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Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 55 records · Page 3Linked to original sources
PubMed2001

A rare premalignant prostate tumor epithelial cell syndecan-1 forms a fibroblast growth factor-binding complex with progression-promoting ectopic fibroblast growth factor receptor 1.

The abnormal appearance and age-dependent loss of resident fibroblast growth factor receptor-2 (FGFR2) and gain of activity of FGFR1 in epithelial cells is a hallmark of the slow progression to malignancy in some models of prostate cancer. Pericellular matrix heparan sulfate (HS) is an integral subunit of the FGFR tyrosine kinase complex that restricts activity in absence of FGF, facilitates binding of an activating FGF, and confers specificity for FGF isoforms. In this report, we isolated and purified HS proteoglycan (HSPG) from premalignant prostate tumor epithelial cells based on the ability of the HS chains to form a binary complex with immunoglobulin module II of the ectopic and progression-promoting FGFR1 that was competent to bind FGF. The FGFR1 affinity-purified product exhibited a specific activity of over 600 times that of crude cellular HSPG enriched from cell lysates by ion exchange chromatography. The purified preparation exhibited a single NH(2)-terminal sequence with 11 of 13 residues identical to syndecan-1. The activity of purified recombinant glutathione S-transferase-tagged syndecan-1 expressed in premalignant epithelial cells confirmed that syndecan-1 bears HS chains that exhibit the rare motif that forms the FGF-binding complex with ectopic FGFR1. These results are the first to identify by affinity purification a specific HSPG core protein, the HS chains of which act as an integral subunit of the FGFR complex. The results suggest that syndecan-1 provides HS chains in premalignant epithelial cells to both the FGFR2- and FGFR1-signaling complexes that are integral to their dual roles in progression to malignancy.

Amino Acid Sequence↗
PubMed2001

A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein.

A new strategy for organ allografts that does not require recourse to immunosuppressants is established in mice. The strategy includes sublethal (7 Gy) irradiation followed by the injection of donor bone marrow cells (BMCs) via the portal vein (P.V.) and organ allografts 1 day after irradiation. Irradiation doses (< or =7 Gy) are found to allow the recipients to survive without the need to reconstitute the BMCs, as the recipient hematolymphoid cells can gradually recover. One hundred percent of recipients irradiated with 7 Gy followed by either P.V. or i.v. injection of donor BMCs accept organ allografts (the skin, pancreas, and adrenal glands) for more than 1 year. However, organ allograft survival rates decrease when irradiation doses are reduced; the skin graft survival rate of mice treated with 6.5 Gy and P.V. injection of BMCs is 79%, whereas that of mice treated with 6.5 Gy and i.v. injection is 50%, indicating that the P.V. injection of BMCs induces persistent tolerance more effectively than the i.v. injection. H-2 typing reveals that almost all the hematolymphoid cells (>98%) in the peripheral blood and hematolymphoid organs are donor-derived even 1 year after the treatment (7 Gy and P.V.). The T cells are tolerant to both donor-type and host-type MHC determinants. The major mechanism underlying the persistent tolerance induced by this strategy seems to be because of clonal deletion. This simple and safe strategy would be of great advantage for human organ transplantation.

Adrenal Glands↗
PubMed2001

Thermodynamic characterization of the human acidic fibroblast growth factor: evidence for cold denaturation.

The thermodynamic parameters characterizing the conformational stability of the human acidic fibroblast growth factor (hFGF-1) have been determined by isothermal urea denaturation and thermal denaturation at fixed concentrations of urea using fluorescence and far-UV CD circular dichroism (CD) spectroscopy. The equilibrium unfolding transitions at pH 7.0 are adequately described by a two-state (native <--> unfolded state) mechanism. The stability of the protein is pH-dependent, and the protein unfolds completely below pH 3.0 (at 25 degrees C). hFGF-1 is shown to undergo a two-state transition only in a narrow pH range (pH 7.0-8.0). Under acidic (pH <6.0) and basic (pH >8.0) conditions, hFGF-1 is found to unfold noncooperatively, involving the accumulation of intermediates. The average temperature of maximum stability is determined to be 295.2 K. The heat capacity change (DeltaC(p)()) for the unfolding of hFGF-1 is estimated to be 2.1 +/- 0.5 kcal.mol(-1).K(-1). Temperature denaturation experiments in the absence and presence of urea show that hFGF-1 has a tendency to undergo cold denaturation. Two-dimensional (1)H-(15)N HSQC spectra of hFGF-1 acquired at subzero temperatures clearly show that hFGF-1 unfolds under low-temperature conditions. The significance of the noncooperative unfolding under acidic conditions and the cold denaturation process observed in hFGF-1 are discussed in detail.

Circular Dichroism↗
PubMed2001

Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance.

Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic-euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. Muscle-lipoprotein lipase mice had a 3-fold increase in muscle triglyceride content and were insulin resistant because of decreases in insulin-stimulated glucose uptake in skeletal muscle and insulin activation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity. In contrast, liver-lipoprotein lipase mice had a 2-fold increase in liver triglyceride content and were insulin resistant because of impaired ability of insulin to suppress endogenous glucose production associated with defects in insulin activation of insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity. These defects in insulin action and signaling were associated with increases in intracellular fatty acid-derived metabolites (i.e., diacylglycerol, fatty acyl CoA, ceramides). Our findings suggest a direct and causative relationship between the accumulation of intracellular fatty acid-derived metabolites and insulin resistance mediated via alterations in the insulin signaling pathway, independent of circulating adipocyte-derived hormones.

Animals↗
PubMed2001

Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects.

Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. (Blood. 2001;97:3390-3400)

Adult↗
PubMed2001

Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes.

The transcription factor NF-kappaB regulates expression of genes that are involved in inflammation, immune response, viral infection, cell survival, and division. However, the role of NF-kappaB in hypertrophic growth of terminally differentiated cardiomyocytes is unknown. Here we report that NF-kappaB activation is required for hypertrophic growth of cardiomyocytes. In cultured rat primary neonatal ventricular cardiomyocytes, the nuclear translocation of NF-kappaB and its transcriptional activity were stimulated by several hypertrophic agonists, including phenylephrine, endothelin-1, and angiotensin II. The activation of NF-kappaB was inhibited by expression of a "supersuppressor" IkappaBalpha mutant that is resistant to stimulation-induced degradation and a dominant negative IkappaB kinase (IKKbeta) mutant that can no longer be activated by phosphorylation. Furthermore, treatment with phenylephrine induced IkappaBalpha degradation in an IKK-dependent manner, suggesting that NF-kappaB is a downstream target of the hypertrophic agonists. Importantly, expression of the supersuppressor IkappaBalpha mutant or the dominant negative IKKbeta mutant blocked the hypertrophic agonist-induced expression of the embryonic gene atrial natriuretic factor and enlargement of cardiomyocytes. Conversely, overexpression of NF-kappaB itself induced atrial natriuretic factor expression and cardiomyocyte enlargement. These findings suggest that NF-kappaB plays a critical role in the hypertrophic growth of cardiomyocytes and may serve as a potential target for the intervention of heart disease.

Angiotensin II↗
PubMed2001

[Clinical observation of the microanatomical relation between pituitary stalk and pituitary adenoma].

OBJECTIVE: To observe the microanatomical relation between the pituitary stalk and pituitary adenoma so as to find practical approach to protect the pituitary stalk during operation. METHODS: At the level of diaphragm sellae, the laterality of pituitary stalk was assessed in 71 cases by its location to the line connecting the mid-points of tuberculum sellae and dorsum sellae. In 46 cases the level of diaphragma sellae was regarded as the clock dial so as to determine the location by hour of the pituitary stalk. RESULTS: The laterality of pituitary stalk was observed in 61 cases, among which the pituitary stalk was on the left side in 17 cases, on the right side in 41 cases, and at the posterior middle site in 13 cases. Location by hour was observed in 46 cases, among which 13 cases were at 5 o'clock, 11 at 6 o'clock, 7 at 7 o'clock, 5 at 4 o'clock, 4 at 3 o'clock, 2 at 2 o'clock, 2 at o'clock, and 2 at 11 o'clock respectively. CONCLUSION: The location of pituitary stalk is related to the direction of growth of tumor in the sella and not related to its extension above the sella. The pituitary stalk can be used as the marker to find normal pituitary tissue.

Adenoma↗
PubMed2001

Catalytic function of nongastric H,K-ATPase expressed in Sf-21 insect cells.

We previously demonstrated that the alpha-subunit of human nongastric H,K-ATPase (Atp1al1) can assemble with the gastric H,K-ATPase beta-subunit (betaHK) into an active ion pump upon coexpression in Xenopus oocytes. To gain insight into enzymatic functions, we have analyzed the Atp1al1-betaHK complex using a baculovirus expression system. The efficient formation of the functional Atp1al1-betaHK complex in membranes of Sf-21 insect cells was obtained upon co-infection with recombinant baculoviruses expressing Atp1al1 and betaHK. Expression of either protein alone did not produce active ATPase. The effects of K(+), Na(+), pH, and ATP and inhibitors on ATPase activity of the recombinant Atp1al1-betaHK complex were analyzed. The Atp1al1-betaHK complex was shown to exhibit significant ATPase activity in nominally K(+)-free medium. The addition of K(+) stimulated the ATP hydrolysis up to 3-fold with K(m) approximately 116 microM K(+). The ATPase activity was moderately sensitive to ouabain and to SCH 28080 with apparent K(i) values in K(+)-free medium of approximately 64 microM and approximately 93 microM, respectively. Potassium exhibited strong antagonism toward both inhibitors. Assays of the ouabain-sensitive ATPase activity revealed inhibitory effects of Na(+) with the apparent K(i) of approximately 24 mM in the absence of added K(+) and with K(i) within the range of 60-70 mM in the presence of > or = 1 mM K(+). Thus, the human nongastric H,K-ATPase represented by the recombinant Atp1al1-betaHK complex exhibits enzymatic properties of K(+)-dependent ATPase sensitive to ouabain, SCH 28080, and Na(+). It differs from Na,K-ATPase in cation dependence and differs from gastric H,K-ATPase and Na,K-ATPase in sensitivity to inhibitors.

Adenosine Triphosphate↗
PubMed2001

[Anatomicopathological relation between facial nerve and large vestibular Schwannoma].

OBJECTIVE: To study the anatomicopathological relation between facial nerve and large vestibular schwannoma. METHODS: Operation by suboccipital retrosigmoid sinus approach was performed on 40 cases with large vestibular schwannoma, During the operation, the anatomicopathological relation between the facial nerve and the vestibular schwannoma was observed directly. RESULTS: The facial nerve was found to be located ventrally (deep under the tumor), dorsally (over the tumor), at the upper pole of the tumor (near the tentorium cerebelli), at the lower pole of the tumor (near the rear group cranial nerves), or aberrant (unable to be identified because of infiltration of tumor). In 31 cases, mainly with parenchymatous tumor, the facial nerve was flat in shape. In 9 cases, mainly with cystic tumor, the facial nerve was bandlike. CONCLUSION: The facial nerve varies greatly in neuroanatomy among patients with large vestibular schwannoma. Strengthening of operative monitoring can increase the safety of operation.

Adult↗
PubMed2001

Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases.

Receptor accessory peptidyl prolyl cis/trans isomerases (PPIases) of the FKBP and cyclophilin types form receptor heterocomplexes with different stabilities. PPIases have been found to associate with other receptor heterocomplex constituents via either proline-directed active sites or additional domains of the enzymes. The single-domain PPIases FKBP12 and FKBP12.6 are shown to interact with receptor protein kinases and calcium channels at their active sites. In contrast, heterooligomeric nuclear receptors contain multi-domain PPIases like FKBP51, FKBP52 or cyclophilin 40 that directly interact with the chaperone hsp90 via the tetratricopeptide repeat modules of the folding helper enzymes. PPIases play a critical role in the functional arrangement of components within receptor heterocomplexes.

Animals↗
PubMed2001

Samarium(0) and 1,1'-dioctyl-4,4'-bipyridinium dibromide: a novel electron-transfer system for the chemoselective reduction of aromatic nitro groups.

A mild and efficient electron-transfer method was developed for the chemoselective reduction of aromatic nitro groups using samarium(0) metal in the presence of a catalytic amount of 1,1'-dioctyl-4,4'-bipyridinium dibromide. This method was found to give the product aromatic amine in 79-99% yield with selectivity over a number of other functional and protecting groups such as alkene, azide, benzyl ether, nitrile, amide, halide, p-toluenesulfonamide, t-Boc, tert-butyldiphenylsilyl ether, and aliphatic nitro groups. Our results also indicate that samarium(0) plays an important role in the reduction process and that 1,1'-dioctyl-4,4'-bipyridinium dibromide acts as an electron-transfer catalyst and is essential in the activation of samarium(0) metal. The major active reducing agent responsible for the reduction is believed to be the radical cation species formed from 1,1'-dioctyl-4,4'-bipyridinium dibromide.

Journal Article↗
PubMed2001

Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in beta-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to beta-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.

Animals↗
PubMed2001

Porous polymer monoliths: simple and efficient mixers prepared by direct polymerization in the channels of microfluidic chips.

Porous monolithic polymers have been prepared by photoinitiated polymerization of mixtures consisting of 2-hydroxyethyl methacrylate, ethylene dimethacrylate, UV-sensitive free radical initiator and porogenic solvent within channels of specifically designed microfluidic chips and used as micromixers. Substituting azobisisobutyronitrile with 2,2-dimethoxy-2-phenylacetophenone considerably accelerated the kinetics of the polymerization. Mixtures of cyclohexanol and 1 -dodecanol and of hexane and methanol were used, respectively, to control the porous properties and therefore the mixing efficiency of the device. The performance of the monolithic mixers has been tested by pumping aqueous solutions of two fluorescent dyes at various flow rates and monitoring the point at which the boundary of both streams completely disappears. Best results were achieved with a monolithic mixer containing very large irregular pores.

Acetophenones↗
PubMed2001

Sonographic features of xanthogranulomatous pyelonephritis.

PURPOSE: The purpose of this study was to describe the various sonographic features of xanthogranulomatous pyelonephritis (XGP). METHODS: We retrospectively reviewed the CT, sonographic, and medical records of patients diagnosed with XGP from January 1981 to December 1998. Twenty-seven patients for whom XGP was histopathologically confirmed were included in the study. There were 12 men and 15 women, with an age range of 21-86 years (mean, 57 years). All patients had undergone sonography of the kidneys. The renal size, shape, and outline were recorded. The presence of perinephric fluid accumulation, of obstructive uropathy, or of internal echoes in the dilated collecting system and the echotexture of the renal parenchyma were documented. RESULTS: We categorized the XGP into 4 groups on the basis of the sonographic features: (1) diffuse hydronephrotic, 12 patients (44%); (2) diffuse parenchymal, 9 patients (33%); (3) diffuse contracted, 4 patients (15%); and (4) segmental or focal, 2 patients (7%). A localized perinephric fluid collection was present in 4 patients (15%). The preoperative sonographic diagnoses were pyonephrosis (n = 14, 52%), renal pelvic tumor with possible associated infection (n = 5, 19%), renal parenchymal mass (n = 2, 7%), hydronephrosis (n = 2, 7%), and chronic pyelonephritis with renal atrophy (n = 4, 15%). XGP was considered a possible diagnosis in only 11 patients (41%). CONCLUSIONS: XGP has no specific sonographic features but is suggested by parenchymal thinning and hydronephrosis, sonographic signs of chronic obstructive uropathy caused by stones; echoes in the dilated collecting system; and a perinephric fluid collection. CT, needle biopsy, or both are recommended to further evaluate and confirm sonographically suspected XGP.

Adult↗
PubMed2001

Fine genetic mapping and BAC contig development for the citrus tristeza virus resistance gene locus in Poncirus trifoliata (Raf.).

A map-based cloning strategy has been employed to isolate Ctv, a single dominant gene from Poncirus trifoliata that confers resistance to citrus tristeza virus (CTV), the most important viral pathogen of citrus. Cloning of this gene will allow development of commercially acceptable, virus-resistant cultivars. A high-resolution genetic linkage map of the Ctv locus region was developed using a backcross population of 678 individuals. Three DNA markers that were closely linked or co-segregated with Ctv were identified and used to screen BAC libraries derived from an intergeneric hybrid of Poncirus and Citrus. Through chromosome walking and landing, two BAC contigs were developed: one encompassing the Ctv region, and the other spanning the allelic susceptibility gene region. The resistance gene contig consists of 20 BAC clones and is approximately 550 kb in length; the susceptibility gene contig consists of 16 BAC clones and extends about 450 kb. The Ctv locus was localized within a genomic region of approximately 180 kb by genetic mapping of BAC insert ends. The BAC contigs were integrated with the genetic map; variation in the ratio of genetic to physical distance was observed in the vicinity of Ctv. Southern hybridization data indicated that a few copies of NBS-LRR class sequences are distributed at or around the Ctv locus. Efforts are being made to assign the Ctv locus to a smaller genomic fragment whose function can be confirmed through genetic complementation of a CTV susceptible phenotype. These results indicate that map-based gene cloning is feasible in a woody perennial.

Blotting, Southern↗
PubMed2001

Sonography of acute right side colonic diverticulitis.

BACKGROUND: To describe the prevalence and sonographic findings and ultrasound diagnostic accuracy of the right side colonic diverticulitis in patients having right lower abdominal pain with indeterminate nature. METHODS: A total of 934 patients with acute right lower abdominal pain of clinically indeterminate nature were referred for ultrasound examination (US). US studies were performed with 3.5 to 7.0 (or occasionally 10) MHz transducers using graded compression method. Twenty-three patients were finally diagnosed to have an uncomplicated acute diverticulitis of the right colon. The gray-scale sonographic images were reviewed. A retrospective study was undertaken to evaluate diagnostic contribution of US. RESULTS: The prevalence of acute right side colonic diverticulitis was 2.5% in patients with clinically indeterminate acute right lower abdominal pain. Locations of the inflamed diverticula include cecum in 6 patients, proximal ascending colon in 15 patients, and distal ascending colon in only 2 patients. Sonography detected 21 inflamed diverticula with 1 false positive and 2 false negative results. The most typical sonographic feature of an inflamed diverticulum of right side colon was a rounded or oval-shaped hypoechoic or nearly anechoic structure (52%) protruding out from the segmentally thickened colonic wall. Some of them might contain strong echoes representing gas or feces (43%), or stone in the lumen (5%). Regional pericolic or peridiverticular fat thickening was noted in 57% of patients, and segmental colon wall thickening in 38%. US examination yielded a sensitivity of 91.3%, a specificity of 99.8%, an overall accuracy of 99.5%, a positive predictive value of 95.5%, and a negative predictive value of 99.7%. A positive sonogram made the likelihood of acute right side diverticulitis 456.5 times greater compared with the pretest clinical impression. US differentiated acute right side colonic diverticulitis from acute appendicitis with a 100% accuracy. CONCLUSIONS: Ultrasound can be extremely useful in diagnosing acute right side colonic diverticulitis. Careful ultrasound evaluation of the right colon and the cecum may facilitate a correct diagnosis and help differentiate from acute appendicitis, and steer the surgeon to a more effective management.

Acute Disease↗
PubMed2001

Efficacy of chemotherapy for prostatic tuberculosis-a clinical and histologic follow-up study.

OBJECTIVES: To characterize the clinical features of prostatic tuberculosis and to evaluate the short and long-term results of antituberculous chemotherapy. METHODS: Eighteen patients (mean age 66.7 +/- 10.2 years) with prostatic tuberculosis were included in this study. The median pretreatment prostate-specific antigen (PSA) level was 2.7 ng/mL (range 0.3 to 31). The PSA level was greater than 4.0 ng/mL in 6 patients (33.3%). Eight patients (44.4%) received a triple-drug regimen of rifampin, ethambutol, and isoniazid for more than 6 months. The mean duration of chemotherapy was 7.6 months (range 6 to 12). Of the 8 patients, 3 underwent chemotherapy longer because of concurrent tuberculosis of other organs. Follow-up studies included digital rectal examination, total PSA determination, and transrectal prostate biopsy. RESULTS: Ten patients were eligible for regular follow-up. All the patients were symptom free during follow-up. The median length of follow-up was 3.4 years (range 1 to 9). The average number of follow-up transrectal prostate biopsies was 2.4 (range 2 to 3). The follow-up histologic findings showed nodular hyperplasia in 7 patients and chronic inflammatory cell infiltration in 3 patients. No acid-fast bacillus was found in any follow-up specimen. Similarly, subsequent transrectal biopsy showed no relapse after a median length of 3.4 years of follow-up. Of the 6 patients with elevated PSA levels, the post-treatment PSA returned to normal in 3 patients. CONCLUSIONS: Our results suggest that a triple-drug regimen of 6 months' duration can successfully control prostatic tuberculosis. Histologic follow-up is a good method for monitoring the efficacy of treatment. Transrectal prostate biopsy is an important tool for the diagnosis and follow-up of prostatic tuberculosis.

Adult↗