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Biomedical subjects

K Shen

Publications and source records attributed to K Shen.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Endometriosis in adolescents: analysis of 6 cases].

OBJECTIVE: To review the diagnosis and treatment of endometriosis in adolescents and to evaluate the surgical and medical treatment options for this special population. METHOD: To review the 6 cases of adolescent endometriosis and to review the literature research. RESULTS: Three hundred and ninety nine cases under age 18 had undergone gynecological operation. So the incidence among this period is 1.8% (6/339) in hospitalized adolescents. Four cases have complicated genital tract anomalies. Preoperative diagnosis is rare. Good prognosis is expected in most patients. Only 1 case relapsed 9 years after medical therapy. Endometriosis is the most common cause of chronic pelvic pain in adolescents. There may be a natural progression of endometriosis from atypical lesions in adolescents to classic lesions in adults. Congenital abnormalities of the reproductive tract are the main reason for the adolescent endometriosis. CONCLUSIONS: Endometriosis should be strongly suspected in adolescent with chronic pelvic pain especially with no response to oral contraceptives and nonsteroidal antiinflammatory medicine. The treatment involves the surgical operation and medicine. Adolescence;

Adolescent↗
PubMed2000

Multiple regions of MAP kinase phosphatase 3 are involved in its recognition and activation by ERK2.

Mitogen-activated protein kinase phosphatase 3 (MKP3) is a specific regulator of extracellular signal-regulated protein kinase 2 (ERK2). Association of ERK2 with MKP3 results in a powerful increase in MKP3 phosphatase activity. To determine the molecular basis of the specific ERK2 recognition by MKP3 and the ERK2-induced MKP3 activation, we have carried out a systematic mutational and deletion analysis of MKP3. Using activation-based and competition-based assays, we are able to quantitatively evaluate the contributions that residues/regions within MKP3 make to ERK2 binding and ERK2-induced MKP3 activation. Our results show that recognition and activation of MKP3 by ERK2 involves multiple regions of MKP3. Thus, the kinase interaction motif (KIM; residues 61--75) in MKP3 plays a major role (135-fold) for high affinity ERK2 binding. The most important residue in the KIM sequence of MKP3 is Arg(65), which probably interacts with Asp(319) in ERK2. In addition to KIM, a unique sequence conserved in cytosolic MKPs (residues 161--177 in MKP3) also contributes to ERK2 binding (15-fold). However, these two regions are not essential for ERK2-induced MKP3 activation. A third ERK2 binding site is localized in the C terminus of MKP3 (residues 348--381). Although deletion of this region or mutation of the putative ERK specific docking sequence (364)FTAP(367) in this region reduces MKP3's affinity for ERK2 by less than 10-fold, this region is absolutely required for ERK2-induced MKP3 activation.

Amino Acid Motifs↗
PubMed2000

Production and processing of erythropoietin receptor transcripts in brain.

The expression of erythropoietin receptor (EpoR) in brain and neuronal cells, and hypoxia-responsive production of erythropoietin (Epo) in the brain suggests that the function of Epo as a survival or viability factor may extend beyond hematopoietic tissue and erythroid progenitor cells. Epo, produced by astrocytes and neurons, can be induced by hypoxia by severalfold, and in animal models Epo administration is neuroprotective to ischemic challenge. We characterized the human EpoR transcript in brain and neuronal cells to determine its contribution in regulating the Epo response in brain. Screening of a human brain cDNA library and quantitative analysis of EpoR transcripts indicate that the EpoR gene locus is transcriptionally active in brain. In addition to the proximal promoter that is active in hematopoietic cells, a significant proportion of transcripts originates far upstream from the EpoR coding region. Unlike erythroid cells with efficient splicing of EpoR transcripts to its mature form, brain EpoR transcripts are inefficiently or alternately processed with a bias towards the 3' coding region. In human EpoR transgenic mice, anemic stress induces expression of the transgene and endogenous EpoR gene in hematopoietic tissue and brain. In culture of neuronal cells, hypoxia induces EpoR expression and increases sensitivity to Epo. Induction of EpoR expression appears to be a consequence of increased transcription from the upstream region and proximal promoter, and a shift towards increased processing efficiency. These data suggest that in contrast to erythropoiesis where erythroid progenitor cells express high levels of EpoR and are directly responsive to Epo stimulation, the neuroprotective effect of Epo and its receptor may require two molecular events: the induction of Epo production by hypoxia and an increase in EpoR expression in neuronal cells resulting in increased sensitivity to Epo.

Adult↗
PubMed2000

Enhanced analgesic potency and reduced tolerance of morphine in 129/SvEv mice: evidence for a deficiency in GM1 ganglioside-regulated excitatory opioid receptor functions.

10-fold higher doses in SW mice. Furthermore, cotreatment of 129/SvEv mice with morphine plus a low dose of naltrexone (ca. 0.1 microgram/kg) that markedly enhances and prolongs morphine's antinociceptive effects in SW mice did not enhance, and often attenuated6 h. The marked GM1-induced attenuation of morphine's antinociceptive effects in 129/SvEv mice may be due to conversion of some of the opioid receptors in these mice from an inhibitory Gi/Go-coupled to an excitatory Gs-coupled mode. Exogenous GM1 supplementation can, therefore, reverse the anomalous lack of morphine tolerance displayed by this mouse strain in comparison to SW and other mice. The present study may provide insights into factors that regulate the marked variability in nociceptive sensitivity and opioid tolerance/dependence liability among individual humans.

Animals↗
PubMed2000

Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.

Binding interactions between the plasma membrane and the cytoskeleton define cell functions such as cell shape, formation of cell processes, cell movement, and endocytosis. Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy between the cytoskeleton and the plasma membrane. Receptor stimuli that hydrolyze PIP2 lowered adhesion energy, a process that could be mimicked by expressing PH domains that sequester PIP2 or by targeting a 5'-PIP2-phosphatase to the plasma membrane to selectively lower plasma membrane PIP2 concentration. Our study suggests that plasma membrane PIP2 controls dynamic membrane functions and cell shape by locally increasing and decreasing the adhesion between the actin-based cortical cytoskeleton and the plasma membrane.

3T3 Cells↗
PubMed2000

Comparison of K-ras point mutations at codon 12 and p21 expression in pancreatic cancer between Japanese and Chinese patients.

BACKGROUND AND OBJECTIVES: K-ras (Kirsten-ras) point mutation (PM) in codon 12 are suggested to be significantly associated with the tumorigenesis of pancreatic cancer. The incidences of K-ras PMs in human pancreatic cancer are reported to be different between Europeans and Japanese. The present study was designed to compare the incidences and profile of K-ras PMs and ras-p21 expression in primary invasive ductal carcinoma (IDC) of the pancreas between Japanese and Chinese. METHODS: The specimens included 51 Japanese and 34 Chinese patients with the primary IDC of the pancreas. K-ras PMs were tested by allele specific oligonucleotide dot blot hybridization methods and ras-p21 expression was stained by the immunohistochemical method. RESULTS: K-ras PMs were detected in 48 Japanese IDCs (94%) and in 24 Chinese ones (71%). There was a significant difference between the two groups. The GAT mutation was more frequent both in Japanese (61%, 33/54) and in Chinese (60%, 18/30) IDCs. The transitions/transversions ratio in the Japanese group was 2.4 in this study. By contrast, that in the Chinese group was 1.5. The expression of p21 was detected in 24 Japanese IDCs (47%) and in 24 Chinese IDCs (71%). There was a significant difference between the two groups. The expression of p21 and the patterns of K-ras PMs did not show any significant influence on the survival of the patients both in Japanese and Chinese. In the present study, Chinese IDC had a lower frequency of K-ras PMs in codon 12 than Japanese IDC. The pattern of K-ras PMs in Chinese IDC was different from that in Japanese and European IDC, respectively. CONCLUSIONS: Ki-ras PM and p21 expression were frequently seen both in Japanese and Chinese patients with pancreatic cancer. Factors such as lifestyle and environment may have influences on pancreatic carcinogenesis in various populations.

Aged↗
PubMed2000

Partial purification and characterization of 12-lipoxygenase in bullfrog erythrocytes.

12-Lipoxygenase (12-LO) in bullfrog (Rana catesbeiana) erythrocytes was purified partially by ion exchange chromatography and affinity chromatography. Bullfrog 12-LO was a single chain protein with a pI of 7.1-7.8 and MW of 7.77 kDa. This enzyme did not show typical Michaelis Menten type kinetics. At low substrate concentrations, it had a lag phase and at higher substrate concentrations, the activity was inhibited. The product of linoleic acid (LA), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), was an activator for the enzyme. When arachidonic acid (AA) was used as substrate, 13-HpODE also affected the Km of bullfrog 12-LO towards AA. The affinity of LA towards bullfrog 12-LO was higher than the affinity of AA. Suicide inactivation was much more rapid than that of any mammalian 12-LO reported. Hemoglobin (Hb) inhibited the activity of 12-LO partially and removing Hb eliminated this inhibition. Both Hb and Met-Hb inhibited the 12-LO activity but did not denatured completely the Hb, suggesting that the inhibition was a direct interaction between 12-LO and Hb protein chain and was not due to competition between 12-LO and Hb for oxygen. This study characterizes bullfrog 12-LO with respect to stability, optimal pH, suicide inactivation and interaction with Hb and provides important evolutionary information about this enzyme.

Animals↗
PubMed2000

In and out of the postsynaptic region: signalling proteins on the move.

Reversible translocation of signalling proteins to and from their sites of action has emerged as an important theme in signal transduction. The recent findings of the stimulus-induced translocation of Ca2+-calmodulin-dependent protein kinase II (CaMKII) and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor to and from the postsynaptic region are model cases for understanding how the dynamic localization of signalling proteins is used to regulate signal transduction.

Animals↗
PubMed2000

Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II.

Synaptic plasticity is thought to be a key process for learning, memory and other cognitive functions of the nervous system. The initial events of plasticity require the conversion of brief electrical signals into alterations of the biochemical properties of synapses that last for much longer than the initial stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin-dependent protein kinase IIalpha (CaMKII), sequentially translocates to postsynaptic sites, undergoes autophosphorylation and gets trapped for several minutes until its dissociation is induced by secondary autophosphorylation and phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation for several minutes. This suggests that trapping of CaMKII by its targets and priming of CaMKII translocation may function as biochemical memory mechanisms that change the signaling capacity of synapses.

Aniline Compounds↗
PubMed2000

Long-term effects of troglitazone: open-label extension studies in type 2 diabetic patients.

OBJECTIVE: To determine the long-term effects of troglitazone as monotherapy or in combination with sulfonylureas or insulin regarding glycemic and lipid measures. RESEARCH DESIGN AND METHODS: Patients who completed one of three double-blind studies (a 6-month troglitazone monotherapy study, a 52-week study of troglitazone in combination with micronized glyburide, or a 6-month study of troglitazone in combination with insulin) were allowed to enter open-label extensions of their respective double-blind studies. Troglitazone dose titrations were allowed to a maximum of 600 mg in response to inadequate glycemic control during the open-label phases of troglitazone monotherapy or sulfonylurea combination therapy but not with insulin combination therapy. This article focuses on the effectiveness of the highest dose of troglitazone used in these studies (600 mg daily). Safety data from all patients studied at all doses are also presented. RESULTS: For patients who received a fixed dose of 600 mg troglitazone, mean changes in fasting serum glucose and HbA1c levels from baseline to the end of the open-label phase were -57 mg/dl and -0.4%, respectively (monotherapy); -49 mg/dl and -1.8%, respectively (sulfonylurea combination); and -31 mg/dl and -1.0%, respectively (insulin combination). The proportion of patients achieving an HbA1c level of < or =8% from the combined cohort of all three studies was 54% versus only 19% at baseline. The mean decrease in triglycerides from baseline to the end of the open-label phase was 18% among all patients in the three studies who received a fixed dose of 600 mg troglitazone. Troglitazone was well tolerated in these three open-label studies; a total of 758 patients completed a total exposure of 16,264 patient-months to troglitazone in these three studies with minimal adverse events. CONCLUSIONS: Long-term use of troglitazone alone or in combination with sulfonylureas or insulin is safe and effective in sustaining glycemic control and in reducing hypertriglyceridemia in type 2 diabetic patients.

Blood Glucose↗
PubMed2000

Nonlinear pharmacokinetics of paclitaxel in ovarian cancer patients.

AIM: To characterize the disposition of paclitaxel in patients with ovarian carcinoma after a 3-h infusion. METHODS: Fifteen patients with advanced ovarian cancer were enrolled and were administered paclitaxel in a 3-h infusion at dosing levels of 135 mg/m2, 175 mg/m2, and 235 mg/m2. Thirteen plasma samples were obtained during the infusion and up to 24 h after the infusion. Paclitaxel concentrations in plasma were determined by HPLC assay. Pharmacokinetic parameters were assessed with noncompartment model and model-dependent method. RESULTS: The disposition of paclitaxel in patients with ovarian cancer conformed to a two-compartment model. The main pharmacokinetic parameters of three groups were T1/2 beta (5.18 +/- 3.49), (6.26 +/- 2.21), and (6.99 +/- 1.45) h, AUC (14.71 +/- 0.76), (39.09 +/- 13.10), and (66.52 +/- 12.23) mg.h.L-1, Cl (14.29 +/- 0.74), (7.52 +/- 2.15), and (6.25 +/- 1.93) L.h-1, respectively. CONCLUSION: The disposition of paclitaxel was nonlinear after a 3-h infusion. There was individual variability of metabolism among patients.

Adult↗
PubMed2000

[Influence of estrogen on the epithelial ovarian cancer cell lines in vitro].

OBJECTIVE: To study the effect of 17-beta estradiol on the growth of the epithelial ovarian carcinoma cell lines in vitro. METHODS: The proliferative capacity of the ovarian carcinoma cell lines CAOV3 and OVCAR3 in the culture medium with 17-beta estradiol was evaluated by the means of the mircoculture tetrazolium assay (MTT) and cell kinetics was analyzed by flow cytometry (FCM). The expression of estrogen receptor (ER) of the two cell lines was examined by the immunohistochemical staining. RESULTS: The growth of both two epithelial ovarian cancer cell lines was slightly inhibited by 17-beta estradiol (0.25-5.00 nmol/L), and the inhibitive rate was 6.3%-36.0%. FCM showed that the kinetics of the two cell lines were obviously changed. Comparing with the kinetics of CAOV3 without estradiol, the cell rate of Stage G0/G1 of CAOV3 with estradiol decreased from 55.0% to 19.0%-30.0%, cell rate of Stage S increased from 30.0% to 52.0%, cell rate of Stage G2/M increased from 14.0% to 17.0%-28.0%; In OVCAR3, cell rate of Stage C2/M decreased from 37% to 22.0%-30.0%, cell rate of Stage S increased from 31.0% to 38.0%-51.0%, cell rate of Stage C0/G1 did not changed much (cell rate without estradiol was 32.0%, while cell rate with estradiol 29.0%-31.0%). Estrogen receptors of the two cell lines were positive and not changed after cultured in the medium with 17-beta estradiol. CONCLUSION: The proliferate capacity of the two epithelial ovarian cancer cell lines CAOV3 and OVCAR3 can be inhibited by the estrogen (0.25-5.00 nmol/L), possibly through the change of the tumor cell kinetics.

Cell Cycle↗
PubMed2000

[Treatment and prognostic factors for stage IV epithelial ovarian cancer].

OBJECTIVE: The aim of the study was to evaluate the influence of surgical debulking and chemotherapy on survival in patients with stage IV epithelial ovarian cancer. METHODS: Medical records and follow-up sheets were retrospectively reviewed for all women with International Federation of Gynecology and Obstetrics stage IV epithelial ovarian cancer treated between January, 1982 and December, 1997 in our hospital. Survival analysis and comparison were performed using Kaplan-Meier method and t-test. The COX proportional hazards regression model was used to identify independent variables associated with survival improvement. RESULTS: Twenty-five women with stage IV epithelial ovarian cancer were available. Median age was 51 years (range 33-72 years). Papillary serous histology was found in 12/75 patients (48%). Thirteen patients (52%) had grade 3 tumors. Metastases by the International Federation of Gynecology and Obstetrics (FIGO) criteria were found in 7 cases in supraclavicular lymph node (28%), 6 cases in liver (24%) and 4 cases with malignant pleural effusion. All patients received surgical debulking with 9 cases (36%) having in optimal cytoreduction. Overall median survival of 15.0 months was achieved, while optimal debulked patients' median survival was 28.4 months compared to 14.7 months for the patients with bulky residual disease (P < 0.01). Median survival for the patients with 6 or more courses of chemotherapy postoperatively was 28.5 months, compared to 6.5 months for the patients with less than 6 courses (P < 0.01). Optimal debulking surgery and courses of chemotherapy retained significance as indepent predictors of survival based on multivariate analysis. CONCLUSION: Optimal surgical debulking and active postoperative chemotherapy appear to improve the prognosis of the patients with stage IV epithelial ovarian cancer under the premise of keeping quality of life.

Adult↗
PubMed2000

[Surgical treatment and prognostic analysis of 39 cases invasive vulvar cancer].

OBJECTIVE: To summarize the procedure of operations and evaluate the prognostic factors in the invasive vulvar cancer. METHODS: Thirty nine cases with invasive vulvar cancer admitted in our hospital from 1979 to 1997 were retrospectively analyzed. Three kinds of operations were used: 5 by local excision, 13 by modified radical vulvectomy and 21 by radical vulvectomy. Statistical package for social sciences (SPSS) was used to compare the different strategy of operation and analyze the prognostic factors. RESULTS: Thirty three patients (84.6%) had squamous cell carcinoma and 26 of them (78.8%) were well differentiated and 2 poorly differentiated. Seven cases (17.9%) were in FIGO stage I; 17 (43.6%) in stage II; 13 (33.3%) in stage III, and 2(5.1%) in stage IV, 58.3% of tumor in stage I and II were lateral while 73.3% of tumor in stage III and IV were median type. Hospitalization time for local excision, modified radical vulvectomy and radical vulvectomy (separated and en-bloc incision) were 9.1, 20.6, 41.2 and 62.2 days (P < 0.01) and the incision infection rate were 0%, 30.8%, 66.7% and 88.9% (P < 0.01) respectively. Median survival time for stage I, II, II and IV were 132.0, 121.5, 67.5 and 21.5 months (P = 0.01) and the 5-year survival rates of them were 85.7%, 70.6%, 46.2% and 0.0% (P < 0.05) respectively. Median survival time for patients with or without lymph nodes involvement were 66.0 and 121.5 months (P < 0.01) and the 5-year survival rates were 30.0% and 71.5% (P < 0.05) respectively. Median survival time for well or poor differentiation were 97.0 and 64.0 months (P > 0.05) and the 5-year survival rates were 62.0% and 43.0% (P > 0.05) respectively. CONCLUSIONS: The important prognostic factors for invasive vulvar cancer were sites(lateral/median), stage, differentiation and lymph nodes involvement. Individualized treatment should be considered.

Adult↗
PubMed2000

[Fiberoptic ductoscopy for patients with intraductal papillary lesions].

OBJECTIVE: To investigate the clinical significance of fiberoptic ductoscopy in patients with intraductal papillary lesions. METHODS: Fiberoptic ductoscopy was applied to patients with nipple discharge. The characteristics of those with intraductal papillary lesion were analysed. RESULTS: 92 patients were found to have intraductal papillary lesions. 68 patients were revealed to have single papillomas and 21 multiple papilloma. Three patients were diagnosed with papillomatosis. A total of 114 lesions were observed. 29.8% of these lesions were located in the segmental duct. 43.9% lesions were located in the first branch of the segmental duct and 17.5% in the second branch. Only 7.9% and 0.9% lesions were located in the third and the fourth branch. The average distance from lacteous pore to papillary lesion was 2.7 cm. Fiberoptic ductoscopy did not find lesions in 5 patients. CONCLUSIONS: Fiberoptic ductoscopy can be used to diagnose and locate intraductal papillary lesions. It is an effective diagnostic method for nipple discharge.

Adult↗
PubMed2000

[The diagnostic and prognostic values of assay of serum vascular endothelial growth factor in epithelial ovarian cancer].

OBJECTIVE: To detect the level of the preoperative serum vascular endothelial growth factor (VEGF) in patients with epithelial ovarian cancer, and to evaluate the correlation between preoperative serum VEGF level and prognosis of epithelial ovarian cancer. METHODS: Forty-one patients with epithelial ovarian cancer (EOC), 10 patients with borderline ovarian tumor (BOT), and 25 women with benign ovarian tumor (BET) were included as three study groups, while 20 healthy women were selected as a control group. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the serum VEGF level. RESULTS: The serum VEGF levels in patients with EOC were higher than those in patients with BOT, or with BET, or those in healthy women. The median and ranges of serum VEGF levels were as follows: EOC: median 415.0 pg/ml, range 110-2,120 pg/ml; BOT: median 312.5 pg/ml, range 100-1,250 pg/ml; BET: median 170 pg/ml, range 70-925 pg/ml; healthy women: median 165 pg/ml, range 100-735 pg/ml. When median preoperative serum VEGF levels were grouped by tumor stages, histological grade of tumor cells, histological type of the tumor, lymph node involvement, and omentum involvement, significant correlations between serum levels of VEGF and histological grade, lymph node involvement and omentum involvement were found. The patients with high serum VEGF appeared to be accompanied with poor 3-year survival. CONCLUSIONS: Preoperative serum VEGF levels seemed to be correlated with the malignant behavior of ovarian cancer, which might provide some prognostic value.

Adult↗
PubMed1999

A versatile microporation technique for the transfection of cultured CNS neurons.

The application of molecular techniques to cultured central nervous system (CNS) neurons has been limited by a lack of simple and efficient methods to introduce macromolecules into their cytosol. We have developed an electroporation technique that efficiently transfers RNA, DNA and other large membrane-impermeant molecules into adherent hippocampal neurons. Microporation allowed the use of either in vitro transcribed RNA or cDNA to transfect neurons. While RNA transfection yielded a higher percentage of transfected neurons and produced quantitative co-expression of two proteins, DNA transfection yielded higher levels of protein expression. Dextran-based calcium indicators also were efficiently delivered into the cytosol. Microporated neurons appear to survive poration quite well, as indicated by their morphological integrity, electrical excitability, ability to produce action potential-evoked calcium signals, and intact synaptic transmission. Furthermore, green fluorescent protein (GFP)-tagged marker proteins were expressed and correctly localized to the cytosol, plasma membrane, or endoplasmic reticulum. The microporation method is efficient, convenient, and inexpensive: macromolecules can be introduced into most adherent neurons in a 3 mm2 surface area while requiring as little as 1 microl of the material to be introduced. We conclude that the microporation of macromolecules is a versatile approach to investigate signaling, secretion, and other processes in CNS neurons.

Animals↗