients with adenomatous polyps, but not hyperplastic polyps. The I1307K mutation represents a novel paradigm for cancer-predisposing genes, as it is associated with moderately increased risk of neoplasia without other associated distinguishing phenotypic features. JAMA. 2000;284:857-860

Aged↗
PubMed2000

Recurrent laryngeal nerve palsy associated with mediastinal amyloidosis.

Amyloidosis affecting peripheral nerves causing isolated nerve palsies is uncommon. Localised amyloidosis occurs less frequently than the reactive or immune related systemic forms, and mediastinal localisation is virtually unknown. We present a case of recurrent laryngeal nerve palsy associated with mediastinal AL amyloidosis in a middle aged man.

Amyloidosis↗
PubMed2000

Pancreatic pseudocyst masquerading as an incarcerated inguinal hernia.

We present a case in which a pancreatic pseudocyst dissected into the right inguinal region, thus masquerading as an incarcerated right inguinal hernia. Computed tomography (CT) confirmed the diagnosis of a pseudocyst, and the patient was treated successfully with percutaneous drainage.

Adult↗
PubMed1999

Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2.

Plasma prekallikrein, a zymogen of the contact phase system, circulates in plasma as heterodimeric complex with H-kininogen. The binding is mediated by the prekallikrein heavy chain consisting of four apple domains, A1 to A4, to which H-kininogen binds with high specificity and affinity (K(D) = 1.2 x 10(-8) M). Previous work had demonstrated that a discontinuous kininogen-binding site is formed by a proximal part located in A1, a distal part exposed by A4, and other yet unidentified portion(s) of the kallikrein heavy chain. To detect relevant binding segment(s) we recombinantly expressed single apple domains and found a rank order of binding affinity for kininogen of A2 > A4 approximately A1 > A3. Removal of single apple domains in prekallikrein deletion mutants reduced kininogen binding by 21 (A1), 64 (A2), and 24% (A4), respectively, whereas deletion of A3 was without effect. Transposition of homologous A2 domain from prekallikrein to factor XI conferred high-affinity kininogen binding from the former to the latter. The principal role of A2 for H-kininogen docking to the prekallikrein heavy chain was further substantiated by the finding that cleavage of a single peptide bond in A2 drastically diminished the H-kininogen binding affinity. Furthermore, the epitope of monoclonal antibody PKH6 which blocks kallikrein-kininogen complex formation with an IC(50) of 8 nM mapped to the center portion of domain A2. Our data indicate that domain A2 and two flanking sequence segments of A1 and A4 form a discontinuous binding platform for H-kininogen on the prekallikrein heavy chain. Domain-specific antibodies directed to these critical sites efficiently interfered with contact phase-induced bradykinin release from H-kininogen.

Binding Sites↗
PubMed1998

Peptides derived from the complementarity-determining regions of anti-Mac-1 antibodies block intercellular adhesion molecule-1 interaction with Mac-1.

Peptides or small molecules that can block the interaction of the integrin Mac-1 with its receptor, intercellular adhesion molecule-1 (ICAM-1), have not previously been developed. We studied this interaction by measuring the adherence of ICAM-1-expressing Chinese hamster ovary (CHO) cells to immobilized, purified Mac-1. Nucleotide sequence information was obtained for the complementarity determining regions (CDRs) of three antibodies (44aacb, MY904, and 118.1) shown to block Mac-1-mediated cell adherence. Peptides were synthesized based on the predicted amino acid sequences of the CDRs and tested for the ability to block cell adhesion to Mac-1. Peptides derived from CDR1 of 44aacb, CDR2 of 118.1, and CDRs 1 and 3 of MY904 heavy chains were found to possess blocking activity at 10-100 muM. This may indicate that one or two CDRs contribute disproportionately to the antibody binding affinity. The binding of ligands to Mac-1 has been shown to require a region of the alpha-chain known as the I- or A-domain. We have recombinantly produced Mac-1 I-domain, and show that it is also capable of supporting the adherence of ICAM-1-expressing CHO cells. The adherence of ICAM-1-CHO cells to the I-domain is inhibited by 44aacb and 118.1 and by the CDR peptides from 44aacb and 118.1. By using phage display of peptide libraries based on the 118.1 CDR peptide with five residues randomized, we were able to identify a novel peptide inhibitor of Mac-1 with substitutions at all five positions. These peptides provide lead structures for development of Mac-1 antagonists.

Amino Acid Sequence↗
PubMed1998

Necrotizing esophagitis presenting as a black esophagus.

A case of necrotizing esophagitis discovered during upper endoscopy is described. An 88-year-old woman was admitted to our hospital with complaints of multiple episodes of coffee ground emesis and dysphagia over 3 months. Ischemia is proposed as the etiology of necrotizing esophagitis on the basis of the patient's significant cardiac history, her age, and low-flow state.

Aged↗
PubMed1998

Lower gastrointestinal bleeding as the initial presenting symptom of renal cell carcinoma.

Renal cell carcinoma is known as one of the "great mimics encountered in clinical medicine," along with syphilis and tuberculosis. It can present clinically as a wide range of symptoms, with a classic triad described as hematuria, pain, and a palpable abdominal mass. However, this triad is present only in <20% of patients with renal cell carcinoma. Gastrointestinal bleeding has been described in renal cell carcinoma, although mainly secondary to metastasis in the upper gastrointestinal tract, with few cases due to local invasion. Lower gastrointestinal bleeding as a presenting symptom of an invasive primary renal cell carcinoma has been described in only one patient in the literature. Our patient is the first in whom a colonoscopic biopsy was used as a successful diagnostic modality.

Aged↗