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Biomedical subjects

K Shen

Publications and source records attributed to K Shen.

At least 73 records · Page 4Linked to original sources
PubMed1997

Regulated human erythropoietin receptor expression in mouse brain.

Erythropoietin (Epo) is known for its role in erythropoiesis and acts by binding to its receptor (EpoR) on the surface of erythroid progenitors. EpoR activity follows the site of hematopoiesis from the embryonic yolk sac to the fetal liver and then the adult spleen and bone marrow. Expression of EpoR has also been observed in selected cells of non-hematopoietic origin, such as the embryonic mouse brain during mid-gestation, at levels comparable to adult bone marrow. EpoR transcripts in brain decrease during development falling by birth to less than 1-3% of the level in hematopoietic tissue. We have now recapitulated this pattern of expression using a human EpoR transgene consisting of an 80-kb human EpoR genomic fragment. The highest level of expression was observed in the embryonic yolk sac and fetal liver, analogous to the endogenous gene, in addition to expression in adult spleen and bone marrow. Although activity of this transgene in brain is initially lower than the endogenous gene, it does exhibit the down-regulation observed for the endogenous gene in adult brain. The expression pattern of hybrid transgenes of an hEpoR promoter fused to beta-galactosidase in 9. 5-day embryos suggested that the hEpoR promoter region between -1778 and -150 bp 5' of the transcription start site is necessary to direct EpoR expression in the neural tube. EpoR expression in the neural tube may be the origin of the EpoR transcripts detected in brain during development. These data demonstrate that both the mouse and human EpoR genes contain regulatory elements to direct significant levels of expression in a developmentally controlled manner in brain and suggest that in addition to its function during erythropoiesis, EpoR may play a role in the development of selected non-hematopoietic tissue.

Animals↗
PubMed1997

DDT stimulates c-erbB2, c-met, and STATS tyrosine phosphorylation, Grb2-Sos association, MAPK phosphorylation, and proliferation of human breast epithelial cells.

Several environmental organochlorines, some of which exhibit estrogenic activity, have been detected in human breast tissue and have been suggested as having a role in tumorigenesis. In this communication, we report the effects of DDT on c-erbB2 and c-met growth factor receptor tyrosine kinase and STATS signal transduction processes in human breast epithelial MCF-10A cells. p,p'-DDT at physiologically relevant concentrations (i.e. 10 nM) elevated c-erbB2, c-met and STAT1 alpha (p84/91) tyrosine phosphorylation, stimulated Grb2-Sos1 association and elevated MAPK phosphorylation. In contrast, o,p'-DDT under identical conditions failed to stimulate either c-erbB2 or c-met tyrosine phosphorylation, demonstrating a structural specificity for this effect. p,p'-DDT also stimulated breast epithelial cell proliferation, as evidenced by 3H thymidine incorporation and analysis of cell doubling times. These results provide evidence of additional pathways by which environmental chemicals may stimulate cell proliferation and/or tumorigenesis and thereby function as xenomitogens.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Fas-signaling and effects on receptor tyrosine kinase signal transduction in human breast epithelial cells.

Fas-mediated cell death was examined in MCF-10AT preneoplastic human breast epithelial cells. Treatment with anti-Fas for 48 h induced apoptosis with cells exhibiting typical apoptotic features including loss of cell contact, condensation of chromatin, and increased staining of the nuclear membrane. DNA fragmentation occurred in response to anti-Fas treatment. Anti-Fas treatment resulted in decreased p53 protein levels, while bcl-2 and bax protein levels remained unaffected. Cells treated with anti-Fas also exhibited increased tyrosine phosphorylation of the c-met growth factor receptor tyrosine kinase. Immunoprecipitation experiments demonstrated that Fas associated with c-erbB2 and c-met in untreated cells. Treatment with anti-Fas, however, significantly decreased Fas-c-erbB2 and Fas-c-met association. Anti-Fas treatment of these cells caused a significant decrease in p120-GAP levels, ERK-1 levels, and phosphorylation, as well as Grb2-Sosl and MEK-1-ERK-1 association. These results show that Fas-signaling exerted a suppressive effect on p53 levels and on downstream effectors of receptor tyrosine kinase signal transduction, thereby ensuring cell death.

Adaptor Proteins, Signal Transducing↗
PubMed1997

[Cox proportion hazard model multivariate analysis of prognosis of 1,484 axillary node-negative breast cancer patients].

OBJECTIVE: To study the prognosis of axillary node-negative breast cancer patients. METHODS: The data were analyzed in 1,484 consecutive axillary node-negative breast cancer patients. Twenty-two individual variables were evaluated statistically using the cumulative survival rate by the computer's Cox multivariate analysis model. RESULTS: Menopausal status, times of pregnancy, duration before diagnosis, pregnancy-associated, tumor size, intramammary lymph node, postoperative radiotherapy and postoperative adjuvant tamoxifen therapy were independent predictors of prognosis. CONCLUSION: Parts of high risk group among axillary node-negative breast cancer patients could be identified by clinical parameters. Postoperative radiotherapy or ovarian ablation was not indicated for axillary node-negative breast cancer patients. Tamoxifen as postoperative adjuvant therapy should not be restricted to postmenopausal or ER-positive patients. The selection of high risk patients with axillary node-negative breast cancer who should receive adjuvant chemotherapy remains to be investigated at present.

Adult↗
PubMed1997

Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the ovary.

OBJECTIVES: To determine overexpression of p53, EGFR, c-erbB-2 and c-erbB-3 in endometrioid carcinoma of the ovary and to evaluate the prognostic significance of these results, especially, coexisting overexpression of p53 and one of the member of type I growth factor receptor family. METHODS: Overexpressions of the p53, EGFR, c-erbB-2 and c-erbB-3 protein were studied by immunohistochemistry in paraffin-embedded tumor tissue from 28 patients with endometrioid carcinoma of the ovary. RESULTS: 11 (39.3%), 13 (46.4%), and 14 (50.0%) were stained positively with p53, c-erbB-2 and c-erbB-3 monoclonal antibodies. 13 (46.4%) was stained positively with EGFR polyclonal antibody. There were no relationship between p53, EGFR, C-erbB-2, c-erbB-3 and histologic grade, lymph node metastasis. The percentage of tumors with over expression of p53, EGFR, C-erbB-2 and c-erbB-3 was higher in those with stage II-III tumors compared with those with stage I, in patients with residual tumor after initial surgery compared with those without. A high survival rate was observed in patients without p53, EGFR, c-erbB-2 and c-erbB-3 overexpression respectively than those with. A highest survival rate was observed in patients with both p53 and one of EGFR, c-erbB-2 and c-erbB-3 negative compared with those both positive or either of both positive. CONCLUSION: Overexpression of p53, EGFR, c-erbB-2 and C-erbB-3 resulted in a poorer prognosis respectively. Overexpression of both p53 and one of the EGFR, c-erbB-2 and c-erbB-3 is a worse prognostic indicator in patients with endometrioid carcinoma of the ovary.

Adult↗
PubMed1997

The prognosis of biopsy-proven lupus nephritis in chinese patients: long term follow-up of 86 cases.

OBJECTIVE: To investigate the prognosis of lupus nephritis (LN) and its influencing factors in patients with lupus nephritis in China. METHODS: A retrospective study was carried out in 86 patients followed up for at least 5 years. Clinical features, serological and immunological tests were investigated. Renal biopsies were performed at the beginning of the study and repeated in some cases during the follow-up period. All the 86 patients had serum creatinine (Scr) level less than 132.6 mumol/L at the initial presentation and were divided into three groups according to the level of Scr at the end of the study. Group I: the patients with normal renal function (Scr < 132.6 mumol/L); Group II: the patients with mild-moderate renal insufficiency (132.6 mumol/L < or = SCR < or = 530.4 mumol/L); Group III: the patients with end stage renal failure (ESRF) (Scr > or = 530.4 mumol/L). RESULTS: Forty-seven patients reached clinical remission with normal renal function, 11 had with stabilization of renal function, although the systemic lupus erythematosis (SLE) activity relapsed repeatedly, while 28 subjects developed renal insufficiency after 60-170 (mean 88.12 +/- 28.23) months of observation. ESRF rate was 11.6% in this group of patients. Eight patients died (2 died of infections and 6 died of ESRF) during the follow-up period. At the beginning of the study the rates of hypertension, persistent anemia and hematuria in Group II were 50%, 70%, and 70% respectively, being much higher than those in Group I. The calculation of AI and CI in 60 patients revealed that there were 65% of patients with AI > or = 7 and 70% of patients with CI > or = 3 in Groups II and III, while in Group I there were only 32% of patients with AI > or = 7 and 19% of patients with CI > or = 3. Sixteen cases had pathologic class changed in 48 repeated biopsies. Seven cases changed to Class IV, 5 to Class II, 3 to Class V from other classes and one to class III from Class II. CONCLUSIONS: Factors associated with the development of renal insufficiency in these lupus patients included hypertension, anemia and hematuria. Renal biopsy evaluation offered additional prognostic information and showed that patients with severe active and chronic histologic changes were at risk for developing renal insufficiency. During the clinical course, the renal classification of LN changed in certain patients, thus the histologic classification of renal morphology at initial presentation did not fully predict the outcome. Renal involvement is very common in systemic lupus erythematosis (SLE) patients. Lupus nephritis (LN) is the most common form of secondary renal disease in China. It has various and unpredictable clinical features. The risks associated with its treatment have challenged investigators to detect the factors which may influence the survival rate of patients with LN and to develop the rational approaches to therapy. Decades of intensive investigation at many centers around the world had underscored the predictive value of demographic, clinical and laboratory data prior to treatment. Controversies still existed due to the difference in environment, race and the selection criteria of patients as well as the method used to evaluate the outcome. There are still some factors which are thought to have an impact on the prognosis of LN. Most of the articles on the prognosis of patients with LN were reported from Europe and America either about Caucasian or African-American patients. The prognosis of LN and its influence in Chinese patients need more elucidation.

Adult↗
PubMed1997

[The relationship between multi-drug resistance gene expression and drug resistance of ovarian carcinoma].

OBJECTIVE: To study the relationship between multi-drug-resistance (MDR1) gene expression and the drug resistance of ovarian carcinoma and the reversing potency of drug-resistance modifying agent--cyclosporin A (CsA). METHODS: Tumor-bearing mice of ovarian carcinoma cell (OVCA3) were divided randomly into three groups: control group, adriamycin (ADM) group and ADM +CsA group. The tumor growth rate and the survival rate of mice were investigated and compared among the groups. 32 frozen specimens of ovarian carcinoma tissue from patients were examined for the expression of MDR1 gene by means of RT-PCR. RESULT: Ovarian carcinoma cells with positive MDR1 gene expression showed cross drug-resistance to ADM, daunorubicin (DNR), vincristine (VCR) and etoposide (VP-16), the value of inhibiting concentration (IC50) is 4.1-15.5 times of that of the cells with negative MDR1 gene expression. To tumor-bearing mice, there was significant difference in tumor growth rate between mice given combined therapy of CsA + ADM and those given ADM only (P<0.01) Of the 32 frozen specimens of ovarian carcinoma tissue, there was no confirmed relationship between MDR1 gene expression and the pathologic type or differential grade. The possibility of poor prognosis of patients with positive MDR1, gene expression was 16.07 (1.78-144.7) times of that of patients with negative MDR1 gene expression. CONCLUSION: MDR-related drug can induce the overexpression of MDR1 gene and result in the appearance of the multidrug resistance phenomenon. CsA can partially reverse the multidrug resistance of ovarian carcinoma cells both in vitro and in vivo. Detection of MDR1 gene expression in patients of ovarian carcinoma could be used as an index to predict the prognosis of the patients.

Animals↗
PubMed1996

Detection of respiratory viruses in nasopharyngeal secretions with immunofluorescence technique for multiplex screening-an evaluation of the Chemicon assay.

BACKGROUND: Antigen detection with immunofluorescence is an efficient method for diagnosis of respiratory tract infections, but has previously not allowed for simple screening of many respiratory viruses. Pools of monoclonal antibodies against various respiratory viruses are now available, and are potentially important tools for improvement of antigen detection in nasopharyngeal samples. OBJECTIVE: To evaluate the commercially available Chemicon immunofluorescence assay (IFA; respiratory viruses panel and identification kit), an indirect IFA containing a pool of monoclonal antibodies for screening for influenza A, B, respiratory syncytial virus (RSV), parainfluenza 1, 2, 3 and adenovirus, and the respective individual antibodies. STUDY DESIGN: Ninety-six frozen preparations from nasopharyngeal secretions or bronchoalveolar lavages were retrospectively examined with the assay, and the results compared with other IFAs for antigen detection and cell culture isolation obtained in the everyday routine. Nasopharyngeal preparations from 300 children with lower respiratory tract infections at Beijing Children's Hospital during the 1994-1995 winter season were also examined. RESULTS: The sensitivity of the Chemicon assay compared to the combined results of routine IFA and isolation was 89% and specificity 92%. If five identifications of RSV made with the Chemicon assay alone were regarded to be truly positive, the specificity was 100%. A viral etiology was identified in 105/280 (38%) evaluable samples drawn from the Chinese children (influenza A 20%, RSV 14%, adenovirus 3% and parainfluenza 1, 2 or 3, 7%). CONCLUSION: One problem with the Chemicon assay was that for around 4-13% of samples there was a non-specific staining in the screening assay, necessitating stainings for verification. Despite this, the assay is an excellent tool for identification of viral respiratory tract infections, giving an increased sensitivity compared to direct immunofluorescence assays.

Journal Article↗
PubMed1996

Viral etiology of acute childhood encephalitis in Beijing diagnosed by analysis of single samples.

OBJECTIVE: To understand the viral etiology of acute childhood encephalitis in Beijing. METHODS: Ninety-seven Chinese children (between 7 months and 13 years of age) with acute encephalitis were retrospectively investigated. They were treated in Beijing Children's Hospital between June, 1991, and October, 1994. Different serologic methods (immunofluorescence assay, enzyme-linked immunosorbent assay, solid phase reverse immunosorbent test) were used for detection of IgM antibody to enteroviruses, herpesviruses, mumps, measles, rubella and Japanese encephalitis virus. The viral DNA of six herpesviruses was detected by polymerase chain reaction. RESULTS: Viral etiology was identified in 35 of 97 (36.0%) cases. The most frequently identified pathogens were enteroviruses (15; 15.4%), followed by mumps (7; 7.2%), rubella (6; 6.1%), Japanese encephalitis virus (5; 5.1%), human herpesvirus 6 (2; 2.0%), herpes simplex virus (2; 2.0%) and Epstein-Barr virus (1; 1.0%). IgM antibody in cerebrospinal fluid was detected for enterovirus, mumps and rubella viruses. CONCLUSIONS: Enteroviruses were the most frequent viral pathogens of acute childhood encephalitis in Beijing. Detection of IgM in cerebrospinal fluid may be useful for diagnosis in certain cases of viral encephalitis.

Acute Disease↗
PubMed1996

Selective arterial embolization in the management of internal bleeding caused by trophoblastic diseases.

OBJECTIVE: To evaluate the efficacy and safety of selective arterial embolization in the management of internal bleeding caused by trophoblastic diseases. PATIENTS AND METHODS: Four patients with internal bleeding caused by trophoblastic diseases were diagnosed with arteriography and treated with selective arterial embolization as a life-saving measure. Effect of controlling bleeding was assessed by follow-up arteriogram and clinical observation. RESULTS: The embolization successfully controlled the bleeding in all patients. Operation time was short with a mean of 42 minutes. The shock was corrected dramatically. Fever and pain were common complications. CONCLUSION: Selective arterial embolization is a life-saving measure in the management of internal bleeding caused by trophoblastic diseases.

Adult↗
PubMed1996

Transgenic mice containing the human erythropoietin receptor gene exhibit correct hematopoietic and neural expression.

The erythropoietin receptor (EpoR), known for its role in the proliferation and differentiation of erythroid cells, has been detected in nonhematopoietic tissues. We have reported previously that in addition to hematopoietic expression, EpoR is expressed at high levels in embryonic mouse brain and decreased to nondetectable levels by birth. While using transgenic mice to characterize human EpoR expression, we observed that a 15-kb human EpoR transgene (expressed in hematopoietic tissues but at a reduced level) also exhibited in the embryonic brain low levels of expression that persisted through adulthood. To examine further the basis of tissue and developmental specificity of the human EpoR gene, we produced additional transgenic mice using an 80-kb human EpoR genomic fragment isolated from a P1 phagemid human library. We found that this transgene is expressed appropriately in hematopoietic tissues (including yolk sac, fetal liver, adult spleen, and bone marrow) at levels comparable to the endogenous murine EpoR. The 80-kb transgene also provided high-level expression in the embryonic brain that paralleled the levels of the endogenous murine EpoR and was no longer detectable after birth. These data suggest that the high level of embryonic brain expression may be relevant to the human EpoR gene and that the transgenic mouse with an 80-kb fragment is a suitable model for studying the regulation and possible functional importance of human EpoR expression in the developing embryo.

Animals↗
PubMed1996

Detection of cytomegalovirus DNA in paraffin-embedded lung tissue specimens using in situ polymerase chain reaction.

OBJECTIVE: To develop a possible alternative laboratory diagnostic method, an in situ polymerase chain reaction (ISPCR) for definitive diagnosis of human cytomegalovirus (HCMV) pneumonia in infants. METHODS: The material involved in this study was formalin-fixed paraffin-embedded lung tissue specimens from 6 infants died of histopathologically diagnosed cytomegalic inclusion body pneumonia (CMIBP) and from 4 infants died of other diseases. When DNA extracts from the specimens of these 10 infants were tested by using a previously applied conventional PCR, the specimens from the 6 infants with CMIBP were positive for HCMV DNA, while those from the other 4 infants were negative. In the ISPCR, biotin-11-dUTP was used for labeling the amplified products and streptavidin, biotin-alkaline phosphatase for in situ color development. RESULTS: The results of the study showed specific staining for HCMV DNA in the lung tissue slices from the 6 cases with CMIBP, while no staining was found in the specimens from the 4 infants who died of other diseases. The control ISPCR tests on the HCMV DNA positive specimens without adding either biotin-11-dUTP or Taq DNA polymerase or the primers for HCMV DNA showed negative results. The specific staining for HCMV DNA was seen in bronchial and alveolar epithelial cells, small vascular endothelial cells and leukocytes in the lumens of small blood vessels. CONCLUSIONS: The results suggested that the ISPCR was able to demonstrate both presence of HCMV DNA in the lung tissues and active HCMV infection; therefore the ISPCR may be applicable in definitive diagnosis of HCMV pneumonia when proper specimens such as lung biopsy material or bronchoalveolar lavage is available for the test.

Cytomegalovirus↗
PubMed1996

[Comprehensive staging laparotomy in stage I epithelial ovarian cancer].

OBJECTIVE: To evaluate the significance of comprehensive staging laparotomy in stage I epithelial ovarian cancer. METHODS: Forty-three patients with stage I epithelial ovarian cancer were divided into 3 groups and retrospectively analysed. Thirty two of these patients allotted to stage I ovarian cancer according to FIGO criteria were ascertained by comprehensive staging laparotomy (group A), 5 patients were upstaged following comprehensive staging laparotomy (group B) and 6 patients were staged without comprehensive laparotomy (group C). RESULTS: The mean operation time was 2 hours and 40 minutes, the mean volume of blood loss was 460 ml and no severe complications occurred during the comprehensive staging laparotomies. 13.5% (5/31) of patients were found to have retroperitoneal metastasis and then therefore were upstaged as stage III. Group A and B had better prognosis. During the 39.7 months followup period, tumor-free survival rates in group A and B were 97% (31/37) and 5/5 respectively. In group C, 2 patients recurrent and one died of the diseases, a tumor-free survival rates of 4/6. There was a significant difference in tumor-free survival rates between group A and C (P = 0.038). CONCLUSION: Comprehensive staging laparotomy should be considered as an important criterion in FIGO staging of epithelial ovarian cancer and a standard procedure in the treatment of stage I epithelial ovarian cancer.

Carcinoma, Endometrioid↗
PubMed1996

[Diagnosis and management strategies of hereditary ovarian cancer syndrome].

OBJECTIVE: To describe the clinical profile of hereditary ovarian cancer syndrome (HOCS), focusing on the diagnosis and management strategies. METHOD: Eight patients from four families were identified with HOCS. The diagnosis was made by pedigree according to the criteria recommended by Lynch. Clinical manifestations and management strategies were discussed. RESULT: The incidence of epithelial ovarian cancer in HOCS family women was 20% which was higher than that in sporadic ovarian cancer (10%) (P < 0.05). The mean onset age in patients with HOCS was 41.6% years which was younger also than that in sporadic ovarian cancer. Serous cystadenocarcinoma was the predominant histological type of the HOCS, and the prognosis seems to be better. CONCLUSION: Women in families with HOCS are in a population of high risk for epithelial ovarian cancer. Management strategies should include periodical counselling, screening and surveillance. For women with established families, above 40 years of age and identified with HOCS or with histories of breast or colorectal cancer, prophylactic oophorectomy should be considered.

Adult↗