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Biomedical subjects

P Tang

Publications and source records attributed to P Tang.

At least 91 records · Page 5Linked to original sources

Effects of polyethyleneglycol chain length and phospholipid acyl chain composition on the interaction of polyethyleneglycol-phospholipid conjugates with phospholipid: implications in liposomal drug delivery.

PURPOSE: The purpose of this study was to investigate polyethyleneglycol(PEG)-phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in an attempt to explain the dependence of liposome circulation time on formulation. METHODS: Differential scanning calorimetry, electron microscopy, dynamic light scattering and NMR were the major methods used in the study. RESULTS: Mixtures of PEG-phospholipid conjugates and phosphatidylcholine existed in three different physical states: a lamellar phase with components exhibiting some miscibility, a lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol-percent of PEG(1,000-3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11 mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency towards mixed micelle formation was observed. All concentrations of PEG(12,000)-DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with phosphatidylcholine. Decreasing the acyl chain length from C(16:0) to C(14:0) caused a decrease in tendency towards micelle formation and phase separation. These tendencies increased upon increasing acyl chain length to C(18:0). Phase separation was at least partly due to PEG chain-chain interaction. This was supported by an increased fraction of PEG chains exhibiting a fast NMR transverse relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE). CONCLUSIONS: These phenomena are discussed in relation to both bilayer and steric stabilization of liposomes, and the lack of prolonged circulation with certain formulations is discussed.

Calorimetry, Differential Scanning↗

Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells.

Infection with Listeria monocytogenes induces the activation of mitogen-activated protein (MAP) kinase in several tissue culture cell lines (P.Tang, I. Rosenshine, and B. B. Finlay, Mol. Biol. Cell 5:455-464, 1994). After various mutants were examined, the bacterial factor responsible for MAP kinase activation was identified as listeriolysin O (LLO). Growth supernatant containing LLO or purified LLO alone can induce MAP kinase tyrosine phosphorylation in HeLa cells. Single-amino-acid mutations in LLO that do not affect its membrane binding capacity but reduce its cytolytic activity also reduced its ability to induce MAP kinase activity in HeLa cells. Streptolysin O, another sulfhydryl-activated hemolysin, and the detergent saponin are also able to activate MAP kinase in target cells. Thus, the increased MAP kinase activity observed in L. monocytogenes-infected cells is most likely a result of the permeabilization of the host cell membrane by LLO and may not be linked with invasion.

Bacterial Toxins↗

Erythropoietin-like activity in vivo of the fusion protein rhIL-6/IL-2 (CH925).

CH925 is a novel cytokine of a fusion protein interleukin-6 (IL-6)/IL-2 exhibiting erythropoietin (Epo)-like effects in vivo and ex vivo, in addition to its enhanced effects compared to IL-2 and IL-6 reported by us previously, which indicates its potential clinical use. Our present study was undertaken to determine the Epo-like activity of CH925 in vivo. The reticulocyte response was observed in transfusion-induced polycythemic mice by using flow cytometry with pyronin Y staining. On day 2 after injection of CH925, the average number of reticulocytes was 2.11% in the group given 250 micrograms/kg/d and 1.01% for 100 micrograms/kg/d. The mean fluorescence intensity (MFI) also significantly increased. Longitudinal studies of CH925 were performed on days 2, 4, and 10, and reticulocyte counts increased up to a peak on day 4. Activity of CH925 (100 micrograms/kg/d) corresponds to 1 U of standard rhEpo in our study.

Animals↗

[The use of hyoid osteomuscular flap in extended partial laryngectomy].

The surgical defect after conventional partial laryngectomy practically needs no special technique to repair. On conservation surgery for late (T3 and T4) cases a large part of the larynx is to be resected so that the margin of surgical clearance is ample and, at the same time, an appropriate method of reconstruction is mandatory to restore the essential functions of the larynx. For this purpose we developed a technique of osteomuscular flap to repair the defect left behind after a three-fourths laryngectomy (for supraglottic case) or an extended vertical partial laryngectomy (for glottic case). In both cases the arytenoid cartilage or the cricoarytenoid joint was resected to ensure the safety margin of resection. The mylohyoid muscle was severed at the upper border of the body of the hyoid bone. A small piece of the hyoid bone (about 5 mm) and its attached strap muscles were used. The muscles were made a 90 degree bent toward the laryngeal cavity. The hyoid bone was used to substitute the removed arytenoid and the muscles to bridge over the laryngeal lumen. The postericoid mucosa was advanced to cover the transplanted hyoid bone. Then the cut edge of the thyroid cartilage was lifted up and sutured with the base of the tongue to close the wound. 108 cases were treated within a period of 12 years (1979-1990). The three year survival rates for stage II and stage IV of supraglottic type (66 cases) were 78.6% and 66.7% respectively, and for stage II of glottic type (42 cases), 79.3%. The decannulation rate was 75%-85%, and 80% of the patients enjoyed a socially acceptable voice. All cases resumed normal mouth-food-taking.

Adult↗

[Antiproliferative effects on Ph+ leukemic cells transfected with antisense bcr/abl fusion gene].

To investigate the possible roles that bcr/abl fusion gene plays in Ph-chromosome positive leukemia cells, in this study the recombinant plasmids expressing antisense transcripts to bcr/abl fusion gene were transfected into K562 and BV173 cell lines by lipofectin reagent. Southern and Northern bilot hybridizations proved the integration and expression of exogenous DNA in target cells. Antisense transcripts to bcr/abl inhibited proliferation and colony-forming ability of target cells. Through flow cytometric cell cycle analysis it was found that during the early period of transfection decrease of cells in G0/G1 and S phases and increase in G2 phase were observed, suggesting block of G2 progression. Later, cells in G0/G1 phase decreased further and retardation of S and G2 progressions was obvious. The results also indicated that proliferative inhibition of target cells was accompanied by genomic DNA degradation.

Cell Division↗

[Research on IgE responsiveness in asthma patients].

OBJECTIVE: To understand the relationship between IgE and asthma, and the genetic background of IgE. METHODS: The authors measured serum total IgE in 121 healty subjects and 100 asthmatic children (CAC-IRMA) and investigated three AA families with total IgE evaluation and genetic linkage analysis between IgE and D11S533. RESULTS: The IgE cutoff point between low and high was defined at 150 kU/L. There were 33.1% population with high level of total IgE. Of the 100 asthmatic children 96% had higher IgE level than controls, the difference was significant (P < 0.001). The IgE level of 22 asthmatic children in their releases had no significant difference compared with that in their attacks. In 40 members of three atopic asthma families, there were 23 persons with high IgE and 15 with asthma. In these families high IgE level were found both in male and female and the affected person occured in consecutive three generations, which fit to AD inheritance. Family 1 and 3 generally showed a high level of IgE, while family 2 showed low level of IgE. Two point linkage analysis between IgE and D11S533 showed that there were two recombinants from 22 meioses in the two families with a maximum lod score 1.074 at a recombination fraction of 0.05. CONCLUSIONS: Most of asthma children have high IgE, which seems obtained from birth. About 1/3 population have high level IgE who are potential atopic persons. IgE level in human beings in inherited by AD mode. IgE gene may be close to 11q13.3-13.4.

Adolescent↗

Irreversible inhibitors of nicotinic acetylcholine receptors: isolation and structural characterization of the biologically active solvolysis products of bipinnatin-A and bipinnatin-C.

The lophotoxins irreversibly inhibit nicotinic acetylcholine receptors by covalent modification of Tyr190 in the alpha-subunits of the receptor. Previous studies have shown that the naturally occurring lophotoxin analogs bipinnatin-A, -B, and -C are actually inactive protoxins and that their ability to irreversibly inhibit nicotinic receptors is enhanced by preincubation in buffer. However, the ability of lophotoxin to irreversibly inhibit nicotinic receptors does not appear to be enhanced by preincubation in buffer. These observations led to the current effort to isolate and determine the structures of biologically active bipinnatins. Disappearance of the lophotoxins from solution followed a simple first-order exponential decay function. Lophotoxin, however, was approximately 40-fold more stable then bipinnatin-A, -B, or -C. Solvolysis of the bipinnatins, but not of lophotoxin, resulted in production of an equimolar amount of acetic acid at a rate similar to the rate of solvolysis, suggesting that the initial event in solvolysis of these toxins involves hydrolysis of an acetate ester. Proton NMR and fast-atom bombardment mass spectroscopy were used to confirm the structures of the active solvolysis products of bipinnatin-A and -C. Their structures and the relative pH insensitivity of the solvolysis reaction suggest that biological activation of the bipinnatins may proceed through an SN1 type of substitution reaction involving elimination of acetate followed by reaction of a carbocation intermediate with solvent.

Cell Line↗

Distribution of the flavohaemoglobin, HMP, between periplasm and cytoplasm in Escherichia coli.

The subcellular distribution of the soluble flavohaemoglobin (HMP) of Escherichia coli has been determined. Cells over-expressing HMP from the cloned hmp gene on a multicopy plasmid were fractionated by osmotic shock and lysozyme treatment. Spectral analysis of subcellular fractions showed the CO-binding haemoprotein to be cytoplasmic. However, Western blotting using antibody raised to purified HMP revealed approximately 30% of the protein to be periplasmic in the over-expressing strain. Western analysis also revealed substantial levels of periplasmic HMP in a strain expressing only chromosomally encoded protein but none in an hmp mutant. The results are discussed in relation to protein function and the similar distribution reported for Vitreoscilla globin.

Amino Acid Sequence↗

ADP-ribosylation inhibitors inhibit cellular RNA synthesis but do not affect expression of manganous superoxide dismutase or heat shock protein 70 in tumor necrosis factor alpha-sensitive and -resistant tumor cells.

We have shown that the cytotoxic response of TNF-sensitive L929 cells and TNF-resistant EMT-6 cells to TNF-alpha can be modulated by ADP-ribosylation inhibitors independently of ADP-ribosylation rates. To explore the possibility that these inhibitors modulate TNF cytotoxicity by interfering with cellular protective mechanisms, we evaluated their effects on general RNA synthesis and on mRNA expression of two proposed protective genes, manganous superoxide dismutase (MnSOD) and heat shock protein 70 (hsp70). We found that ADP-ribosylation inhibitors could inhibit general RNA synthesis in a dose-dependent fashion to a similar extent in both EMT-6 and L929 cells, although these inhibitors increased or decreased the sensitivity of the cells to TNF, respectively. In EMT-6 cells, combination of actinomycin D with these inhibitors further inhibited the RNA synthesis rate, and it actually decreased the TNF sensitivity of the EMT-6 cells. Furthermore, the expression of MnSOD or hsp70 was not regulated by these inhibitors. Thus, TNF resistance must depend on other mechanisms in addition to the expression of these protective genes.

Animals↗

Fluorine-19 nuclear magnetic resonance imaging and spectroscopy of sevoflurane uptake, distribution, and elimination in rat brain.

BACKGROUND: Determination of macroscopic and microscopic distribution of general anesthetics can facilitate identification of anatomic, cellular, and molecular loci of anesthetic action. Previous attempts to measure brain anesthetic distributions with fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging were conducted at magnetic field strengths lower than 2 Tesla. All have produced only silhouettes of brain tissue. Difficulties intrinsic to NMR imaging of anesthetics include higher anesthetic solubility in extracranial tissues and the lower limits to spin-echo delay times that can be used in conventional NMR imaging methods. So far, such methods have been unable to capture rapidly decaying brain 19F NMR signals. METHODS: 19F NMR imaging and spectroscopy were conducted at 4.7 Tesla using a specially developed NMR probe and new imaging methods. With the new techniques, it was possible to observe directly the uptake, distribution, and elimination in brain of sevoflurane, a fluorinated general anesthetic with special advantages for NMR investigations. RESULTS: 19F NMR images, acquired at different times after sevoflurane administration, clearly showed the distribution of a fluorinated general anesthetic within the brain. Based on continuous transverse relaxation time measurements, sevoflurane signals could be separated into two components, attributable respectively to sevoflurane in a mobile or immobile microenvironment. During washin, there was a delayed accumulation of anesthetic in the mobile microenvironment. During washout, there was a rapid elimination from the immobile microenvironment. CONCLUSIONS: At anesthetizing concentrations, sevoflurane distributes heterogeneously in the brain. Sevoflurane in the brain tissue contributes mostly to the immobile component of the 19F signal, whereas that in the surrounding adipose and muscle tissues contributes mostly to the mobile component. Imaging and spectroscopic results suggest that the immobile component of sevoflurane is associated with the general anesthetic effects of the agent.

Anesthetics↗

Human pro-tumor necrosis factor: molecular determinants of membrane translocation, sorting, and maturation.

Human pro-tumor necrosis factor (pro-TNF) is a type II transmembrane protein with a highly conserved 76-residue leader sequence. We have analyzed the behavior, both in a microsomal translocational system and by transfection, of a series of mutants with deletions from the cytoplasmic, transmembrane, and linking domains. Cytoplasmic deletions included the Arg doublet at -49 and -48 and/or the Lys doublet at -58 and -57; additional mutants included deletion of residues -73 to -55 and -73 to -55, -49, and -48. The transmembrane and linking domain mutants included deletions in the -42 to -35 region, combined with the deletion of residues -32 to -1. Two hybrid mutants combined the cytoplasmic deletions with the deletion of residues -32 to -1. All of the cytoplasmic deletion mutants were properly translocated, as were the transmembrane deletion mutants with deletions up to residues -36, -35, -32 to -1, although the last one exhibited reduced efficiency; further incremental deletions, including deletions of residues -38 to -35 and -32 to -1, completely blocked translocation. Both hybrid mutants were effectively translocated; furthermore, transfection analysis revealed competent expression and maturation of both the cytoplasmic and hybrid mutants. Thus, proper expression and maturation of human pro-TNF can be accomplished with as few as approximately 12 of the 26 residues of the native transmembrane domain and with a net negative charge in the cytoplasmic domain flanking the transmembrane region.

Amino Acid Sequence↗

Laryngeal reconstruction and survival after function-sparing laryngectomy for selected T3 and T4 lesions.

Most patients lost their vocal ability after ablative surgery for the laryngeal cancer. Total laryngectomy has a history of over 100 years, hence many surgeons are accustomed to the en bloc organ resection and the loss of ability for communication after surgery. The recent advance of surgery introduces the concept and technique of radical cure and functional preservation of the cancer-afflicted-organ at the same setting. For lesions of late T categories (T3, T4), the maintenance of normal function after wide resection to ensure radicality demands a special technique to repair the crippled larynx. For this purpose a local osteomuscular flap was designed to reconstruct a functioning larynx. The surgical manoeuvre was described and the result proved to be successful. The outcome of 138 patients with T3 and T4 laryngeal carcinomas following conservation laryngectomy was analyzed. The five-year survival rate was 69% for supraglottic type and 75% for glottic type. The quality of life was much improved.

Adult↗

[A preliminary study of surgical therapy and combined therapy for cervical esophageal carcinoma].

52 patients with carcinoma of cervical esophagus were treated surgically. Their 3- and 5-year survival rate of was 38.5% and 35.1% respectively. The 3- and 5-year survival rate for surgery alone was 15.4% (2/13) and 9.1% (1/11). The 3- and 5-year survival rate for combined therapy (pre- or postoperative radiation and surgery) was 48.1% (13/27) and 52.9% (9/17). The 3- and 5-year survival rate for surgical salvage after failure of radical radiotherapy was 41.7% (5/12) and 33.3% (3/9). Our data suggest that the result of combined therapy is much better than the result of surgery or radiotherapy. The invation of recurrent nerve, hypopharynx, trachea, larynx and thyroid gland by tumor is contracindicated to surgery.

Adult↗

[A clinicopathological study of cor pulmonale with coronary heart disease].

The necropsy findings of 18 patients with cor pulmonale and coronary heart disease (CHD) were compared with those of a control group of 30 patients with cor pulmonale alone. The results showed that there was no significant statistical difference between the two groups on average heart weight and average left and right ventricular thickness (P > 0.05). The results suggest that at the end stage of cor pulmonale left ventricule may be involved whether there are complicating left ventricular disease or not. In this study, cor pulmonale and CHD were both accurately diagnosed in 33.3%, CHD failed to be diagnosed in 38.9% and cor pulmonale failed to be diagnosed in 27.8% of the patients. Single diagnostic factor analysis for cor pulmonale with CHD indicated that age, history of hypertension, history of angina pectoris, history of MI, accentuation A2, presence of bundle branch block, abnormal Q wave and left axis or normal deviation, Cheng Xiansheng diagostic criteria and Selvester MI screening criteria are of significance (P < 0.05). Multiple factor logistic regression analysis indicated that independent prognostic factors including history of angina pectoris, Selvester MI screening criteria and Cheng Xiansheng diagnostic criteria are of help for diagnosis (P < 0.03-0.000). The above-mentioned diagnostic methods are, however, not so specific. At present the best method for diagnosis of CHD is coronary arteriography.

Adult↗

[The management of cervical esophageal cancer by head and neck surgeons].

Fifty-five cases of cervical esophageal cancer treated at the Department of Head and Neck Surgery, Cancer Hospital, are reported. The three and five year survival rates were 38.2% and 35%, respectively. There are advantages for head and neck surgeons over thoracic surgeons to deal with such cases. The low recurrence rate (7.3%) of this series was a result of high resection and anastomosis at the level of the hypopharynx and hence the better safety margin of tumor clearance. The lymph node metastasis of the neck and the involvement of other neck organs were no longer contraindications of surgery as observed by thoracic surgeons. However, the head and neck surgeons have difficulties in dissecting the mediastinal lymph nodes and in preparing the abdominal viscera while the stomach or colon is to be used to restore the continuity of the upper alimentary tract. Authors concluded that since the cervical esophageal cancer is a disease in the neck, it is reasonable to be managed mainly by head and neck surgeons and otolaryngologists under the support of thoracic and abdominal surgeons and radiotherapists.

Adult↗

Management of the orbital contents in radical surgery for squamous cell carcinoma of the maxillary sinus.

We reviewed retrospectively 139 patients with squamous cell carcinoma of the maxillary sinus who were treated with planned combinations of preoperative radiotherapy and maxillectomy between 1958 and 1987. The 5-year survival rate of these patients was 30%. In 111 patients who had tumor invasion of the orbital floor 88 underwent radical surgery with orbital exenteration and 23 had their orbital contents preserved. If orbital exenteration was performed, the 5-year survival rate was 27.3% (24/88) and the rate of recurrence within the orbit was 12.5%. In patients with preservation of the orbital contents, the corresponding rates were 34.8% (8/23) and 8.6% respectively (P = 0.65). Histological study after maxillectomy with orbital exenteration showed that in 95% of 65 specimens (62/65) invasion of the orbit was limited. These tumors could be completely resected by total maxillectomy with limited removal of the periorbital tissues after preoperative radiotherapy. We conclude that after preoperative radiation, the eyeball could be safely preserved in most selected patients with maxillary sinus carcinoma invading the orbital floor.

Adult↗