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Biomedical subjects

M F Wu

Publications and source records attributed to M F Wu.

At least 19 recordsLinked to original sources
PubMed2006

An open, multi-centre, phase II clinical trial to evaluate the efficacy and safety of paclitaxel, UFT, and leucovorin in patients with advanced gastric cancer.

The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.

Adult↗
PubMed2006

Photocatalysis of 2,2',3,4,4',5'-hexachlorobiphenyl and its intermediates using various catalytical preparing methods.

Four etching solutions used on support materials and two coating methods of TiO(2) were conducted to investigate the effects of catalytical preparing methods on the photocatalysis of 2,2',3,4,4',5'-hexachlorobiphenyl (PCB congener 138). The results of XRD analyses confirmed that various etching solutions used on support substrates did not influence the characteristics of titanium(IV) oxide. The XRD patterns of crystallization for the catalysts before and after purification remained unchanged. Hydrofluoric acid used as an etching solution for the support substrates provided the best adhesion stability for the catalysts that demonstrated the highest photocatalytic efficiency for congener 138. Xenon and ultraviolet lamps were used to compare the irradiation effect on photocatalysis. The shortest half-lives of congener 138 were 7.4 and 12.2 h using xenon and UV reactors, respectively. Lower chlorinated biphenyls (lower congener numbers) were identified through the continuous dechlorination of congener 138. PCB congeners 99, 87, 66, 49, 28, 17, 9, and 7 were detected as a result of dechlorination from higher chlorinated congeners to lower chlorinated congeners along with the extension of exposure times. The concentrations of chloride ion were increased with increasing exposure time through dechlorination, while the concentrations of organic chlorine of congener 138 were decreased. Meta-dechlorination was the most commonly found mechanism for the photocatalysis of PCB 138. The activation energy of the photocatalysis of congener 138 was 70.8 kJ mol(-1).

Catalysis↗
PubMed2005

Prolonged membrane potential depolarization in cingulate pyramidal cells after digit amputation in adult rats.

The anterior cingulate cortex (ACC) plays an important role in higher brain functions including learning, memory, and persistent pain. Long-term potentiation of excitatory synaptic transmission has been observed in the ACC after digit amputation, which might contribute to plastic changes associated with the phantom pain. Here we report a long-lasting membrane potential depolarization in ACC neurons of adult rats after digit amputation in vivo. Shortly after digit amputation of the hind paw, the membrane potential of intracellularly recorded ACC neurons quickly depolarized from approximately -70 mV to approximately -15 mV and then slowly repolarized. The duration of this amputation-induced depolarization was about 40 min. Intracellular staining revealed that these neurons were pyramidal neurons in the ACC. The depolarization is activity-dependent, since peripheral application of lidocaine significantly reduced it. Furthermore, the depolarization was significantly reduced by a NMDA receptor antagonist MK-801. Our results provide direct in vivo electrophysiological evidence that ACC pyramidal cells undergo rapid and prolonged depolarization after digit amputation, and the amputation-induced depolarization in ACC neurons might be associated with the synaptic mechanisms for phantom pain.

Journal Article↗
PubMed2004

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer.

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

Adult↗
PubMed2002

The stage-dependent inhibitory effect of porcine follicular cells on the development of preantral follicles.

The objective of this study was to examine the effects of follicular cells on the in vitro development of porcine preantral follicles. In Experiment 1, one preantral follicle alone (Trt 1) was cocultured with a follicle of the same size with oocytes (Trt 2) or without oocytes (Trt 3). Preantral follicles cultured alone in vitro for 12 days had greater follicle diameters (1017 +/- 96 microm versus 706 +/- 69 or 793 +/- 72 microm, P < 0.05), growth rates (201 +/- 0.3 versus 103 +/- 0.2 or 128 +/- 0.2, P < 0.05) and oocyte survival rates (73% versus 48, or 25%, P < 0.05) than other groups. The inhibitory effects of follicle cells on the growth of preantral follicles and oocyte survival rates were not enhanced by the addition of oocytectomized preantral follicles (Experiment 2). Follicles were cocultured with different sources of follicular cells in other experiments. Coculture with cumulus cells enhanced oocyte survival compared to the control (without coculture) and mural follicular cell groups (Experiment 3). The growth and survival rates of oocytes collected from the group of follicles cocultured with cumulus cells from large antral follicles (>3 mm) were greater (P < 0.05) than those from small antral follicles (<3 mm), or than the control group (without cumulus cells, experiment 4). No significant differences in the follicular diameters (674 +/- 30 microm versus 638 +/- 33 and 655 +/- 28 microm) and growth rate (105% versus 94 and 105%) were observed among the preantral follicles of the different treatments (P > 0.05). Taken together, coculture with the cells from large antral follicles (>3 mm) exerted a significant positive effect on oocyte survival. The growth and oocyte survival of preantral follicle cocultured with the same size of follicles (with or without oocyte) were inhibited. Growth and survival rates of preantral follicles and oocytes are improved by coculturing them with the cumulus cells derived from larger antral follicles.

Animals↗
PubMed2001

A model of chronic lymphocytic leukemia with Ritcher's transformation in severe combined immunodeficiency mice.

OBJECTIVE: The major aim of the study was to establish a murine model of chronic lymphocytic leukemia with B-1 cells derived from a New Zealand white mouse. MATERIAL AND METHODS: Malignant B-1 cells (named CLL-RT cells) derived from a New Zealand white mouse were injected into the peritoneal cavity of severe combined immunodeficiency mice. Upon follow-up of recipient mice, the lymphomas showed characteristics similar to chronic lymphocytic leukemia (CLL) with Ritcher's transformation. RESULTS: Blood samples from the recipient mice showed that CLL-RT cells increased rapidly in peripheral blood after 5 weeks. Serum interleukin-10 also increased significantly in recipient mice, as in human chronic lymphocytic leukemia patients. These CLL-RT cells showed a high nucleus-to-cytoplasm ratio. These cells could metastasize via circulation in the recipients and form diffuse lymphomas in various tissues. These aggressive and diffuse lymphomas were similar to Ritcher's transformation of human CLL. The cell surface antigens of the spleen and peritoneal resident cells were analyzed by flow cytometry. The CLL-RT cells constantly expressed surface immunoglobulins M and G, and CD5, CD19, B220, and CD40 molecules. They did not express any CD11b, CD3, MAC-3, CD23, NK1.1, or H-2K(d) molecules. CONCLUSIONS: The characteristics of our animal model are very similar to human CLL. This animal system could be an ideal model for the human disease. We believe the animal model would be valuable in therapeutic studies and aid in the identification of the specific genetic alleles associated with the disease.

Animals↗
PubMed2001

Global transcriptional response of Bacillus subtilis to heat shock.

In response to heat stress, Bacillus subtilis activates the transcription of well over 100 different genes. Many of these genes are members of a general stress response regulon controlled by the secondary sigma factor, sigma(B), while others are under control of the HrcA or CtsR heat shock regulators. We have used DNA microarrays to monitor the global transcriptional response to heat shock. We find strong induction of known sigma(B)-dependent genes with a characteristic rapid induction followed by a return to near prestimulus levels. The HrcA and CtsR regulons are also induced, but with somewhat slower kinetics. Analysis of DNA sequences proximal to newly identified heat-induced genes leads us to propose ~70 additional members of the sigma(B) regulon. We have also identified numerous heat-induced genes that are not members of known heat shock regulons. Notably, we observe very strong induction of arginine biosynthesis and transport operons. Induction of several genes was confirmed by quantitative reverse transcriptase PCR. In addition, the transcriptional responses measured by microarray hybridization compare favorably with the numerous previous studies of heat shock in this organism. Since many different conditions elicit both specific and general stress responses, knowledge of the heat-induced general stress response reported here will be helpful for interpreting future microarray studies of other stress responses.

Arginine↗
PubMed2001

Selected contribution: plasticity of airway smooth muscle stiffness and extensibility: role of length-adaptive mechanisms.

Airway smooth muscle exhibits the property of length adaptation, which enables it to optimize its contractility to the mechanical conditions under which it is activated. Length adaptation has been proposed to result from a dynamic modulation of contractile and cytoskeletal filament organization, in which the cell structure adapts to changes in cell shape at different muscle lengths. Changes in filament organization would be predicted to alter muscle stiffness and extensibility. We analyzed the effects of tracheal muscle length at the time of contractile activation on the stiffness and extensibility of the muscle during subsequent stretch over a constant range of muscle lengths. Muscle strips were significantly stiffer and less extensible after contractile activation at a short length than after activation at a long length, consistent with the prediction of a shorter, thicker array of the cytoskeletal filaments at a short muscle length. Stretch beyond the length of contractile activation resulted in a persistent reduction in stiffness, suggesting a stretch-induced structural rearrangement. Our results support a model in which the filament organization of airway smooth muscle cells is plastic and can be acutely remodeled to adapt to the changes in the external physical environment.

Adaptation, Physiological↗
PubMed2001

Cutaneous B cell lymphoma in a Mongolian gerbil (Meriones unguiculatus).

A mass was noticed on the right mandible of an aged male Mongolian gerbil. Because of rapid enlargement of the mass, the animal was euthanized and submitted for pathology. The mass was firm, pink in color, 15 mm in diameter, and tightly adherent to adjacent tissues. Staining with hematoxylin and eosin revealed that the mass was a lymphoid tumor. Neoplastic cells had a large, round, dense nuclei and little cytoplasm. The tumor contained numerous mitotic figures. Immunohistochemical stains showed that the neoplastic cells expressed CD19 and IgM but lacked CD3 and CD5. Flow cytometric analysis showed that the neoplastic cells were positive for B220, IgG, and CD40. We concluded that the tumor was a primary cutaneous B cell lymphoma. In addition, the antibodies we used for the present diagnosis were anti-mouse reagents; therefore, they also were useful for subtyping gerbil lymphoid cells.

Animals↗
PubMed2001

Congenital multiple plaque-like glomangiomyoma in trunk--a case report.

Congenital glomus tumor is a rare variant of glomus tumor, and glomangiomyoma is the least frequent histological type of glomus tumor. We present a case of congenital multiple plaque-like glomangiomyoma in an 11-year-old child with multiple diffuse plaques on his right lateral trunk. Histopathologic study showed a picture of typical glomus cell undergoing transition to smooth muscle cell. After literature review, this might be the first case report of congenital multiple plaque-like glomus tumor in trunk with histological appearance of a glomangiomyoma.

Child↗
PubMed2000

Role of Rho in Ca(2+)-insensitive contraction and paxillin tyrosine phosphorylation in smooth muscle.

We investigated whether Rho activation is required for Ca(2+)-insensitive paxillin phosphorylation, myosin light chain (MLC) phosphorylation, and contraction in tracheal muscle. Tyrosine-phosphorylated proteins have been implicated in the Ca(2+)-insensitive contractile activation of smooth muscle tissues. The contractile activation of tracheal smooth muscle increases tyrosine phosphorylation of the cytoskeletal proteins paxillin and focal adhesion kinase. Paxillin is implicated in integrin-mediated signal transduction pathways that regulate cytoskeletal organization and cell motility. In fibroblasts and other nonmuscle cells, paxillin tyrosine phosphorylation depends on the activation of Rho and is inhibited by cytochalasin, an inhibitor of actin polymerization. In permeabilized muscle strips, we found that ACh induced Ca(2+)-insensitive contraction, MLC phosphorylation, and paxillin tyrosine phosphorylation. Ca(2+)-insensitive contraction and MLC phosphorylation induced by ACh were inhibited by C3 transferase, an inhibitor of Rho activation; however, C3 transferase did not inhibit paxillin tyrosine phosphorylation. Ca(2+)-insensitive paxillin tyrosine phosphorylation was also not inhibited by the Rho kinase inhibitor Y-27632, by cytochalasin D, or by the inhibition of MLC phosphorylation. We conclude that, in tracheal smooth muscle, Rho mediates Ca(2+)-insensitive contraction and MLC phosphorylation but that Rho is not required for Ca(2+)-insensitive paxillin tyrosine phosphorylation. Paxillin phosphorylation also does not require actomyosin activation, nor is it inhibited by the actin filament capping agent cytochalasin D.

ADP Ribose Transferases↗
PubMed2000

Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs.

Recent work has implicated the hypocretin (orexin) system in the genesis of narcolepsy. In the current study we demonstrate that systemically administered hypocretin-1 (Hcrt-1) produces an increase in activity level, longer waking periods, a decrease in REM sleep without change in nonREM sleep, reduced sleep fragmentation and a dose dependent reduction in cataplexy in canine narcoleptics. Repeated administration of single daily doses of Hcrt-1 led to consolidation of waking and sleep periods and to a complete loss of cataplexy for periods of three or more days after treatment in animals that were never asymptomatic under control conditions. Systemic administration of Hcrt-1 may be an effective treatment for narcolepsy.

Animals↗
PubMed2000

[Evoked responses of visceral nociceptive neurons in cat anterior cingulate gyrus revealed by intracellular recording techniques].

With intracellular recording techniques, we investigated evoked responses and electrophysiological properties of neurons in anterior cingulate gyrus (ACG) to stimulating greater splanchnic nerve (GSN) in cats. Among 461 neurons, 176 were stimulus-relative and 285 stimulus-irrelative. According to the characteristics of the evoked responses, stimulus-relative neurons were classified into specific visceral nociceptive neurons (SVNNs, 64.77%), non-specific visceral nociceptive neurons (NSVNNs, 19.32%) and non-visceral nociceptive neurons (NVNNs, 15.91%). Modes of the evoked responses could be excitatory, inhibitory, or mixed ones. The results suggest that ACG may be one of the representative areas of the GSN afferent pathway, and there exist two kinds of VNNs in ACG, which may be differently involved in pain modulation.

Animals↗
PubMed1999

Use of a recombinant parvovirus to facilitate screening for human melanoma cell clones expressing tetracycline-responsive transactivators.

The tetracycline regulatory (TET) system provides a useful means of controlling foreign gene expression in mammalian cells. Exploiting this system in cultured cells requires the prior isolation, from the cells of interest, of transfectant clones expressing the necessary TET transactivator, tTA, or reverse transactivator, rtTA. We describe a simple screening procedure for identifying transfectant clones expressing a properly regulated transactivator, and the application of this method to isolating clones of human melanoma cells expressing either tTA or rtTA. Clones in multi-well plates are transduced by exposure to a recombinant parvovirus containing a luciferase reporter, under control of a promoter responsive to the TET system transactivators. Transactivation of reporter expression in the presence or absence of doxycycline (DOXY) is determined after one to two days, using a rapid luciferase assay. Screening is easier and more reproducible with this transduction method than with conventional transient transfection of analogous reporter plasmids. Clones of two human melanoma cell lines showing >100-200-fold transactivation after transfection with either tTA or rtTA were readily identified using this method.

Clone Cells↗
PubMed1999

Neuronal degeneration in canine narcolepsy.

Narcolepsy is a lifelong illness characterized by persistent sleepiness, hypnagogic hallucinations, and episodes of motor paralysis called cataplexy. We have tested the hypothesis that a transient neurodegenerative process is linked to symptom onset. Using the amino-cupric silver stain on brain sections from canine narcoleptics, we found elevated levels of axonal degeneration in the amygdala, basal forebrain (including the nucleus of the diagonal band, substantia innominata, and preoptic region), entopeduncular nucleus, and medial septal region. Reactive neuronal somata, an indicator of neuronal pathology, were found in the ventral amygdala. Axonal degeneration was maximal at 2-4 months of age. The number of reactive cells was maximal at 1 month of age. These degenerative changes precede or coincide with symptom onset. The forebrain degeneration that we have observed can explain the major symptoms of narcolepsy.

Animals↗
PubMed1999

Application of FTA sample collection and DNA purification system on the determination of CTG trinucleotide repeat size by PCR-based Southern blotting.

Myotonic dystrophy (DM) is caused by a CTG trinucleotide expansion mutation at exon 15 of the myotonic dystrophy protein kinase gene. The clinical severity of this disease correlates with the length of the CTG trinucleotide repeats. Determination of the CTG repeat length has been primarily relied on by Southern blot analysis of restriction enzyme-digested genomic DNA. The development of PCR-based Southern blotting methodology provides a much more sensitive and simpler protocol for DM diagnosis. However, the quality of the template and the high (G+C) ratio of the amplified region hamper the use of PCR on the diagnosis of DM. A modified PCR protocol to amplify different lengths of CTG repeat region using various concentrations of 7deaza-dGTP has been reported (1). Here we describe a procedure including sample collection, DNA purification, and PCR analysis of CTG repeat length without using 7-deaza-dGTP. This protocol is very sensitive and convenient because only a small number of nucleate cells are needed for detection of CTG expansion. Therefore, it could be very useful in clinical and prenatal diagnosis as well as in prevalence study of DM.

Blood Specimen Collection↗
PubMed1999

Locus coeruleus neurons: cessation of activity during cataplexy.

Cataplexy, a symptom of narcolepsy, is a loss of muscle tone usually triggered by sudden, emotionally significant stimuli. We now report that locus coeruleus neurons cease discharge throughout cataplexy periods in canine narcoleptics. Locus coeruleus discharge rates during cataplexy were as low as or lower than those seen during rapid-eye-movement sleep. Prazosin, an alpha1 antagonist, and physostigmine, a cholinesterase inhibitor, both of which precipitate cataplexy, decreased locus coeruleus discharge rate. Our results are consistent with the hypothesis that locus coeruleus activity contributes to the maintenance of muscle tone in waking, and that reduction in locus coeruleus discharge plays a role in the loss of muscle tone in cataplexy and rapid-eye-movement sleep. Our results also show that the complete cessation of locus coeruleus activity is not sufficient to trigger rapid-eye-movement sleep in narcoleptics.

Adrenergic alpha-Antagonists↗