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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 91 records · Page 5Linked to original sources

Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model.

Flexor tendon repair in zone II is complicated by adhesions that impair normal postoperative gliding. Transforming growth factor-beta (TGF-beta) is a family of growth factors that has been implicated in scar formation. The TGF-beta family of proteins binds to three distinct classes of membrane receptors, termed RI, RII, and RIII. In this study, we analyzed the temporal and spatial distribution of TGF-beta receptor isoforms (RI, RII, and RIII) in a rabbit zone II flexor tendon wound healing model.Twenty-eight adult New Zealand White rabbit forepaws underwent isolation of the middle digit flexor digitorum profundus tendon in zone II. The tendons underwent transection in zone II and immediate repair. The tendons were harvested at increasing time points: 1, 3, 7, 14, 28, and 56 days postoperatively (n = 4 at each time point). The control flexor tendons were harvested without transection and repair (n = 4). Immunohistochemical analysis was used to detect the expression patterns for TGF-beta receptors RI, RII, and RIII. Immunohistochemical staining of the transected and repaired tendons demonstrated up-regulation of TGF-beta RI, RII, and RIII protein levels. TGF-beta receptor production in the experimental group (transection and repair) was concentrated in the epitenon and along the repair site. Furthermore, the TGF-beta receptor expression levels peaked at day 14 and decreased by day 56 postoperatively. In contrast, minimal receptor expression was observed in the untransected and unrepaired control tendons. These data provide evidence that (1) TGF-beta receptors are up-regulated after injury and repair; (2) peak levels of TGF-beta receptor expression occurred at day 14 and decreased by day 56 after wounding and repair; and (3) both the tendon sheath and epitenon have the highest receptor expression, and both may play critical roles in flexor tendon wound healing. Understanding the up-regulation of TGF-beta isoforms and the up-regulation of their corresponding receptors during flexor tendon wound healing provides new targets for biomolecular modulation of postoperative scar formation.

Animals↗

An iterative EPID calibration procedure for dosimetric verification that considers the EPID scattering factor.

There has been an increasing interest in the application of electronic portal imaging devices (EPIDs) to dosimetric verification, particularly for intensity modulated radiotherapy. Although not water equivalent, the phantom scatter factor of an EPID, Spe, is generally assumed to be that of a full phantom, Sp, a slab phantom, Sps, or a mini phantom. This assumption may introduce errors in absolute dosimetry using EPIDs. A calibration procedure that iteratively updates Spe and the calibration curve (pixel value to dose rate) is presented. The EPID (Varian Portal Vision) is irradiated using a 20 x 20 cm2 field with different beam intensities. The initial guess of dose rates in the EPID is calculated from ionization chamber measurements in air, multiplied by Sp or Sps. The calibration curve is obtained by fitting EPID readings from pixels near the beam central axis and dose rates in EPID to a quadratic equation. The Spe is obtained from EPID measurements in 10 X 10 cm2 and 20 x 20 cm2 field and from the calibration curve, and is in turn used to adjust the dose rate measurements and hence the calibration curve. The above procedure is repeated until it converges. The final calibration curve is used to convert portal dose to dose in the slab phantom, using the calibrated Spe, or assuming Spe = Sp or Spe=Sps . The converted doses are then compared with the dose measured using an ionization chamber. We also apply this procedure to off-axis points and study its dependence on the energy spectrum. The hypothesis testing results (on the 95% significance level) indicate that systematic errors are introduced when assuming Spe = Sp or Spe=Sps and the dose calculated using Spe is more consistent with ionization chamber measurements. Differences between Spe and Sps are as large as 2% for large field sizes. The measured relative dose profile at dmax using the EPID agrees well with the measured profile at dmax of the isocentric plane using film in a polystyrene phantom with full buildup and full backup, for open and wedged fields, and for a broad range of field sizes of interest. The dependence of the EPID response on the energy spectrum is removed once the calibration is performed under the same conditions as the actual measurements.

Algorithms↗

Replication of the human hepatitis delta virus genome Is initiated in mouse hepatocytes following intravenous injection of naked DNA or RNA sequences.

As early as 5 days after DNA copies of the hepatitis delta virus (HDV) genome or even in vitro-transcribed HDV RNA sequences were injected into the mouse tail vein using the hydrodynamics-based transfection procedure of F. Liu et al. (Gene Ther. 6:1258-1266, 1999), it was possible to detect in the liver by Northern analyses of RNA, immunoblots of protein, and immunostaining of liver sections what were considered typical features of HDV genome replication. This transfection strategy should have valuable applications for in vivo studies of HDV replication and pathogenesis and may also be useful for studies of other hepatotropic viruses.

Animals↗

Benign and malignant breast masses and axillary nodes: evaluation with echo-enhanced color power Doppler US.

PURPOSE: To evaluate microbubble contrast enhancement in distinguishing malignant from benign breast masses and malignant from benign axillary nodes in patients with breast cancer. MATERIALS AND METHODS: Eighty-six patients with 86 breast masses and 32 patients with breast cancer (subgroup of 86 patients) with 32 axillary nodes underwent color power Doppler ultrasonography with and without contrast material. Vascular features and contrast material transit times were recorded. Nodal enhancement was compared with corresponding primary breast cancer enhancement in the subset of 32 patients. RESULTS: Pathologic analysis revealed 58 breast carcinomas and 28 benign breast lesions and 20 malignant and 12 benign axillary nodes in the 32 patients with breast cancer. Breast cancers had a greater total number and greater number of peripheral vessels than did benign lesions before and after contrast material administration (P <.001). Malignant nodes had a greater total number and greater number of peripheral vessels at baseline and after contrast enhancement (P <.05), and a longer enhancement duration (P =.004) compared with benign nodes. Malignant nodes enhanced more than did corresponding primary breast cancers. Postcontrast number of peripheral vessels was an independent predictor of primary breast cancer (P <.05), and increased number of peripheral vessels after contrast enhancement and enhancement duration were independent predictors of nodal malignancy (P <.05). CONCLUSION: Primary breast cancers and malignant axillary nodes had a greater total number and greater number of peripheral vessels compared with benign breast masses and axillary nodes, respectively.

Adult↗

Activation of the heat shock response: relationship to energy metabolites. A (31)P NMR study in rat hearts.

Heat shock factor (HSF), the transcription factor for the heat shock proteins, is activated by cardiac ischemia, but the mechanism of activation is unknown. Ischemia is accompanied by changes in the energy state and acid-base conditions. We hypothesized that decreased ATP and/or intracellular pH (pH(i)) might activate HSF. To test this hypothesis, we perfused rat hearts within an NMR spectrometer. NMR data showed that after 6.5, 13, and 20 min of ischemia, ATP dropped to 62.7, 23.1, and 6.9% of the control level, and pH(i) was 6.16, 5.94, and 5.79, respectively. Reperfusion after ischemia partially restored ATP levels, and this was associated with greater activation of HSF1. HSF1 was also activated after 6.5 min of ischemia. Activation of HSF1 was less after 13 min of ischemia and barely detectable after 20 min of ischemia. In conclusion, 1) a moderate decrease in intracellular ATP correlates with activation of HSF1 in the heart; and 2) a severe depletion in ATP correlates with an attenuation in HSF1 activation, and the restoration of ATP leads to greater activation of HSF1, suggesting that a critical ATP level is required for activation of HSF1.

Adenosine Triphosphate↗

Ultrastructural study of anterograde transport of glial cell line-derived neurotrophic factor from dorsal root ganglion neurons of rats towards the nerve terminal.

The glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic substance in the central and peripheral nervous systems. The present immunohistochemical study clarified the ultrastructural localization of GDNF-immunoreactive substance (GDNF-IR) accumulated at transfected sciatic nerve stumps and also at normal spinal dorsal horn, and has demonstrated that GDNF-IR products appear to be located in dense-cored vesicles within the axons. Furthermore, to determine the source of proximally accumulated GDNF in the transected sciatic nerve, we attempted a transection and a double ligation maneuver involving the sciatic nerve. In the early period after the ligation (20 h), GDNF-IR fibers were observed in the proximal and distal segment of the ligations, but no immunoreactivities were detected in the middle segment. On the other hand, at a late period (8 days) after the transection, GDNF-IR fibers had almost disappeared, but weak GDNF-IR was observed in Schwann cells in the proximal and distal stumps of transected nerve. These findings suggest that most of GDNF-IR was transported from the proximal or distal side in the early period, but was locally synthesized by Schwann cells around the ligations in the late period. Spinal rhizotomy caused prominent accumulation of GDNF-IR products at the cut end of the ganglion side of the dorsal root, but not at the ventral root. These results suggested that dorsal root ganglionic (DRG) sensory neurons are one of the origins of GDNF. The fact that small- to medium-sized DRG neurons show enhanced GDNR-IR after the colchicine treatment may support the above suggestion. In conclusion, the present results strongly suggest that a subgroup of DRG sensory neurons synthesized GDNF-containing dense-cored vesicles in the neuronal somata and anterogradely transports the vesicles to peripheral or central axon terminals.

Animals↗

Cord blood G(0) CD34+ cells have a thousand-fold higher capacity for generating progenitors in vitro than G(1) CD34+ cells.

We examined the functional differences between G(0) and G(1) cord blood CD34+ cells for up to 24 weeks in serum-free suspension culture, containing Flt-3 ligand, thrombopoietin and stem cell factor. By week 24, there is more than a 1,000-fold difference in granulocyte, macrophage-colony-forming cells (GM-CFC) cumulative production between the two populations, with cultures initiated from G(0) demonstrating an amplification of 1.1 x 10(5)-1.8 x 10(6) of GM-CFC compared to 45-2.7 x 10(3) for the G(1) cells. Cells from the initial G(0) population are able to produce about 250-fold higher numbers of BFU-E than those from G(1) which translates to 3 x 10(3)-1.1 x 10(5)-fold expansion and 25-390-fold expansion for G(0) and G(1), respectively. This amplification of the progenitor cells is reflected in finding that a greater proportion of the progeny of the G(0) population are CD34+, resulting in a 600-fold expansion of CD34+ cells at week 8. As in other in vitro systems, total cell expansion is less discriminatory of stem cell behavior than progenitor cells, and there is no significant difference in total cell numbers between G(0) and G(1) cultures with a mean fold expansion of 2 x 10(7) at 24 weeks.

Antigens, CD34↗

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in bronchial asthma and allergic rhinitis.

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.

Adult↗

Photodynamic therapy in the canine prostate using motexafin lutetium.

Our purpose was to determine the feasibility of comprehensive treatment of the canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex) and to evaluate the toxicity and tissue effects associated with this treatment. Twenty-five adult male beagles with normal prostate glands were given an i.v. injection of the second-generation photosensitizer Lu-Tex (2-6 mg/kg). An additional two dogs were used as controls and did not receive any photosensitizing drug. All 27 dogs underwent laparotomy to expose the prostate. Three hours postinjection, a total dose of 75-150 J/cm of 732 nm laser light was delivered interstitially and/or transurethrally to the prostate via cylindrical diffusing fibers. Dogs were euthanized between 2 days and 3 months after PDT. All subjects were monitored for clinical evidence of toxicity. Specimens were examined macroscopically and microscopically to characterize the tissue reaction and assess extent of tissue effect as a result of treatment. Interstitial and/or transurethral PDT were successfully delivered in all dogs with no perioperative complications. No clinical evidence of acute urinary obstruction or rectal bleeding was noted. At all dose levels, macroscopic and microscopic evaluation revealed a prostatic tissue reaction characterized initially (within 48 h) by inflammation and necrosis followed by fibrosis and glandular epithelial atrophy. Comprehensive treatment of the entire prostate could be achieved using the interstitial alone approach or combined transurethral and interstitial approach. The transurethral alone approach did not result in complete coverage of the prostate. Dogs receiving transurethral or combined interstitial and transurethral treatment developed erythema and urethral epithelial disruption at all dose levels. Those receiving combined treatment at the highest dose level (Lu-Tex 6 mg/kg, 150 J/cm light) developed urethral fistulae and peritonitis. Dogs treated with the interstitial alone approach were found to have the least amount of urethral damage. Comprehensive treatment of the canine prostate with Lu-Tex PDT is feasible using an interstitial alone or combined interstitial and transurethral approach. The interstitial alone technique results in the least amount of toxicity. The prostatic tissue reaction to treatment is characterized by initial inflammation and necrosis followed by fibrosis and glandular epithelial atrophy.

Animals↗

Pathological features and BRCA1 mutation screening in premenopausal breast cancer patients.

PURPOSE: Risk calculations for carrying BRCA1/BRCA2 mutations are based on family history and the age of onset of cancers. However, women may carry these deleterious mutations without a strong family history. Additional criteria for risk estimation would be of value. It has been recently established that BRCA1-associated breast cancers are associated with poor tumor differentiation (TD3) and estrogen receptor (ER) negativity. The aim of this study is to determine whether morphological features of breast cancers in premenopausal patients (age < 45 years) could determine additional women who may benefit from BRCA1 screening. EXPERIMENTAL DESIGN: In a prospective, systematic study of 76 consecutive breast cancer patients (age < 45 years), genomic DNA was obtained from peripheral blood, and eight mutations in BRCA1 (10.5%) were found. Archival paraffin-embedded breast cancer specimens were then analyzed for tumor differentiation and ER status. RESULTS: In patients < 45 years of age, 25% (6 of 24) of ER-negative and TD3 breast cancers were found to harbor mutations in BRCA1. Only 5.6% (2 of 36) of BRCA1-associated breast cancers did not have this morphological profile, compared with 94.4% (34 of 36) patients without BRCA1 mutations, giving an odds ratio of 5.67 (95% confidence interval, 1.04-32; P = 0.05). Finally, only one patient with BRCA1 mutations had a significant family history. CONCLUSIONS: In patients with early-onset breast cancer, the use of morphological criteria provides an additional strategy to determine those patients who might benefit from genetic testing.

Adult↗

Frequently deleted loci on chromosome 9 may harbor several tumor suppressor genes in human renal cell carcinoma.

PURPOSE: Loss of various loci on chromosome 9 has been reported in various cancers. To determine the frequency of deletions at different loci of chromosome 9 in renal cell carcinoma microdissected samples of normal renal epithelium and carcinoma from the same patients were analyzed. MATERIALS AND METHODS: DNA was isolated from microdissected sections of normal and tumor cells of 60 renal specimens, amplified by polymerase chain reaction and analyzed for loss of heterozygosity on chromosome 9 using the 16 microsatellite markers D9S178, D9S157, D9S274, D9S168, D9S285, D9S156, D9S1839, D9S162, IFNA, D9S736, D9S171, D9S1749, D9S273D9S270, D9S153 and D9S170. Loss of heterozygosity was analyzed by a polymerase chain reaction based technique developed at our laboratory. RESULTS: This study showed a high incidence of loss of heterozygosity on chromosome 9 in renal cell carcinoma. Of 60 cases 44 (73%), 24 (40%) and 14 (23%) showed loss of heterozygosity at a minimum of 1, at a minimum of 3 and at 4 or more loci, respectively. The main deletion was found on the 9p21 region at loci DS171 in 38% of cases, D9S1749 in 42% and DS270 in 14%. Overall deletion on chromosome 9p21 was noted in 57% of renal cancer cases. Other deleted regions were on chromosome 9p'0022 to 23 at loci D9S157 in 37% of cases, D9S274 in 20%, D9S168 in 27%, D9S285 in 20%, D9S156 in 12%, D9S1839 in 17% and D9S162 in 24%. Overall deletion at chromosome 9q32 to 33 was noted in 46% of renal cell carcinoma cases. Chromosome 9q32 to 33 also showed deletion at locus D9S170 in 22% of renal cell carcinoma cases. When we compared the incidence of deletion at various loci on chromosome 9 according to renal cell carcinoma grade, we found a higher rate of deletion in advanced grades of renal cell carcinoma. A candidate target tumor suppressor gene, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in various cancers. In our study the expression of p16 protein was absent or low in renal cell cancer samples, suggesting that loss of the p16 gene may be involved in renal cell carcinogenesis. CONCLUSIONS: Our study demonstrates a high incidence of loss of heterozygosity on chromosome 9, mainly 9p21 and 9p22 to 23, in renal cell carcinoma, suggesting several putative tumor suppressor genes on these regions. The identification of other tumor suppressor genes on the 9p21 and 9p22 to 23 regions warrants further studies.

Carcinoma, Renal Cell↗

Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking.

The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The cholesterol microdomains were visualized with a monoclonal antibody that specifically detects ordered cholesterol arrays. These unique cholesterol microdomains were induced on macrophages and fibroblasts when they were enriched with cholesterol in the presence of an ACAT inhibitor, to block esterification of excess cellular cholesterol. Induction of the plasma membrane cholesterol microdomains could be blocked by agents that inhibit trafficking of cholesterol to the plasma membrane and by cholesterol acceptors that remove cholesterol from the plasma membrane. In addition, plasma membrane cholesterol microdomains did not develop in mutant Niemann-Pick type C fibroblasts, consistent with the defect in cholesterol trafficking reported for these cells. The induction of plasma membrane cholesterol microdomains on inhibition of ACAT helps explain how ACAT inhibition promotes cholesterol efflux from cells in the presence of cholesterol acceptors such as HDL. The anti-cholesterol monoclonal antibody also detected extracellular cholesterol-containing particles that accumulated most prominently during cholesterol enrichment of less differentiated human monocyte-macrophages. For the first time, cholesterol microdomains have been visualized that function in cholesterol trafficking to and from the plasma membrane.

Animals↗

The CNS midline cells control the spitz class and Egfr signaling genes to establish the proper cell fate of the Drosophila ventral neuroectoderm.

The spitz class genes, pointed (pnt), rhomboid frho), single-minded (sim), spitz (spi)and Star (S), as well as the Drosophila epidermal growth factor receptor (Egfr) signaling genes, argos (aos), Egfr, orthodenticle (otd) and vein (vn), are required for the proper establishment of ventral neuroectodermal cell fate. The roles of the CNS midline cells, spitz class and Egfr signaling genes in cell fate determination of the ventral neuroectoderm were determined by analyzing the spatial and temporal expression patterns of each individual gene in spitz class and Egfr signaling mutants. This analysis showed that the expression of all the spitz class and Egfrsignaling genes is affected by the sim gene, which indicates that sim acts upstream of all the spitz class and Egfr signaling genes. It was shown that overexpression of sim in midline cells fails to induce the ectodermal fate in the spi and Egfr mutants. On the other hand, overexpression of spi and Draf causes ectopic expression of the neuroectodermal markers in the sim mutant. Ectopic expression of sim in the en-positive cells induces the expression of downstream genes such as otd, pnt, rho, and vn, which clearly demonstrates that the sim gene activates the EGFR signaling pathway and that CNS midline cells, specified by sim, provide sufficient positional information for the establishment of ventral neuroectodermal fate. These results reveal that the CNS midline cells are one of the key regulators for the proper patterning of the ventral neuroectoderm by controlling EGFR activity through the regulation of the expression of spitz class genes and Egfr signaling genes.

Animals↗

[Effect of rare earth elements on the seedling ratio of crops].

The effects of rare earth elements(REEs) on the relative seedling ratio of three crops(rice, rape and soybean) in three soil(red soil, yellow fluvo-aquic soil and yellow cinnamon soil) were studied according to OECD method, and the LC50 were obtained. Toxicity effect of REEs on rice was minimum among the crops tested. The toxicity on crops in yellow cinnamon soil was lower, whereas on soybean in yellow fluvo-aquic soil and on rape in red earth were higher.

Crops, Agricultural↗

Combined innominate artery reconstruction and coronary artery bypass grafting.

Two patients having significant coronary artery disease with innominate artery near-total occlusion presented neurological deficit of syncope events or cerebellar and brain stem infarct. Both of them were successfully treated with one-stage reconstruction combined with aorto-carotid-subclavian bypass and coronary artery bypass grafting (CABG). While it could not be over-emphasized how to protect both myocardium and cerebrum during CABG, cerebral perfusion through the reconstructed carotid bypass graft is the key maneuver during cardiac arrest and moderate hypothermia. Hypoperfused cerebral hemispheres were both improved extensively in the follow-up angiography. The absence of cerebral deficit and the free from coronary angina suggested that surgical technique to combine innominate with coronary artery surgery is feasible with acceptable mortality and morbidity rate.

Aged↗

Endovascular aortic graft exclusion of abdominal aortic aneurysm.

Endovascular repair of abdominal aortic aneurysms has evolved dramatically within the past few years. This study reports the first successful case in Taiwan area of infrarenal abdominal aortic aneurysm treated with endovascular aortic bifurcational stent-graft. Minimally invasive surgery leading to early recovery, mobilization and shortened hospital day was promising. In addition, there were no local, remote or systemic complications during a 18-month follow-up. Thus, the procedure is an attractive alternative in its potential to reduce morbidity and mortality associated with open surgical repair, especially for patients who are not surgical candidates because of comorbidities. Careful patient selection and more experiences with refined endograft models will elucidate the feasible alternative to conventional surgical repair.

Aged↗

[Effects of pyracantha fortuneana extract on blood coagulation].

OBJECTIVE: To study the effect of the Pyracantha fortuneana extract and its defferent polar fractions on blood coagulation. METHODS AND RESULTS: The Pyracantha fortuneana extract could noticeably shorten the coagulation time of glass slide in mice (P < 0.05) after oral administration, and also shorten the recalcification time and prothrombin time in vitro (P < 0.01, P < 0.05), while in three polar fractions of the extract, the effects of the chloroform phase that could shorten the coagulation time of glass slide in mice(P < 0.01) after oral administration, and also shorten the recalcification time and prothrombin time in vitro (P < 0.01) are more noticeable than that of the acetic ether phase (P < 0.01, P < 0.05). The petroleum ether phase has no above-mentioned effect (P > 0.05). CONCLUSION: The Pyracantha fortuneana extract can reduce the blood coagulation. Both the chloroform phase and the acetic ether phase of the extract have activity of blood coagulation, but the petroleum ether phase does not.

Animals↗