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Biomedical subjects

M C Wu

Publications and source records attributed to M C Wu.

At least 55 records · Page 3Linked to original sources
PubMed1999

Chlorpromazine inhibits hepatocyte apoptosis caused by withdrawal of phenobarbital in mice.

AIM: To study the inhibitory effect of chlorpromazine (Chl), verapamil, and aspirin on hepatocyte apoptosis induced by the cessation of phenobarbital (Phe) treatment in mice. METHODS: Liver DNA content, ratio of liver weight/body weight, DNA fragmentation, DNA electrophoresis, the end-labeling test (TUNEL), and the morphologic changes of liver cells as indices of liver mass and hepatocyte apoptosis were applied to investigate (1) the kinetic process of hepatocyte proliferation induced by Phe 75 mg.kg-1 i.p. and the regression of hyperplastic liver caused by withdrawal of Phe in mice, (2) the effect of Chl 25 mg.kg-1, verapamil 50 mg.kg-1 or aspirin 60 mg.kg-1 i.p. on mouse hepatocyte apoptosis, and (3) the time course of effects of Chl on the regression of liver size and DNA fragmentation content after withdrawal of Phe. RESULTS: The process of hepatocyte proliferation and regression induced by administration and withdrawal of Phe in mice consisted of 4 phases: proliferation, plateau, rapid regression, and slow regression phases. In the rapid regression phase, the typic changes of hepatocyte apoptosis were found, which was prevented in early period by the Ca(2+)-calmodulin antagonist Chl, but not by verapamil or aspirin. CONCLUSION: The Ca(2+)-calmodulin played an important role in the hepatocyte apoptosis caused by withdrawal of Phe.

Animals↗
PubMed1998

Glial cell line-derived neurotrophic factor protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice.

To mimic chronic exposure to neurotoxins in inducing dopaminergic cell damage, multiple doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were injected in C57BL/6 mice. Effects of pre- and post-treatment with the glial cell line-derived neurotrophic factor (GDNF) by injections into the striatum were investigated. GDNF exerts protective and reverse effects on the dopaminergic damage, supporting the potential application of GDNF in prevention and treatment of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Cerebral perfusion in children with Alice in Wonderland syndrome.

Alice in Wonderland syndrome (AIWS) is characterized by visual hallucinations and bizarre perceptual distortions. Technetium-99m hexamethylpropyleneamine tomography (SPECT) brain scans were performed in four patients during the acute stage of AIWS. Two patients were demonstrated to have Epstein-Barr virus infections. One had abnormal (EEG) findings. The visual-evoked potential, cranial CT, and MRI findings were negative. The decreased cerebral perfusion areas in all patients were near the visual tract and visual cortex. All involved some regions of the temporal lobe. In most patients with AIWS, the EEG, CT, and MRI are unable to determine the precise pathologic areas. However, a SPECT brain scan may demonstrate abnormal perfusion areas and explain the clinical presentations.

Cerebrovascular Circulation↗
PubMed1998

The radiation induced magnetic resonance image intensity change provides a more efficient three-dimensional dose measurement in MRI-Fricke-agarose gel dosimetry.

A detailed methodology has been developed to map the spatial dose distribution in a Fricke-agarose gel based on the radiation induced image intensity change in the gel's magnetic resonance (MR) images. Besides the linear correlation between the change in the gel's spin-lattice relaxation rate and the absorbed dose, it is shown here that the radiation induced image intensity change for T1-weighted spin-echo images with TE << TR correlates exponentially to the absorbed dose. Furthermore, at the lower dose region (< 15 Gy), the correlation is fairly linear and its sensitivity is high. The minimum detectable dose is shown to be equivalent to the one obtained using the conventional R1-based approach. Since only one T1-weighted image is required for the dose evaluation, compared to the R1-based method, the total MR imaging time can be reduced from hours to a few minutes. This extensive time reduction avoids ferric ion diffusion effects and provides a practical way to simply and effectively measure the three-dimensional dose distribution using the Fricke-agarose dosimeter gel.

Gels↗
PubMed1998

Induction of hepatocyte proliferation and prevention of hepatocyte apoptosis by phenobarbital related to local humoral factor in mouse liver.

AIM: To study the association of phenobarbital (Phe) inducing hepatocyte proliferation and blocking hepatocyte apoptosis with local humoral factor in liver. METHODS: The ratio of liver/body weight, DNA content, regressive rate of hyperplastic liver, and DNA fragmentation were used to investigate whether the Phe-treated mouse liver extract (PMLE) and PMLE-95 (PMLE heated at 95 degrees C for 30 min) possessed Phe-like effects on mouse liver. Meantime, the effects of pretreatment with trypsin, RNAase, and DNAase on the activity of PMLE-95 were observed, and the differences of components between PMLE-95 and NMLE-95 (normal mouse liver extract, NMLE heated at 95 degrees C for 30 min) were analyzed with HPLC. RESULTS: PMLE-95 stimulated hepatocyte proliferation and prevented hepatocyte apoptosis caused by withdrawing Phe in mice, and the activity of PMLE-95 was eliminated after the pretreatment with trypsin. On the chromatograms PMLE-95 had 5 main peaks, while NMLE-95 had only 4 peaks. CONCLUSION: The effects of Phe on the liver were mediated by an intrinsic protein or peptide substance produced in response for the stimulation of Phe in mouse liver.

Animals↗
PubMed1998

Decreased expression of the adenomatous polyposis coli (Apc) and mutated in colorectal cancer (Mcc) genes in mouse lung neoplasia.

A decrease in the intracellular concentrations of the transcripts for some tumor suppressor genes has been found during murine lung tumorigenesis; for p15INK4b and p16INK4a, this was due to homozygous deletions. We report here a decrease in the mRNA levels of the mutated in colorectal cancer (Mcc) and adenomatous polyposis coli (Apc) genes in mouse lung tumors and some neoplastic cell lines. This was assessed both by northern blotting and reverse transcriptase-polymerase chain reaction of RNA isolated from lung tumors that had been induced by urethane, N-nitrosodiethylamine, or 3-methylcholanthrene in (A/J x C57BL/6) F1 or A/J mice. A reduced amount of both Mcc and Apc messages was also seen when two neoplastic cell lines, a spontaneous transformant (E9) and a line derived from a chemically induced solid tumor (82-132), were compared with two independently derived nontumorigenic cell lines (E10 and C10); E9 was derived from E10, and all of these lines are probably of alveolar type 2 cell origin. A cell line derived from a chemically induced papillary lung tumor probably of bronchiolar Clara cell origin (LM2) had Mcc mRNA levels similar to those of C10 and E10 but reduced Apc mRNA levels. A line (p53-823) derived from a papillary tumor that arose in a mouse with a mutated p53 transgene had a reduced amount of the Mcc gene product only. These differential changes in the relative amounts of Apc and Mcc messages in LM2 and p53-823) cells may serve as useful models for studying the regulation of their expression. Both messages had half-lives of 6-9 h in normal E10 and neoplastic E9 cells, so decreased message stability does not account for these reductions. This is the first report of estimated degradation rates of these mRNAs. Apc and Mcc message content did not vary as a function of growth status of the cell lines. Single-strand conformation polymorphism analysis did not reveal mutations in Apc coding regions known to have a high mutation frequency in human colon tumors. Loss of heterozygosity of Apc and Mcc was not found in tumors that developed in the F1 mice, implying a lack of allelic deletions. These changes in tumor suppressor gene expression may contribute to the development and maintenance of neoplasia in lung epithelium.

Animals↗
PubMed1997

Genome wide search for genetic damage in p53 transgenic mouse lung tumours reveals consistent loss of chromosome 4.

The tumour which develops most frequently in mice carrying a p53 Val135 transgene is adenocarcinoma of the lung. We established 10 cell lines from these tumours and investigated their karyotypes by detailed cytogenetic analysis using a complete set of mouse chromosome-specific paints. Consistent loss of chromosome 4 material was noted in 9 out of 10 cell lines; this loss was detected in tetraploid but not diploid cells of the same cell line, suggesting that mouse chromosome 4 plays a critical role in the progression of lung adenocarcinomas. Other frequently observed chromosome aberrations involved chromosomes 7, 5 and 8. Atypical bronchial epithelium was observed together with lung tumours and in tumour-free, apparently normal lungs indicating that mouse lung tumours induced due to the presence of a mutant p53 transgene may develop via pre-invasive lesions and thus may be effective models for the study of lung tumour progression.

Adenocarcinoma↗
PubMed1997

Effective tumor vaccines generated by in vitro modification of tumor cells with cytokines and bispecific monoclonal antibodies.

Antitumor immune responses are mediated primarily by T cells. Downregulation of the major histocompatibility complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation. In vitro treatment with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells in vitro. Immunization with the modified tumor cells elicits an immune response mediated by CD8+ T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy.

Animals↗
PubMed1997

Atrophic pigmented dermatofibrosarcoma presenting as infraorbital hyperpigmentation.

BACKGROUND: Pigmented dermatofibrosarcoma is a rare tumor of the skin and constitutes 1-5% of all dermatofibrosarcoma. Most cases present as polypoid multinodular growth. Occasional cases may be atrophic. We report an extraordinary case with progressive infraorbital atrophy. OBSERVATION: A 24-year-old woman came to us for a diffuse bluish atrophic lesion over the left infraorbital area. The lesion progressed gradually over 2 years. Histologic examination revealed mature spindle cell proliferation in the lower dermis and hypodermis. Interspersed were some heavily pigmented melanocytes. CONCLUSION: We report an unusual case of progressive bluish discoloration and atrophy of the infraorbital area. This is a rare manifestation of dermatofibrosarcoma.

Adult↗
PubMed1996

An evaluation of the accuracy of magnetic-resonance-guided Gamma Knife surgery.

An evaluation of the systematic accuracy of magnetic resonance (MR)-guided Gamma Knife surgery was performed. In two experiments, a cylinder phantom filled with dosimeter gel containing ferrous sulfate was fixed to a stereotactic frame. The gel phantom was irradiated with the Gamma Knife with a single shot using 4-mm collimators. The target point was set at the frame center of the stereotactic system giving coordinate values of X = 100, Y = 100, Z = 100. The maximum target dose was 15 Gy. MR imaging was undertaken immediately after the irradiation, using a superconductive 1.5-T MR scanner. Spin echo T1-weighted images, with transaxial, coronal, and sagittal views, were obtained. On the images, points with the highest signals were defined as the target point which received the maximum dose. Within the dose range of the experiment, this definition is based on a linear relationship between the dose to the gel and the T1 relaxation shortening after irradiation. The distances between the frame center and the target point defined on the MR images in the experiments were 0.12 mm (0.2375 pixels) and 0.43 mm (0.8515 pixels), respectively. Both are within the mechanical accuracy of the Gamma Knife. The imaging study confirms the accuracy of the Gamma Knife surgery used in the institution.

Evaluation Studies as Topic↗
PubMed1995

Interaction of cationic liposomes with cells of electrically active neuronal networks in culture.

Incubation of rhodamine-labeled cationic liposomes with mature murine spinal cultures results in strong fluorescence that is evenly distributed on somata and neurites of neurons in 7 different cultures. Staining of the glial carpet is minimal. Rhodamine-labeled dextran, encapsulated in liposomes, also stains neurons. Electron microscope data show external attachment and intact internalization of liposomes. Spontaneous electrical bursting activity is altered but not lost after incubation.

Animals↗
PubMed1995

The use of neuronal networks on multielectrode arrays as biosensors.

Mammalian spinal neuronal networks growing on arrays of photoetched electrodes in culture provide a highly stable system for the long-term monitoring of multichannel, spontaneous or evoked electrophysiological activity. In the absence of the homeostatic control mechanisms of the central nervous system, these networks show remarkable sensitivities to minute chemical changes and mimic some of the properties of sensory tissue. These sensitivities could be enhanced by receptor up-regulation and altered by the expression of unique receptors. The fault-tolerant spontaneous network activity is used as a dynamic platform on which large changes in activity signify detection of chemical substances. We present strategies for the expression of novel supersensitivities to foreign molecules via genetic engineering that involves the grafting of ligand binding cDNA onto truncated native receptor DNA and the subsequent expression of such chimeric receptors.

Animals↗
PubMed1995

Inference for the association between coefficients in a multivariate growth curve model.

This paper generalizes the work of Blomqvist (1977, Journal of the American Statistical Association 72, 746-749) on inference for the relationship between the individual-specific slope and the individual-specific intercept in a linear growth curve model. The paper deals with longitudinal data involving one or more response variables and irregular follow-up times, with each response variable postulated to follow a linear growth curve model. The problem considered is inference concerning the association between one growth curve coefficient and another--for example, the slope and intercept for a selected response variable, or the two slopes for two different response variables--after adjusting for all remaining coefficients among all of the response variables. An inferential approach based on the method of moments and an inferential approach based on maximum likelihood are described, and the asymptotic properties of these procedures are presented. Extensions of the methodology to allow polynomial growth curves and baseline covariates are outlined. The methodology is illustrated with a practical example arising from a clinical trial in lung disease.

Body Height↗
PubMed1994

Use of surrogate information time for monitoring the effect of treatment on the change in a response variable in clinical trials.

We discuss the monitoring of clinical trials data and propose two surrogates for total information for use with the spending function approach where there are repeated measurements and we wish to compare the rates of change in a response variable under different treatments. These surrogates are applied to a setting similar to the Lung Health Study. Although the surrogates do not require estimation of the variance parameters, they do require some knowledge of the ratio R of the within- to the between-individual variances. The effects of overestimating and underestimating R are illustrated. In situations of uncertainty we recommend overestimating R, to provide a conservative estimate of information time at each interim analysis.

Adult↗
PubMed1994

Point mutations in the chloroplast 16s rRNA gene confer streptomycin resistance in Nicotiana plumbaginifolia.

In a previous paper we reported the isolation of streptomycin-resistant mutants from Nicotiana plumbaginifolia and presented evidence for chloroplast control of the resistance trait. To understand the molecular basis of the resistance in these mutants, we sequenced three regions in the chloroplast 16s rRNA gene, which correspond to the 5' terminus, the 530 loop, and the 900 stem/loop of Escherichia coli 16s rRNA, and compared them with the sequences of the wild-type. Our results show that: (1) nine mutants have a C to T change at position 912, (2) one mutant (SR1021) has a G to A change at position 885, (3) one mutant has a C to T change at position 526, based on E. coli numbering; and (4) three mutants do not have any change in the regions analyzed. The point mutation detected in SR1021 has not been reported previously. In E. coli 16s rRNA, position 885 is protected from chemical probing by ribosomal protein S12 and is closely juxtaposed with the streptomycin-binding region (positions 912-915) in the predicted secondary structure. It is likely that the G to A transition at this position is a novel mutation for streptomycin resistance.

Amino Acid Sequence↗
PubMed1994

Production and characterization of antibodies against C-terminal peptide of protein F1: a novel phosphorylation at serine 209 of the peptide by protein kinase C.

Protein F1 (GAP-43, B-50, neuromodulin, P-57), a neural tissue-specific phosphoprotein enriched in the growth cones of elongating neurites, is suggested to be involved in synaptic plasticity, neuronal development, and neurotransmitter release. In this study, a 21 amino acid polypeptide (AKPKES*ARQDEGKEDPEADQE) that corresponds to the C-terminus sequence of protein F1 (from position 204-224) was synthesized and used to produce anti-protein F1 antibodies. Immunoblot analysis has demonstrated that the prepared antibodies recognized intact protein F1. Protein F1 and the synthesized F1 peptide were phosphorylated in vitro by PKC. Furthermore, phosphorylated protein F1 was immunoprecipitated by anti-F1 peptide antibodies demonstrating that these antibodies recognized both native, non-phosphorylated and phosphorylated protein. The anti-protein F1 antibodies also stained the plasma membranes of cell bodies and neuritis of mouse neuronal cultures obtained from 14-day old spinal embryonic tissue. By contrast, no glial cells were stained. These data suggest that serine 209 at the C-terminus of protein F1 may be a substrate for PKC phosphorylation in vivo. In addition, antibodies raised against F1 peptide revealed protein F1 immunoreactivity that outlined all neurites of cultured mouse spinal neurons.

Amino Acid Sequence↗