Biomedical subjects

P Tang

Publications and source records attributed to P Tang.

At least 55 records · Page 3Linked to original sources

PubMed1999

Is end-to-side neurorrhaphy effective? A study of axonal sprouting stimulated from intact nerves.

The purpose of this study was to determine if axonal sprouting across an end-to-side coaptation could be stimulated and if so, to identify the source of the regenerating axons. Mechanical trauma, the method used to stimulate axonal sprouting, was compared to a control group with coaptation only and an additional non-grafted control group. After a 20-week recovery period, electrical stimulation revealed that the target muscles had been reinnervated in all groups except the non-grafted control group. Axonal counting demonstrated a significant increase for the mechanical trauma group compared to the control group with coaptation only [ratio of the density of axons/microm2 of the experimental to the contralateral control side: 2.78+/-0.11 vs. 0.96+/-0.15, respectively, p<0.002). Tibialis anterior muscle weights were significantly increased for both groups vs. the non-grafted control group (ratio of experimental to the contralateral control side: coaptation-only control, 0.539+/-0.024; mechanical trauma, 0.538+/-0.036 vs. nongrafted control, 0.220+/-0.003, p<0.002). Of importance, this study provides evidence that the intact tibial nerve functions as a bridge for regenerating axons derived from the proximal peroneal stump. This suggests an alternative explanation to successful end-to-side axonal sprouting, and questions the clinical utility of end-to-side coaptation.

Anastomosis, Surgical↗

PubMed1999

Once daily, high dose versus divided, low dose gentamicin for open fractures.

A prospective, randomized study was performed on 75 Gustilo Grades II and III open fractures to determine the efficacy of once daily, high dose aminoglycoside therapy, compared with more conventional dosing, in reducing the infection rate when used in conjunction with an aggressive operative treatment protocol. All patients enrolled in the study were treated with immediate irrigation, debridement, operative stabilization of the fracture, and 1 g of cefazolin every 8 hours. At the time of admission patients were randomized to two groups. Patients in Group I received gentamicin 5 mg/kg divided into twice daily doses, and patients in Group II received gentamicin 6 mg/kg given once daily. All patients were monitored for renal toxicity and observed for radiographic and clinical signs of infection until fracture union. The results of the study revealed no statistically significant difference between once daily, high dose versus divided, low dose gentamicin in infection rates. Thus, daily dosing of gentamicin was found to be safe, effective, and cost efficient in the treatment of open fractures when combined with a cephalosporin and aggressive operative debridement and stabilization.

Adolescent↗

PubMed1999

Topiramate pharmacokinetics in infants.

PURPOSE: This study's goal was to provide preliminary data on the pharmacokinetics of topiramate (TPM) in a cohort of infants (younger than 4 years) participating in an open-label trial of TPM in refractory infantile spasms. METHODS: The pharmacokinetics of TPM were assessed in infants receiving a stable TPM dose for >7 days during the extension phase of this trial. Blood samples were drawn just before and 0.5. 1, 1.5, 2, 4, 6, 8, and 12 h after the morning TPM dose. TPM plasma concentrations were determined by fluorescence polarization immunoassay. The noncompartmental analysis module of WinNonlin was used to calculate individual patient pharmacokinetics profiles. RESULTS: Five infants (ages, 23.5-29.5 months) formed the study cohort. These infants had been given TPM for a median of 9 months (range, 6-11 months) and were currently receiving between 11 and 38.5 mg/kg/day TPM. One was receiving TPM monotherapy, whereas four were taking concomitant antiepileptic medications (AEDs; n = 2, enzyme-inducing agents; n = 2, non-enzyme-inducing drugs). TPM pharmacokinetics in infants appears to be linear. In this cohort, mean TPM plasma clearance (CL/F, 66.6+/-27.4 ml/h/kg) was slightly higher than that reported for children and adolescents and therefore substantially higher than that reported for adults. TPM CL/F was higher and the calculated half-life shorter in the infants receiving concomitant enzyme-inducing AEDs. CONCLUSIONS: Based on this small cohort of patients, it appears that infants may require significantly larger TPM doses, based on weight, than children, adolescents, or adults. Titration to effect and not absolute TPM dose should guide therapy in this age group.

Adolescent↗

PubMed1999

[Expression of human flt3 ligand and thrombopoietin genes in a bone marrow stromal cell line by internal ribosome entry site (IRES) sequence].

OBJECTIVE: To explore the feasibility of retroviral-mediated Flt 3 ligand (FL) and thrombopoietin (Tpo) genes transferred into and expressed in a bone marrow stromal cell line HFCL by internal ribosome entry site(IRES) sequence. METHODS: IRES sequence, FL and Tpo cDNA were recombined with retroviral vector pLXSN by gene recombination technology. The recombinant plasmid was transferred into retrovirus packaging cell line PA317 by lipofectamine, and the resistant clones were selected by G418 selective medium. mRNA expression in HFCL cells and integration of genome DNA were assayed by RT-PCR and genomic DNA PCR. The biological activities of FL and Tpo in the culture were investigated by CFU-GM assay and Tpo dependent cell line TD-3, respectively. RESULTS: The recombinant plasmid pLFTSN was successfully constructed. In the genome of these transfected target cells, Neo gene and FL and Tpo cDNA were integrated, the expression of FL and Tpo mRNA was detected in HFCL cells. The specific activities of FL and Tpo in the culture indicated that HFCL cells transfected with FL and Tpo cDNA could significantly express FL and Tpo in vitro. CONCLUSION: FL gene and Tpo gene were simultaneously expressed in bone marrow stromal cell line by the regulation of IRES sequence. These results provide a basis for studies on hematopoietic regulation by gene transfected bone marrow stromal cells.

Bone Marrow Cells↗

PubMed1999

[The role of surgery in the management of thyroid lymphoma].

OBJECTIVE: To evaluate the role of surgery in the management of thyroid lymphoma. METHODS: A retrospective analysis was performed of 14 patients with thyroid lymphoma treated at the Cancer Hospital, Peking Union Medical College, Chinese Academy Medical Science from 1964 to March 1998. There were 5 males and 9 females, with a median age of 54 years (range 15-75). There were 4 cases in stage IEA, 9 in stage IIEA, 1 in stage II EB. Fine needle aspiration biopsy was performed in 1 case, excision biopsy in 4, thyroid lobectomy in 8, and total thyroidectomy in 1. Radiotherapy was used alone in 4 patients, chemotherapy alone in 2, radiotherapy combined with chemotherapy in 7, no postoperative treatment in 1. RESULTS: All but 1 patients were histopathologically diagnosed as non-Hodgkin's lymphoma. It was of B cell origin in 11 cases, T cell origin in 2. Seven patients were alive without evidence of recurrent disease at follow-up, ranging from 5 to 112 months. Three patients died of lymphoma, 1 died of treatment complication, 2 died of other diseases, and 1 lost from follow-up. The major surgical resection did not appreciably affect survival. CONCLUSION: Radiotherapy or chemotherapy, alone or in combination, is the treatment of choice for thyroid lymphoma. Surgical resection combined with radiotherapy or chemotherapy may be beneficial to survival in patients with intrathyroid lymphoma. It is otherwise limited to make a tissue diagnosis.

Adolescent↗

PubMed1999

[Treatment and outcome of cervical lymph nodal metastases of unknown primary sites].

OBJECTIVE: To ascertain the optimal management of cervical nodal metasta of unknown primary sites. METHODS: The clinical data of 114 patients of cervical nodal metastases of unknown primary sites were retrospectively analyzed. RESULTS: For metatic masses of the upper and/or middle part of the neck, the optimal approach varied depnding on the histologic type. Poorly-differentiated carcinoma was treated with radiotherapy, squamous-cell carcinoma was treated with radiotherapy plus surgery, while papillary adenocarcinoma was treated by combined radical thyroidectomy. Their 5-year survival rate was 45.2%, 53.8% and 62.5%, respectively. For metastatic masses in the supraclavicular region, chemotherapy was the first treatment of choice in all patients. In only 12 of the 114 patients (11.2%) the primary sites were found in the follow-up period. CONCLUSION: For patients with cervical lymph node metastases from unknown primary sites, the management should be given according to the location of lymph node involved and histopathologic type of the tumor.

Adolescent↗

PubMed1999

[Cervical management in the N0 squamous cell carcinoma of the tongue].

OBJECTIVE: To assess whether the elective neck dissection would be beneficial as a routine management in the N0 squamous cell carcinoma of the tongue. METHODS: Cox regression model was used for analysis of tongue cancer cases treated by our hospital in a period from 1958 to 1996. RESULTS: Size of primary tumor and preoperative radiation showed significant difference in relation to cervical lymph node recurrence or metastasis. Neck dissection in the series was not a factor to influence the rate of cervical recurrence or survival. 5-years survival was 73.5% versus 69.3% in patients who underwent elective neck dissection and those without neck dissection (difference not statistically significant). CONCLUSION: We suggest that elective neck dissection would be avoided in T1 or T2 patients who have no neck node metastases.

Adult↗

PubMed1998

Adenoviral transgene expression of MMAC/PTEN in human glioma cells inhibits Akt activation and induces anoikis.

The MMAC/PTEN tumor suppressor gene encodes for a phosphatase that recently has been shown to have phosphotidylinositol phosphatase activity, implicating its possible involvement in phosphatidylinositol 3'-kinase-mediated signaling. To investigate possible alterations in growth factor-mediated signal transduction, an adenovirus containing MMAC/PTEN, Ad-MMAC, previously shown to inhibit growth and tumorigenicity in glioma cells, was used to acutely express the transgene. Human glioma cells infected with Ad-MMAC but not with control adenoviruses exhibited an inhibition of phosphorylation of both activating residues of Akt, Ser-473, and Thr-308, along with Akt's serine/threonine kinase activity, without significantly altering Akt expression. The effects of functional MMAC/PTEN expression were relatively specific, because members of several other growth factor-mediated signaling pathways showed no altered responses. The presence of MMAC/PTEN also inhibited phosphorylation of BAD, although no evidence of apoptosis in the in situ treated cells was observed. However, U251 glioma cells infected with Ad-MMAC were induced to undergo anoikis at a significantly higher rate than U251 cels treated with control viruses or mock infected with media. These results demonstrate that the acute administration of MMAC/PTEN results in the inhibition of Akt-mediated signaling, growth inhibition, and anoikis, implying that loss of MMAC/PTEN increases cellular proliferation and significantly augments a cell's survival potential during cellular processes that are associated with malignancy.

Adenoviridae↗

PubMed1998

Unifying characteristics of sites of anesthetic action revealed by combined use of anesthetics and non-anesthetics.

1. The usefulness of nonanesthetics in the study of mechanisms of general anesthesia lies in the possibility to identify the unifying characteristics of molecular sites that are shared by the anesthetics but not by the structurally similar nonanesthetics. 2. In model membranes, pairs of structurally similar anesthetics and nonanesthetics showed distinctly different submolecular distributions. 3. This difference may be the underlying cause for the different anesthetic and nonanesthetic interaction with gramicidin A, a model transmembrane cation channel. 4. Generalization of our findings suggests that the nature of the sites, whether in lipids or proteins, must be neither extremely hydrophilic nor extremely lipophilic, but amphiphilic.

Anesthetics↗

PubMed1998

Identification of an allosteric binding site on the transcription factor p53 using a phage-displayed peptide library.

Monoclonal antibody PAb1620 recognizes a conformational epitope on the transcription factor p53 and, upon binding, allosterically inhibits p53 binding to DNA. A highly diverse (1.5 x 10(10) members) phage-displayed library of peptides containing 40 random amino acids was used to identify the PAb1620 binding site on p53. Panning this library against PAb1620 resulted in three unique peptides which have statistically significant sequence identities with p53 sufficient to identify the binding site as being composed of amino acids 106-113 and 146-156. Based on these results, we propose a mechanism by which PAb1620 can allosterically inhibit p53 binding to DNA through an indirect interaction between the antibody binding site and the L1 loop (amino acids 112-124) of p53, which is a component of the DNA binding region.

Allosteric Regulation↗

PubMed1998

Comparison of anaesthetic and non-anaesthetic effects on depolarization-evoked glutamate and GABA release from mouse cerebrocortical slices.

1. Investigation with substances that are similar in structure, but different in anaesthetic properties, may lead to further understanding of the mechanisms of general anaesthesia. 2. We have studied the effects of two cyclobutane derivatives, the anaesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F3), and the non-anaesthetic, 1,2-dichlorohexafluorocyclobutane (F6), on K+-evoked glutamate and gamma-aminobutyric acid (GABA) release from isolated, superfused, cerebrocortical slices from mice, by use of h.p.l.c. with fluorescence detection for quantitative analysis. 3. At clinically relevant concentrations, the anaesthetic, F3, inhibited 40 mM K+-evoked glutamate and GABA release by 72% and 47%, respectively, whereas the structurally similar non-anaesthetic, F6, suppressed evoked glutamate release by 70% but had no significant effects on evoked GABA release. A second exposure to 40 mM KCl after a approximately 30 min washout of F3 or F6 showed recovery of K+-evoked release, suggesting that F3 and F6 did not cause any non-specific or irreversible changes in the brain slices. 4. Our findings suggest that suppression of excitatory neurotransmitter release may not be directly relevant to the primary action of general anaesthetics. A mechanism involving inhibitory postsynaptic action is implicated, in which a moderate suppression of depolarization-evoked GABA release by the anaesthetic may be consistent with the enhancement of postsynaptic GABAergic activities.

Anesthetics↗

PubMed1998

[31P]/[1H] nuclear magnetic resonance study of mitigating effects of GYKI 52466 on kainate-induced metabolic impairment in perfused rat cerebrocortical slices.

PURPOSE: Kainic acid (KA) has long been used in experimental animals to induce status epilepticus (SE). A mechanistic implication of this is the association between excitotoxicity and brain damage during or after SE. We evaluated KA-induced metabolic impairment and the potential mitigating effects of GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] in superfused rat cerebral cortical slices. METHODS: Interleaved [31P]/[1H] magnetic resonance spectroscopy (MRS) was used to assess energy metabolism, intracellular pH (pHi), N-acetyl-L-aspartate (NAA) level, and lactate (Lac) formation before, during, and after a 56-min exposure to 4 mM KA in freshly oxygenated artificial cerebrospinal fluid (oxy-ACSF). RESULTS: In the absence of GYKI 52466 and during the KA exposure, NAA, PCr, and ATP levels were decreased to 91.1 +/- 0.8, 62.4 +/- 3.9, and 59.1 +/- 4.3% of the control, respectively; Lac was increased to 118.2 +/- 2.1 %, and pH, was reduced from 7.27 +/- 0.02 to 7.13 +/- 0.02. During 4-h recovery with KA-free ACSF, pHi rapidly and Lac gradually recovered, NAA decreased further to 85.5 +/- 0.3%, and PCr and ATP showed little recovery. Removal of Mg2+ from ACSF during KA exposure caused a more profound Lac increase (to 147.1 +/- 4.0%) during KA exposure and a further NAA decrease (to 80.4 +/- 0.5%) during reperfusion, but did not exacerbate PCr, ATP, and pHi changes. Inclusion of 100 microM GYKI 52466 during KA exposure significantly improved energy metabolism: the PCr and ATP levels were above 76.6 +/- 2.1 and 82.0 +/- 2.9% of the control, respectively, during KA exposure and recovered to 101.4 +/- 2.4 and 95.0 +/- 2.4%, respectively, during reperfusion. NAA level remained at 99.8 +/- 0.6% during exposure and decreased only slightly at a later stage of reperfusion. CONCLUSIONS: Our finding supports the notion that KA-induced SE causes metabolic disturbance and neuronal injury mainly by overexcitation through non-N-methyl-D-aspartate (NMDA) receptor functions.

Adenosine Triphosphate↗

PubMed1998

Listeria monocytogenes invasion of epithelial cells requires the MEK-1/ERK-2 mitogen-activated protein kinase pathway.

PD98059, a specific inhibitor of MEK-1 mitogen-activated protein (MAP) kinase kinase, blocked Listeria monocytogenes invasion into HeLa epithelial cells. The effects of PD98059 were reversible, as adherent extracellular bacteria were internalized upon removal of the drug. Previously, we reported that L. monocytogenes could activate ERK-1 and ERK-2 MAP kinases through the action of listeriolysin O (LLO) on the host cell (P. Tang, I. Rosenshine, P. Cossart, and B. B. Finlay, Infect. Immun. 64:2359-2361, 1996). We have now found that two other MAP kinase pathways, those of p38 MAP kinase and c-Jun N-terminal kinase, are also activated by wild-type L. monocytogenes. Mutants lacking functional LLO (hly mutants) were still invasive but only activated ERK-2 and only activated it at later (90-min) postinfection times. Two inhibitors of L. monocytogenes invasion, cytochalasin D, which disrupts actin polymerization, and wortmannin, which blocks phosphatidylinositol (PI) 3-kinase activity, did not block ERK-2 activation by wild-type L. monocytogenes and hly mutants. However, genistein, an inhibitor of tyrosine kinases, and PD98059 both blocked invasion and decreased ERK-2 activation. These results suggest that MEK-1 and ERK-2 activities are essential for L. monocytogenes invasion into host epithelial cells. This is the first report to show that a MAP kinase pathway is required for bacterial invasion.

Androstadienes↗

PubMed1998

A reproducible model of circulatory arrest and remote resuscitation in rats for NMR investigation.

BACKGROUND AND PURPOSE: Because noninvasive physiological monitoring of cerebral blood flow, metabolic integrity, and brain ion and water homeostasis can now be accomplished with new, state-of-the-art MR spectroscopy and imaging techniques, it is appropriate to develop controllable and reproducible animal models that permit prolonged circulatory arrest and resuscitation in the magnet and also allow for studies of long-term survival and outcome. We have developed such a model in rats that involves minimal surgical preparations and can achieve resuscitation remotely within precisely controlled time. METHODS: Cardiac arrest was induced by asphyxiation, the duration of which ranged from 8 to 24 minutes. Resuscitation was achieved remotely by a slow, intra-aortic infusion of oxygenated blood (withdrawn either from the same rat before asphyxia or from a healthy donor rat) along with a resuscitation cocktail containing heparin (50 U/100 g), sodium bicarbonate (0.1 mEq/100 g), and epinephrine (4 micrograms/100 g). The body temperature was measured by a tympanic thermocouple probe and was controlled either by a heating pad (constant tympanic temperature = 37 degrees C) or by warm ambient air (constant air temperature = 37 degrees C). Interleaved 31P/1H nuclear magnetic resonance (NMR) spectroscopy was used in a selected group of rats to measure the cerebral metabolism before and during approximately 20 minutes of circulatory arrest and after resuscitation. RESULTS: The overall success rate of resuscitation, irrespective of the duration of cardiac arrest, was 82% (51 of 62). With a programmed infusion pump, the success rate was even higher (95%). The survival time for rats subjected to 15 and 19 minutes of asphyxia with core temperature tightly controlled was significantly lower than that with ambient temperature control (P < 0.001 and P < 0.04, respectively). High-quality NMR spectra can be obtained continuously without interference from the resuscitation effort. Final histological examinations taken 5 days after resuscitation showed typical neuronal damages, similar to those found in other global ischemia models. CONCLUSIONS: Because the no-flow time and resuscitation time can be precisely controlled, this outcome model is ideally suited for studies of ischemic and reperfusion injuries in the brain and possibly in other critical organs, permitting continuous assessment of long-term recovery and follow-up in the same animals.

Animals↗

PubMed1998

[Application of pectoralis major myocutaneous flap in the reconstruction of tongue: an analysis of 86 cases].

OBJECTIVE: To analyze the results of the use of pectoralis major myocutaneous (PMM) flap in the reconstruction of tongue. METHODS: From 1984 to 1995, PMM flap was applied in 86 cases with cancer of tongue after radical resection for the immediate reconstruction of the lingual defect. RESULTS: Notwithstanding the advanced lesions in stages T3 and T4, patients had good survival and functional results. The 1-, 3- and 5-year survival rate was 86.0%, 51.2% and 23.3%, respectively. There was complete flap necrosis in one case and partial necrosis in fifteen cases, but the latter spontaneously regressed. The swallowing and speech rehabilitations following surgical treatment for tongue cancer were acceptable, considering the advanced disease status. CONCLUSION: The PMM flap with its abundant tissue and excellent blood supply and anatomic proximity provides a reliable method of primary reconstruction of the substance of the tongue. The surgical procedure is simple, easy to perform. Reconstruction of the tongue with PMM flap meets the clinical requirements in the shape, communication and swallowing rehabilitations. The PMM flap is a reliable material for the reconstruction of tongue with major defect following subtotal glossectomy.

Adult↗

PubMed1998

[Supraglottic horizontal laryngectomy for supraglottic carcinoma].

OBJECTIVE: To evaluate the therapeutic results of supraglottic horizontal laryngectomy (SHL) for T1 and selected T2, T3 and T4 supraglottic carcinoma. METHODS: One hundred and seven patients undergone SHL during the period of 1979 through 1991 were reviewed retrospectively. All patients were followed up for at least 5 years. RESULTS: The 5 year-survival rate of 6 cases in stage I, 24 cases in stage II, 53 cases in stage III, and 24 cases in stage IV was 100.0%, 83.3%, 71.7% and 41.7%, respectively. Of the 102 patients, 92.2% were decannulated, and 91.6% of all patients achieved satisfactory recovery of phonation. CONCLUSION: SHL is a reliable surgical approach for selected supraglottic carcinoma, even for some advanced lesions, provided the tumor has not extended below the ventricle. The upper neck dissection can be used as an exploratory measure. For N0 neck patients with supraglottic cancer, comprehensive neck dissection is not invariably performed to avoid overtreatment.

Adult↗

PubMed1998

[Preoperative radiotherapy reduces cervical metastasis of supraglottic carcinoma: a prospective randomized trial in 201 patients].

OBJECTIVE: To evaluate the effectiveness of preoperative radiotherapy in the control of overall cervical lymph node metastasis from supraglottic carcinoma. METHODS: A prospective randomized study on 210 patients with supraglottic carcinoma was performed. Nine patients were lost from follow-up and therefore excluded. The analysis was based on the remained 201 patients including fifteen who did not complete the treatment protocol. Surgery alone(S) was carried out in 102 patients and radiotherapy(40 Gy) followed by surgery (R + S) in 99 patients. All the patients were followed up for more than three years. RESULTS: No statistically significant difference in survival rates between S and R + S groups was found by using the Kaplan-Meier analysis. However, relative risk of overall cervical recurrence had a trend of reduction for patients in R + S group, versus patients in S group. There was a statistically significant reduction of lymph node metastasis in R + S group compared to S group in stage I-III(P = 0.0198) while in stage IV no such difference was observed. Patients with stage I-III disease who did not receive preoperative radiation were 1.766 times more likely to develop neck recurrence compared to patients who did. Among all the factors, only TNM stage and histological nodal status were found to be independent risk factors for regional control. Contralateral neck failure occurred more frequently in patients with advanced lesion(P = 0.020) and in patients without preoperative radiation(P = 0.018). CONCLUSION: There may be a trend towards improved control of cervical lymph node metastasis with preoperative radiation of 40 Gy dose in patients with supraglottic cancer in stage I-III of the disease.

Combined Modality Therapy↗

PubMed1998

Supraglottic carcinoma: does preoperative radiotherapy reduce the incidence of cervical metastasis?

OBJECTIVE: To compare surgery (S) alone with combined radiotherapy and surgery (R + S) in the management of patients with supraglottic laryngeal cancer. METHODS: Between 1981 and 1994, patients were stratified according to stage and randomised to either surgery (S) or 4000cGy of radiotherapy and surgery. There were 102 patients in the S group and 99 in the R + S group who completed at least 3-year follow-up. RESULTS: Using Kaplan-Meier survival method showed no significant difference between the two groups. When the patients were grouped according to tumour stage, a significant reduction in the regional recurrence was noted in the R + S group for stage I-III disease (Cox multivariate analysis, P < 0.02). They had an increased relative risk of 1.8 (95% confidence 1.1-2.9) for neck recurrence. There was no significant difference in neck recurrence rates in the two groups for stage IV disease. When Cox proportional hazard model was used, only TNM stage (P < 0.02) and histological nodal status (positive lymph nodes, P < 0.01) were found to be independent risk factors for regional control. CONCLUSION: Preoperative radiotherapy can improve regional cervical control of stage I-III supraglottic cancer as compared with surgery alone.

Adult↗