Biomedical subjects

P Tang

Publications and source records attributed to P Tang.

At least 37 records · Page 2Linked to original sources

PubMed2000

NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors.

New lines of evidence suggest that volatile anesthetics interact specifically with proteins. Direct binding analysis, however, has been largely limited to soluble proteins. In this study, specific interaction was investigated between isoflurane, a clinically important volatile anesthetic, and membrane-bound nicotinic acetylcholine receptors (nAChRs) from Torpedo electroplax, using (19)F nuclear magnetic resonance spectroscopy and gas chromatography. The receptors were reconstituted into 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid vesicles. After correcting for nonspecific partitioning into the lipid, the equilibrium dissociation constant, K(d), of isoflurane binding to nAChR at 15 degrees C was found to be 0.36 +/- 0.03 mM. This value is within the clinically relevant concentration range of the agent. Based on the receptor concentrations in the vesicle suspension assayed by the bicinchoninic acid method and the fraction of bound isoflurane, X(b), determined by gas chromatography, an estimate of an average of 9-10 specifically bound isoflurane molecules can be made for each receptor, or two for each subunit. Upon binding, the transverse relaxation time constant (T(2)) of (19)F resonance of isoflurane is decreased by nearly three orders of magnitude, indicating a dramatic reduction in the mobility of specifically bound isoflurane. Kinetic analysis reveals that the off rate of binding, k(-1), is 1.7 x 10(4) s(-1). The on rate, k(+1), can thus be calculated to be approximately 4.8 x 10(7) M(-1) s(-1), suggesting a nearly diffusion-limited association. This is in contrast to anesthetic binding to a soluble protein, bovine serum albumin (BSA), where k(+1) and k(-1) are at least an order of magnitude slower. It is concluded that the presence of lipids may be critical for the correct evaluation of binding kinetics between volatile anesthetics and neuronal receptors.

Anesthetics, Inhalation↗

PubMed2000

General anesthetic binding to gramicidin A: the structural requirements.

There is a distinct possibility that general anesthetics exert their action on the postsynaptic receptor channels. The structural requirements for anesthetic binding in transmembrane channels, however, are largely unknown. High-resolution (1)H nuclear magnetic resonance and direct photoaffinity labeling were used in this study to characterize the volatile anesthetic binding sites in gramicidin A (gA) incorporated into sodium dodecyl sulfate (SDS) micelles and into dimyristoylphosphatidylcholine (DMPC) bilayers, respectively. To confirm that the structural arrangement of the peptide side chains can affect anesthetic binding, gA in nonchannel forms in methanol was also analyzed. The addition of volatile anesthetic halothane to gA in SDS with a channel conformation caused a concentration-dependent change in resonant frequencies of the indole amide protons of W9, W11, W13, and W15, with the most profound changes in W9. These frequency changes were observed only for gA carefully prepared to ensure a channel conformation and were absent for gA in methanol. For gA in DMPC bilayers, direct [(14)C]halothane photolabeling and microsequencing demonstrated dominant labeling of W9, less labeling of W11 and W13, and no significant labeling of W15. In methanol, gA showed much less labeling of any residues. Inspection of the 3-D structure of gA suggests that the spatial arrangements of the tryptophan residues in the channel form of gA, combined with the amphiphilic regions of lipid, create a favorable anesthetic binding motif.

Amino Acid Sequence↗

PubMed2000

'Smart' homes and telecare for independent living.

Telecare services and 'smart' homes share a common technological base in information technology and telecommunications. There is growing interest in both telecare services and smart homes, although they have been studied in isolation. Telecare has been driven largely by perceived cost savings and improved service delivery to the home, leading to improved quality of life and independent living. Smart homes are also expected to provide better and safer living conditions. The integration of the two should produce more secure and autonomous living. There are different forms of telecare services, as there are different types of smart homes, each ranging from basic systems involving the use of alarms and the ordinary telephone to intelligent monitoring with sensors and interactive communication. The introduction of these systems has policy implications, such as the need for coordination between health, social services and housing policy makers, which will reduce duplication and inefficient allocation of resources. Successful delivery of telecare to the home is as much dependent on the construction and condition of the housing stock as it is on the ability of the care provider to meet users' needs. If the UK National Health Service (NHS) could replace a significant proportion of domiciliary nursing visits by telephone calls, then savings of up of 200 million Pounds per annum would be possible.

Delivery of Health Care↗

PubMed2000

Chondroblastoma of bone.

BACKGROUND: Chondroblastoma of bone is a rare lesion, and few large series have been reported. The purpose of this paper is to report forty-seven cases treated by one group of surgeons and to identify factors associated with more aggressive tumor behavior. METHODS: Seventy-three patients with chondroblastoma of bone were treated between 1977 and 1998. We were able to obtain historical data, imaging studies, histological findings, and adequate personal or telephone follow-up to determine the outcome for forty-seven patients. RESULTS: The lesions were distributed widely in the skeleton, but most were in the epiphyses or apophyses of the long bones, especially the proximal part of the tibia (eleven tumors) and the proximal part of the humerus (ten tumors). The principal presenting symptoms were pain and limitation of movement. The treatment consisted of a variety of procedures, but the majority of the patients had intralesional curettage and packing with allograft or autograft bone chips or polymethylmethacrylate. Most of the patients had an excellent functional result, although in three osteoarthritis developed in the adjacent joint. Seven patients (15 percent) had a local recurrence; three of them had a second recurrence and one, a third recurrence. One patient died of widespread metastases, and another who had metastases to multiple sites was alive and disease-free after aggressive treatment of the metastatic lesions. CONCLUSIONS: While the size of the lesion, the age and gender of the patient, the status of the growth plate, and an aneurysmal-bone-cyst component to the tumor had no significant effect on the recurrence rate, lesions around the hip (the proximal part of the femur, the greater trochanter, and the pelvis) accounted for the majority (five) of the seven recurrent tumors and one of the two metastatic lesions.

Adolescent↗

PubMed2000

[A comparison of malignant fibrous histiocytoma of head, neck and extremities].

OBJECTIVE: To compare the epidemiology, local and regional invasion and prognosis of head and neck, malignant fibrous histiocytoma (MFH) and extremity MFH. METHODS: Between January 1, 1972 and December 31, 1993, 173 patients with MFH (71 head and neck, 102 extremities and trunk) were referred to the Cancer Hospital for surgical treatment. They were 101 men and 72 women, with age ranging from 13 to 83 years (median: 45 years). The extent of surgery was classified into radical, wide and local resection. RESULTS: For head and neck, local recurrence of MFH after wide resection was 80.4% (37/46), compared with 36.4% (8/22) after radical surgery (P = 0.000). The five-year survival was 50.79% in all the head and neck patients (74.75% in patients free of local recurrence, 37.74% in patients with local recurrence; P = 0.0181), compared with 70.71% in extremity patients (P = 0.0005). Repeated surgery after recurrence of MFH could cure 40.9% of the head and neck patients and 80.7% of the extremity patients. CONCLUSION: Inadequate resection of head and neck MFH in initial surgery is associated with a high incidence of local recurrence, which is always correlated with worse prognosis. Repeated surgery for recurrent head and neck MFH is not as effective as for recurrent extremity MFH. Therefore, we suggest that the initial surgery for head and neck MFH should be as radical as allowed to avoid a possible local recurrence.

Adolescent↗

PubMed2000

[Management of the neck for patients with thyroid papillary carcinoma].

OBJECTIVE: To search an optimal management of the neck for patients with thyroid papillary carcinoma. METHODS: Clinical data of 424 cases with thyroid papillary carcinoma treated in our hospital from Jan, 1965 to Jan, 1987 were analyzed retrospectively. Patients with positive cervical lymph nodes (N+) were treated with radical excision of the primary tumor and neck dissection. For patients without cervical lymph node involvement (N0), neck dissection was spared. On follow-up, whenever cervical lymphatic node metastasis occurred, neck dissection was performed. All patients were followed up for more than 10 years. RESULTS: The 5- and 10-year survival rate of the 258 N+ patients was 84.3% and 80.4% respectively, and that of the 166 N0 patients was 94.1% and 91.3% respectively. Twenty-three N0 cases later developed cervical lymph node metastasis. Their 5- and 10-year survival rate was 91.4% and 82.2% respectively after neck dissection. CONCLUSION: Since only 13.9% of N0 thyroid papillary carcinoma patients who did not receive neck dissection develop cervical lymph node metastases later, and their survival rate was just as good where neck dissection is postponed until metastases occur, prophylactic neck dissection seems unnecessary.

Adolescent↗

PubMed2000

[The treatment of tongue squamous cell with N0].

OBJECTIVE: To evaluate the validity of selective surgery for the N(0) neck in squamous cell carcinoma of the mobile tongue. METHODS: 116 patients with N(0) neck of the mobile tongue cancer who underwent comprehensive RND and 5 patients who had a selective RND were reviewed retrospectively. RESULTS: According to the suggestion of division of neck level, 7 patients had metastasis at level I; 21, level II; 10, level III, 1 case for level IV or V each. There were 5 cases with level III involvement as a first echelon of metastasis which was peculiar for the neck metastasis of mobile tongue. CONCLUSIONS: For N(0) neck of the mobile tongue cancer, a neck dissection of level I-III or level I-IV is more than enough.

Aged↗

PubMed2000

[Effects of methylmercury on intracellular free calcium content in cerebral cortical neurons].

OBJECTIVE: This study was conducted to explore effects and potential mechanism of methylmercury on concentration of intracellular free calcium (Ca(2+)) in the acutely isolated cerebral cortical neurons. METHODS: Calcium ion indicator Fura-2 two wave-length fluorophotometry was used to measure concentration of Ca(2+). RESULTS: (0.10 - 5.00) x 10(-6) mol/L of methylmercury could increase level of free intracellular Ca(2+) in cerebral cortical neurons significantly (P < 0.01), in a dose-response manner. Increase in intracellular free Ca(2+) of neurons caused by methylmercury associated with large influx of Ca(2+) outside cells and release of stored Ca(2+) inside cells, especially by influx of Ca(2+) outside cells. Influx of Ca(2+) outside cells associated with Ca(2+) channels regulated by receptor gate and potential gate, but not associated with sodium-dependent channel. CONCLUSION: Methylmercury lead to abnormal increase of intracellular free Ca(2+) in neurons, which is closely related to Ca(2+) channel.

Animals↗

PubMed2000

[Pedicled galeal flap in the reconstruction of head and neck tumor defects].

OBJECTIVE: To evaluate the advantage and applications of pedicled galeal flap in head and neck region. METHODS: A consecutive series of 17 patients underwent surgical reconstruction with pedicled galeal flaps after head and neck tumor resection. The defects included nasopharynx, skull base, maxilla, orbital base, oropharynx and oral cavity and the size ranged from 5 cm x 5 cm to 10 cm x 10 cm. The technique for using this flap was described and application was illustrated with 3 case reports. RESULTS: Complete success of galeal flaps for the reconstruction of head and neck defects was achieved in 13 of the 17 cases (76.5%) and partial necrosis was observed in the remaining 4 cases (23.4%). Immediate wound complications occurred in four cases, which resolved spontaneously. Four delayed complications were observed in 4 of 9 survival cases that included trismus (3) and alopecia (1). CONCLUSION: Galeal flap is a thin, pliable and well vascularised reconstruction tissue and is highly reliable. The donor site morbidity is minor. We have found the flap to be useful in the reconstruction of a variety of defects in head and neck, especially in skull base, orbital base, nasopharynx and oropharynx.

Adolescent↗

PubMed2000

[Laryngeal function-sparing surgery for pyriform sinus cancer].

OBJECTIVE: To evaluate the oncologic effect of laryngeal function-sparing surgery for the patients with pyriform sinus carcinoma. METHODS: A retrospective analysis was performed. Forty-four patients with pyriform sinus cancer who underwent operations were included. There were 10 patients in T1, 14 in T2, 18 in T3 and 2 in T4 categories. 42 patients received preoperative radiation and 2 cases, post-operative radiation. Surgery for the local lesions: 36 patients underwent pyriform sinusectomy and 8, partial laryngectomy and pyriform sinusectomy. RESULTS: Five year survival rate is 50% for the whole series, 80% for stage I, 71.4% for stage II, 52.9% for stage III, 26.7% for stage IV and 45% for all T3 + T4 patients. Local control rate is 81.8% for all patients and 75% for T3, T4 patients. CONCLUSION: For selected pyriform sinus cancer patient a conservative laryngeal surgery is warranted with the combination of preoperative radiative therapy.

Adult↗

PubMed2000

[The status of protein P16 and P53 in the surgical margins of laryngeal carcinoma and the association with local recurrence].

OBJECTIVE: To assess the status of P53 and P16 of surgical margins in laryngeal carcinoma and the association with the local recurrence following surgical treatment METHODS: The status of P53 and P16 of surgical margins in laryngeal carcinoma was studied using immunohistochemistry (IHC) staining method in 100 cases of laryngeal carcinoma. Fifty-two of them had recurrent tumors while 48 cases were free of local recurrence after 5-year follow up. The original tumor sites and T stages, which bear important influence over the risk of local recurrence, were strictly matched between the two groups, and the ages and preoperative doses of radiation were also considered. RESULTS: The percentage of local recurrence was 85% in these patients who showed positive staining for P53 and simultaneous negative staining for P16 in both the cancer tissues and the surgical margins. No association was found between the expression of P53 and P16 and the clinical types or T stages. CONCLUSION: The status of P53 and P16 in combination demonstrated by IHC technique in surgical margins of laryngeal carcinoma may predict the possibility of local recurrence.

Adult↗

PubMed2000

[Lateral neck dissection of hypopharyngeal cancer with clinically regional metastasis].

OBJECTIVE: To assess whether lateral neck dissection can control the hypopharyngeal cancer with clinically regional metastasis. METHODS: A retrospective review of medical chart from 1975 to 1992 was performed. Ninety-three hypopharyngeal squamous cell carcinoma patients who had performed RND were included. The distribution of metastatic neck lymph node was analyzed. RESULTS: Submandibular triangle lymph node metastasis was occult in only 3 patients. Histological lymph node metastasis to the posterior triangle was found in 5.9% of patients with N0, 7.0% with N1, 37.5% with N2a and 36% with N2b-N3. Histological neck lymph node metastasis to the posterior triangle was found in 4.0% of patients without inferior jugular lymph node metastasis and 34.1% of patients with inferior jugular lymph node metastasis. CONCLUSIONS: Lateral neck dissection was recommended to treat hypopharyngeal cancers of N0 and N1. N2 and N3 should be treated with neck dissection including II-V group lymph nodes. After lateral neck dissection, frozen section of the inferior jugular lymph node should be performed. If the result of the frozen section is positive, V group dissection should be performed.

Adult↗

PubMed1999

Squamous cell carcinoma of temporal bone: reported on 33 patients.

BACKGROUND: This study assessed the treatment results of a series of 33 patients with squamous cell carcinoma (SCC) of the temporal bone and evaluated the efficacy of mastoidectomy combined with perioperative radiation therapy protocol. METHODS: Thirty-three patients with biopsy-proven SCC invaded to the temporal bone were reviewed retrospectively and staged into three subgroups according to the University of Pittsburgh TNM Staging System. There were 3 patients with Stage I and II disease(tumor confined to auditory canal), 17 patients with Stage III (tumor involving the middle ear or mastoid), and 13 patients with Stage IV(more extensive disease). Two patients were treated by surgery alone. Eleven patients received irradiation only, and the remaining 20 patients underwent combined surgery and perioperative radiotherapy. The surgical intervention included sleeve resection for patients with Stage I and II lesions and mastoidectomy for all patients with Stage III and IV lesions except 1 who had subtotal temporal bone resection. The radiation dose delivered was in the range of 3500 approximately 10 000 cGy, with an average dose of 6560 cGy. RESULTS: The five-year survival rate for the whole series was 51.7% by the life-table analysis. After being staged into three subgroups (ie, Stage I + II, Stage III, and Stage IV), the estimated five-year survival rates were 100%, 68. 8%, and 19.6%, respectively (p = 0.04). Radiation alone yielded a 28. 7% five-year survival, while combined surgery and irradiation gave a result of 59.6% (p = 0.80). For patients treated with planned combined therapy, the actuarial five-year survival rates were 72.7% (8/11) for Stage III disease and 12.5% (1/8) for Stage IV disease (p = 0.02). Twelve patients who died of disease did so of local recurrence (10 cases), cervical metastases (1 case), and liver metastases (1 case), with 70% of succumbing to their diseases within two years. Complications include osteonecrosis (n = 1), osteitis (n = 3), radiation dermatitis (n = 2), facial nerve palsy (n = 2), and delayed healing (n = 2). Data on clinical presentation and treatment modality were also analyzed. CONCLUSION: The results of mastoidectomy with removal of all gross tumor, combined with planned perioperative irradiation therapy, seems to be a useful approach for SCC of the temporal bone. This gives at least as good, and possibly better, five-year survival than temporal bone resection. The mastoidectomy procedure creates less operative morbidity and mortality. To facilitate the development of more effective means of treating advanced disease, an accepted staging system and cooperative group investigation is necessary.

Adult↗

PubMed1999

Using affinity capillary electrophoresis to evaluate average binding constant of 18-mer diphosphotyrosine peptide to antiphosphotyrosine Fab.

We used affinity electrophoresis in capillaries to investigate the interaction between a monovalent antiphosphotyrosine antibody fragment, antigen-binding fragment (Fab), and a divalent antigen (dAg), an 18-mer diphosphopeptide phosphorylated on two-site tyrosine residues. The migration shift behavior of Fab in electrophoretic solution was observed and the quantitative expression was presented to estimate the arithmetical average value of the intrinsic affinities for two epitopes on the dAg with the Ag binding site on the Fab. In dAg excess, based on measurement of mobility changes of Fab analytes at different dAg concentrations, the experimental average dissociation constant (Kd = 27.7 microM) was calculated. It was also found that the structural variation of the two epitopes for binding specificity to the Ag-binding domain of Fab is not apparent. Moreover, the Kd values of Fab-dAg complexes were measured at higher electric fields and shown to be independent of changes in the electric field. Thus, under conditions where the total dAg concentration is in excess of the total Fab concentration, the method and quantitative expression which we developed is generally useful for the understanding of molecular interaction for an unlabeled monovalent receptor and its divalent ligand in free solution.

Amino Acid Sequence↗

PubMed1999

Distinctly different interactions of anesthetic and nonimmobilizer with transmembrane channel peptides.

Although it plays no clinical role in general anesthesia, gramicidin A, a transmembrane channel peptide, provides an excellent model for studying the specific interaction between volatile anesthetics and membrane proteins at the molecular level. We show here that a pair of structurally similar volatile anesthetic and nonimmobilizer (nonanesthetic), 1-chloro-1,2,2-trifluorocyclobutane (F3) and 1, 2-dichlorohexafluorocyclobutane (F6), respectively, interacts differently with the transmembrane peptide. With 400 microM gramicidin A in a vesicle suspension of 60 mM phosphatidylcholine-phosphatidylglycerol (PC/PG), the intermolecular cross-relaxation rate constants between (19)F of F3 and (1)H in the chemical shift regions for the indole and backbone amide protons were 0.0106 +/- 0.0007 (n = 12) and 0.0105 +/- 0.0014 (n = 8) s(-1), respectively. No cross-relaxation was measurable between (19)F of F6 and protons in these regions. Sodium transport study showed that with 75 microM gramicidin A in a vesicle suspension of 66 mM PC/PG, F3 increased the (23)Na apparent efflux rate constant from 149.7 +/- 7.2 of control (n = 3) to 191.7 +/- 12.2 s(-1) (n = 3), and the apparent influx rate constant from 182.1 +/- 15.4 to 222.8 +/- 21.7 s(-1) (n = 3). In contrast, F6 had no effects on either influx or efflux rate. It is concluded that the ability of general anesthetics to interact with amphipathic residues near the peptide-lipid-water interface and the inability of nonimmobilizer to do the same may represent some characteristics of anesthetic-protein interaction that are of importance to general anesthesia.

Amino Acid Sequence↗

PubMed1999

Structural consequences of anesthetic and nonimmobilizer interaction with gramicidin A channels.

Although interactions of general anesthetics with soluble proteins have been studied, the specific interactions with membrane bound-proteins that characterize general anesthesia are largely unknown. The structural modulations of anesthetic interactions with synaptic ion channels have not been elucidated. Using gramicidin A as a simplified model for transmembrane ion channels, we have recently demonstrated that a pair of structurally similar volatile anesthetic and nonimmobilizer, 1-chloro-1,2,2-trifluorocyclobutane (F3) and 1,2-dichlorohexafluorocyclobutane (F6), respectively, have distinctly different effects on the channel function. Using high-resolution NMR structural analysis, we show here that neither F3 nor F6 at pharmacologically relevant concentrations can significantly affect the secondary structure of the gramicidin A channel. Although both the anesthetic F3 and the nonimmobilizer F6 can perturb residues at the middle section of the channel deep inside the hydrophobic region in the sodium dodecyl sulfate micelles, only F3, but not F6, can significantly alter the chemical shifts of the tryptophan indole N-H protons near the channel entrances. The results are consistent with the notion that anesthetics cause functional change of the channel by interacting with the amphipathic domains at the peptide-lipid-water interface.

Anesthetics, General↗

PubMed1999

Transforming growth factor-alpha antisense vectors can inhibit glioma cell growth.

The effects of transforming growth factor-alpha (TGF-alpha) on cell growth were studied in human glioma U251 cells transfected with antisense TGF-alpha vectors (pcDNAI.neo). Several antisense clones showed a marked decrease in growth rate in serum-free medium but not in medium containing 10% FBS, compared with those of parental cells and clones from sense or vector transfectants. Antisense clones also produced fewer and smaller colonies in anchorage-independent growth assays. Moreover, there was a reduction in TGF-alpha expression in these antisense clones at both the protein and mRNA levels, as determined by enzyme linked immuno-sorbent assay and reverse transcriptase polymerase chain reaction analysis. A U251 clone transfected by TGF-alpha antisense in a different vector (pMT/Ep) also showed a marked suppression in cell growth and TGF-alpha mRNA level. Finally, transfected clones with either vector system, showed decreased tumorigenicity in nude mice. In summary, a strong correlation between the inhibition of glioma cell growth and TGF-alpha expression was obtained from two different plasmid vectors, indicating that the expression of TGF-alpha could be specifically and effectively down-regulated by TGF-alpha antisense vector, which in turn led to growth inhibition. These studies suggests that TGF-alpha plays an essential role in controlling human glioma cell proliferation and may serve as a potential target for treatment of malignant glioma.

Animals↗

PubMed1999

Concentration-dependent isoflurane effects on depolarization-evoked glutamate and GABA outflows from mouse brain slices.

The synaptic concentrations of glutamate and gamma-aminobutyric acid (GABA) are modulated by their release and re-uptake. The effects of general anaesthetics on these two processes remain unclear. This study evaluates the effects of isoflurane, a clinically important anaesthetic, on glutamate and GABA release and re-uptake in superfused mouse cerebrocortical slices. Experiments consisted of two 1.5-min exposures to 40 mM KCl in 30 min intervals. During the second exposure, different concentrations of isoflurane with and without 0.3 mM L-transpyrrolidine-2,4-dicarboxylic acid (PDC, a competitive inhibitor of glutamate uptake transporter) or 1 mM nipecotic acid (a competitive inhibitor of GABA uptake transporter) were introduced. The ratios of the second to first KCl-evoked increases in glutamate and GABA were used to determine the isoflurane concentration-response curves. The results can be described as a sum of two independent processes, corresponding to the inhibitions of release and re-uptake, respectively. The EC50 values for the inhibitions of release and re-uptake were 295+/-16 and 805+/-43 microM for glutamate, and 229+/-13 and 520+/-25 microM for GABA, respectively. Addition of PDC did not significantly affect glutamate release but shifted the re-uptake curve to the left (EC50= 315+/-20 microM). Nipecotic acid completely blocked GABA uptake, rendering isoflurane inhibition of GABA re-uptake undetectable. Our data suggest that isoflurane inhibits both the release and re-uptake of neurotransmitters and that the inhibitions occur at different EC50's. For GABA, both EC50's are within the clinical concentration range. The net anaesthetic effect on extracellular concentrations of neurotransmitters, particularly GABA, depends on the competition between inhibition of release and that of re-uptake.

Anesthetics, Inhalation↗