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Biomedical subjects

D Fang

Publications and source records attributed to D Fang.

At least 37 records · Page 2Linked to original sources

Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase.

Genetic studies identified Itch, which is a homologous to the E6-associated protein carboxyl terminus (Hect) domain-containing E3 ubiquitin-protein ligase that is disrupted in non-agouti lethal mice or Itchy mice. Itch-deficiency results in abnormal immune responses and constant itching in the skin. Here, Itch was shown to associate with Notch, a protein involved in cell fate decision in many mammalian cell types, including cells in the immune system. Itch binds to the N-terminal portion of the Notch intracellular domain via its WW domains and promotes ubiquitination of Notch through its Hect ubiquitin ligase domain. Thus, Itch may participate in the regulation of immune responses by modifying Notch-mediated signaling.

Animals↗

Racial and ethnic disparities in faculty promotion in academic medicine.

CONTEXT: Previous studies have suggested that minority medical school faculty are at a disadvantage in promotion opportunities compared with white faculty. OBJECTIVE: To compare promotion rates of minority and white medical school faculty in the United States. DESIGN AND SETTING: Analysis of data from the Association of American Medical Colleges' Faculty Roster System, the official data system for tracking US medical school faculty. PARTICIPANTS: A total of 50,145 full-time US medical school faculty who became assistant professors or associate professors between 1980 and 1989. Faculty of historically black and Puerto Rican medical schools were excluded. MAIN OUTCOME MEASURES: Attainment of associate or full professorship among assistant professors and full professorship among associate professors by 1997, among white, Asian or Pacific Islander (API), underrepresented minority (URM; including black, Mexican American, Puerto Rican, Native American, and Native Alaskan), and other Hispanic faculty. RESULTS: By 1997, 46% of white assistant professors (13,479/28,953) had been promoted, whereas 37% of API (1123/2997; P<.001), 30% of URM (311/1053, P<.001), and 43% of other Hispanic assistant professors (256/598; P =.07) had been promoted. Similarly, by 1997, 50% of white associate professors (7234/14,559) had been promoted, whereas 44% of API (629/1419; P<.001), 36% of URM (101/280; P<.001), and 43% of other Hispanic (122/286; P =.02) associate professors had been promoted. Racial/ethnic disparities in promotion were evident among tenure and nontenure faculty and among faculty who received and did not receive National Institutes of Health research awards. After adjusting for cohort, sex, tenure status, degree, department, medical school type, and receipt of NIH awards, URM faculty remained less likely to be promoted compared with white faculty (relative risk [RR], 0.68 [99% confidence interval CI, 0.59-0.77] for assistant professors and 0.81 [99% CI, 0.65-0.99] for associate professors). API assistant professors also were less likely to be promoted (RR, 0.91 [99% CI, 0.84-0.98]), whereas API associate professors and other Hispanic assistant and associate professors were promoted at comparable rates. CONCLUSION: Our data indicate that minority faculty are promoted at lower rates compared with white faculty. JAMA. 2000;284:1085-1092

Career Mobility↗

A case of Penicillium marneffei osteomyelitis involving the axial skeleton.

Fungal infection of bone by Penicillium marneffei is rare. We report on a case of Penicillium marneffei infection in a Filipino woman, which involved multiple soft-tissue abscesses and infection of the axial skeleton. Early diagnosis and treatment of this potentially reversible disease is emphasised. Such an approach is essential to prevent bony destruction from becoming too advanced and, more importantly, to prevent any damage to the spinal cord from occurring.

Adult↗

Reproducible echocardiography in juvenile sheep and its application in the evaluation of a pulmonary valve homograft implant.

Increased use of the ovine animal model in cardiovascular surgical research has created a salient need for standardized echocardiography techniques. To demonstrate a reproducible image in this species and confirm the validity of echocardiography as a diagnostic tool, we implanted 10 sheep with a pulmonary valve homograft and monitored them through weekly echocardiographic examinations until 20 weeks after implantation. We obtained good images from the left cranial and the left caudal transducer windows without needing to sedate the animals. Sedated sheep yielded adequate views from the right apical window. Echocardiographic data on the implanted homografts (including functional capacity, presence of calcification, and hemodynamic information and measurements), completely agreed with the results of the post-explantation examinations.

Animals↗

[Different flow augmentations in coronary, carotid and renal arteries with ECP in experimental canines].

Different flow augmentations were found in canine's coronary, carotid and renal arteries with ECP because of their different anatomical locations in aorta. We used the Electromagnetic Blood Flowmeters to measure the blood flow pre-ECP and during ECP. The results showed ECP increased the diastolic flow of coronary, carotid and renal arteries by 24.48% +/- 1.29%, 27.18% +/- 0.94% and 20.68% +/- 0.80% respectively, decreased their systolic flow by 4.77% +/- 0.48%, 6.45% +/- 0.99% and 9.60% +/- 0.70%, but augmented their mean flow by 18.24% +/- 2.01%, 19.38% +/- 1.47% and 8.42% +/- 0.94% respectively in experimental dogs. These data demonstrate that ECP can greatly increase the mean flow of coronary and carotid arteries but at the same time patently decrease the systolic flow of renal artery.

Animals↗

Induction of intestinal metaplasia in stomach of dogs and expression of tumor-related proteins in animal gastric mucosa lesions.

OBJECTIVE: To observe the development and progression of intestinal metaplasia (IM) in dog's stomach and expression of tumor-related proteins in gastric mucosa lesions. METHODS: IM animal model was induced in stomach of Beagle dog by combining treatment of oral administration of N-methyl-N'-nito-N-nitrosoguanidine (MNNG) and ranitidine (R) with X-ray irradiation to the target organ. Expression of APC, p53, K-ras and bcl-2 gene proteins in animal gastric mucosa lesions were determined with immunohistochemical method. RESULTS: IM animal model was successfully induced and the dynamic pathological changes were observed by means of this model. It was confirmed that the progression from normal epithelial cells to IM cells may require several stages, including superficial gastritis, chronic atrophic gastritis, slight focal IM and moderate or severe IM. Aberrant bcl-2 protein can be detected in the atrophic mucosa epithelium and the abnormal expression of APC, K-ras and bcl-2 can be found in IM of mucosa. CONCLUSIONS: IM model in stomach of Beagle dog can be successfully induced by our method (MNNG + R + X-ray). The progression from normal to IM in dog resembles that of human being and the expression of tumor-related proteins (APC, bcl-2, K-ras) may play a role in the malignant transformation of IM.

Adenomatous Polyposis Coli Protein↗

[Aberrant expression of MUC2 and MUC3 genes in gastric carcinoma and its significance].

OBJECTIVES: To explore the clinicopathological significance of the expression of MUC2 (mucin 2) and MUC3 (mucin 3) genes in tissues of the normal gastric mucosa, intestinal metaplasia (IM) and gastric carcinoma. METHODS: MUC2 and MUC3 apomucins were detected by immunohistochemistry; MUC2 and MUC3 mRNAs were detected by in situ hybridization. RESULTS: In the normal stomach, antibody detecting MUC2 apomucin and oligonucleotide probe detecting MUC2 mRNA were not reactive with mucus-producing cells in the superficial epithelium and neck, which were weakly reactive with antibody and probe detecting MUC3. In the duodenum, MUC2 apomucin and mRNA were found at the peri- and supranuclear area of goblet cells, but MUC3 apomucin and mRNA were at the cytoplasm of goblet cells and columnar cells. MUC2 and MUC3 apomucins and its mRNAs were found in 85.2%, 88.9% and 31.6%; 57.1% of specimens of IM, 67.4%, 66.7% and 57.9%, 43.6% of specimens of gastric carcinoma. There were no associations between expressions of MUC2 and MUC3 genes and different types of IM. Patients with moderate/well differentiation had higher proportion of MUC2 apomucin expression than those with poor differentiation (P < 0.05), and patients with positive staining of MUC3 apomucin in the cancerous tissues had higher proportions of metastasis of lymph nodes (P < 0.01), serosal invasion (P < 0.05) and clinical stages III-IV (P < 0.05). CONCLUSIONS: MUC2 and MUC3 genes are mainly expressed in the mucosa of the duodenum, and marked expression is seen during the neoplastic transformation of stomach mucosa. MUC3 apomucin might have a poor prognostic significance.

Adult↗

[Relationship between the expression of cell cycle regulators and microsatellite instability in colorectal carcinomas].

OBJECTIVE: To explore the relationship between the expression of cell cycle regulators and microsatellite instability (MSI) in colorectal carcinomas(CRC). METHODS: The expression of cell cycle regulators cyclin D1, P16, P21WAF1/CIP1, P53, Rb and PCNA were detected by immunohistochemical staining, and MSI at six microsatellite loci (D18S34, D17S799, D5S409, TCF-2, Rb and P53) were examined by PCR-SSLP in 56 cases of colorectal carcinomas. RESULTS: The overall positive rate of MSI of CRC was 44.6% (25/56). MSI was positive at 1 locus in 7 cases, at 2 and more than 2 loci in 18 cases. In CRC with MSI, the positive rate of cyclin D1 and P53 protein was significantly lower, while that of P21 protein was significantly higher than those without MSI (P < 0.05). The positive rate of P16 in CRC with MSI was higher than those without MSI. The expression of Rb proteins was similar in frequency in CRC with or without MSI. CONCLUSION: Overexpression of P21 may play an important role in MSI genesis in CRC. It may also be related to decreased expression of cyclin D1 and P53 and overexpression of P16.

Cell Cycle↗

[Correlation study of the longest diameter of gastric cardia cancer and its prognosis].

OBJECTIVE: Based on the longest diameter of cancer of gastric cardia, to formulate a new way of staging for better assessment of prognosis. METHODS: A total of 1,536 cases of resected carcinoma of the gastric cardia through left thoracic approach was statistically analyzed using STATA 5.0 software. The survival rate was estimated using life table method. The difference in survival rate between groups was evaluated by the log-rank test. The ratio difference between groups was evaluated by chi 2 test. RESULTS: The longest tumor diameter was divided into 6 grades according to its length: grade I, < 2 cm; grade II, 2 cm-< 4 cm; grade III, 4 cm-< 6 cm; grade IV, 6 cm-< 8 cm; grade V, 8 cm-< 11 cm and grade VI, > or = 11 cm. The 5-year survival rate was 61.5% in grade I, 44.4% in grade II, 26.4% in grade III, 20.5% in grade IV, 16.1% in grade V and 5.7% in grade VI, respectively. There was statistically significant difference (P < 0.05) in 5-year survival rate between 2 grades from grade II to grade VI. CONCLUSION: The longest tumor diameter is of prognostic significance in cancer of gastric cardia.

Adult↗

[A modified assay for phospholipids in blood serum].

An antiscorbutate reduction method for serum phospholipids assay was modified by decreasing the consumed quantity of sulphuric acid and perchloric acid to 30% of that before modification, and the quantity of serum to 40% of that before modification. The digesting time was only 50%-62% of that before modification. The coefficients of variation (CV) were 3.4% and 3.7% for two batches of assays. Recovery of phosphotidylcholine added to serum ranged form 94% to 109%, averagely 100.8%. Serum phospholipids assay of 50 normal adults by the methods before and after modification showed statistically no significant difference (2.813 +/- 0.333 mmol/L vs 2.828 +/- 0.316 mmol/L, P > 0.05), but good correlation (r = 0.991). The results indicate that the modified assay for serum phospholipids can decrease the use of serum and reagents, especially the harmful acids, and get the same result as that before modification.

Ascorbic Acid↗

[Effect of dengue virus infection on the production of ET-1 and PGI2 by human vascular endothelial cells].

OBJECTIVE: To study the effect of dengue virus infection on the production of endothelin 1(ET-1) and prostacyclin 2(PGI2) by human umbilical cord vein endothelial cells (HUVECs). METHODS: HUVECs were infected by dengue-2 virus (DV-2), the culture supernatants were collected at 4, 24, 48, 72 and 96 hours postinfection, and the levels of ET-1 and PGI2 were measured by radio-immunoassay. RESULTS: The results showed that inhibition of production of ET-1 and PGI2 was induced by dengue virus infection in HUVECs. Marked inhibition of ET-1 and PGI2 production was observed as early as 4 h postinfection and the inhibitory effect continued until 96 h postinfection. Significant differences were shown between the ET-1 concentration of the virus-infected and non-infected cells. Nevertheless, the inhibitory effect of dengue virus infection on the production of PGI2 gradually decreased and the PGI2 concentration reverted to normal level at 96 h postinfection. No significant difference between the PGI2 concentration of the virus-infected and non-infected cells was seem. CONCLUSION: The present study suggests that dengue virus infection of vascular endothelial cells could affect their normal functions of secretion of vasoactive substances, resulting in increased vascular permeability and impairment of homostasis and blood coagulation. Therefore, functional impairment of vascular endothelial cells induced by dengue virus might be an important aspect in the pathogenesis of DHF/DSS.

Cells, Cultured↗

Heat shock cognate protein 70 is a cell fusion-enhancing factor but not an entry factor for human T-cell lymphotropic virus type I.

Heat shock cognate protein 70 (HSC70) has been shown to bind to the peptide corresponding to amino acids 197 to 216 of human T-cell lymphotropic virus type I (HTLV-I) envelope protein, gp46, and an anti-HSC70 monoclonal antibody (mAb) inhibits HTLV-I-induced syncytium formation. These findings suggest that HSC70 is necessary for the entry of HTLV-I into its target cells. Here we showed that HSC70 directly binds to gp46 by co-immunoprecipitation of HSC70 and gp46 from HTLV-I-producing human T-cell lysate. However, transduction of human HSC70 cDNA into BaF3 cells, which were found to be highly resistant to HTLV-I infection, did not support the HTLV-I entry, and HSC70 expressed in NIH3T3 cells, which were found to be almost resistant to syncytium formation upon cocultivation with HTLV-I-producing cells but sensitive to infection with cell-free HTLV-I, enhanced cell fusion induced by HTLV-I-producing cells, but did not enhance the entry of cell-free HTLV-I into these cells. The mAb against HSC70 inhibited syncytium formation in NIH3T3 cells expressing HSC70, but showed little effect on infection of these cells with cell-free HTLV-I. These findings indicate that HSC70 markedly enhances syncytium formation induced by HTLV-I but does not facilitate HTLV-I entry into target cells.

3T3 Cells↗

Identification and characterization of receptor for mammalian hepatopoietin that is homologous to yeast ERV1.

Hepatopoietin (HPO) is a novel polypeptide mitogen specific for hepatocytes and hepatoma cell lines, which is derived from liver and supports its regeneration. To determine whether HPO acts via a receptor-based signal transduction, recombinant human hepatopoietin was labeled by iodination and used to characterize its binding activity by specific displacement test and Scatchard analysis in primarily cultured rat hepatocytes and human hepatoma Hep-G2 cells. The binding was saturable and specific because it was replaceable by HPO but not by epidermal growth factor, transforming growth factor-alpha, or insulin. Scatchard analysis indicated the presence of a single class of high affinity receptor with dissociation constant (Kd) of 2 and 0.7 pM, and a receptor density of about 10, 000 sites/cell and 55,000 sites/cell in the rat hepatocytes and human hepatoma cells, respectively. The Kd values were consistent with the half-maximum dose of HPO activity. Affinity cross-linking of the receptor with 125I-HPO revealed a polypeptide of molecular mass approximately 90 kDa by SDS-polyacrylamide gel electrophoresis. Thus, the molecular mass of the HPO receptor was calculated to be about 75 kDa. These data demonstrated the existence of an HPO receptor in hepatocytes and hepatoma cells, which may account for biological effect.

Animals↗

Role of microphthalmia transcription factor in regulation of melanocyte differentiation marker TRP-1.

Tyrosinase and a family of tyrosinase-related proteins (TRPs) are melanocyte differentiation gene products involved in melanin pigmentation. Members of the tyrosinase family share upstream transcriptional regulatory elements suggesting that expression of these genes is regulated by shared mechanisms. Microphthalmia transcription factor MITF, a melanocyte-specific basic helix-loop-helix protein, has been shown to transactivate tyrosinase and TRP-1 genes in vitro by binding to a shared regulatory sequence known as M box. The role of MITF in concomitant regulation of these genes in vivo is not clear. We showed earlier that in human melanoma cells TRP-1 can be regulated independently of tyrosinase and pigmentation. To investigate the role of MITF in TRP-1 regulation, we studied the effect of pharmacological agents that modulate transcription of tyrosinase and TRP-1 on MITF. In melanoma cells treated with hexamethylene bisacetamide (HMBA), transcription of TRP-1 gene was selectively and completely inhibited while steady state levels of tyrosinase, TRP-2, MITF mRNA and melanin content showed a modest increase. HMBA caused no detectable change in cellular MITF or its nuclear localization. This MITF-independent regulation of TRP-1 required continued synthesis of RNA and protein. Selective down-regulation of TRP-1 by HMBA occurred even in the presence of cholera toxin which up-regulates TRP-1 by cAMP-mediated pathways. These data show that TRP-1 gene can be down-regulated independently of MITF by de novo activation of negative regulatory factors. Thus, both activation of positive factors such as MITF and inactivation of negative regulatory factors may be required for TRP-1 gene expression during melanocytic differentiation.

Acetamides↗

Separation of double-stranded DNA fragments in plastic capillary electrophoresis chips by using E99P69E99 as separation medium.

The separation of double-stranded DNA (dsDNA) fragments in polymethylmethacrylate (PMMA) capillary electrophoresis (CE) chips by using E99P69E99 as a separation medium has been demonstrated. The PMMA CE chips were simply manufactured by micromachining and adhesive tape sealing. To make the separation channel compatible with the separation medium, a dynamic nonionic surfactant coating procedure was developed, which made the plastic separation channel sufficiently hydrophilic to allow the separation medium to fill the channel by capillary action. Subsequent separation of DNA fragments was successful with a separation efficiency of the order of 10(4) theoretical plates over an effective separation distance of 1.5 cm. By using an applied electric field strength of 200 V/cm, the separation of low DNA mass ladder was completed within 5 min. The simple coating procedure, together with the self-assembled viscosity-adjustable separation medium, should be useful to meet some of the essential requirements for developing single-use disposable CE chips. Coating the channels with polymer blends of PMMA and the separation medium also showed promise.

Animals↗

When are students most at risk of encountering academic difficulty? A study of the 1992 matriculants to U.S. medical schools.

The authors carried out the study reported here to assess which variables are most predictive of the risk of medical students' experiencing academic difficulties and to assess when these students are most susceptible to encountering those difficulties. The entering class of 1992 was chosen as the study population because it was the first matriculating class in which the majority of students (88%) applied to medical school with scores from the revised Medical College Admission Test (MCAT), first implemented in 1991. The primary event of interest in this study was the first occurrence of one of the following events because of academic difficulty: withdrawal, leave of absence, dismissal, or delay of graduation date. The variables examined were MCAT scores undergraduate science GPA, undergraduate institutional selectivity, undergraduate major, racial-ethnic background, sex, and age upon entering medical school. Survival analysis was used to assess which variables were most predictive of the risk of academic difficulty and when students with different characteristics were most at risk. The results of the survival analysis indicated that (1) while the risk and timing of academic difficulty varied across the groups studied, a majority of the students who experienced academic difficulty eventually graduated from medical school and (2) students with non-science undergraduate majors did not have a greater risk of academic difficulty. The results confirm previous findings that increased risk of academic difficulty is associated with low MCAT scores, low science GPA, low undergraduate institutional selectivity, being a woman, being a member of a racial-ethnic underrepresented minority, or being older. The study findings can be generalized to help in early identification of students who are more likely to be at risk of experiencing academic difficulty. Knowing when these students are more likely to be at risk can help medical schools develop targeted remedial and enrichment programs. Further studies are needed to investigate school-related factors associated with risk.

Adult↗

[Gene transfer efficiency enhancement by inactivated Coxsakie virus B1 in primary skeletal muscle cells].

OBJECTIVE: To study the effect of inactivated Coxsackie virus B1(CVB1), which was considered to have high affinity to skeletal muscle cell, on gene transfer efficiency of reporter gene, pCDNA3-LacZ, in primary muscle cells. METHODS: Viruses were purified by polyethylene sedimentation followed by sucrose supercentrifugation. Virus, transferrin-polylysine(TfpL) and LacZ were designed as different concentrations and groups, then positive cells contained beta-galactosidase were calculated as gene transfer efficiency. RESULTS: Inactivated CVB1 made an enhancement of gene transfer efficiency from less than 1% in TfpL+LacZ group to 15-20 per cent in CVB1+TfpL+LacZ group. CONCLUSION: Like adenovirus, inactivated CVB1 can also increase gene transfer efficiency in muscle cells, which provides experimental basis for constructing new vector targeting to muscle cells.

Cells, Cultured↗

[The possible role of loss of heterozygosity at APC, MCC and DCC genetic loci in esophageal carcinoma].

OBJECTIVE: To investigate the alterations of APC, MCC and DCC genes in human esophageal carcinoma. METHODS: A total of 46 human esophageal cancer specimens were analyzed for the loss of heterozygosity (LOH) at APC, MCC and DCC genetic loci by means of polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The incidence of LOH was 29.0%(9/31) at APC locus, 33.3%(8/24) at MCC locus, and 32.4%(12/37) at DCC locus, respectively. However, there was no statistically significant correlation between LOH at these three loci with such clinical parameters as pathological types, tumor size, invasiveness, and lymph-node metastasis. CONCLUSION: These data suggest that LOH at APC, MCC and DCC loci in esophageal carcinoma is, to certain extent, a common genetic alteration which might play a role in esophageal carcinogenesis.

Chromosome Mapping↗