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Biomedical subjects

W Tao

Publications and source records attributed to W Tao.

At least 37 records · Page 2Linked to original sources

[Effect of radiotherapy on penetration of 5-FU in blood-pancreatic barrier in rats].

OBJECTIVE: To investigate the effect of radiotherapy dose on penetration of 5-FU (5-fluorouracil) in blood-pancreatic barrier in rats. METHODS: After the pancreatic region of the rats were irradiated by 2, 10, 20, 30 and 40 (Gy) doses of gamma-ray, we investigated the penetration ratio (PR) of 5-FU in the pancreatic tissue with HPLC assay. RESULTS: When treated with low-dose of gamma-ray (2 Gy), the PR of 5-FU increased obviously after 8 hours. But in the high-dose groups (>/= 10 Gy), the PR was less than or had no difference with control group. At the same time, we found that the islets had appeared pathological degeneration, while the pancreatic lobular structure, acini and ducts had no visible changes in 20 Gy group. CONCLUSIONS: After the treatment of low-dose of gamma-ray combined with 5-FU, the effect of chemoradiotherapy may be improved for enhanced PR of 5-FU in pancreatic tissue, and at the same time, chemotherapy and radiotherapy cooperate with each other. But in high dose groups (>/= 10 Gy), radiotherapy may reduce the effect of chemotherapy in acute phase. After high-dose radiotherapy, we should pay attention to the change of glucose-resistance of patient to reduce the incidence of radiotherapy complication.

Animals↗

[Screening and fermentation conditions of a bacterial strain over-producing xylanase].

A xylanase producer WXULI-11 was isolated and identified as Pseudomonas sp. By combination treatment of WXULI-11 with UV and NTG, a mutant WLUN024 was obtained and its enzyme activity reached 354 IU/mL in 36 h by shaking flask. The mechanism of its xylanase production was primarily studied. The results showed that this enzyme was induced by xylan, xylose and some other xylosic material, while xylose had "two-way effect" on xylanase synthesis. Effects of nitrogen and other factors on enzyme production were also investigated.

Culture Media↗

[Influences of counterfeits on RAPD results of Semen Cuscutae].

Compared the differences of the RAPD results between pure Semen Cuscutae and 12 commercial samples, it comes into the conclusion that the exiting other sample influences the RAPD results when its content is over 60% and the results is same as its content being under 60%.

Cuscuta↗

[Change of 5-fluorouracil penetration in blood-pancreatic barrier of rats after high-dose radiotherapy].

OBJECTIVE: The high-dose intraoperative radiotherapy has become an important therapy to control local recur of pancreatic carcinoma. But the relevant effect of high-dose radiotherapy on chemotherapy is not clear now. METHODS: We studied the effect of high-dose radiotherapy to the penetration of 5-FU (5-Fluorouracil) in blood-pancreatic barrier of rats after the pancreatic region of the rats had treated with 10(Gy) external beam radiotherapy, the penetration ratio (PR) of 5-FU in the pancreatic tissue was investigated with HPLC assay. RESULTS: We found the PR increased with the time processing. And reached the peak on the 6th day, (PR = 0.8300 +/- 0.1662, P < 0.05). Then, the PR began to descend and was 0.7028 on the 10th day. But it was still significantly higher than control group (P < 0.05). CONCLUSION: After the treatment of high-dose radiotherapy, in addition to chemotherapy on the 4th day, and finished the course on the 10th day, the effect of radiotherapy may improve chemotherapy significantly.

Animals↗

Diagnosis and treatment of insidious recurrent small intestinal hemorrhage.

OBJECTIVE: To improve the localized diagnosis of insidious recurrent small intestinal hemorrhage. METHODS: This retrospective analysis include 64 cases of such diseases, which were admitted from 1988 to 1998 to our hospital. RESULT: Ultrasonography, CT, small bowel pneumobariumgraphy, diluted barium enema, isotopic examination, DSA and intraoperative small-bowel endoscopy were used for diagnosis of hemorrhagic site, and 37 cases got a definite location before operation, while 10 cases were confined the diagnosis during the operation. Forty-seven cases were treated surgically, while the other 17 cases had non-surgical treatment. Of the 47 cases, 39 cases underwent partial enterectomy, 5 cases had suture and ligature of vascular deformity, 2 cases had Whipple's operation, and one patient had ectomy of the end of ileum and right colon. CONCLUSION: DSA, Isotopic examination and intraoperative enteroscopy are of considerable importance for the location judgement of recurrent small intestinal hemorrhage.

Adolescent↗

Oligomerized Ced-4 kills budding yeast through a caspase-independent mechanism.

In Caenorhabdtis elegans, Ced-3, Ced-4, and Ced-9 are components of a cell suicide program. Ced-4 facilitates the proteolytic activation of the caspase, Ced-3, while Ced-9 opposes Ced-3/Ced-4 killing. To examine the interactions among these proteins they were expressed in Saccharomyces cerevisiae. Ced-3 and Ced-4 were lethal when expressed alone, revealing an intrinsic Ced-4 killing activity. Coexpression of Ced-9 blocked Ced-3- and Ced-4-induced killing, showing Ced-9 can independently antagonize the action of both proteins. Ced-3- but not Ced-4-toxicity was attenuated by coexpression of the caspase inhibitors, CrmA and p35. Thus, besides its Ced-3- and Ced-9-dependent action in C. elegans, Ced-4 has an additional Ced-9-dependent, Ced-3-independent killing mechanism in yeast. Two-hybrid analysis confirmed that Ced-4 formed heteromers with Ced-9. In addition, Ced-4 formed homomers and mutation of its nucleoside triphosphate binding motif eliminated both homomerization and cell killing. We suggest the caspase-independent lethality of Ced-4 in yeast is mediated by a Ced-4 homomer.

Animals↗

P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2.

The INK4a-ARF locus encodes two distinct tumor suppressors, p16(INK4a) and p19(ARF). Whereas p16(INK4a) restrains cell growth through preventing phosphorylation of the retinoblastoma protein, p19(ARF) acts by attenuating Mdm2-mediated degradation of p53, thereby stabilizing p53. Recent data indicate that Mdm2 shuttles between the nucleus and the cytoplasm and that nucleo-cytoplasmic shuttling of Mdm2 is essential for Mdm2's ability to promote p53 degradation. Therefore, Mdm2 must export p53 from the nucleus to the cytoplasm where it targets p53 for degradation. We show here that coexpression of p19(ARF) blocks the nucleo-cytoplasmic shuttling of Mdm2. Moreover, subnuclear localization of Mdm2 changes from the nucleoplasm to the nucleolus in a shuttling time-dependent manner, whereas p19(ARF) is exclusively located in the nucleolus. In heterokaryons containing Mdm2 and p19(ARF), the longer the Mdm2 shuttling is allowed, the more Mdm2 protein colocalizes with p19(ARF) in the nucleolus, implying that Mdm2 moves from the nucleoplasm to the nucleolus and then associates with p19(ARF) there. Furthermore, whether or not Mdm2 colocalizes with p19(ARF) in the nucleolus, p19(ARF) prevents Mdm2 shuttling. This observation suggests that Mdm2 might be exported through the nucleolus and p19(ARF) could inhibit the nuclear export of Mdm2 by tethering Mdm2 in the nucleolus. Taken together, p19(ARF) could stabilize p53 by inhibiting the nuclear export of Mdm2.

Animals↗

Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53.

The Hdm2 oncoprotein inhibits p53 functions by two means: (i) it blocks p53's transactivation activity and (ii) it targets p53 for degradation in a proteasome-dependent manner. Recent data indicate that Hdm2 shuttles between the nucleus and the cytoplasm and that the regulation of p53 levels by Hdm2 requires its nuclear export activity. Two different models are consistent with these observations. In the first, Hdm2 binds to p53 in the nucleus and shuttles p53 from the nucleus to the cytoplasm, and then it targets p53 to the cytoplasmic proteasome. Alternatively, Hdm2 and p53 could be exported separately from the nucleus and then associate in the cytoplasm, where Hdm2 promotes the degradation of p53. To distinguish between these two models, several Hdm2 mutants were employed. Hdm2NLS lacks the ability to enter the nucleus, whereas Hdm2NES is deficient in nuclear export. Hdm2NLS, Hdm2NES, or the combination of both mutants were unable to promote p53 degradation in the cotransfected 2KO cells (which were null for both the p53 and mdm2 genes), although wild-type Hdm2 efficiently reduced p53 levels under the same conditions. This observation is not a result of the differences in expression levels or stability between Hdm2 and these mutants. Moreover, coexpression of these mutants had no effect on wild-type Hdm-2-induced p53 destabilization. Thus, Hdm2 must shuttle p53 from the nucleus to the cytoplasm to target it for degradation in the cytoplasm.

Amino Acid Sequence↗

Intracellular glycerol levels modulate the activity of Sln1p, a Saccharomyces cerevisiae two-component regulator.

The HOG mitogen-activated protein kinase pathway mediates the osmotic stress response in Saccharomyces cerevisiae, activating genes like GPD1 (glycerol phosphate dehydrogenase), required for survival under hyperosmotic conditions. Activity of this pathway is regulated by Sln1p, a homolog of the "two-component" histidine kinase family of signal transduction molecules prominent in bacteria. Sln1p also regulates the activity of a Hog1p-independent pathway whose transcriptional output can be monitored using an Mcm1p-dependent lacZ reporter gene. The relationship between the two Sln1p branches is unclear, however, the requirement for unphosphorylated pathway intermediates in Hog1p pathway activation and for phosphorylated intermediates in the activation of the Mcm1p reporter suggests that the two Sln1p branches are reciprocally regulated. To further investigate the signals and molecules involved in modulating Sln1p activity, we have screened for new mutations that elevate the activity of the Mcm1p-dependent lacZ reporter gene. We find that loss of function mutations in FPS1, a gene encoding the major glycerol transporter in yeast activates the reporter in a SLN1-dependent fashion. We propose that elevated intracellular glycerol levels in the fps1 mutant shift Sln1p to the phosphorylated state and trigger the Sln1-dependent activity of the Mcm1 reporter. These observations are consistent with a model in which Sln1p autophosphorylation is triggered by a hypo-osmotic stimulus and indicate that the Sln1p osmosensor is tied generally to osmotic balance, and may not specifically sense an external osmolyte.

Base Sequence↗

Differential in vivo effects of neurturin and glial cell-line-derived neurotrophic factor.

Glial cell-line derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally homologous, and they seem to produce similar effects in vitro. Tissue distributions of their respective receptors, GFR alpha-1 and GFR alpha-2, reveal overlapping but distinct patterns of expression, which implies that the in vivo actions of GDNF and NTN may be different. In the present study, a direct comparison of the in vivo effects of GDNF and NTN was performed using osmotic minipumps delivering either GDNF or NTN over a 30-day period into rat lateral cerebral ventricles. Amphetamine-induced activity levels were increased in both NTN- and GDNF-treated animals, with higher activity levels achieved by GDNF than NTN. The increase in amphetamine-induced activity levels persisted for 2 weeks and returned to control levels at the end of the third week. NTN-treated rats showed higher dopamine levels in the mediodorsal striatum, relative to the ventrolateral striatum. In contrast, no significant change in the regional distribution of dopamine levels was observed in GDNF treated or control animals. On the other hand, an increase in ventrolateral and mediodorsal striatal dopamine utilization was apparent in GDNF-treated animals, while NTN-treated animals showed increased levels of dopamine utilization only in the ventrolateral striatum. With respect to potential adverse effects, GDNF administration resulted in weight loss and the emergence of allodynia. No weight loss or allodynia was detectable with chronic NTN administration. These results suggest that although GDNF and NTN share structural and functional similarities, they may have differential effects in vivo.

3,4-Dihydroxyphenylacetic Acid↗

Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity.

We have previously used mosaic flies to screen for tumour suppressors or negative regulators of cell proliferation. The cellular composition of these flies resembles that of cancer patients who are chimaeric individuals carrying a small number of mutated somatic cells. One of the genes we identified is the large tumour suppressor gene, lats (also known as wts), which encodes a putative serine/threonine kinase. Somatic cells mutant for lats undergo extensive proliferation and form large tumours in many tissues in mosaic adults. Homozygous mutants for various lats alleles display a range of developmental defects including embryonic lethality. Although many tumour suppressors have been identified in Drosophila melanogaster, it is not clear whether these fly genes are directly relevant to tumorigenesis in mammals. Here, we have isolated mammalian homologues of Drosophila lats. Human LATS1 suppresses tumour growth and rescues all developmental defects, including embryonic lethality in flies. In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis. LATS1-associated CDC2 has no mitotic cyclin partner and no kinase activity for histone H1. Furthermore, lats mutant cells in Drosophila abnormally accumulate cyclin A. These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A, a finding supported by genetic data in Drosophila demonstrating that lats specifically interacts with cdc2 and cyclin A.

Amino Acid Sequence↗

Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction.

The lats gene has been identified as a tumour suppressor in Drosophila melanogaster using mosaic screens. Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the functional conservation of this gene. Biochemical and genetic analyses have revealed that LATS1 functions as a negative regulator of CDC2 (ref. 3). These data suggest that mammalian LATS1 may have a role in tumorigenesis. To elucidate the function of mammalian LATS1, we have generated Lats1-/- mice. Lats1-/- animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Lats1-/- mice develop soft-tissue sarcomas and ovarian stromal cell tumours and are highly sensitive to carcinogenic treatments. Our data demonstrate a role for Lats1 in mammalian tumorigenesis and specific endocrine dysfunction.

Animals↗

Reduced ventilator pressure and improved P/F ratio during percutaneous arteriovenous carbon dioxide removal for severe respiratory failure.

OBJECTIVE: To evaluate the effect of percutaneous arteriovenous carbon dioxide removal (AVCO2R) on ventilator pressures and P/F ratio in a clinically relevant large-animal model of severe respiratory failure. SUMMARY BACKGROUND DATA: AVCO2R was developed as a simple arteriovenous shunt with a commercially available low-resistance gas exchange device of sufficient surface area for near-total CO2 removal. With an AV shunt 10% to 15% of cardiac output, AVCO2R allows a reduction in ventilator airway pressures without hypercapnia or the complex circuitry and monitoring required for conventional ECMO. METHODS: AVCO2R was applied to a new, clinically relevant large-animal model of severe respiratory failure created by smoke inhalation and cutaneous flame bum injury. Adult sheep (n = 9, 38+/-6 kg) received a 40% total body surface area, third-deinsufflation. After injury, all animals were placed on volume-controlled mechanical ventilation to achieve PaO2 > 60 mmHg and PacO2 < 40 mmHg. Animals were placed on AVCO2R within 40 to 48 hours of injury when the PaO2/FiO2 was <200. Animals underwent cannulation of the carotid artery and jugular vein with percutaneous 10F arterial and 14F venous cannulas. Shunt flow was continuously monitored using an ultrasonic flow probe and calculated as a percentage of cardiac output. RESULTS: AVCO2R flows of 800 to 900 ml/min (11% to 13% cardiac output) achieved 77 to 104 ml/min of CO2 removal (95% to 97% total CO2 production) while maintaining normocapnia. Significant reductions in ventilator settings were tidal volume, 421.3+/-39.8 to 270.0+/-6.3 ml; peak inspiratory pressure, 24.8+/-2.4 to 13.7+/-0.7 cm H2O; minute ventilation, 12.7+/-1.4 to 6.2+/-0.8 L/min; respiratory rate, 25.4+/-1.3 to 18.4+/-1.8 breaths/min; and FiO2, 0.88+/-0.1 to 0.39+/-0.1. The P/F ratio increased from 151.5+/-40.0 at baseline to 320.0+/-17.8 after 72 hours. CONCLUSIONS: Percutaneous AVCO2R allows near-total CO2 removal and significant reductions in ventilator pressures with improvement in the P/F ratio.

Algorithms↗

Laboratory testing of femoral venous cannulae: effect of size, position and negative pressure on flow.

Femoral venous cannulae (17-28 French) were tested to compare flows obtained by their placement in a simulated inferior vena cava (IVC) or right atrium (RA) and by varying drainage pressures using gravity siphon drainage or a centrifugal pump in the venous line. The circuit consisted of conventional tubing and equipment including a segment of thin-walled latex tubing to simulate the IVC connected to a flexible reservoir to simulate the RA. The test fluid was a 40% glycerin solution. Flow was measured at height differentials of 30-60 cm (cannula-to-inlet of hard-shell venous reservoir) and with a -10 to -80 mmHg negative pressure created by the centrifugal pump. A roller pump returned the test fluid to a flexible bag to maintain a filling pressure of 0-1 mmHg. Flow increased modestly with an increasing height differential. When negative pressure was applied with the centrifugal pump, flow increased 10% and 18% (IVC and RA positions, respectively) compared to gravity siphon drainage conditions. There also was a tendency for flow to plateau or cease when the centrifugal pump was used at higher levels of negative pressure or when larger cannulae were used. We conclude: (1) position of smaller cannulae in the RA yield better flows than when the cannulae are larger and placed in the IVC; (2) smaller-sized cannulae are capable of achieving higher flows when the centrifugal pump is used; (3) cannulae must be properly positioned to achieve maximum flow; (4) the centrifugal pump will augment flow, but should be regulated to avoid extreme negative pressures; and (5) cannula design has no demonstrable effect on flow.

Catheterization↗

PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development.

Mutations in the tumor suppressor gene PTEN (MMAC1/TEP1) are associated with a large number of human cancers and several autosomal-dominant disorders. Mice mutant for PTEN die at early embryonic stages and the mutant embryonic fibroblasts display decreased sensitivity to cell death. Overexpression of PTEN in different mammalian tissue culture cells affects various processes including cell proliferation, cell death and cell migration. We have characterized the Drosophila PTEN gene and present evidence that both inactivation and overexpression of PTEN affect cell size, while overexpression of PTEN also inhibits cell cycle progression at early mitosis and promotes cell death during eye development in a context-dependent manner. Furthermore, we have shown that PTEN acts in the insulin signaling pathway and all signals from the insulin receptor can be antagonized by either Drosophila or human PTEN, suggesting a potential means for alleviating symptoms associated with altered insulin signaling.

Amino Acid Sequence↗

[Distribution of 5-fluorouracil in plasma and pancreatic tissue of rats during the regional arterial infusion chemotherapy].

OBJECTIVE: Compare the pharmacokinetic parameters of 5-FU in the regional arterial infusion chemotherapy with those in the intravenous chemotherapy. METHODS: Wistar rats were randomly divided into two groups: the intravenous group and the regional arterial infusion group. HPLC was used to measure the concentration of 5-FU in the plasma and the pancreas tissue. Penetration index was calculated. RESULTS: In the intravenous group, maximum concentration (Cmax) of 5-FU in the pancreas was 8.42 micrograms/g and the clearance time of the pancreas was 50 min. In the regional arterial infusion group, Cmax of 5-FU in the pancreas was 20.00 micrograms/g and the clearance time of the pancreas was 90 min. They were both greater than those of the intravenous group. Rd was 2.42. CONCLUSIONS: The regional arterial infusion chemotherapy is a better way for treating pancreatic carcinoma than the intravenous chemotherapy.

Animals↗