Search PubMed⌕ Search

Biomedical subjects

H C Cheng

Publications and source records attributed to H C Cheng.

At least 37 records · Page 2Linked to original sources
PubMed2000

Molecular characteristics and functional diversity of CLCA family members.

1. In the present brief review, we describe some of the molecular and functional characteristics of a novel mammalian family of putative Ca2+-activated chloride channels (CLCA). 2. So far, two bovine (bCLC1; bCLCA2 (Lu-ECAM-1)), three mouse (mCLCA1; mCLCA2; mCLCA3) and four human (hCLCA1; hCLCA2; hCLCA3; hCLCA4) CLCA family members have been cloned. Each CLCA exhibits a distinct, often overlapping, tissue expression pattern. 3. With the exception of the truncated secreted hCLCA3, all CLCA proteins are synthesized as an approximately 125 kDa precursor transmembrane glycoprotein that is rapidly cleaved into 90 and 35 kDa subunits. 4. The CLCA proteins expressed on the luminal surface of lung vascular endothelia (bCLCA2; mCLCA1; hCLCA2) serve as adhesion molecules for lung metastatic cancer cells, mediating vascular arrest and lung colonization. 5. Expression of hCLCA2 in normal mammary epithelium is consistently lost in human breast cancer and in all tumorigenic breast cancer cell lines. Re-expression of hCLCA2 in human breast cancer cells abrogates invasiveness of Matrigel (BD Biosciences-Labware, Bedford, MA, USA) in vitro and tumorigenicity in nude mice, implying that hCLCA2 acts as a tumour suppressor in breast cancer.

Animals↗
PubMed1999

Identification and structure characterization of a Cdk inhibitory peptide derived from neuronal-specific Cdk5 activator.

The activation of cyclin-dependent kinase 5 (Cdk5) depends on the binding of its neuronal specific activator Nck5a. The minimal activation domain of Nck5a is located in the region of amino acid residues 150 to 291 (Tang, D., Chun, A. C. S., Zhang, M., and Wang, J. H. (1997) J. Biol. Chem. 272, 12318-12327). In this work we show that a 29-residue peptide, denoted as the alphaN peptide, encompassing amino acid residues Gln145 to Asp173 of Nck5a is capable of binding Cdk5 to result in kinase inhibition. This peptide also inhibits an active phospho-Cdk2-cyclin A complex, with a similar potency. Direct competition experiments have shown that this inhibitory peptide does not compete with Nck5a or cyclin A for Cdk5 or Cdk2, respectively. Steady state kinetic analysis has indicated that the alphaN peptide acts as a non-competitive inhibitor of Cdk5. Nck5a complex with respect to the peptide substrate. To understand the molecular basis of kinase inhibition by the peptide, we determined the structure of the peptide in solution by circular dichroism and two-dimensional 1H NMR spectroscopy. The peptide adopts an amphipathic alpha-helical structure from residues Ser149 to Arg162 which can be further stabilized by the helix-stabilizing solvent trifluoroethanol. The hydrophobic face of the helix is likely to be the kinase binding surface.

Amino Acid Sequence↗
PubMed1999

Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530.

Elevated levels of Src kinase activity have been reported in a number of human cancers, including colon and breast cancer. We have analysed four human breast tumor cell lines that exhibit high levels of Src kinase activity, and have determined that these cell lines also exhibit a high level of a phosphotyrosine phosphatase activity that recognizes the Src carboxy-terminal P-Tyr530 negative regulatory site. Total Src kinase activity in these cell lines is elevated as much as 30-fold over activity in normal control cells and specific activity is elevated as much as 5.6-fold. When the breast tumor cells were grown in the presence of the tyrosine phosphatase inhibitor vanadate, Src kinase activity was reduced in all four breast tumor cell lines, suggesting that Src was being activated by a phosphatase which could recognize the Tyr530 negative regulatory site. In fractionated cell extracts from the breast tumor cells, we found elevated levels of a membrane associated tyrosine phosphatase activity that preferentially dephosphorylated a Src family carboxy-terminal phosphopeptide containing the regulatory tyrosine 530 site. Src was hypophosphorylated in vivo at tyrosine 530 in at least two of the tumor cell lines, further suggesting that Src was being activated by a phosphatase in these cells. In preliminary immunoprecipitation and antibody depletion experiments, we were unable to correlate the major portion of this phosphatase activity with several known phosphatases.

Breast Neoplasms↗
PubMed1999

Is the Fischer 344/CRJ rat a protein-knock-out model for dipeptidyl peptidase IV-mediated lung metastasis of breast cancer?

Fischer 344/CRJ rats harbor a G633R substitution in dipeptidyl peptidase IV (DPP IV) that leads to retention and degradation of the mutant protein in the endoplasmic reticulum (Tsuji E, Misumi Y, Fujiwara T et al. Biochemistry 1992; 31 (47): 11921-7). However, when these rats were used as a 'protein knock-out' model in further evaluating the previously established role of DPP IV in metastasis, lung colonization of the highly metastatic MTF7 rat breast cancer cell line was reduced by only 33% relative to normal Fischer 344 rats. To examine whether lung endothelia leak expression of mutant DPP IV and whether mutant DPP IV exhibits the same adhesion qualities as wild type DPP IV, detailed immunohistochemical, biochemical, transfection, and FACS analyses were performed to assess the surface expression of mutant DPP IV on lung endothelia and transfected HEK293 cells and adhesion assay to compare the adhesion qualities of wild-type and mutant DPP IV. Both endothelial and transfected HEK293 cells expressed mutant, enzymatically inactive DPP IV on their surfaces, albeit at greatly reduced levels when compared to expression of wild type DPP IV. Purified mutant DPP IV had identical adhesion qualities for lung-metastatic MTF7 cells as wild type DPP IV, and competitive inhibition of MTF7 lung colonization by truncated DPP IV confirmed involvement of mutant DPP IV in lung metastasis of Fischer 344/CRJ rats. Although metastasis appears to be mediated by several, often parallel mechanisms involving multiple tumor and host factors, these data indicate that altered expression of a single component can drastically change the outcome of metastatic disease.

Adenocarcinoma↗
PubMed1999

Treatment of experimental brain tumors with trombospondin-1 derived peptides: an in vivo imaging study.

Antiangiogenic and antiproliferative effects of synthetic D-reverse peptides derived from the type 1 repeats of thrombospondin (TSP1) were studied in rodent C6 glioma and 9L gliosarcomas. To directly measure tumor size and vascular parameters, we employed in vivo magnetic resonance (MR) imaging and corroborated results by traditional morphometric tissue analysis. Rats bearing either C6 or 9L tumors were treated with TSP1-derived peptide (D-reverse amKRFKQDGGWSHWSPWSSac, n=13) or a control peptide (D-reverse amKRAKQAGGASHASPASSac, n=12) at 10 mg/kg, administered either intravenously or through subcutaneous miniosmotic pumps starting 10 days after tumor implantation. Eleven days later, the effect of peptide treatment was evaluated. TSP1 peptide-treated 9L tumors (50.7+/-44.2 mm3, n=7) and C6 tumors (41.3+/-34.2 mm3, n=6) were significantly smaller than tumors treated with control peptide (9L: 215.7+/-67.8 mm3, n=6; C6: 184.2+/-105.2 mm3, n=6). In contrast, the in vivo vascular volume fraction, the mean vascular area (determined by microscopy), and the microvascular density of tumors were not significantly different in any of the experimental groups. In cell culture, TSP1, and the amKRFKQDGGWSHWSPWSSac peptide showed antiproliferative effects against C6 with an IC of 45 nM for TSP1. These results indicate that TSP1-derived peptides retard brain tumor growth presumably as a result of slower de novo blood vessel formation and synergistic direct antiproliferative effects on tumor cells. We also show that in vivo MR imaging can be used to assess treatment efficacy of novel antiangiogenic drugs non-invasively, which has obvious implications for clinical trials.

Animals↗
PubMed1999

The anesthetic management of a preterm infant weighing 500 grams undergoing ligation of patent ductus arteriosus--a case report.

PDA (patent ductus arteriosus) is a common congenital heart disease. Usually surgical intervention through left thoracotomy or recently through video assisted thoracoscopy will be recommended if the preceding or intent medical treatment fails or is contraindicated. However, once surgical intervention is decided, various complications are still a real fear in the mind of the surgeon and the anesthesiologist, particularly if the infant is premature or very sick. Here we report an anesthetic management in a female preterm infant weighing 500 grams, who underwent PDA ligation. She was born at gestation age of 28 weeks at our hospital, and since her birth she was noted to have infant respiratory distress syndrome associated with renal dysfunction. She was admitted to the neonatal intensive care unit (NICU) straightaway. After thorough examination, a severe PDA was disclosed. The possibility of pulmonary hemorrhage and heart failure could be predicted in view of the large left to right shunt. Worst of all was that her poor renal function contradicted a medical treatment. So we decided to carry out the ligation procedure at once although she was premature and only 5 days old. The NICU was chosen as the operation theater for transferring concerns. General anesthesia was induced and maintained by atropine 0.01 mg, pancuronium 0.1 mg, fentanyl 2 micrograms, and ketamine 0.15 mg intravenously. Supplemental oxygen was given throughout the operation. The PDA was ligated through left thoracotomy and blood loss was minimal. The peri-operative course was uneventful. The patient recovered well following surgery and anesthesia.

Adult↗
PubMed1999

Anesthetic managements of the patients with giant mediastinal tumors--a report of two cases.

Anesthesia for patients with a huge anterior mediastinal tumor is a well-known challenge and trial to all the anesthesiologists. The tumor mass which directly compresses the trachea and bronchus induces hypoxia and asphyxia, eventuating in cardiac arrest or even fatality in the process of general anesthesia. In selection of anesthetic technique, general anesthesia is deliberately avoided if not mandatory or spontaneous respiration should be strictly preserved by all means if obligatory. Our surgical colleagues are usually not so familiar with this potentially life-threatening situation as are the anesthesiologists, and bad communications and interactions between the two may court disaster. Here we reported 2 cases: the former was an immediate mortality in a youth with a giant anterior mediastinal tumor undergoing excisional biopsy of a neck mass under general anesthesia, and the latter was a successful anesthetic management in a woman with a giant mediastinal tumor receiving abdominal total hysterectomy for cervical cancer in situ under spinal anesthesia. The hazards of general anesthesia in these patients and the importance of comprehending preanesthetic preparations were reviewed and discussed. Moreover, we address that whenever one has shot his bolt still futile to improve the respiratory crisis in a case with mediastinal tumor, try to ventilate the patient in a prone position as it has clinical importance in ventilation and oxygenation.

Adolescent↗
PubMed1998

A peptide corresponding to residues Asp177 to Asn208 of human cyclin A forms an alpha-helix.

Cyclins are essential activators of eukaryotic cell cycle-regulating enzymes called cyclin-dependent kinases (CDKs). The binding of cyclins to CDKs is mediated by a structural motif comprising a five-helix bundle called the cyclin fold and an additional helix (the N-terminal alpha-helix) located N-terminal to the cyclin fold. In this work, we examine, using CD and NMR spectroscopy, the structure of a 32-residue synthetic peptide derived from the segment (Asp177 to Asn208) corresponding to the N-terminal alpha-helix of human cyclin A. CD spectroscopic analysis of the peptide revealed that trifluoroethanol (TFE) can induce the peptide to assume a stable alpha-helix conformation. Two-dimensional 1H NMR spectroscopy showed that the alpha-helix is formed by the Asp181 to Cys193 segment of the peptide. The alpha-helical structure of the peptide in the TFE/H2O cosolvent was found to be identical to that in the crystal structure of intact cyclin A. Taken together, these results suggest that the N-terminal alpha-helix of cyclins may exist as an independent structural unit that plays essential functional roles in activating CDKs.

Amino Acid Sequence↗
PubMed1998

Roles of transforming growth factor-alpha and epidermal growth factor in chick limb development.

We have examined the distribution of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and the chicken EGF receptor (c-erbB), in embryonic chick limbs. Prior to limb budding, TGF-alpha is present in prospective limb-forming mesoderm and in prospective apical ectodermal ridge (AER)-forming ectoderm, but is not detected in non-limb-forming flank mesoderm or ectoderm, nor in presumptive non-AER-forming limb ectoderm, suggesting possible roles in initial limb formation and AER induction. Consistent with this possibility, TGF-alpha is present in the mesoderm of the wing buds of the amelic chick mutants limbless and wingless, which form and bud normally, but is absent from limbless and wingless ectoderm, which fails to form an AER. TGF-alpha and EGF are present in the AER of the developing limb, and TGF-alpha, EGF, and c-erbB are present in the underlying subridge mesoderm, suggesting possible roles in reciprocal AER/subridge mesoderm interactions required for limb outgrowth. We found that exogenous TGF-alpha and EGF can promote the outgrowth of limb mesoderm in the absence of the AER in vitro and can also promote the outgrowth of limbless and wingless wing bud explants. EGF is present in ventral but not dorsal limb ectoderm, suggesting a role for EGF in specification of ventral ectoderm. TGF-alpha and EGF are not detected in the differentiating cartilaginous elements or muscle primordia of the limb, suggesting that cessation of TGF-alpha and EGF expression may be required for cartilage and muscle formation. We have found that exogenous TGF-alpha and EGF inhibit chondrogenesis and myogenesis of limb mesenchyme in vitro. Together these results indicate that signaling through the EGF receptor via endogenous TGF-alpha and EGF may be important for initial limb formation, AER induction, outgrowth of limb mesoderm, and regulation of limb chondrogenic and myogenic differentiation.

Animals↗
PubMed1998

Lung endothelial dipeptidyl peptidase IV promotes adhesion and metastasis of rat breast cancer cells via tumor cell surface-associated fibronectin.

Endothelial cell adhesion molecules are partly responsible for the distinct organ distribution of cancer metastases. Dipeptidyl peptidase IV (DPP IV) expressed on rat lung capillary endothelia is shown here to be an adhesion receptor for rat breast cancer cells and to mediate lung colonization by these tumor cells. Fibronectin (FN) assembled on breast cancer cell surfaces into multiple, randomly dispersed globules from cellular and plasma FN is identified as the principal ligand for DPP IV. Ligand expression correlates quantitatively with the tumor cells' capabilities to bind to DPP IV and to metastasize to the lungs. DPP IV/FN-mediated adhesion and metastasis are blocked when tumor cells are incubated with soluble DPP IV prior to conducting adhesion and lung colony assays. Adhesion is also blocked by anti-DPP IV monoclonal antibody 6A3 and anti-FN antiserum. However, adhesion to immobilized FN is unaffected by soluble plasma FN and, thus, can happen during hematogenous spread of cancer cells at high plasma FN concentrations. The ability of many cancer cells to capture FN molecules on their surface and to augment such deposits by FN self-association during passage in the blood suggests that DPP IV/FN binding may be a relatively common mechanism for lung metastasis.

Adenocarcinoma↗
PubMed1998

Common in vitro substrate specificity and differential Src homology 2 domain accessibility displayed by two members of the Src family of protein-tyrosine kinases, c-Src and Hck.

Hck and Src are members of the Src family of protein- tyrosine kinases that carry out distinct and overlapping functions in vivo (Lowell, C. A., Niwa, M., Soriano, P., and Varmus, H. E. (1996) Blood 87, 1780-1792). In an attempt to understand how Hck and Src can function both independently and in concert, we have compared 1) their in vitro substrate specificity and 2) the accessibility of their Src homology 2 (SH2) domain. Using several synthetic peptides, we have demonstrated that Hck and Src recognize similar structural features in the substrate peptides, suggesting that both kinases have the intrinsic ability to carry out overlapping cellular functions by phosphorylating similar cellular proteins in vivo. Using a phosphotyrosine-containing peptide that has previously been shown to bind the SH2 domain of Src family kinases with high affinity, we found that although Src could bind to the phosphopeptide, Hck showed no interaction. The inability of Hck to bind the phosphopeptide was not a result of a stable intramolecular interaction between its SH2 domain and C-terminal regulatory phosphotyrosine residue (Tyr-520), as most Hck molecules in the purified Hck preparation were not tyrosine-phosphorylated. In contrast to intact Hck, a recombinant truncation analog of Hck was able to bind the phosphopeptide with an affinity similar to that of the Src SH2 domain, suggesting that conformational constraints are imposed on intact Hck that limit accessibility of its SH2 domain to the phosphopeptide. Furthermore, the difference in SH2 domain accessibility is a potential mechanism that enables Src and Hck to perform their respective unique functions by 1) targeting them to different subcellular compartments, whereupon they phosphorylate different cellular proteins, and/or 2) facilitating direct binding to their cellular substrates.

Amino Acid Sequence↗
PubMed1998

Pictorial review: Radiological diagnosis of duodenal abnormalities.

This article depicts the radiological findings of many common gastrointestinal entities. Specifically, examples of disease processes that affect the stomach, gall bladder, small intestine, pancreas and colon are shown. In most cases there is correlation between ultrasound, computed tomography (CT) and fluoroscopic imaging. The major emphasis of the article, however, is to demonstrate classic barium imaging of a large number of gastrointestinal disease processes.

Barium Sulfate↗
PubMed1998

MDL 101,002, a free radical spin trap, is efficacious in permanent and transient focal ischemia models.

The present work describes the neuroprotective effects of the free radical spin trap, MDL 101,002, in models of permanent and transient focal ischemia. Permanent focal ischemia was carried out by occlusion of the distal segment of the middle cerebral artery (MCA) and CCA's in Spontaneously Hypertensive (SH) and Wistar rats. Transient focal ischemia was undertaken by occluding the origin of the MCA for 180 min by the intraluminar monofilament method in Wistar rats. With permanent distal MCA occlusion in SH rats, 100 mg/kg i.v. at 30 min post-ischemia resulted in a significant 40% reduction in infarct volume. Similarly, a 75 mg/kg bolus + 45 mg/kg-h dose of MDL 101,002 given i.v. at 5 min post-ischemia resulted in a 90% or 60% decrease in infarct volume in the mixed permanent/transient distal MCA model with Wistar rats using 120 or 180 min of CCA occlusion, respectively. When full reperfusion was established, after 180 min of occlusion in the proximal MCA model, a dose of 40 mg/kg + infusion and 75 mg/kg + infusion resulted in a significant 50% and 70% decrease in ischemic damage, respectively. MDL 101,002 is clearly an effective neuroprotective agent in all models examined. This work would suggest that this novel cyclic nitrone spin trap affords effective neuroprotection and is useful for the treatment of ischemic stroke.

Animals↗
PubMed1998

Non-invasive in vivo mapping of tumour vascular and interstitial volume fractions.

Non-invasive measurement of haemodynamic parameters and imaging of neovasculature architecture is of importance in determining tumour prognosis, in directing tissue sampling and in assessing treatment efficacy. In the current research we investigated a dual tracer nuclear magnetic resonance (NMR) technique to map the tumour vascular (VVF) and interstitial volume fraction (IVF) non-invasively in vivo. We hypothesised that a NMR signal emanating after intravenous administrations of a vascular paramagnetic probe (MPEG-PL-GdDTPA) can be maximised so that additional signal after administration of a second interstitial probe (GdDTPA) would only reflect the IVF but not the VVF. The method and its assumptions were verified and experimental conditions optimised both in phantoms and in C6 glioma bearing rats. Data derived from in vivo studies show tumoral VVF and IVF values that are consistent with histology data and literature values; the relative ranking order of values was tumour > muscle > brain. Image maps showed intratumoral and intertumoral heterogeneity of both parameters at submillimetre pixel resolution. The method is applicable to a wide variety of tumour models and can theoretically be performed repeatedly to study tumour growth or involution during therapy.

Animals↗
PubMed1997

Cloning and characterization of lung-endothelial cell adhesion molecule-1 suggest it is an endothelial chloride channel.

Lung-endothelial cell adhesion molecule-1 (Lu-ECAM-1) is an endothelial cell surface molecule that mediates adhesion of metastatic melanoma cells to lung endothelium. Here we analyze the organization of the Lu-ECAM-1 protein complex, report the sequence of Lu-ECAM-1 cDNAs, and reveal a novel function of the protein. Lu-ECAM-1 immunopurified from bovine aortic endothelial cells (BAEC) consists of tightly associated glycoproteins of 90, 38, and 32 kDa, with minor components of 130 and 120 kDa. We present evidence that all of these protein species are encoded by a single open reading frame whose initial translation product is proteolytically processed to yield the other products. Correct processing in vitro was demonstrated by transfection of the longest cDNA into human embryonic kidney 293 cells; immunoblot analysis showed that the approximately 120-kDa precursor gave rise to 90- and 38-kDa products. RNA blots of BAEC mRNA detected messages in agreement with the sizes of the cDNA clones in addition to several of high molecular weight. DNA blot analysis showed that Lu-ECAM-1 is conserved throughout its length in all mammals tested, usually as a single or low copy gene. In the bovine, Lu-ECAM-1 protein is 88% identical to a calcium-dependent chloride channel described recently in tracheal epithelium, Ca-CC. Probes for Lu-ECAM-1 mRNA and protein confirmed the presence of a homolog in this tissue. We show that messages for both proteins are present in lung while only Ca-CC is present in trachea and only Lu-ECAM-1 is present in BAEC. These results suggest that endothelial cells express a chloride channel that is related to, but distinct from, that expressed in tracheal epithelium. They further suggest that an adhesion molecule can also be a chloride channel.

Amino Acid Sequence↗
PubMed1997

Frozen shoulder: correlation between the response to physical therapy and follow-up shoulder arthrography.

OBJECTIVE: To study the correlation between improvement of shoulder motion and shoulder joint space capacity determinated by arthrography. DESIGN: Case series. SETTING: General community hospital. PATIENTS: Twelve patients with clinically diagnosed frozen shoulder without rotator cuff tear. All subjects were divided as "primary" and "secondary" according to spontaneous onset or not, and "acute" or "chronic" depending on whether duration of disease was less than 2 months or longer. INTERVENTIONS: Outpatient rehabilitation programs, including physical modalities, exercise intervention, and regular weekly outpatient clinic follow-up. MAIN OUTCOME MEASURES: Shoulder range of motion (ROM) and joint space capacity in shoulder arthrography. RESULTS: In acute patients, the joint space capacity increased significantly after treatment (t = 2.82; p < .05). Increased joint space capacity was most significantly correlated with improvement in external rotation (r = .77, p < .05), followed by abduction (r = .43, p > .05), but was poorly correlated with flexion and internal rotation. In chronic patients, both primary and secondary groups, there was no obvious joint space capacity increase despite significant shoulder motion improvement. Follow-up arthrograms showed the reappearance and/or enlargement of the axillary recess and smoother capular margins in all the patients except one chronic case (disease duration for 1 year). These findings were more obvious in acute than in chronic patients. CONCLUSIONS: For frozen shoulder, generally described as "adhesive capsulitis," the adhesion was reversible in the acute stage. The increase of joint space capacity was significant and was correlated with improvement of external rotation. In chronic patients, ROM restoration occurred independent of change in joint space capacity, which increased slightly. The stretching of other contracted soft tissues around the shoulder, in addition to the adhesive capsule, may contribute to the recovery of chronic frozen shoulder.

Acute Disease↗
PubMed1997

Convergent flow phenomenon mimics the appearance of venous thrombosis in gradient-echo images with or without the presence of a contrast agent.

We have observed signal voids at the junction of the renal vein and the inferior vena cava in the Spoiled Grass images. They mimicked the magnetic resonance appearance of an intraluminal thrombus with and without the presence of a contrast agent. The patency of the vessels was unveiled by fast Spoiled Grass sequence with reduced echo time as well as by Doppler ultrasound. Phantom studies revealed patterns of counterrotating vortices at the confluence. The cause of this image artifact was subsequently deduced as the intravoxel spin phase dispersion arising from the impinging flows of the renal vein and inferior vena cava. It is concluded that in regions where complex flow patterns reside, fast imaging sequences that reduce spin phase variations should always be conducted in addition to other routine sequences to exclude uncertainties in image interpretation.

Aged↗