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Biomedical subjects

M Tan

Publications and source records attributed to M Tan.

At least 73 records · Page 4Linked to original sources
PubMed1999

Heregulin beta1-activated phosphatidylinositol 3-kinase enhances aggregation of MCF-7 breast cancer cells independent of extracellular signal-regulated kinase.

Heregulin (HRG) is a family of polypeptide growth factors derived from alternatively spliced genes. HRG can bind to receptor tyrosine kinases erbB3 and erbB4, thereby inducing erbB3 and erbB4 heterodimerization with erbB2, leading to receptor tyrosine phosphorylation and activating downstream signal transduction. Cell-cell homophilic adhesion (cell aggregation) is important in determining the structural organization and behavior of cells in tissues. In addition, tumor cell homophilic adhesion may affect invasive and metastatic potentials of cells. We report that HRG-beta1 can enhance aggregation of MCF-7 and SKBR3 human breast cancer cells. While investigating the downstream signals involved in HRG-beta1-enhanced cell aggregation, we observed that HRG-beta1 induced tyrosine phosphorylation of erbB2 and crbB3 receptor heterodimers and increased the association of the dimerized receptors with the 85-kDa subunit of phosphatidylinositol 3-kinase (PI3K). HRG-beta also increased the kinase activities of extracellular signal-regulated protein kinase (ERK) and PI3K in these cells. By using the mitogen-activated protein kinase/ERK 1 (MEK1) inhibitor PD98059 and PI3K inhibitors wortmannin and LY294002, we found that blocking the MEK1-ERK pathway had no effect on HRG-pbeta1-enhanced cell aggregation; however, blocking the PI3K pathway greatly inhibited HRG-beta1-mediated cell aggregation. Our study indicated that the HRG-beta1-activated MEK1-ERK pathway has no demonstrable role in the induction of cell aggregation, whereas HRG-beta1-activated PI3K is required for enhancing breast cancer cell aggregation. Because aggregation can contribute to invasion/metastasis phenotype of cancer cells, our results have provided one mechanism by which HRG-beta1-activated signaling of erbB receptors may affect invasive/metastatic properties of MCF-7 and SKBR3 breast cancer cells.

Breast Neoplasms↗
PubMed1999

Transcriptional activation of the human S100A2 promoter by wild-type p53.

S100A2, a calcium binding protein of the EF-hand family, was recently identified to be inducible by etoposide, a p53 activator. A potential p53 binding site was identified in the promoter of the S100A2 gene, which binds to purified p53 as well as p53 in nuclear extract activated by etoposide. Transactivation assays using the promoter driven luciferase reporters revealed that the S100A2 promoter was transcriptionally activated by wild-type p53, but not by p53 mutants, in a dose-dependent as well as a p53 binding site-dependent manner. The p53-induced transactivation of the S100A2 promoter was enhanced by etoposide and blocked by a dominant negative p53 mutant. Furthermore, endogenous S100A2 mRNA expression is induced by etoposide in p53 positive, but not in p53 negative cells. Thus, p53 appears to positively regulate S100A2 expression.

Binding Sites↗
PubMed1999

Anal pressures impaired by stapler insertion during colorectal anastomosis: a randomized, controlled trial.

PURPOSE: The significance of anal sphincter injury from transanal inserted staplers was studied. A randomized, controlled comparison was made of anorectal manometry and clinical function after sigmoid colectomy (avoiding nerve injury from rectal mobilization), anastomosed by either transanal inserted stapler or biofragmentable anastomotic ring (avoiding anal manipulation). METHOD: Fifty-eight consecutive patients with sigmoid adenocarcinoma were randomly assigned to transanal inserted stapler or biofragmentable anastomotic ring groups. Anorectal manometry and clinical bowel function assessment were performed by an independent blinded observer before surgery and six weeks and six months after surgery. RESULTS: At six weeks after surgery, there was significant impairment of mean anal resting pressures (mean impairment, 23 percent; P < 0.001) and physiologic anal length (mean impairment, 31 percent; P < 0.01) in the transanal inserted stapler group (27 completed the trial), but not in the biofragmentable anastomotic ring group (18 completed the trial). Pressures remained impaired at six months. When changes in the anal pressures were compared between groups, the mean anal resting pressure (P < 0.001) and maximum squeeze pressure (P < 0.01) at six weeks and mean anal resting pressure at six months (P < 0.01) were significantly more impaired in the transanal inserted stapler group. Postoperative bowel function was not different between the two groups. Postoperative complications were similar. In the transanal inserted stapler group one patient died of anastomotic leak sepsis and one had wound infection; in the biofragmentable anastomotic ring group one patient died of myocardial infarct and one had wound infection. CONCLUSION: Direct injuries to the internal anal sphincter occurred after transanal inserted stapler but not biofragmentable anastomotic ring anastomoses. Clinical function was not correspondingly affected, probably because of the adequate residual rectal reservoir after sigmoid colectomy.

Adenocarcinoma↗
PubMed1999

Determination of trace elements in tissue of human uterine cancer by instrumental neutron activation analysis.

In this article, the low-temperature freeze-drying pretreated technique and instrumental neutron activation analysis were used to determine 29 trace elements in samples of human uterine cancer tissue. The content of these trace elements in uterine cancer tissue was compared with that in cervicitis tissue and in healthy tissue, respectively. Preliminary results indicated that significant differences in contents of Au, I, and Se were observed in these tissues.

Female↗
PubMed1999

Determination of zinc contents in rabbits with cerebral ischemia by NAA and ICP-AES.

Cerebral ischemia is an important cerebral vascular disease, and zinc is a necessary trace element for humans. In this work, a cerebral ischemia model of rabbit was established by operation. The samples of brain and serum in the animal models were collected. The Zn contents in the samples were determined by neutron activation analysis and inductively coupled plasma-atomic emission spectrometry. The results show the Zn contents in brain decreased 2 mo after cerebral ischemia, and Zn contents in serum decreased even more obviously. In addition, a positive correlation of Zn contents between left and right cerebral hemispheres was observed, and the positive correlation between brain and serum was also observed. A test of Chinese medicine was also carried out in the work. Two Chinese medicines were fed to rabbits with cerebral ischemia in the experiments. The results showed they probably can prevent the decrease of Zn contents in serum.

Animals↗
PubMed1999

Changing glomerular filtration with progression from impaired glucose tolerance to Type II diabetes mellitus.

Glomerular filtration rate (iothalamate clearance) was measured serially for 48 months in 26 Pima Indians with impaired glucose tolerance and 27 with normal glucose tolerance. At baseline, the mean glomerular filtration rate (SEM) was 133+/-8 ml/min in subjects with impaired glucose tolerance and 123+/-5 ml/min in those with normal glucose tolerance (p = 0.12). In the 12 subjects with impaired glucose tolerance who progressed to Type II (non-insulin-dependent) diabetes during follow-up, mean glomerular filtration rate increased by 30% (p = 0.011). Among the remaining 14 subjects with impaired glucose tolerance, 12 reverted to normoglycaemia. The glomerular filtration rate both at baseline and after 48 months in this subgroup exceeded the values of subjects with normal glucose tolerance by 20 % (p = 0.008) and 14% (p=0.013), respectively. A pronounced rise in the glomerular filtration rate occurs at the onset of Type II diabetes but a trend to hyperfiltration is also present in those with impaired glucose tolerance.

Analysis of Variance↗
PubMed1999

Interpatient variability in bioavailability of the intravenous formulation of topotecan given orally to children with recurrent solid tumors.

PURPOSE: Evaluation of inter- and intrapatient variability of topotecan oral bioavailability and disposition was performed in children with malignant solid tumors. PATIENTS AND METHODS: Topotecan i.v. formulation was given orally on schedules of daily for 21 consecutive days (d x 21) or daily for 5 days per week for 3 weeks [(d x 5)3], in both cases repeated every 28 days. Topotecan doses of 0.8 and 1.1 mg/m2 per day were evaluated on both schedules. Serial plasma samples were obtained after oral and i.v. administration of topotecan at the beginning and end of the first course of therapy. Topotecan lactone and total concentrations were measured by a high-performance liquid chromatography (HPLC) assay, and a one-or two-compartment model was fit to the plasma concentration-time data after oral or i.v. administration, respectively. Topotecan oral bioavailability (F) was calculated as the ratio of the AUC determined after oral treatment (AUCpo) divided by the AUC calculated after i.v. administration. RESULTS: Pharmacokinetics studies were performed on 15 and 11 patients receiving 0.8 and 1.1 mg/m2 per day, respectively. After oral administration the topotecan lactone AUCpo and F determined for 0.8 and 1.1 mg/m2 per day were 13.6 +/- 5.8 and 25.1 +/- 12.9 ng ml(-1) h and 0.34 +/- 0.14 and 0.34 +/- 0.16, respectively. The within-patient variance for AUCpo and F was much smaller than the between-patient variance. The ratio of topotecan lactone to total concentration was consistently higher after oral as compared with i.v. administration. CONCLUSIONS: Large interpatient variability was noted in topotecan pharmacokinetics, whereas intrapatient variability was relatively small. Further studies of oral topotecan are warranted to evaluate the tolerance of shorter courses and to define further the interpatient variability.

Administration, Oral↗
PubMed1999

Nitric oxide mediates the lipopolysaccharide dependent upregulation of the heme oxygenase-1 gene expression in cultured rat Kupffer cells.

BACKGROUND/AIMS: Heme oxygenase catalyzes the rate-limiting enzymatic step of heme degradation. The inducible isoform of heme oxygenase, heme oxygenase-1, is expressed at a low level in most tissues and is upregulated by its substrate heme and various stress stimuli. Kupffer cells which represent the largest population of the body's tissue macrophages serve physiological functions in the defense against various pathogens such as lipopolysaccharide. The goal of the present study was to investigate the heme oxygenase-1 gene expression in Kupffer cells of rat liver and in isolated Kupffer cell cultures during treatment with lipopolysaccharide. METHODS: Cryostat sections of normal rat liver were investigated by immunofluorescence double-staining using specific antibodies for rat heme oxygenase-1 and ED2. Isolation and cell culture of Kupffer cells and primary hepatocytes from rat liver, as well as Northern and Western blot analysis, were performed with standard protocols. RESULTS: Heme oxygenase-1 protein was highly expressed in large sinusoidal cells of normal rat liver, which were identified as Kupffer cells by staining with the macrophage surface marker ED2. By contrast, no expression of heme oxygenase-1 was detected in liver parenchymal cells. High expression of heme oxygenase-1 was also found in isolated Kupffer cells in culture by immunocytochemical staining as well as by Western and Northern blot analysis. After treatment of Kupffer cells cultures with lipopolysaccharide, heme oxygenase-1 was upregulated on the protein and mRNA level in a time- and dose-dependent manner. This increase in heme oxygenase-1 expression by lipopolysaccharide was prevented by the nitric oxide inhibitor N(G)-monomethyl-L-arginine which was reversed by an excess of L-arginine. Various nitric oxide donors up-regulated heme oxygenase-1 mRNA expression in Kupffer cells. CONCLUSIONS: The lipopolysaccharide-dependent upregulation of the heme oxygenase-1 gene which is highly expressed in Kupffer cells is mediated by a nitric oxide-dependent mechanism.

Animals↗
PubMed1999

Natural history of primary Epstein-Barr virus infection in children of mothers infected with human immunodeficiency virus type 1.

The natural history of Epstein-Barr virus (EBV) infection in 556 infants born to 517 human immunodeficiency virus (HIV) type 1-infected mothers was studied in a prospective, multicenter, cohort study. HIV-1-infected children had a cumulative EBV infection rate similar to HIV-1-uninfected children at age 3 years (77.8% vs. 84. 9%) but had more frequent oropharyngeal EBV shedding (50.4% vs. 28. 2%; P<.001). The probability of shedding decreased with longer time from EBV seroconversion and was similar to that of HIV-1-uninfected children 3 years after seroconversion. HIV-1-infected children identified as rapid progressors shed EBV more frequently than nonrapid progressors (69.4% vs.41.0%; P=.01). HIV-1-infected children with EBV infection had higher mean CD8 cell counts. EBV infection did not have an independent effect on mean CD4 cell counts, percent CD4, IgG levels, HIV-1 RNA levels, lymphadenopathy, hepatomegaly, or splenomegaly. Early EBV infection is common in children born to HIV-1-infected mothers. Children with rapidly progressive HIV-1 disease have more frequent EBV shedding.

Black or African American↗
PubMed1999

Consistency, inter-rater reliability, and validity of 441 consecutive mock oral examinations in anesthesiology: implications for use as a tool for assessment of residents.

BACKGROUND: Oral practice examinations (OPEs) are used extensively in many anesthesiology programs for various reasons, including assessment of clinical judgment. Yet oral examinations have been criticized for their subjectivity. The authors studied the reliability, consistency, and validity of their OPE program to determine if it was a useful assessment tool. METHODS: From 1989 through 1993, we prospectively studied 441 OPEs given to 190 residents. The examination format closely approximated that used by the American Board of Anesthesiology. Pass-fail grade and an overall numerical score were the OPE results of interest. Internal consistency and inter-rater reliability were determined using agreement measures. To assess their validity in describing competence, OPE results were correlated with in-training examination results and faculty evaluations. Furthermore, we analyzed the relationship of OPE with implicit indicators of resident preparation such as length of training. RESULTS: The internal consistency coefficient for the overall numerical score was 0.82, indicating good correlation among component scores. The interexaminer agreement was 0.68, indicating moderate or good agreement beyond that expected by chance. The actual agreement among examiners on pass-fail was 84%. Correlation of overall numerical score with in-training examination scores and faculty evaluations was moderate (r = 0.47 and 0.41, respectively; P < 0.01). OPE results were significantly (P < 0.01) associated with training duration, previous OPE experience, trainee preparedness, and trainee anxiety. CONCLUSION: Our results show the substantial internal consistency and reliability of OPE results at a single institution. The positive correlation of OPE scores with in-training examination scores, faculty evaluations, and other indicators of preparation suggest that OPEs are a reasonably valid tool for assessment of resident performance.

Anesthesiology↗
PubMed1999

Robustness of the latent variable model for correlated binary data.

The marginal regression model offers a useful alternative to conditional approaches to analyzing binary data (Liang, Zeger, and Qaqish, 1992, Journal of the Royal Statistical Society, Series B 54, 3-40). Instead of modelling the binary data directly as do Liang and Zeger (1986, Biometrika 73, 13-22), the parametric marginal regression model developed by Qu et al. (1992, Biometrics 48, 1095-1102) assumes that there is an underlying multivariate normal vector that gives rise to the observed correlated binary outcomes. Although this parametric approach provides a flexible way to model different within-cluster correlation structures and does not restrict the parameter space, it is of interest to know how robust the parameter estimates are with respect to choices of the latent distribution. We first extend the latent modelling to include multivariate t-distributed latent vectors and assess the robustness in this class of distributions. Then we show through a simulation that the parameter estimates are robust with respect to the latent distribution even if latent distribution is skewed. In addtion to this empirical evidence for robustness, we show through the iterative algorithm that the robustness of the regression coefficents with respect to misspecifications of covariance structure in Liang and Zeger's model in fact indicates robustness with respect to underlying distributional assumptions of the latent vector in the latent variable model.

Algorithms↗
PubMed1999

[Identification of medicinal and edible tender shoots of Aralia in China].

OBJECTIVE: To Study the identification of medicinal and edible tender shoots of Aralia in China. METHODS: Morphological identification and differential thermal analysis(DTA). RESULTS: Important morphological and DTA features for identification were found. CONCLUSION: It is difficult to identify these tender shoots merely on morphological characteristics, but the combination of morphological features with distinctive aspects of DTA curve helps distinguish these species and give an identification index.

Aralia↗
PubMed1999

[Analysis for the auditory brainstem responses of guinea pigs with wavelet transform].

OBJECTIVE: To fine out the advantages of wavelet transform when it is applied in analysis of auditory brainstem responses. METHOD: Thirty of male, albino guinea pigs weighing 300 to 400 g were divided into three groups: 1. normal hearing; 2. conductive hearing loss; 3. sensorineural hearing loss. ABR of the animals was collected and represented with wavelet transform respectively. The signals before and after being transferred was contrasted and dealt with statistics. RESULT: The ABR signals are distorted in wavelet transform scale 2 and background noises are increased in scale 4. The conventional time feature of ABR signals can be conserved and the present of I wave can be increased in wavelet transform scale 3. CONCLUSION: Wavelet transform scale 3 is proper to analyze the ABR signals of guinea pig. Compared with conventional method, it can conserve the ABR signal's time feature and increase the emerged rate of I wave.

Animals↗
PubMed1999

[Study on GMA-DNA adducts in vivo].

OBJECTIVE: To investigate whether glycidly mechacrylate (GMA-DNA) adducts can be produced in various organs of rat in vivo. METHODS: Rats divided into 5 groups were orally administrated with mutagen, GMA 31.25, 62.5, 125, 250 mg/kg respectively for 14 days. DNA adducts produced in liver, kidney, white blood cells and testis had been analyzed by nuclease P1 mediated 32P-postlabelling method. RESULTS: Several GMA-DNA adducts were formed in various organs (in white blood cells, 4 types, liver and kidney, 3 types and testis 1 type). The amount of GMA-DNA adducts increased with GMA dosage within 0-125 mg/kg dosages, degree of the overall level of GMA-DNA adducts in various organs were kidney > liver > white blood cells > testis. N3-methacrylate-2-hdroxypropyl-deoxycytidine monophosphate was found in kidney, liver and white blood cells. CONCLUSIONS: GMA with electrophilic group could react with negatively charged centers on DNA and form GMA-DNA adducts.

Animals↗
PubMed1998

The two gamma-tubulin-encoding genes of the ciliate Euplotes crassus differ in their sequences, codon usage, transcription initiation sites and poly(A) addition sites.

We have isolated and sequenced two gamma-tubulin (gamma-Tub)-encoding macronuclear genes of the ciliate Euplotes crassus (Ec), as well as their corresponding cDNAs. Our results reveal that the two genes (gamma-tub 1 and gamma-tub 2) have introns in homologous positions, but differ in their sequences, codon usage, transcription initiation sites and poly(A) addition sites. They both consist of three exons, two introns and two short non-coding sequences on both ends, and they both code for polypeptides of 462 amino acids (aa). The two genes share 76% identity at the nucleotide (nt) level, 86% at the deduced aa level and show 61-92% aa homology to the gamma-Tubs of other organisms. The gamma-tub 2 gene contains two in-frame UGA codons which, like UGA codons in other Euplotes genes, probably code for cysteines. No UGA triplet was found in the gamma-tub 1 gene. Further studies on the cDNA ends indicate that gamma-tub 1 uses at least three transcription initiation sites and two poly(A) addition sites. In contrast, only one transcription initiation site and one poly(A) addition site were identified in gamma-tub 2.

Amino Acid Sequence↗