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Biomedical subjects

D Yu

Publications and source records attributed to D Yu.

At least 163 records · Page 9Linked to original sources

Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease.

Hepsin is a type II transmembrane serine protease highly expressed on the surface of hepatocytes. The physiological function of hepsin is not known, although in vitro studies indicate that hepsin plays a role in the initiation of blood coagulation and in hepatocyte growth. To determine the functional importance of hepsin, we generated hepsin-deficient mice by homologous recombination. Homozygous hepsin-/- mice were viable and fertile, and grew normally. In functional assays including tail bleeding time, plasma clotting times, and tissue factor- or LPS-induced disseminated intravascular coagulation models, no significant difference was found between hepsin-/- and wild-type litter mates. Liver weight and serum concentrations of liver-derived proteins or enzymes were similar in hepsin-/- and wild-type mice. Interestingly, serum concentrations of bone-derived alkaline phosphatase were approximately twofold higher in hepsin-/- mice of both sexes when compared with wild-type litter mates. No obvious abnormalities were found in major organs in hepsin-/- mice in histological examinations. Our results indicate that hepsin is not essential for embryonic development and normal hemostasis. Hepsin-/- mice will help to evaluate the long-term effects of hepsin deficiency in these animals.

Alkaline Phosphatase↗

Study on the relationship between the Bcl-2/Bax ratio and the growth types of leukemic cells and drug resistance in acute myelogenous leukemia.

The ratio of Bcl-2 to Bax (Bcl-2/Bax) in 40 patients with acute myelogenous leukemia (AML) were determined. At the same time, the CFU-L of AML patients and drug resistance were detected by cell culture and MTT assay. The results showed that Bcl-2/Bax in AML was significantly higher than that in normal control (P < 0.001). Bcl-2/Bax ratio in colony growth group was higher than that in no-growth group (P < 0.05). Between drug resistance group and drug sensitivity group there was a significant difference in Bcl-2/Bax ratio (P < 0.05). There were more cases of drug resistance in high ratio group (H) than in low ratio group (L) (P < 0.05). Meanwhile, Complete Remission(CR) rate in group H was obviously lower than that in group L (P < 0.05) and patients in group H tended to have poor response. The above results indicated that the alteration of Bcl-2 and Bax is an important mechanism in the pathogenesis, progress and the development of drug resistance in AML. The determination of Bcl-2/Bax ratio has far-reaching implication in the treatment, choice of chemotherapeutic agents, and prediction of prognosis.

Adult↗

Hepatocyte growth factor up-regulates SGLT1 and GLUT5 gene expression after massive small bowel resection.

BACKGROUND/PURPOSE: Hepatocyte growth factor (HGF), originally known to stimulate hepatocyte DNA synthesis, also has been shown to stimulate growth of intestinal epithelial cells in vitro. The authors recently demonstrated that HGF can dramatically increase substrate absorption beyond the normal adaptive response after massive small bowel resection in the rat. However, the mechanism for this enhanced substrate absorption is unknown. This study was designed to determine if up-regulation of gene expression by HGF of the Na+/glucose cotransporter SGLT1 and the facilitative glucose transporter GLUT5 is a possible mechanism of action. METHODS: Young adult Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later, an osmotic minipump was connected to the subcutaneously placed jejunostomy tube. The rats were divided into two groups based on the contents in the minipumps: group 1, saline (control, n = 5); and group 2, HGF at 75 microg/kg/d (n = 5). After a 14-day infusion, biopsy specimens of the small bowel mucosa were obtained. After total RNA extraction, Northern blot analysis was performed with SGLT1 and GLUT5 cDNA probes. Auto radiographs were quantitated by image analysis. RESULTS: SGLT1 mRNA levels were significantly up-regulated in the HGF-treated animals (121% increase, P<.01) when compared with the control. Up-regulation of GLUT5 mRNA levels was also seen in the HGF-treated animals (96% increase, P < .01). CONCLUSIONS: These data, demonstrating that HGF upregulates intestine epithelial glucose transporter gene expression after massive small bowel resection, may elucidate a mechanism of action for the enhanced carbohydrate absorption after HGF administration. This growth factor may be useful for patients with short bowel syndrome.

Animals↗

Enhancement of intestinal adaptation by hepatocyte growth factor.

BACKGROUND/PURPOSE: Hepatocyte growth factor (HGF) was originally shown to enhance hepatocyte DNA synthesis. Recently, the expression of HGF and its receptor (c-met) were observed in the intestinal tract. In a previous study, we demonstrated that HGF can increase normal rat intestinal epithelial mass and function in vivo. This study was designed to determine if HGF, given either systemically or luminally, can enhance intestinal epithelial mass and function beyond the normal adaptive response after massive small bowel resection. METHODS: Twenty young adult male Sprague-Dawley rats underwent an 80% small bowel resection. Seven days after resection, systemic infusion (via the jugular vein) or luminal perfusion (via the jejunum) were performed using subcutaneously placed osmotic minipumps. The rats were divided into four groups: group 1, systemic saline, (control, n=5); group 2, systemic HGF at 150 microg/kg/d (n=5); group 3, luminal saline, (control, n=5); and group 4, luminal HGF at 75 microg/kg/d (n=5). After a 14-day infusion, [C14] galactose and [C14] glycine absorption (micromol/cm2 intestine), mucosal DNA content (microg/mg mucosa) and protein content (microg/mg mucosa) were measured in the remaining small intestine of each rat. RESULTS: Systemic infusion of HGF increased galactose absorption 68% (P<.05), glycine absorption 57% (P<.05), DNA content 17% (P<.01), and protein content 57% (P<.01), when compared with the appropriate control. Luminal perfusion of HGF also increased galactose absorption 114% (P<.01), glycine absorption 126% (P<.01), DNA content 32% (P<.01), and protein content 45% (P<.01), when compared with the appropriate control. CONCLUSIONS: These data demonstrate for the first time that HGF can significantly enhance intestinal epithelial cell function and mucosal mass beyond the normal adaptive response. Luminal administration appeared to produce a greater response when compared with systemic administration but was significant only for galactose absorption (P<.05). HGF may be clinically useful in patients with short bowel syndrome.

Adaptation, Physiological↗

Enteral glutamine does not enhance the effects of hepatocyte growth factor in short bowel syndrome.

PURPOSE: This study was designed to determine if luminally administered glutamine alone functions as a growth factor or is synergistic with hepatocyte growth factor (HGF) after massive small bowel resection (MSBR). METHODS: Twenty Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later the rats were divided into four groups: group 1, control, no further treatment (n = 5); group 2 received glutamine (4% of total food intake per day) via an orogastric tube (n = 5); group 3 received intraluminal HGF via a jejunostomy tube at 75 microg/kg/d (n = 5); and group 4 received glutamine and HGF at the same doses, respectively. After a 14-day HGF infusion, glutamine feeding, or both combined, [C14] glycine absorption (micromol/L/cm2 intestine) and mucosal DNA and protein content (microg/mg mucosa) were measured in the remaining small bowel. RESULTS: Glutamine alone had no effect on substrate absorption and protein or DNA content. HGF increased galactose absorption (106% increase over control, P<.01), glycine absorption (95% increase over control, P<.05), protein content (44% increase over control, P<.01), and DNA content (32% increase over control, P<.01). The combination of glutamine and HGF did not prove to be synergistic. CONCLUSIONS: These data demonstrate that in this short bowel model, glutamine alone did not enhance intestinal function. Furthermore, glutamine is not synergistic with HGF. This study suggests that glutamine alone may not be useful clinically in patients with inadequate intestinal function.

Adaptation, Physiological↗

Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase.

Overexpression of the receptor tyrosine kinase p185ErbB2 confers Taxol resistance in breast cancers. Here, we investigated the underlying mechanisms and found that overexpression of p185ErbB2 inhibits Taxol-induced apoptosis. Taxol activates p34Cdc2 kinase in MDA-MB-435 breast cancer cells, leading to cell cycle arrest at the G2/M phase and, subsequently, apoptosis. A chemical inhibitor of p34Cdc2 and a dominant-negative mutant of p34Cdc2 blocked Taxol-induced apoptosis in these cells. Overexpression of p185ErbB2 in MDA-MB-435 cells by transfection transcriptionally upregulates p21Cip1, which associates with p34Cdc2, inhibits Taxol-mediated p34Cdc2 activation, delays cell entrance to G2/M phase, and thereby inhibits Taxol-induced apoptosis. In p21Cip1 antisense-transfected MDA-MB-435 cells or in p21-/- MEF cells, p185ErbB2 was unable to inhibit Taxol-induced apoptosis. Therefore, p21Cip1 participates in the regulation of a G2/M checkpoint that contributes to resistance to Taxol-induced apoptosis in p185ErbB2-overexpressing breast cancer cells.

Animals↗

99mTc-ethylenedicysteine-folate: a new tumor imaging agent. Synthesis, labeling and evaluation in animals.

It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs such as methotrexate and overexpressed on various tumor cells. However, these receptors are highly restricted in normal differentiated tissues. Results of limited in vitro and in vivo animal studies suggest that folate receptors could be a potential target for tumor imaging. This study aimed to develop a 99mTc-labeled folic acid using ethylenedicysteine (EC) as a chelator and evaluate its labeling efficiency and potential use as a tumor seeking agent. Tissue distribution of 99mTc-EC-folate was determined in breast tumor-bearing rats at 20 min, 1, 2, and 4 h (n = 3/time interval, 370 KBq/rat, i.v.). Blocking study was employed to determine receptor-mediated process; 99mTc-EC-folate was co-administrated with 50 and 150 mumol/kg of cold folic acid to tumor-bearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 99mTc-EC (control). In animal studies, tumor/blood count density ratios at 20 min-4 h increased from 0.81 +/- 0.09 to 1.23 +/- 0.13 with 99mTc-EC-folate. Conversely, these values showed time-dependent decrease from 0.77 +/- 0.32 to 0.65 +/- 0.01 with 99mTc-EC in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with folic acid co-administrations. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with 99mTc-EC-folate.

Animals↗

Herpes simplex virus type 1 cleavage and packaging proteins UL15 and UL28 are associated with B but not C capsids during packaging.

At least seven viral genes encode proteins (UL6, UL15, UL17, UL25, UL28, UL32, and UL33) that are required for DNA cleavage and packaging of herpes simplex virus type 1 (HSV-1) DNA. Sequence analysis reveals that UL15 shares homology with gp17, the large catalytic subunit of the bacteriophage T4 terminase. Thus, UL15 may play a direct role in the cleavage of viral DNA replication intermediates into monomers. In this study, we asked whether UL15 and other cleavage and packaging proteins could be detected in capsids isolated from infected cells. Consistent with previous studies showing that UL6 and UL25 are minor protein constituents of the capsids, we detected these proteins in both B and C capsids. In contrast, the previously identified full-length version (81 kDa) of UL15 was found predominantly in B capsids and in much smaller amounts in C capsids. In addition, the UL28 protein was found predominantly in B but not C capsids in a distribution similar to that of the 81-kDa version of UL15. These results suggest that UL28 and the 81-kDa form of UL15 are transiently associated with capsid intermediates during the packaging process. Surprisingly, however, a previously unidentified 87-kDa form of UL15 was found in the B and C capsids and in virions. Analysis of cells infected with mutants individually lacking UL6, UL15, UL25, UL28, or UL32 demonstrates that the lack of one cleavage and packaging protein does not affect the expression of the others. Furthermore, this analysis, together with guanidine HCl extraction analysis of purified capsids, indicates that UL6, UL25, and UL28 are able to associate with B capsids in the absence of other DNA cleavage and packaging proteins. On the other hand, the two UL15-related proteins (81 and 87 kDa) do not associate efficiently with B capsids in cells infected with UL6 and UL28 mutants. These results suggest that the ability of the UL15-related proteins to bind to B capsids may be mediated through interactions with UL6 and UL28.

Animals↗

Stereotyped behavior in developmentally delayed or autistic populations. Rhythmic or nonrhythmic?

Stereotypies are high-frequency, highly repetitive, nonfunctional behaviors that are also often characterized as rhythmic. Rhythmicity suggests that the behavior is periodic, occurring at fixed intervals. Few studies, however, have rigorously demonstrated periodicity in stereotypy. This study examined various topographies of stereotypy in 9 participants and used spectral methods to detect existence of periodicties. Two general patterns emerged in the spectral analysis. Participants who engaged in stereotypic rocking showed peaks in their power spectra; participants who engaged in other topographies of stereotypy did not show peaks. Thus, it appears that although some stereotypies--notably, rocking--have a periodic component, rhythmicity does not appear to be a characteristic of stereotypy in general.

Adolescent↗

A crash course in spinal cord injury.

The complex management issues related to spinal cord injury traditionally have been the purview of physical medicine and rehabilitation specialists. However, changes in the healthcare system now offer primary care physicians an expanded role in helping affected patients live a healthier and more functional life. With proper understanding of the mechanisms of spinal cord injury, primary care physicians can become important members of the medical management team. Dr Yu presents a comprehensive overview of medical care issues and common complications in spinal cord injury.

Family Practice↗

The influence of stress on edentulous maxillary bone with different artificial anterior tooth arrangements by three-dimensional photoelasticity.

OBJECTIVE: To investigate the influence of stress on edentulous maxillary bone different artificial anterior tooth arrangements, with the goal to establish theoretical evidence for optimal anterior tooth arrangements in complete denture restoration. MATERIALS AND METHODS: Three-dimensional photoelasticity experimental stress analysis was conducted. Shear stresses were measured and principal stresses were separated into six different models of maxillary central incisor arrangements. RESULTS: The value of maximum stresses and the absolute values of principal stresses and positive stresses were obtained. The distribution curve of shear stresses and principal stresses was also shown. CONCLUSIONS: The horizontal distance between the incisive papilla center and the incisal margin of the maxillary central incisor should be no more than 8 mm, if the anterior mandibular arch is larger than the maxillary arch. The principal stress is a better indicator of stress on edentulous maxillary bone when load is applied at the protrusive occlusal position.

Alveolar Process↗

[The diagnosis and therapy of tinnitus].

Selection criteria for the therapeutic strategy are provided by a classification on the basis of the following points: 1. can be masked by a sound, 2. response to parenteral lidocaine. This classification was used to treat 119 patients with tinnitus. Masking is the first therapy for tinnitus. If masking had no effect, lidocaine test were undergone. The patient who has a positive response to lidocaine were treated by antiepileptic drugs. Patients with negative response to lidocaine negative were treated by suppressant. The prognosis for patients with positive masking effect was more better than the negative one. The mechanisms of tinnitus were discussed.

Anticonvulsants↗

[Endoscopic transnasal repair of congenital choanal atresia].

Two cases of congenital choanal atresia treated with endoscopic transnasal repairing were reported. Nasal endoscopy and axial CT scanning are important for establishing the diagnosis. Endoscopic plastic operation for choanal atresia is the best procedure. There are following advantages: short approach, clear field of vision, complete resection of atresia plate, well preservation of mucosa on the nasopharyngeal side of atresia plate, no side injury, less bleeding and higher success. The mucosa preserved completely on the nasopharyngeal side can totally cover the bare bony edges. The endoscopy after operation is important to remain nasal patency.

Adolescent↗

Reevaluation of effect of albendazole on echinococcus multilocularis infection in mice and gerbils.

OBJECTIVE: To study the effect for albendazole therapy for alveolar echinococcus infection in gerbils and mice. METHODS: Mice and gerbils were infected of metacestode tissues by intraperitoneal (i.p.) transplantation and treated with albendazole-medicated feeds. The effects were evaluated by comparison of the treated and control groups in terms of host mortality, larval metastases to lungs and liver, final larval weight, histopathological, and ultrastructural examination of metacestode tissues. Viability of metacestode tissues at necropsy of treated animals was tested by intraperitoneal transplantation into uninfected animals. RESULTS: Albendazole-medicated feeds significantly inhibited larval growth of Echinococcus multilocularis (E. multilocularis) both in mice and gerbils with markedly reduced host mortality and pulmonary and liver metastases. Viability test showed that albendazole therapy was parasiticidal in early stage of experimental infection. Light microscopic and ultrastructural examination of metacestode tissues of the treated animals revealed severe destruction and massive necrosis with marked calcification of protoscoleces and residual tissues. CONCLUSION: Continuous long term albendazole therapy in animal models is parasiticidal against larval E. multilocularis especially in early stage of infection.

Albendazole↗

[The relationship between severe burn injury and systemic inflammatory response syndrome].

OBJECTIVE: To study course of systemic inflammatory response syndrome (SIRS). METHODS: The relationship was observed between SIRS and the effect of burn injury on cellular and humoral immunity between survivors. Nonsurvivors were also compared. The gastric mucosal pHi was measured. RESULTS: The SIRS initiated 22 hours after burn injury and peaked 3 days to 7 days postburn. Compared to the survivors significan increase of content of TNF and decrease of content of G-CSF were detected in the nonsurvivors serum. Obvious immunosuppression could be found. In patients with SIRS accompanied with infection or organ failure, marked increase of mortality was seen. The value of pHi was very low. CONCLUSION: Severe burn injury can lead to the release of massive inflammatory mediators. The second insult such as infection can further amplify the process leading to a vicious cycle of inflammation which cause tissue damage and immunosuppression. To prevent MODS, early diagnosis and treatment including organ supply, use of antibacterial agents, oxygen supply and immunity therapy were necesary.

Adolescent↗

[Study on the polyoxygenated cyclohexenes from Uvaria boniana].

Seven new polyoxygenated cyclohexenes, named uvaribonol A-G (1-7) have been isolated from the ethanol extract of the stems of Uvaria boniana Finet. (Annonaceae), and their structures, including the absolute configuration, were determined by spectral and chemical methods. In vitro cytotoxicity test against several human tumor cell lines indicated that all of the new natural compounds are inactive, but some of the derivatives showed obvious activities. Compound 2a is the most active, exhibiting significant cytotoxicities against KB and Bel7402 cells with IC50 < 1 microgram.ml-1, and against HCT-8 cell with IC50 < 0.1 microgram.ml-1.

Annonaceae↗

[Studies on the synthesis and antitumor activities of howiinol A and its analogues].

Howiinol A(1), one of the active antitumor constituents from the root and stem bark of Goniothamus howii Meer. (Annonaceae) has been synthesized in nine steps from alpha-D-glucoheptonic gamma-lactone with an over all yield of 13.3%. It shows that all data of the synthetic product are identical to those of the natural howiinol A, thus the absolute configuration of natural howiinol A is further confirmed as 1. In the search for new antitumor compounds with high potency, 26 analogues have been synthesized. In pharmacological tests most of them showed antitumor activities in vitro, some of them are significant.

Animals↗