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Biomedical subjects

W Li

Publications and source records attributed to W Li.

At least 1,297 records · Page 72Linked to original sources
PubMed1991

Duodenal ulcer. Discovery of a new mechanism and development of angiogenic therapy that accelerates healing.

The complete purification of the first angiogenic molecule, basic fibroblast growth factor (bFGF), was carried out in the authors' laboratory in 1983. Application of this peptide to chronic wounds enhances angiogenesis and accelerates wound healing. The authors showed that an acid-stable form of bFGF (i.e., bFGF-CS23) could be administered orally to rats with duodenal ulcers. The peptide promoted a ninefold increase of angiogenesis in the ulcer bed and accelerated ulcer healing more potently than cimetidine. Basic fibroblast growth factor did not reduce gastric acid. The authors now show that bFGF exists as a naturally occurring peptide in rat and human gastric and duodenal mucosa. This endogenous bFGF is present also in the bed of chronic ulcers in rats. Sucralfate binds bFGF and protects it from acid degradation. The sucralfate is angiogenic, based on its affinity for bFGF. When sucralfate is administered orally to rats, it significantly elevates the level of bFGF in the ulcer bed. Cimetidine, by its capacity to reduce gastric acid, also elevates bFGF in the ulcer bed. A hypothetical model is proposed in which prevention of ulcer formation or accelerated healing of ulcers by conventional therapies may be FGF dependent. Acid-stable bFGF-CS23 may be considered as a form of replacement therapy in the treatment of duodenal ulcers.

Aluminum Hydroxide↗
PubMed1991

A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1.

Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR; encoded by the flg gene) and other receptors with tyrosine kinase activity. It has been demonstrated that the src homology region 2 (SH2 domain) of PLC-gamma and of other signalling molecules such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85 direct their binding toward tyrosine-autophosphorylated regions of the epidermal growth factor or platelet-derived growth factor receptor. In this report, we describe the identification of Tyr-766 as an autophosphorylation site of flg-encoded FGFR by direct sequencing of a tyrosine-phosphorylated tryptic peptide isolated from the cytoplasmic domain of FGFR expressed in Escherichia coli. The same phosphopeptide was found in wild-type FGFR phosphorylated either in vitro or in living cells. Like other growth factor receptors, tyrosine-phosphorylated wild-type FGFR or its cytoplasmic domain becomes associated with intact PLC-gamma or with a fusion protein containing the SH2 domain of PLC-gamma. To delineate the site of association, we have examined the capacity of a 28-amino-acid tryptic peptide containing phosphorylated Tyr-766 to bind to various constructs containing SH2 and other domains of PLC-gamma. It is demonstrated that the tyrosine-phosphorylated peptide binds specifically to the SH2 domain but not to the SH3 domain or other regions of PLC-gamma. Hence, Tyr-766 and its flanking sequences represent a major binding site in FGFR for PLC-gamma. Alignment of the amino acid sequences surrounding Tyr-766 with corresponding regions of other FGFRs revealed conserved tyrosine residues in all known members of the FGFR family. We propose that homologous tyrosine-phosphorylated regions in other FGFRs also function as binding sites for PLC-gamma and therefore are involved in coupling to phosphatidylinositol breakdown.

Amino Acid Sequence↗
PubMed1991

Platelet-derived growth factor (PDGF)-induced disulfide-linked dimerization of PDGF receptor in living cells.

It is well established that epidermal growth factor and platelet-derived growth factor (PDGF) are able to induce noncovalent dimerization of their surface receptors. It is thought that receptor dimerization plays an important role in activation of the tyrosine kinase function and in the process of receptor autophosphorylation. Here we show that the addition of either PDGF-BB or PDGF-AA to intact 3T3 cells induces formation of 400- and 430-kDa species, respectively, recognized by either anti-PDGF receptor antibodies or anti-phosphotyrosine antibodies. Interestingly, the 400- and the 430-kDa species are detected in nonreducing gels but not in reducing gels. Moreover, an alkylating agent, N-ethylmaleimide, inhibits PDGF-induced formation of high-molecular-mass species. Comparisons of V8 protease peptide maps of [35S]methionine-labeled PDGF receptors and high-molecular-mass proteins indicate that they represent dimers of PDGF receptors. It appears therefore that in addition to noncovalent dimerization, PDGF receptors undergo ligand-dependent disulfide-linked dimerization.

Animals↗
PubMed1991

MR imaging of liver metastases at 1.5 T: similar contrast discrimination with T1- and T2-weighted pulse sequences.

The authors evaluated soft-tissue contrast on spin-echo (SE) proton density-weighted, SE T2-weighted, SE short-echo-time (TE) T1-weighted, and gradient-echo (GRE) images of 34 patients with known hepatic tumors who underwent high-field-strength (1.5-T) magnetic resonance imaging. For solid liver tumors, the difference in the mean lesion-liver contrast-to-noise ratios (C/Ns) with T1- (GRE and SE) and T2-weighted pulse sequences was not statistically significant (P greater than .05). For nonsolid liver tumors, the T2-weighted images provided significantly greater (P less than .05) mean lesion-liver C/N than T1-weighted GRE images. Mean liver signal-to-noise ratio was significantly greater on T1-weighted GRE (P less than .0001) and T1-weighted SE (P less than .05) images than on T2- and proton density-weighted images. Qualitative analysis of T1-weighted (SE and GRE) images and proton density- plus T2-weighted images showed that lesion conspicuity was similar in 25 of 32 patients (78%). The results suggest that liver tumor imaging at high field strength can be performed with short-TE T1-weighted (SE or GRE) or conventional T2-weighted pulse sequences.

Humans↗
PubMed1991

[Pulsed-wave Doppler ultrasound evaluation of flow velocity waveforms of fetal umbilical artery and uterine artery as predictors of neonatal outcome].

A pulsed-wave doppler ultrasound system was used to record arterial flow velocity time waveforms from the fetal umbilical artery (UmA) and the branches of the uterine artery (UtA) in the placental bed in term pregnancies. The systolic-diastolic ratio (S/D) of flow velocity was measured as an index of peripheral resistance in the placental bed. The UmA S/D ratio was measured in 123 pregnant women between 37- less than 42 gestational weeks and the UtA S/D ratio was measured in 121 of them simultaneously. The cutoff value of an abnormal UmA S/D ratio was 3.0 or higher, and UtA S/D ratio 2.5 or higher. Furthermore, the neonatal poor outcome was observed more frequently in both the abnormal ratio groups than in both the normal ratio groups. The sensitivity of the UmA, and UtA S/D ratios to predict an adverse neonatal outcome was 72.7%, 27.3%, respectively. The data showed the abnormal UmA S/D and abnormal UtA S/D ratios were associated with the neonatal poor outcome, but the former was the better test for screening for adverse neonatal outcome.

Arteries↗
PubMed1991

Increased phosphorylation of the colony stimulating factor-1 receptor following transmembrane signaling.

The receptor for colony-stimulating factor-1 (CSF-1) is a 165-kDa tyrosine kinase phosphorylated on serine residues in quiescent macrophages. Addition of CSF-1 to macrophages induces the following sequence of events: (1) formation of a 380-kDa noncovalently associated receptor dimer that is tyrosine phosphorylated; (2) protein tyrosine phosphorylation; (3) disulfide bond crosslinking of the noncovalently associated receptor monomers; and (4) conversion of the receptor homodimer to a heterodimeric 450-kDa species in which the apparent molecular mass of one of the subunits is increased from 165 to approximately 240 kDa (Li and Stanley, 1991). To study the kinetics of early phosphorylation/dephosphorylation events associated with these changes in the CSF-1R, we stimulated a CSF-1-dependent macrophage cell line with CSF-1 at 4 degrees C to slow reaction rates and prevent internalization. CSF-1 induced a rapid (2-4 min) initial increase in tyrosine phosphorylation of the 165-kDa subunits of the noncovalent 380-kDa homodimer. At 60-120 min after ligand binding, the conversion of some of the 165-kDa species to a approximately 240-kDa species on reducing SDS-PAGE was indicative of the transition of 380-kDa homodimer to 450-kDa heterodimer. Both the approximately 200 and 165-kDa subunits of the heterodimer were more highly phosphorylated in tyrosine than the subunits of the homodimer 2-4 min after ligand binding. The 165-kDa subunit of the heterodimer also exhibited increased phosphorylation in serine. However, in vitro dephosphorylation experiments indicated that a modification other than phosphorylation is involved in the conversion of the 165-kDa to the approximately 240-kDa CSF-1R species. The possibility that the increased tyrosine and serine phosphorylation of the subunits of the 450-kDa heterodimer may be involved in regulation of receptor kinase activity and/or internalization is discussed.

Alkaline Phosphatase↗
PubMed1991

Glycosaminoglycan and collagen metabolism in arylsulfatase B-deficient retinal pigment epithelium in vitro.

Regional differences in retinal pigment epithelial (RPE) cell glycosaminoglycan (GAG) and collagen metabolism were studied using cells obtained from normal cats and those with deficient activity of arylsulfatase B (ASB), a lysosomal enzyme involved in GAG catabolism. Control and ASB-deficient RPE cultures initiated from superior equatorial (superior) and inferior equatorial (inferior) regions of the eye were radiolabeled for 72 hr with 35SO4, and GAGs from the media and cell layers were analyzed separately. In ASB-deficient RPE, there was an accumulation of dermatan/chondroitin sulfate in the cell layer of cultures initiated from the superior region of the eye but not in those initiated from the inferior region. This agrees with previous in situ and in vitro morphologic observations that accumulation of inclusions in ASB-deficient RPE was greater in the superior region of the eye than in the inferior region. By contrast, media from ASB-deficient cultures initiated from the inferior region of the eye contained much higher levels of radiolabeled dermatan/chondroitin sulfate than ASB-deficient cultures from the superior region or normal cultures. Increased GAG content in the media may result from increased secretion of proteoglycans, increased turnover of cell surface or extracellular matrix components, or extrusion of lysosomal contents. These results indicate that one or more of these mechanisms vary regionally throughout the eye in the RPE of ASB-deficient animals. Collagen production was determined in normal and ASB-deficient RPE cultures. In normal RPE, no differences in collagen synthesis were noted between the inferior and superior regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Room temperature characterization of the dioxygen intermediates of cytochrome c oxidase by resonance Raman spectroscopy.

Resonance Raman spectroscopy was employed to investigate the heme structures of catalytic intermediates of cytochrome c oxidase at room temperature. The high-frequency resonance Raman spectra were obtained for compound C (the two-electron-reduced dioxygen intermediate), ferryl (the three-electron-reduced dioxygen intermediate), and the fully oxidized enzyme. Compound C was formed by photolyzing CO mixed-valence enzyme in the presence of O2. The ferryl intermediate was formed by reoxidation of the fully reduced enzyme by an excess of H2O2. Two forms of the oxidized enzyme were prepared by reoxidizing the fully reduced enzyme with O2. Our data indicate that, in compound C, cyt a3 is either intermediate or low spin and is nonphotolabile and its oxidation state marker band, v4, appears a higher frequency than that of the resting form of the enzyme. The ferryl intermediate also displays a low-spin cyt a3, which is nonphotolabile, and an even higher frequency for the oxidation state marker band, v4. The reoxidized form of cytochrome c oxidase with a Soret absorption maximum at 420 nm has an oxidation state marker band (v4) in a position similar to that of the resting form, while the spin-state region resembles that of compound C. This species subsequently decays to a second oxidized from of the enzyme, which displays a high-frequency resonance Raman spectrum identical with that of the original resting enzyme.

Animals↗
PubMed1990

Primary malignant tumors of the trachea. A radiologic and clinical study.

Fifty-four cases (55 foci) of primary tracheal malignancies were reviewed retrospectively. Radiologic material was available in 32 cases (33 tracheal foci). The most frequent primary malignant tumor of the trachea was squamous cell carcinoma (54.5%), followed by adenoid cystic carcinoma (18%) and adenocarcinoma (9%). The radiologic appearance of the tumors could be divided into intraluminal, wall-thickening, and exophytic forms. Wall-thickening and exophytic forms in this study accounted for 62% of the tumors. This indicates that malignant tumors of the trachea tend to extraluminal invasion. Tomography and computed tomography are the most helpful methods of radiologic examination for tracheal tumors. Bronchoscopy and radiologic examination are complementary procedures. The chief advantage of imaging is the demonstration of tracheal wall thickening and extraluminal changes. Hemoptysis, dyspnea, and cough were the most common symptoms. Four cases (7%) in our series presented as thyroid tumors due to direct extension into the thyroid gland. Fifteen of the 54 cases (28%) were associated with other carcinomas of the head and neck and the lung.

Adult↗
PubMed1990

Inhibitory effect of androgen on cell death of mouse uterine epithelium.

The protective effect of androgen against the cell death of mouse uterine epithelium was evaluated by examining the retention of 5'-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) incorporated into the whole uterus and the apoptotic index (percentage of the apoptotic cells to the total cells) which is a good index of physiological cell death. Castrated adult female mice were daily injected with oestradiol-17 beta for 3 days, followed by the injection of [125I]IdUrd. Thereafter, these mice were daily injected with only the vehicle or 5 alpha-dihydrotestosterone (DHT), and the 125I-radioactivity retained in the whole uterus was determined. When only the vehicle was injected, the 125I-radioactivity retained in the whole uterus rapidly decreased but injections of DHT reduced the loss of 125I-radioactivity. The effect of DHT on the retention of 125I-radioactivity depended on doses of DHT and was abolished by the pure antiandrogen, flutamide. The apoptotic index of uterine cells was examined by a similar experimental protocol, but without an injection of [125I]IdUrd. Injections of only the vehicle caused marked increases in the apoptotic indices of both luminal and glandular epithelia, but injections of DHT decreased them significantly. The apoptotic index of stroma was not affected by the injection of DHT. The present results indicated that androgen reduces the cell death of mouse uterine epithelium through the androgen receptor.

Animals↗
PubMed1990

Structure of the ABC ring subunit of 3-hydroxy-2-oxodendrobine.

(1S*, 4S*, 5R*, 6S* ,8S*, 11R*)-5,6-Epoxy-1-hydroxy-6-isopropyl-3,11- dimethyl-3-azatricyclo-[6.2.1.0(4,11)]undecan-2-one, C15H23NO3, Mr = 265.35, triclinic, P1, a = 7.2170 (6), b = 8.5578 (10), c = 12.4342 (14) A, alpha = 97.017 (9), beta = 91.733 (8), gamma = 109.799 (8) degree, V = 715.04 (13) A3, Z = 2, D chi = 1.23 g cm-3 (298 K), lambda(Mo K alpha) = 0.7107 A, mu = 0.7949 cm-1, F(000) = 288, T = 298 K, R = 0.0482 for 2464 reflections. The molecules exist as hydrogen-bonded dimers in the crystal involving the hydroxyl group and the carbonyl O atom [O13...O14 (related by 2 - x, - y, - z) 2.719 (2) A; H13...O14 1.90 (2) A; O13--H13...O14 165 (2) degrees]. The bonds from the bridgehead atom of the tricyclic ring to other ring atoms appears to be elongated [av. 1.557 (1) A] compared to the other Csp3--Csp3 bonds in the molecule. The lactam ring is essentially planar [maximum deviation is 0.010 (3) A for N3].

Bridged-Ring Compounds↗
PubMed1990

Dendrobine support studies. The structure of a novel 3-azatricyclo[6.2.1.0(4,11)]-undecane derivative.

(1S*, 4R*, 8S*, 11R*)-3-Diphenylmethyl-11-methyl-3- azatricyclo[6.2.1.0(4,11)]undec-5-en-2-one, C24H25NO, Mr = 343.47, monoclinic, P2(1), a = 10.248 (3), b = 8.859 (2), c = 10.344 (2) A, beta = 99.816 (14) degrees, V = 925.4 (3) A3, Z = 2, D chi = 1.23 g cm-1 (163 K), lambda(Mo K alpha) = 0.7107 A, mu = 0.6927 cm-1, F(000) = 368, T = 163 K, R = 0.0423 for 2569 reflections. The compound is spontaneously resolved upon crystallization. The N atom appears to be sp2 hybridized [N is 0.0901 (13) A from plane through three ligand atoms] and in conjugation with the carbonyl group [short N--C bond 1.351 (2) A]. The tricyclic ring system is concave. Ring strain appears to affect C--C bond lengths of the central atom of the 3-ring system. The average C--C bond length for this atom to other ring atoms is 1.551 (2) while the average for all other sp3 C--sp3 C bonds is 1.530 (2) A.

Alkaloids↗
PubMed1990

Oviductal epithelium of the baboon: hormonal control and the immuno-gold localization of oviduct-specific glycoproteins.

Oviducts were obtained from a series of cycling and ovariectomized steroid-treated baboons. The lining epithelium of the ampulla and isthmus was analyzed by light and electron microscopy. Both morphological and cytomorphometric analyses revealed that the morphological and functional state of the oviductal epithelium in the baboon is controlled by the ovarian steroids. Additionally, a clear cephalocaudal steroid-responsive gradient was observed when the data from the ampulla and isthmus of the same animal were compared. Within the ampulla, estradiol induced hypertrophy, hyperplasia, ciliogenesis, and secretory activity, whereas adding progesterone to the treatment regimen (+/- estradiol) resulted in atrophy, deciliation, apoptosis, and loss of the secretory activity. These cyclic processes were less evident in the isthmus. We also used an indirect electron microscopic immunogold technique and a previously characterized polyclonal antibody to determine the localization of oviduct-specific glycoproteins. These glycoproteins were present in every secretory granule observed, regardless of oviduct region, electron density, or size of the secretory granule. In summary, our data show that 1) estradiol induces and maintains the mature epithelium of the baboon oviduct, 2) steroid withdrawal or the administration of progesterone causes regression of the epithelium, and 3) the previously identified estradiol-dependent oviduct-specific glycoproteins are synthesized within and released from the secretory epithelial cells.

Animals↗
PubMed1990

Developmental expression, synthesis, and secretion of insecticyanin by the epidermis of the tobacco hornworm, Manduca sexta.

Insecticyanin was found to be synthesized in several isoelectric forms and stored in the pigment granules in the epidermis. Both major epidermal forms (INS-a, pl 5.5; INS-b, pl 5.7) were found in the cuticle, but only the most basic form, INS-b, was present in the hemolymph. In vitro the epidermis synthesized and secreted both forms into both the cuticle and the medium. Isolation of two cDNA clones for insecticyanin followed by hybridization to epidermal mRNA showed the presence of only one 1.1 kb mRNA, but transcription of the longer cDNA yielded a RNA which produced INS-a but no INS-b. Insecticyanin mRNA was present during the intermolt feeding stages of the 4th and 5th instars and absent during the larval molt and after the onset of metamorphosis. Exposure of either day 2 4th-instar or day 1 5th-instar larval epidermis to 20-hydroxyecdysone (20HE) in vitro caused a dose-dependent decline in this mRNA that was not prevented by simultaneous exposure to JH. When synthesis resumes just before ecdysis, INS-b appears before INS-a; then on the final day of feeding, synthesis of INS-a ceases before that of INS-b. Culture experiments showed that exposure of day 15th epidermis to a small pulse of 20HE followed by an ecdysteroid-free period was best to mimic the in vivo situation, indicating that the small rise of ecdysteroid in the absence of JH on day-2 was responsible for this differential cessation.

Animals↗