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Biomedical subjects

H E Wang

Publications and source records attributed to H E Wang.

At least 19 recordsLinked to original sources

A high yield robotic synthesis of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F] FHPG) for gene expression imaging.

The aim of this study was to develop an automated synthesis of 9-(4-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG) and 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG) using a Scanditronix Anatech RB III robotic system. [(18)F]HF was produced via (18)O(p, n)(18)F using a Scanditronix MC17F cyclotron. On average, a typical run produced [(18)F]FHBG and [(18)F]FHPG with an uncorrected radiochemical yield of 19% and 16%, respectively, at end of synthesis (EOS) from irradiation of 95% enriched [(18)O]water. The total synthesis time was 80 min. The retention time of [(18)F]FHBG and [(18)F]FHPG (the radio-peak) was 3.9 and 4.0 min, respectively, which was consistent with the [(19)F]FHBG and [(19)F]FHPG ultraviolet peak. The radiochemical purity was greater than 97%. A robotic, automated method for [(18)F]FHBG and [(18)F]FHPG radiosynthesis is therefore feasible. The radiation burden for the operator can be reduced as much as possible. Sufficient radioactivities of [(18)F]FHBG and [(18)F]FHPG could be obtained for non-invasive monitoring the expression of transfected gene in vivo with positron emission tomography (PET).

Equipment Design↗

A simple model for quantification of the radiobiological effectiveness of the 10B(n,alpha)7Li capture reaction in BNCT.

A simple model has been developed for predicting radiobiological effectiveness of the neutron capture reaction in boron neutron capture therapy. This model was derived from the relationship between the cell survival from the boron capture reaction, the intracellular boron concentration, and the thermal neutron fluence. We found that the cell-killing effect of the boron capture reaction was well described using a power function of the intracellular boron concentration. Hence the relationship between cell survival from the boron capture reaction, intracellular boron concentration, and the thermal neutron fluence could be determined using a simple mathematical equation. We consider that our current approach is more appropriate and realistic than the conventional theoretical mathematical model used to estimate the radiobiological effectiveness of the neutron capture reaction in boron neutron capture therapy.

Animals↗

MicroPET-based pharmacokinetic analysis of the radiolabeled boron compound [18F]FBPA-F in rats with F98 glioma.

Boron neutron capture therapy (BNCT) is one of the effective methods of radiation therapy for the treatment of tumors such as malignant glioma. Boronophenylalanine ((10)B-BPA) solution has been used as a potential boron carrier for such a treatment. The aim of this study is to investigate 4-borono-2-[(18)F]-fluoro-l-phenylalanine-fructose ([(18)F]FBPA-F) in rats injected in the brain with glioma using in vivo small animal positron emission tomography (PET) imaging (microPET). Male Fischer 344 rats with F98 glioma in the left brain were used for these studies. Dynamic PET imaging of [(18)F]FBPA-F was performed on the 13th day after tumor inoculation. Arterial blood sampling was performed to obtain an input function for tracer kinetic modeling. The accumulation ratios of [(18)F]FBPA-F for the glioma-to-normal brain approached 3. The uptake characteristics of BPA-F and [(18)F]FBPA-F were similar. The results indicate that 4h after BPA-F injection would be the optimal irradiation time for BNCT. Rate constants were estimated using a three-compartment model. This study provides useful information for the clinical application of BNCT in patients with brain tumors.

Animals↗

Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.

Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells. We now show that Tsg101 protein, which functions in vacuolar protein sorting (Vps), is required for HIV-1 budding. The UEV domain of Tsg101 binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein and also to ubiquitin. Depletion of cellular Tsg101 by small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of Tsg101. Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. These observations suggest that retroviruses bud by appropriating cellular machinery normally used in the Vps pathway to form multivesicular bodies.

Adenosine Triphosphatases↗

Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals.

UNLABELLED: In this study, the effectiveness of a 188Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. METHODS: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF(1) mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10(5) B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16 approximately 18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (<3 microm:80.4 +/-7.2%, colloid 1) and the other receiving larger particle sizes (<3 microm:12.3+/-1.0%, colloid 2). The animals were checked daily until death and their survival recorded. RESULTS: Colloid 2 showed higher accumulation in almost all tissues, the highest accumulation organ was tumor ( approximately 40%), then spleen ( approximately 20%), stomach ( approximately 15%), diaphragm ( approximately 3%), and liver ( approximately 2%). There was a significant increase in survival time with increasing amount of the larger-particle-size colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with higher amounts the survival times decreased significantly below that of the controls. There was a significant difference in the dose-response curves for the two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved using the larger colloid size, and nearly 30 using the smaller colloid size. An amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies. On the one hand, the survival data agreed well with the biodistribution data, where higher accumulation was found in tumor with colloid 2. CONCLUSION: Rhenium-188 offers on-site availability, medium half-life, higher beta-particle energy of 2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging. The present study demonstrated that 188Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals.

Animals↗

The use of diltiazem for treating rapid atrial fibrillation in the out-of-hospital setting.

STUDY OBJECTIVE: We sought to evaluate the use of intravenous diltiazem for treatment of rapid atrial fibrillation or flutter (RAF) in the out-of-hospital setting. METHODS: This study is a retrospective review of data with historical control subjects. Data were drawn from out-of-hospital patients reported to a statewide paramedic system who presented with atrial fibrillation or flutter and a ventricular response rate (VRR) of 150 beats/min or greater. The intervention (diltiazem) group included patients who received diltiazem during a 9-month period in 1999. The control group included patients from 1998 who did not receive diltiazem. Patients who were intubated or underwent cardioversion were omitted. Therapeutic response was defined as the occurrence of change to sinus rhythm, reduction of VRR to 100 beats/min or less, or reduction of baseline VRR by 20% or greater. Data were analyzed by using the chi(2) test, the Student's t test, and odds ratios (ORs). A Bonferroni adjusted P value of.005 was used to define statistical significance. RESULTS: Forty-three patients receiving diltiazem and 27 control subjects were included in the study. The mean total diltiazem dose was 19.8 mg (95% confidence interval 17.8 to 21.8). The diltiazem and control groups did not significantly differ with respect to age; sex; history of atrial fibrillation; prior use of digitalis, beta-blockers, or calcium channel blockers; concurrent out-of-hospital therapies; or baseline VRR or systolic blood pressure (P =.09 to 1.00). The difference in VRR reduction between the diltiazem and control groups was 38 beats/min (95% confidence interval 24 to 52); this difference was statistically significant (P <.001). The mean percentage reduction of VRR in the diltiazem group was -33.1%. The difference in systolic blood pressure change between the diltiazem and control groups was not statistically significant (P =.17). The diltiazem group had a higher prevalence of achieving VRR reduction to 100 beats/min or less than did the control group (OR 22.6; P <.001), of achieving a VRR reduction of 20% or greater (OR 19.3; P <.001), and of achieving overall therapeutic response (OR 19.3; P <.001). Few changed to sinus rhythm in either group (estimated OR 6.3; P =.15). No patients in the diltiazem group required treatment for hypotension, endotracheal intubation, resuscitation from cardiac arrest, or emergency treatment of unstable dysrhythmias. CONCLUSION: The effects of diltiazem on RAF can be appreciated within the constraints of the out-of-hospital environment. Diltiazem should be considered as a viable field therapy for rate control of RAF.

Aged↗

Effects of biphasic vs monophasic defibrillation on the scaling exponent in a swine model of prolonged ventricular fibrillation.

OBJECTIVE: Mathematical analyses of ventricular fibrillation (VF) have resulted in the derivation of a measure termed the scaling exponent (ScE) that characterizes the duration of VF and probability of defibrillation success. The purpose of this study was to compare the effects of biphasic defibrillation waveform (BDW) and monophasic defibrillation waveform (MDW) rescue shocks on ScE in a swine model of prolonged VF. METHODS: Utstein guidelines for the laboratory study of cardiopulmonary resuscitation were followed. Twenty mixed-breed domestic swine (mass range 20.5-26.8 kg) were instrumented and randomized to receive either MDW or BDW rescue shocks. Ventricular fibrillation was induced and untreated for a nonintervention interval of 8 minutes. Rescue shocks were delivered at 8, 10, and 12 minutes of elapsed VF time. The energy sequence for the three MDW shocks was 70, 100, and 150 J (approximately 3, 4, and 6 J/kg). All BDW shocks were delivered at 50 J (approximately 2.5 J/kg). Only VF was shocked. Chest compressions and drugs were not provided. Rhythm analysis and ScE calculation were performed offline. Continuous and discontinuous linear regression models were fit to plots of ScE vs time. Defibrillation success and progression of ScE slope were analyzed using Fisher's exact test, paired t-tests, and repeated-measures analysis of variance (ANOVA). RESULTS: Baseline characteristics were similar for both groups. Successful termination of VF occurred on the first rescue shock in 1 of 10 (10%) in the MDW group and 3 of 10 (30%) in the BDW group; this difference was not statistically significant (p = 0.58). No other defibrillation successes were observed. No animals achieved return of spontaneous circulation. The ScE values during the protocol progressed from 1.330 (95% CI = 1.287 to 1.373) to 1.724 (95% CI = 1.603 to 1.845) for MDW and 1.338 (95% CI = 1.261 to 1.415) to 1.639 (95% CI = 1.530 to 1.745) for BDW. Both groups showed a trend toward increasing ScE values with successive rescue shocks. Repeated-measures ANOVA using both continuous and discontinuous models demonstrated no difference in overall ScE slope progression between study groups. CONCLUSIONS: Mode of defibrillation waveform (BDW vs MDW) does not appear to impact ScE trends. Additional studies must be performed to better evaluate the clinical implications of this finding.

Animals↗

Sensitization of a tumor, but not normal tissue, to the cytotoxic effect of ionizing radiation using Panax notoginseng extract.

The aim of the present study was to investigate any sensitization effect of the Panax notoginseng extract (PNE) and the purified Saponin (Rb1) on the radiation response of an experimental tumor (KHT sarcoma) in mice, in comparison with any effects on a normal tissue (bone marrow). PNE at a concentration of 0.1-100 mg/kg produced an increase in tumor radiosensitivity. The sensitization effect was maximal at 10 mg/kg and at 30 minutes after injection. Higher doses were toxic to the bone marrow stem cells. Similarly Rb1 at a concentration 0.001 to 1 mg/kg also produced an increase in tumor radiosensitivity, with maximum effect at 1 mg/kg. Higher doses were not toxic to the bone marrow stem cells in this case. Radiosensitization factors were calculated as ratios of D0 (the radiosensitivity parameter), and these were highly significant for the tumor and very similar for both compounds at the doses used, namely 1.18-1.19. There was no significant effect for bone marrow stem cells (sensitization factors of 0.99 +/- 0.01 for both compounds). The differential effect on tumor, and the magnitude of the radiosensitization, suggest that further purified or synthetic versions of this extract may be useful not only in vascular-related diseases but also in cancer therapy.

Animals↗

Preclinical evaluation of locoregional delivery of radiolabeled iododeoxyuridine and thymidylate synthase inhibitor in a hepatoma model.

UNLABELLED: We report improved incorporation of the radiolabeled-thymidine analog [125I/131I]5-iodo-2'-deoxyuridine ([125I/131I]IdUrd) into DNA by the addition of Thymitaq, a thymidylate synthase inhibitor, as a strategy of molecular radiotherapy for hepatoma treatment. METHODS: The synergistic effect of combination [125I]IdUrd and Thymitaq in clonogenic survival and DNA incorporation was shown on the human hepatoma cell line Hep3B. Radiobiodistribution of intrahepatic arterially injected [125I]IdUrd and Thymitaq was studied in a rat N1S1 hepatoma model. In vivo therapeutic effects of locoregional delivery of both drugs were evaluated in mouse subcutaneous hepatoma and ascitic hepatoma models. RESULTS: In a clonogenic assay, Thymitaq showed a synergistic effect with [125I]IdUrd but not cold IdUrd. Thymitaq had a dose-dependent modulation effect on DNA-[125I]IdUrd incorporation. The biodistribution study indicated a slower clearance rate of [125I]IdUdR in the hepatoma as well as an initially higher uptake of [125I]IdUrd into DNA when the [125I]IdUrd was combined with Thymitaq. In vivo studies showed a superior therapeutic effect of combination Thymitaq and [125I]IdUrd in both subcutaneous and ascites tumor models, but the combination of [131I]IdUrd and [125I]IdUrd may be more effective than Auger electron emitters alone for the treatment of subcutaneous tumor. CONCLUSION: The strategy of locoregional delivery of [125I/131I]IdUrd to a tumor site through an intrahepatic arterial, intratumoral, or intraperitoneal route in combination with Thymitaq is promising and may also have a favorable therapeutic index in vivo.

Animals↗

Early catastrophic failure of rotating hinge total knee prosthesis.

The mechanical failure of a prosthesis component is usually observed as a late complication of total knee arthroplasty (TKA). In knees with severe ligament instability and bone deficiency, either a true hinge prosthesis or a rotating hinge implant is commonly used. Failure of the polyethylene bearing bush in a hinge-type prosthesis is a complication that has not been reported to date. We report the cases of 2 rotating hinge TKA prostheses that dislocated as a result of mechanical failure of the prosthetic component within 5 months of initial implantation. Clinicians should be aware of this potential complication when selecting rotating hinge prostheses for certain patients.

Arthroplasty, Replacement, Knee↗

Robotic synthesis of 6-[18F]fluoro-L-dopa.

The aim of this study was to develop a method of semi-automated 6-[18F]fluoro-L-dopa (6-[18F]FDOPA) synthesis using a robotic system (Scanditronix Anatech RB III, Uppsala, Sweden). [18F]Fluorine was produced via 20Ne(d,alpha)18F using a Scanditronix MC17F cyclotron (Uppsala). The radiosynthesis was performed by the Scanditronix Anatech RB III robotic system. On average, a typical run produced 16-19 mCi of 6-[18F]FDOPA at end of synthesis (EOS) after 2 h irradiation of the F2/neon gas target. The total synthesis time was 110 min. The retention time of 6-[18F]FDOPA (the radio peak) was 8.2 min, which was consistent with the 6-[19F]FDOPA ultraviolet peak. The radiochemical purity was greater than 97%. A robotic, semi-automated method for 6-[18F]FDOPA radiosynthesis is therefore feasible. The radiation burden for the operator can be reduced as much as possible. Sufficient activity of 6-[18F]FDOPA could be obtained for positron emission tomography studies of dopaminergic function.

Dihydroxyphenylalanine↗

[Expression of EGFR and PCNA, and DNA content in squamous cell carcinoma of larynx].

OBJECTIVE: To investigate the expression of epidermal growth factor (EGF), proliferating cell nuclear antigen (PCNA) and DNA index (DI) in laryngeal carcinoma, to analyse the correlation between these index and the biological characteristics of laryngeal carcinoma and their values of clinical prognosis. METHOD: Immunohistochemical staining was used to detect the expression of EGFR and PCNA in laryngeal cancer and normal tissue, and with MIPS-I image analysis system DNA contents of cancer cell were measured and made out DNA index. RESULT: The positive rate of EGFR in laryngeal carcinoma was 54.8%, and it was negative in all 10 normal laryngeal mucosa specimens (P < 0.01). The expression of EGFR did not correlate with histological grading and 5-years survival rate (P > 0.05), The positive expression of PCNA and DNA contents in the laryngeal carcinoma were increased with the decrease of tumorous differentiation (P < 0.05). With the increasing of PCNA positive expression and DI, the prognosis of the patients were poorer (P < 0.05). CONCLUSION: EGFR may be related to the process of carcinogenesis in laryngeal carcinoma and was used as an early biomarker identifying premalignant lesions which had the greatest risk of carcinogenesis. PCNA and DI were simultaneously detected can be used as the prediction of tumor malignancy and prognosis.

Carcinoma, Squamous Cell↗

Angiotensin converting enzyme inhibitor-induced angioedema: a report of two cases.

Angioedema is a rare but potentially fatal side effect of angiotensin converting enzyme (ACE) inhibitors. We report for the first time, two children with systemic lupus erythematosus who developed acute angioedema after the long-term use of enalapril. Prompt recognition and appropriate management of ACE-induced angioedema prevented life-threatening complications. This report highlights the potential risks of angioedema associated with the use of ACE inhibitors in children. Patients should be advised to seek medical treatment immediately if they experience swelling of the face, neck, or tongue, and especially if they have trouble breathing, speaking, or swallowing.

Adolescent↗

Dislocation of total knee arthroplasty. A report of 6 cases with 2 patterns of instability.

We report 6 cases of dislocation of total knee arthroplasty (TKA). We identified 2 patterns of instability in the sagittal plane, one with posterior translation of the tibia, occurring mainly in the postoperative period and usually resulting from a trauma, and the other with anterior translation of the tibia, occurring 6 months to 7 years postoperatively and with no preceding trauma. In the latter group, instability was manifested gradually as a lengthening of the posterior cruciate ligament and the posterior capsule, leading to a recurvatum deformity of the knee.

Aged↗

Angiotensin II stimulates the release of phospholipid-derived second messengers through multiple receptor subtypes in heart cells.

The octapeptide angiotensin II (Ang-II) induces both acute functional changes and longer lasting molecular changes in cultured mammalian heart myocytes, yet the underlying molecular mechanisms are poorly understood. In this study, Ang-II was found to stimulate a sustained release (> 30 min) of arachidonic acid (ARA) from cultured neonatal rat cardiac myocytes, with a half-maximal response observed at 0.1 nM. Mass spectroscopy analysis showed that Ang-II stimulated a specific release equivalent to 104 fmol of ARA/micrograms of protein in 10 min. Only Ang-II type 1 (AT1) receptor-specific antagonists were potent inhibitors of hormone-evoked [3H]inositol phosphate accumulation (DuP 753 IC50 approximately 7 nM compared to CGP 42112A IC50 > 1 microM). In contrast, only AT2 receptor-specific antagonists were potent inhibitors of [3H]ARA release (CGP 42112A IC50 approximately 7 nM, EXP 3880 IC50 approximately 2 nM, and PD 123177 IC50 approximately 10 nM). Further studies with phospholipase inhibitors (p-amylcinnamoylanthranilic acid and U73122) revealed that the production of [3H]-inositol phosphates and [3H]ARA occurs through parallel and independent pathways involving phospholipase C and phospholipase A2, respectively. Ang-II also increased the level of lysophosphatidylcholine by 49%, direct evidence that this peptide activated phospholipase A2. Thus, Ang-II stimulates distinct phospholipases in parallel through AT1 and AT2 receptors. These results reveal coordinate signaling roles for multiple Ang-II receptor subtypes in heart.

Angiotensin II↗

Monitoring underground radiation fields using powdered calcium sulfate thermoluminescent dosimeters.

Powered thermoluminescent dosimeters, CaSO4:Dy, were used to monitor underground radiation fields. Methods of monitoring at selected sites in Taiwan are described; exposure rates above ground at the monitoring sites are also included for comparison. Differences in exposure rates between above ground at 1 m and underground at -2 m may reach 0.516 nC kg-1 h-1. The key factor affecting exposure rates underground is the water content in soil or precipitation that may reduce the diffusion of Rn. The difference in exposure rates between rainy days and sunny days may reach 0.774 nC kg-1 h-1. An example of applying this monitoring technique at a radwaste repository is given.

Calcium Sulfate↗