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P Bai

Publications and source records attributed to P Bai.

At least 19 recordsLinked to original sources
PubMed2002

Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure.

Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury in conditions associated with oxidative stress. Increased oxidative stress is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), a widely used antitumor anthracycline antibiotic. Thus, we hypothesized that the activation of PARP may contribute to the DOX-induced cardiotoxicity. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ34, we now demonstrate the role of PARP in the development of cardiac dysfunction induced by DOX. PARP-1+/+ and PARP-1-/- mice received a single injection of DOX (25 mg/kg i.p). Five days after DOX administration, left ventricular performance was significantly depressed in PARP-1+/+ mice, but only to a smaller extent in PARP-1-/- ones. Similar experiments were conducted in BALB/c mice treated with PJ34 or vehicle. Treatment with a PJ34 significantly improved cardiac dysfunction and increased the survival of the animals. In addition PJ34 significantly reduced the DOX-induced increase in the serum lactate dehydrogenase and creatine kinase activities but not metalloproteinase activation in the heart. Thus, PARP activation contributes to the cardiotoxicity of DOX. PARP inhibitors may exert protective effects against the development of severe cardiac complications associated with the DOX treatment.

Acute Disease↗
PubMed2001

Partial protection by poly(ADP-ribose) polymerase inhibitors from nitroxyl-induced cytotoxity in thymocytes.

Nitroxyl (NO(-)/HNO), has been proposed to be one of the NO(*)-derived cytotoxic species. Although the biological effect of nitroxyl is largely unknown, it has been reported to cause DNA breakage and cytotoxicity. We have therefore investigated whether NO(-)/HNO-induced DNA single-strand breakage activates the nuclear nick sensor enzyme poly(ADP-ribose) polymerase (PARP) and whether PARP activation affects the mode of NO(-)/HNO- induced cell death. NO(-)/HNO generated from Angeli's salt (AS, sodium trioxodinitrate) (0-300 microM) induced DNA single-strand breakage, PARP activation, and a concentration-dependent cytotoxicity in murine thymocytes. AS-induced cell death was also accompanied by decreased mitochondrial membrane potential and increased secondary superoxide production. The cytotoxicity of AS, as measured by propidium iodide uptake, was abolished by electron acceptors potassium ferricyanide, TEMPOL, the intracellular calcium chelator BAPTA-AM, and by PARP inhibitors 3-aminobenzamide (3-AB) and PJ-34. The cytoprotective effect of 3-AB was paralleled by increased output of AS-induced apoptotic parameters such as phosphatidylserine exposure, caspase activation, and DNA fragmentation. No significant increase in tyrosine nitration could be observed in AS-treated thymocytes as opposed to peroxynitrite-treated cells, indicating that tyrosine nitration is not likely to contribute to NO(-)/HNO-induced cytotoxicity. Our results demonstrate that NO(-)/HNO-induced PARP activation shifts the default apoptotic cell death toward necrosis in thymocytes. However, as total PARP inhibition resulted only in 30% cytoprotection, PARP-independent mechanisms dominate NO(-)/HNO-induced cytotoxicity in thymocytes.

Animals↗
PubMed2001

Cooperative folding of the isolated alpha-helical domain of hen egg-white lysozyme.

Proteins in the alpha-lactalbumin and c-type lysozyme family have been studied extensively as model systems in protein folding. Early formation of the alpha-helical domain is observed in both alpha-lactalbumin and c-type lysozyme; however, the details of the kinetic folding pathways are significantly different. The major folding intermediate of hen egg-white lysozyme has a cooperatively formed tertiary structure, whereas the intermediate of alpha-lactalbumin exhibits the characteristics of a molten globule. In this study, we have designed and constructed an isolated alpha-helical domain of hen egg-white lysozyme, called Lyso-alpha, as a model of the lysozyme folding intermediate that is stable at equilibrium. Disulfide-exchange studies show that under native conditions, the cysteine residues in Lyso-alpha prefer to form the same set of disulfide bonds as in the alpha-helical domain of full-length lysozyme. Under denaturing conditions, formation of the nearest-neighbor disulfide bonds is strongly preferred. In contrast to the isolated alpha-helical domain of alpha-lactalbumin, Lyso-alpha with two native disulfide bonds exhibits a well-defined tertiary structure, as indicated by cooperative thermal unfolding and a well-dispersed NMR spectrum. Thus, the determinants for formation of the cooperative side-chain interactions are located mainly in the alpha-helical domain. Our studies suggest that the difference in kinetic folding pathways between alpha-lactalbumin and lysozyme can be explained by the difference in packing density between secondary structural elements and support the hypothesis that the structured regions in a protein folding intermediate may correspond to regions that can fold independently.

Animals↗
PubMed2001

Structure and dynamics of the alpha-lactalbumin molten globule: fluorescence studies using proteins containing a single tryptophan residue.

The fluorescence properties of three variants of alpha-lactalbumin (alpha-LA) containing a single tryptophan residue were investigated under native, molten globule, and unfolded conditions. These proteins have levels of secondary structure and stability similar to those of the wild type. The fluorescence signal in the native state is dominated by that of W104, with the signal of W60 and W118 significantly quenched by the disulfide bonds in their vicinity. In the molten globule state, the magnitude of the fluorescence signal of W60 and W118 increases, due to the loss of rigid, specific side chain packing. In contrast, the magnitude of the signal of W104 decreases in the molten globule state, perhaps due to the protonation of H107 or quenching by D102 or K108. The solvent accessibilities of individual tryptophan residues were investigated by their fluorescence emission maximum and by acrylamide quenching studies. In the native state, the order of solvent accessibility is as follows: W118 > W60 > W104. This order changes to W60 > W104 > W118 in the molten globule state. Remarkably, the solvent accessibility of W118 in the alpha-LA molten globule is lower than that in the native state. The dynamic properties of the three tryptophan residues were examined by time-resolved fluorescence anisotropy decay studies. The overall rotation of the molecule can be observed in both the native and molten globule states. In the molten globule state, there is an increase in the extent of local backbone fluctuations with respect to the native state. However, the fluctuation is not sufficient to result in complete motional averaging. The three tryptophan residues in the native and molten globule states have different degrees of motional freedom, reflecting the folding pattern and dynamic heterogeneity of these states. Taken together, these studies provide new insight into the structure and dynamics of the alpha-LA molten globule, which serves as a prototype for partially folded proteins.

Amino Acid Substitution↗
PubMed2001

Peroxynitrite production, DNA breakage, and poly(ADP-ribose) polymerase activation in a mouse model of oxazolone-induced contact hypersensitivity.

Peroxynitrite-induced poly(ADP-ribose) polymerase activation has been implicated in the pathogenesis of various inflammatory conditions. Here we have investigated whether peroxynitrite and poly(ADP-ribose) polymerase may play a role in the pathophysiology of the elicitation phase of contact hypersensitivity. We have detected nitrotyrosine, DNA breakage, and poly(ADP-ribose) polymerase activation in the epidermis of mice in an oxazolone-induced contact hypersensitivity model. As tyrosine nitration is mostly mediated by peroxynitrite, a nitric-oxide-derived cytotoxic oxidant capable of causing DNA breakage, we have applied peroxynitrite directly on mouse skin and showed poly(ADP-ribose) polymerase activation in keratinocytes and in some scattered dermal cells. We have also investigated the cellular effects of peroxynitrite in HaCaT cells, a human keratinocyte cell line. We found that peroxynitrite inhibited cell proliferation and at higher concentrations also caused cytotoxicity. Peroxynitrite activates poly(ADP-ribose) polymerase in HaCaT cells and poly(ADP-ribose) polymerase activation contributes to peroxynitrite-induced cytotoxicity, as indicated by the cytoprotective effect of the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide. The cytoprotective effect of 3-aminobenzamide cannot be attributed to inhibition of apoptosis, as apoptotic parameters (caspase activation and DNA fragmentation) were not reduced in the presence of 3-aminobenzamide in peroxynitrite-treated cells. Moreover, poly(ADP-ribose) polymerase inhibition by 3-aminobenzamide dose-dependently reduced interferon-induced intercellular adhesion molecule 1 expression as well as interleukin-1beta-induced interleukin-8 expression. Our results indicate that peroxynitrite and poly(ADP-ribose) polymerase regulate keratinocyte function and death in contact hypersensitivity.

Adjuvants, Immunologic↗
PubMed2001

A model of dynamic side-chain--side-chain interactions in the alpha-lactalbumin molten globule.

Proteins in the molten globule state contain high levels of secondary structure, as well as a rudimentary, nativelike tertiary topology. Thus, the structural similarity between the molten globule and native proteins may have a significant bearing in understanding the protein-folding problem. To explore the nature of side-chain--side-chain interactions in the alpha-lactalbumin (alpha-LA) molten globule, we determined the effective concentration for formation of the 28--111 disulfide bond in 14 double-mutant proteins, each containing two hydrophobic core residues replaced by alanine. We compared our results with those of single-alanine substitutions using the framework of double-mutant cycle analysis and found that, in the majority of cases, the effects of two alanine substitutions are additive. Based on these results, we propose a model of side-chain-side-chain interactions in the alpha-LA molten globule, which takes into consideration the dynamic nature of this partially folded species.

Alanine↗
PubMed2001

[The clinical value of surgical-pathological staging for endometrial carcinoma].

OBJECTIVE: To explore the practical value of surgical-pathological staging for endometrial carcinoma. METHODS: Ninety-six patients with endometrial carcinoma accepted primary surgical treatment from January 1995 to December 1999 were analyzed retrospectively in our hospital. The clinical and surgical pathologic staging of these patients were compared. RESULTS: The total differences between clinical and surgical-pathologic staging were 44 cases (45.8%), in stage I 24.0%, stage II 76.9%, in stage III 2 of 5 cases. The metastasis rate of pelvic lymph nodes was 10.3%, in stage I 1 of 16 cases, stage II 14.7%. Fourteen patients (14.6%) with extrauterine pelvic metastasis were found, of which 2 of 19 cases in stage I b, 23.1% in stage II. 9.4% with ovarian metastasis, in stage I a 9.7%, stage II 10.3%. 7.9% with positive peritoneal cytology, in stage I 4.0%, stage II 10.3%. 5.2% with omentum metastasis. 2.1% with appendix metastasis. Clinical stages, depth of myometrial invasions, pathological grades and histological types were related to the extent of pelvic and abdominal cavity by univariate analysis (P < 0.01, 0.05). The first three factors were significantly correlated to dissemination by multivariate (P < 0.05). CONCLUSIONS: The surgical-pathological staging is more accurate than the clinical staging, especial in stage II clinical stage depth of myoinvasion, patho-histological grades were closely related to the dissemination in pelvic-abdominal cavity. The surgical-pathological staging is able to assess prognosis objectively and guide therapy for endometrial carcinoma.

Abdominal Neoplasms↗
PubMed2001

[The effect of tamoxifen of endometrium].

OBJECTIVE: To evaluate the effect of tamoxifen on the endometrium. METHODS: Hysteroscopy and endometrial biopsies were performed in 26 patients with breast cancer receiving tamoxifen and having vaginal bleeding or endometrial thickness detected by ultrasound. In addition 78 women with postmenopausal bleeding without receiving tamoxifen underwent the same examination. RESULTS: Thirteen (50.0%) patients receiving tamoxifen had endometrial or endocervical polyps, whereas 14 cases(17.9%) not receiving tamoxifen developed the polyps (P < 0.05). Nine (34.6%) patients receiving tamoxifen had thyperplasias, which was significantly higher than that of women not receiving tamoxifen (P < 0.05). CONCLUSIONS: The incidence of endometria disease in the patient with breast cancer receiving tamoxifen was increased. These patients should be closely monitored by transvaginal sonography and hysteroscopy.

Antineoplastic Agents, Hormonal↗
PubMed2001

[Radiotherapy in the treatment of uterine sarcomas].

OBJECTIVE: To study radiotherapy in the treatment of uterine sarcomas and response to radiation in primary or recurrent uterine sarcomas. METHODS: A total of 102 uterine sarcomas treated in the Cancer Hospital from May 1960 to June 1999. A retrospective review of 45 patients receiving surgery alone, 29 patients for postoperative radiotherapy, 4 radiotherapy alone, 24 recurrent sarcomas receiving radiotherapy. RESULTS: The 5-year overall survival for 45 patients treated with surgery alone and 29 patients managed by postoperative radiotherapy were 56.7% and 58.6% respectively (P > 0.05). The addition of radiotherapy significantly reduced the local recurrence rate from 42.2% to 20.7% (P < 0.05). The tumor was disappeared completely by treatment of radiotherapy alone in 3 patients of primary uterine cervix sarcomas. 1 patient was free of disease at 36 months. Other 2 patients died 9 and 11 months later because of distant metastases. The complete and partial response rate of radiotherapy was 50.0% for recurrent tumors. The radiotherapeutic sensibility of endometrial stromal sarcomas, mixed mesodermal sarcomas and leiomyosarcomas was downward tendency in turn. CONCLUSIONS: The postoperation adjuvant radiotherapy reduced the pelvic recurrent significantly. Radiotherapy should be used in the treatment of uterine sarcomas as an important part of combination therapy.

Female↗
PubMed2000

Side chain accessibility and dynamics in the molten globule state of alpha-lactalbumin: a (19)F-NMR study.

The molten globule state of alpha-lactalbumin (alpha-LA) has been considered a prototype of partially folded proteins. Despite the importance of molten globules in understanding the mechanisms of protein folding and its relevance to some biological phenomena, site-specific information on the structure and dynamics of a molten globule is limited, largely because of the high conformational flexibility and heterogeneity. Here, we use selective isotope labeling and (19)F NMR to investigate the solvent accessibility and side-chain dynamics of aromatic residues in the molten globule of alpha-LA. Comparison of these properties with those of the native and unfolded protein indicates that the alpha-LA molten globule is highly heterogeneous; each residue has its unique solvent accessibility and motional environment. Many aromatic residues normally buried in the interior of native alpha-LA remain significantly buried in the molten globule and the side-chain dynamics of these residues are highly restricted. Our results suggest that hydrophobic and van der Waals interactions mediated by the inaccessible surface area could be sufficient to account for all the stability of the alpha-LA molten globule, which is approximately 50% of the value for the native protein.

Fluorine↗
PubMed2000

[Combination chemotherapy of uterine sarcomas].

OBJECTIVE: To study the results of combination chemotherapy of uterine sarcoma after operation and recurrent tumor. METHODS: One hundred seventy-four cases of three major pathological subtypes of uterine sarcomas were treated in the Cancer Hospital from 1960 to 1996. Clinical data were analyzed of 51 cases of uterine sarcomas treated with postoperative adjuvant chemotherapy and 38 cases with recurrent tumors received 98 courses of chemotherapy. They were divided into 4 groups according to the adjuvant chemotherapy regimen: single drug, VAC, VAD, and other regimens. Chemotherapy regimens for recurrent tumors were VAD, PA/PAC, and other combination regimens including etoposide, ifosfamide, cisplatin, adriamycin. RESULTS: The 5-year survival rate of stage I-II uterine sarcoma patients was 54.9% receiving adjuvant chemotherapy. It was 72.7% in VAD group which was significantly higher than that in other regimen groups. The survival rate was related to the number of chemotherapy course. The chemo-sensitivity of various pathological types of recurrent uterine sarcomas was not different. CONCLUSION: The 5-year survival rate does not improve in patients with stage I-II uterine sarcomas given postoperative chemotherapy. VAD is among the best regimens and at least 3 courses should be performed. The results of new treatment regimens such as EPA, IA, etc., must await further clinical observation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Contribution of individual residues to formation of the native-like tertiary topology in the alpha-lactalbumin molten globule.

Molten globules are partially folded forms of proteins that have native-like secondary structure and a compact geometry, but often without rigid, specific side-chain packing. Recently, the molten globule of alpha-lactalbumin (alpha-LA) has been shown to adopt a native-like tertiary topology, mainly localized in the alpha-helical domain. This native-like topology is reflected by the high effective concentration (Ceff) for formation of the 28-111 disulfide bond, which is approximately 10 to 40 times higher than the Ceff for formation of any non-native disulfide bond in the alpha-helical domain. In order to understand the mechanism for formation of the native-like tertiary topology, we substituted alanine for each of the 23 buried residues in the alpha-helical domain of alpha-LA and determined the effect of these substitutions on the Ceff for formation of the 28-111 disulfide bond. Our results indicate that a subset of hydrophobic residues is most important for formation of the native-like topology. These residues form a densely packed core in the three-dimensional structure of alpha-LA. In contrast, the less important residues consist of both hydrophobic and hydrophilic amino acids located at peripheral positions. These results suggest that a relatively small number of hydrophobic residues may be sufficient for specifying the overall structure of a protein during early stages of protein folding.

Cysteine↗
PubMed1997

[A clinical analysis of 153 uterine sarcomas].

OBJECTIVE: To evaluate the prognostic factors and treatment methods of 153 uterine sarcomas. METHODS: 153 cases of the uterine sarcoma were eligible for this retrospective study. Of the 153 cases, 48 were leiomyosarcomas, 47 mixed mesodermal sarcomas, 37 endometrial stromal sarcomas, 8 carcinosarcomas, 4 sarcoma botryoides, 1 fibrosarcoma, and 8 malignant lymphomas. 81 cases were in stage I, 11 stage II, 33 stage III and 11 stage IV. 38 cases were treated by surgery alone, 24 by surgery combined with radiation therapy, 50 by surgery plus chemotherapy, 23 by surgery plus radiation therapy and chemotherapy, 4 by radiation therapy alone, 3 by chemotherapy alone, and 11 by radiation therapy plus chemotherapy. RESULTS: The overall 5-year survival rate was 49.0%, and that of leiomyosarcomas, mixed mesodermal sarcomas and endometrial stromal sarcomas was 46.9%, 34.1% and 69.3% respectively (P < 0.01). The 5-year survival rate of lesions limited to the uterus (stage I + II), and that of pelvic cavity invasion (stage III) and distant metastases was 59.6%, 25.6% and 10.0% respectively (P < 0.01. When the uterus was smaller than a 3 months pregnant uterus, the 5-year survival rate was 49.9%. When the uterus size larger than a 3 months pregnant uterus, the survival rate was 18.8% (P < 0.05). Premenopausals surviving 5-year accounted for 56.3% and post-menopausal 28.9% (P < 0.01). CONCLUSIONS: The prognosis of uterine sarcoma is significantly associated with histologic type, clinical and surgico-pathological stage, uterine size and pre- or post-menopausal status. Radiation or chemotherapy alone is palliative. Postsurgical adjuvant radiotherapy significantly decreased vaginal and pelvic recurrences rates. A combination of surgery, radiotherapy and chemotherapy can reduce pelvic recurrence as well as enhance survivals.

Adolescent↗
PubMed1995

[Primary malignant lymphoma of the female genital tract clinical analysis of 15 cases].

OBJECTIVE: To review fifteen cases with primary malignant lymphoma of the female genital tract at Cancer Hospital, Chinese Academy of Medical Sciences from 1980 approximately 1994. METHODS: This is a clinical retrospective analysis. There were 7 cases of lymphoma originating in the cervix, 2 in the vagina, 3 in the ovary, 1 in the vulva, endometrium and pelvic cavity respectively. All of the 15 cases were given combination therapy. 3 ovarian lymphoma were treated by surgery and chemotherapy, 2 cervical lymphoma and 1 endometrial lymphoma by surgery, chemotherapy and radiotherapy, 1 pelvic lymphoma by surgery and radiotherapy, others by radiotherapy and chemotherapy. RESULTS: Two patients are living more than 5 years, 3 patients more than 3 years. 4 patients were followed up for less than 2 years and 6 patients relapsed or died. CONCLUSIONS: The prognosis of ovarian lymphoma is worse than that of other genital sites. Combined and sequential chemotherapy-radiotherapy-chemotherapy is the proper treatment sequence for lymphoma of the cervix, vagina and vulva. Extensive chemotherapy may be an appropriate choice for highly malignant pathological type. Radiation should be given early for large cervical lymphoma.

Adult↗
PubMed1994

[Operative treatment for vulvar cancer by different methods].

A retrospective analysis of 88 patients with vulvar cancer treated by radical vulvectomy and groin lymphadenectomy from July, 1958 to December, 1990 is presented. 88 cases are divided into two groups based on different operative methods: the enbloc group (25 cases) and the non-enbloc group (63 cases). No significant statistic differences are found in the 5-year survival rates (76.0% vs 79.8%) and the complications (erysipelas, lower extremity edema) between the two groups. The wound healing time is 14.4 days shorter in the non-enbloc group than enbloc group. Factors such as clinical staging, metastasis to the inguinal lymph nodes and histopathological classification are also investigated for correlation with the prognosis.

Adult↗
PubMed1993

Detection of antigens of Mycobacterium tuberculosis in patients of infertility by monoclonal antibody based sandwiched enzyme linked immunosorbent assay (ELISA).

A sandwich ELISA to detect specific protein antigens of Mycobacterium tuberculosis was developed by using polyclonal anti-BCG rabbit antibodies as the primary capture antibodies. The mycobacterial antigens were detected with horseradish peroxidase conjugated monoclonal antibodies (P 6) as secondary antibodies. The enzyme was detected by using 1,2 Phenylenediamine dihydrochloride (OPD) and Hydrogen peroxide as substrate. The antigen could be quantitated through linear regression analysis with lower detection limit of 1.25 micrograms/ml. 50 consecutive cases of infertility were examined by laparoscopy and tested for the presence of the antigen in the serum. Mycobacterial antigen could be detected in 9 of the 12 cases with definitive diagnosis of tuberculosis, 5 of the 23 where the diagnosis of tuberculosis was probable and in only 1 of 15 patients who had no laparoscopic abnormalities indicative of tuberculosis.

Adult↗
PubMed1992

Glycation alters collagen fibril organization.

Incubation of rat tail tendon in 0.2M ribose results in accelerated non-enzymatic glycosylation of collagen, with the formation of fluorescent cross-links between molecules and decreased solubility. Electron micrographs of tendon cross-sections show an increased fibril packing density with increasing degrees of glycation. After a one-week incubation in ribose, every fibril appears in close contact with all of its neighbors, and the packing density has increased to 76%, from a value of 62% in controls. Irregular diameters and fusion of fibrils also are seen. All of the fibrils in a bundle appear to become cross-linked together, creating a larger stress bearing unit. This model is consistent with stress-strain curves showing a large increase in tensile stress and stiffness after a one-week incubation period in ribose. The diameters of the collagen fibrils increase in size in glycated tendon. We hypothesize larger diameters result from an increased resistance to shrinkage during the specimen preparation process, as a result of the rigid sugar derived cross-links. Closer fibril packing, increased fibril diameters, and irregular diameters have been reported in diabetic tissues, and may result from decades of glycation induced cross-link accumulation.

Animals↗