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Biomedical subjects

T Wong

Publications and source records attributed to T Wong.

At least 55 records · Page 3Linked to original sources

Identification and characterization of SKAT-2, a novel Th2-specific zinc finger gene.

We have identified a novel Kruppel-type zinc finger (ZF) gene, SKAT-2, which is selectively expressed by murine Th2 cells. The protein encoded by this gene has 14 C2H2-type ZF tandemly arrayed at its C terminus and N-terminal SCAN box and KRAB domains. SKAT-2 is tissue restricted in expression at the RNA level, detectable only in brain and at low levels in kidney and spleen and few hematopoietic cell lines. By in situ hybridization, SKAT-2 expression was found to peak in antigen-stimulated CD4(+) T cells after 2-3 days of culture under Th2 but not Th1 biasing conditions. This pattern of expression closely mirrored that of GATA-3 in the same cells. In transient transfection experiments in phorbol 12-myristate 13-acetate/ionomycin-stimulated EL4 cells, SKAT-2 was found to up-regulate the activity of the IL-4 but not the IL-5 promoter, contrasting with the ability of GATA-3 to activate both promoters. This result was confirmed using clones of EL4 cells stably expressing an inducible form of SKAT-2, thus SKAT-2 is a novel Th2-specific gene that may play a role in selective regulation of cytokine genes in T cells.

Amino Acid Sequence↗

Antiretroviral therapy and declining AIDS mortality in New York City.

The objective was to evaluate the association between antiretroviral therapy and AIDS mortality in New York City (NYC). Design was a population-based case-control study. We randomly selected 150 case patients and 150 control patients whose AIDS diagnosis was made during 1994 to 1996 (male:female, 2:1) from among 19,238 persons reported to the NYC Health Department HIV/AIDS Reporting System (HARS). Case patients had died of AIDS-related causes in 1996. Control patients, category matched with case patients on gender, were not known to have died by the end of 1996. Analysis was performed on 279 patients (142 cases and 137 controls). Cases and controls were similar in age, gender, race, HIV transmission category, and health insurance coverage. The median baseline CD4 count was 30 cells/microL for those who died and 103 cells/microL for survivors (p < 0.001). The prescription of HAART (antiretroviral combination that includes at least one protease inhibitor) in 1996 was strongly associated with survival in univariate analysis (OR = 5.1, 95%CI = 2.5-10.2). This association remained in a logistic regression analysis after adjusting for sex, age, race, health insurance status, HIV transmission categories, year of AIDS diagnosis, baseline CD4 count, and other antiretroviral therapy (AOR = 8.6, 95%CI = 3.5-20.7). Prescription of combination therapy other than HAART in 1996 and baseline CD4 count were also associated with survival, but less strongly so. The survival benefit of HAART extends beyond the confines of a few highly selected patients into the "real world," reducing AIDS deaths at the population level. This population-based study supports the likelihood that the introduction of HAART in 1996 played a primary role in the decline in NYC AIDS mortality.

Acquired Immunodeficiency Syndrome↗

Oxidative neuropathology and putative chemical entities for Alzheimer's disease: neuroprotective effects of salen-manganese catalytic anti-oxidants.

Considerable evidence exists that the brains of individuals with Alzheimer's disease are subject to elevated levels of oxidative stress, particularly in regions exhibiting pathological damage. A major contributor to this oxidative stress appears to be the inflammatory process. Activation of rodent microglial cells by LPS or beta-amyloid peptide results in a marked up-regulation of inducible nitric oxide synthase (iNOS) and corresponding nitric oxide (NO) production. Elevated levels of iNOS are also observed in the brains of Alzheimer patients. The reaction of NO with superoxide leads to the generation of the highly reactive and damaging peroxynitrite free radical species. Peroxynitrite appears to play a key role in the generation of an oxidative stress in the Alzheimer brain as evidenced by widespread nitrotyrosine immunoreactivity. We have employed SIN-1 as a peroxynitrite generating system in cell cultures in order to characterize the effects of this free radical on neurons. SIN-1 treatment of primary rat hippocampal neurons in culture results in neurotoxicity by a necrosis mechanism according to electron microscopic criteria. One approach to limiting peroxynitrite mediated damage is to limit superoxide production. An approach we have evaluated is treatment with salen manganese compounds, a class of catalytic antioxidant compounds which behave as superoxide dismutase (SOD)/catalase mimetics to detoxify superoxide. A number of such salen manganese compounds, including EUK-8 and EUK-134, can markedly protect primary rat cortical neurons from hydrogen peroxide mediated oxidative stress. Such salen manganese compounds can similarly afford marked neuroprotection to an oxidative stress imposed by SIN-1, potentially attributable at least in part to their inherent SOD activity. The salen manganese SOD/catalase mimetics represent a promising class of catalytic antioxidant for attenuating oxidative stress.

Journal Article↗

Kappa-opioid receptor stimulation increases the expression of Na+-H+ exchange gene in the heart.

Kappa-opioid receptor (OR) stimulation increases intracellular pH (pHi) via activating the Na+-H+ exchange (NHE). In the present study, we determined the expression of the gene of NHE1, the predominant NHE isoform in the heart, and intracellular pH (pHi) upon kappa-OR stimulation in the rat heart. We found that 1 microM U50,488H (trans-3,4-dichloro-N-methyl-N-(2-(1 pyrrolidinyl)cyclohexyl)benzeneacetamide), a selective kappa-OR agonist, increased the expression of the NHE1 gene. We also found that U50,488H dose-dependently increased pHi in the heart. The effects were abolished by 1 microM nor-binaltorphimine (nor-BNI), a selective kappa-OR antagonist, indicating that the events were kappa-OR mediated. The effects on both NHE1 gene expression and pHi were also abolished by 5 microM chelerythrine and 5 microM BSM (bisyndolylmaleimide), protein kinase C (PKC) inhibitors, indicating that PKC mediated the actions. In addition, the effect of U50,488H on pHi was blocked by 10 microM EIPA (ethylisopropyl amiloride), a NHE1 inhibitor, indicating that NHE1 also mediated the action of U50,488H. The present study provides evidence for the first time that kappa-OR stimulation increased the NHE1 gene expression in the heart via a PKC dependent pathway. Kappa-OR stimulation also increases pHi via PKC and NHE in the heart.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Phacoemulsification time and power requirements in phaco chop and divide and conquer nucleofractis techniques.

PURPOSE: To evaluate the differences in phaco time and power required between the divide and conquer and phaco chop nucleofractis techniques. SETTING: Department of Ophthalmology, Central Middlesex Hospital, London, United Kingdom. METHODS: A retrospective pilot study of 125 patients was followed by a prospective randomized study of 117 patients comparing the phaco chop with divide and conquer techniques in terms of phaco time (minutes), phaco power (%), equivalent phaco time (calculated time required if 100% power had been used throughout), intraoperative and postoperative complications, and postoperative visual acuity. RESULTS: In the pilot study, mean phaco time in the phaco chop group was 1.4 minutes +/- 0.09 (SD) and in the divide and conquer group, 3.4 +/- 0.1 minutes (P <.0001). Mean equivalent phaco time was also less in the phaco chop group (0.39 +/- 0.03 minutes) than in the divide and conquer group (0.98 +/- 0.08 minutes) (P <.0001). In the prospective study, phaco chop required significantly less phaco time (1.2 +/- 0.1 minutes) than divide and conquer (2.4 +/- 0. 1 minutes) (P <.0001), less phaco power (25.3% +/- 1.2% versus 35.1% +/- 1.2%) (P <.0001), and less equivalent phaco time (0.29 +/- 0.02 minutes versus 0.84 +/- 0.05 minutes) (P <.0001). The operating time was shorter in the phaco chop group. There were no differences in complications and postoperative visual acuity. CONCLUSION: This study showed a significant advantage of the phaco chop over the divide and conquer technique in phaco power and duration. Phaco chop also required less operative time and intraocular manipulation without an apparent increase in intraoperative or postoperative complications.

Aged↗

Dosimetry errors in endovascular high-dose-rate brachytherapy.

Monte Carlo data were used to demonstrate the dosimetry of the microSelectron high-dose-rate (HDR) iridium 192 (192Ir) stepping source. These data were used to assess the accuracy of the Nucletron brachytherapy planning system (BPS version 13) for peripheral vessel endovascular brachytherapy. Dose rates from the high-dose-rate (HDR) source are calculated using the Monte Carlo code MCNP4A. Calculations are made at 0.25-cm intervals in the longitudinal direction on sleeves of radii of 1 and 0.25 cm. The Monte Carlo data are summed and weighted to simulate the longitudinal dose distribution at a distance of 1 and 0.25 cm from an 192Ir source stepping through a straight pathway. A comparison is made between the simulated Monte Carlo dosimetry and the Nucletron brachytherapy planning system's dosimetry. This study illustrates and quantifies the dosimetric errors at small distances associated with a point source dose calculation algorithm. The effects of step size, dwell time optimization, and active length on the accuracy of BPS v.13 for HDR endovascular brachytherapy are demonstrated.

Algorithms↗

27. PET Image Interpretation. Attenuation-Corrected (ATN) Vs Non-Attenuation Corrected (NATN) Images.

Purpose: The purpose of this study was to evaluate the difference, if any, in lesion detection in ATN and NATN images.Methods: Sixty-one consecutive patients having clinical whole body FDG PET scans for oncologic indications were included. The patients were administered 10-20 mCi FDG intravenously, and imaging on the Advance (GE Medical Systems) was started 45 min-1 h after injection. The emission images were acquired for 4 min and the transmission images for 3 min per bed position. The images were reviewed on the vendor-provided workstation. Four of the interpreting physicians read the ATN images first, and the other read the NATN images first. The interpreting physicians were asked to determine if any lesions were seen on only the ATN or NATN images (discordant findings) and to describe differences in the images not affecting overall interpretation.Results: In the 61 patients, 3 discordant findings with abnormalities on the ATN images but not on the NATN images included the following: lung nodule, AP window node, and small para-aortic node. Observations that did not affect overall interpretation include the following: transmission scan helped localize lesion to be below instead of above the diaphragm; AT-N image better demonstrated liver metastasis; benign lung lesion seen only on ATN image (3 cases); pretracheal node seen better on NATN images; and low grade hilar activity on NATN not seen on ATN images.Conclusion: These results demonstrate that the ATN images detect more lesions than the NATN images, and that reviewing NATN images may not be necessary. A different method for performing this evaluation is now being undertaken.

Journal Article↗

A prospective, randomized comparison of the ease and safety of variceal ligation using a multiband vs. a conventional ligation device.

BACKGROUND AND STUDY AIMS: Recent advances in endoscopic technology have led to the development of multiple-banding devices which avoid the use of an overtube in endoscopic variceal ligation. In the present study we prospectively examined the safety and efficacy of one such device compared with the conventional single-band ligator. PATIENTS AND METHODS: A total of 45 patients undergoing band ligation were randomly assigned to receive ligation using conventional techniques (n = 22), or multiband ligation (n = 23). RESULTS: The use of the multiband device was associated with a significant reduction in sedation requirements (midazolam 7.1 mg vs. 9.9 mg, P < 0.01, multiband vs. conventional, respectively), less discomfort (4% vs. 23% severe discomfort, P < 0.05). The total time of the endoscopic session was reduced in the multiband group (8 minutes 25 seconds vs. 12 minutes 21 seconds, P < 0.01), as was the time required for application of all the bands (2 minutes 22 seconds vs. 5 minutes 34 seconds, P < 0.001), and average time taken per individual band application (36 seconds vs. 1 minute 36 secs, P < 0.01). In three patients who underwent ligation using the conventional method, the procedure was stopped because of trauma secondary to overtube application. CONCLUSIONS: Multiband ligation is safer, quicker, and associated with less patient discomfort and morbidity when compared with conventional ligation.

Adult↗

Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand.

Bone remodelling and bone loss are controlled by a balance between the tumour necrosis factor family molecule osteoprotegerin ligand (OPGL) and its decoy receptor osteoprotegerin (OPG). In addition, OPGL regulates lymph node organogenesis, lymphocyte development and interactions between T cells and dendritic cells in the immune system. The OPGL receptor, RANK, is expressed on chondrocytes, osteoclast precursors and mature osteoclasts. OPGL expression in T cells is induced by antigen receptor engagement, which suggests that activated T cells may influence bone metabolism through OPGL and RANK. Here we report that activated T cells can directly trigger osteoclastogenesis through OPGL. Systemic activation of T cells in vivo leads to an OPGL-mediated increase in osteoclastogenesis and bone loss. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe joint inflammation, bone and cartilage destruction and crippling, blocking of OPGL through osteoprotegerin treatment at the onset of disease prevents bone and cartilage destruction but not inflammation. These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology.

Animals↗

The use and advantages of a multichannel vaginal cylinder in high-dose-rate brachytherapy.

PURPOSE: This paper describes California Endocurietherapy's (CET) high-dose-rate (HDR) multichannel cylinder, the rationale for its design, procedure for its insertion, and the dosimetry involved in its use. A study was done that compared the doses achieved using the CET multichannel cylinder to the same cylinder if it only had a central channel. METHODS AND MATERIALS: The CET multichannel vaginal cylinder was inexpensively constructed, using parts from various suppliers. After insertion in the patient, the cylinder is affixed to a base plate to prevent displacement. Two sets of orthogonal films (without and with rectal barium) are taken in preparation for digitization of the catheters, bladder, rectal, and pelvic sidewall points. Using HDR brachytherapy planning software, the dose distribution is adjusted to achieve the prescribed dose (5 Gy HDR) 5 mm lateral to the cylinder surface, 5 mm lateral at the proximal parametrial tissue, and 4 mm superior to the vaginal apex. Doses to the bladder and rectum are limited to approximately 85% and 75%, respectively, of the prescribed dose. The plan is optimized on geometric parameters. For dose comparison to treatment using a central channel cylinder, the lateral channels are de-activated, leaving only the central channel activated. Dose points are placed 5 mm laterally and superiorly from the cylinder surface, and the plan is optimized to deliver a uniform dose to the defined dose points. The doses and treatment volumes are statistically compared. RESULTS: The CET multichannel cylinder allows much better dose control than the central channel cylinder. The multichannel cylinder achieves lower bladder and rectal doses by 14% and 15%, respectively, when compared to the central channel cylinder. By increasing the dwell times of certain dwell positions, the prescription dose is achieved in the vaginal apex and proximal parametrial tissues and along the length of the cylinder. CONCLUSION: The multichannel cylinder enables more flexibility in isodose shaping and dose control to various points and structures when compared to the conventional central channel cylinder.

Brachytherapy↗

Caring attributes, professional self concept and technological influences in a sample of Registered Nurses in eleven countries.

Caring, the theoretical foundation of nursing, is identified as one of the core values by Hospital Authorities world-wide to be actualised in clinical practice. Exactly how caring attributes relate to nurses' professional self image and quality nursing service in the context of a contemporary technological environment have yet to be operationalised. In total, 1957 Registered Nurses from 11 different countries were involved in the study which aimed to: develop an understanding of and compare the responses to items relating to caring, professional self concept and technological influences. To collect data an instrument containing 104 Likert items was administered to RNs working in general hospitals. The instrument contained sections which examined professional self concept, technological influences and caring attributes. Descriptive and inferential statistics revealed that many of the Asian nurses in the sample were younger, had less experience yet were more qualified than their 'western' colleagues. The mean scores for the caring attributes for nurses from the Philippines, Sweden and South Africa were significantly higher than those from China (Beijing), Korea, China (Hong Kong) and Scotland. The Korean sample demonstrated the lowest mean score for professional self concept while the New Zealand sample the highest. The Australian, Canadian, NZ, Scotland and Swedish samples were strongly of the opinion that the increase in technology has not brought about the any more spare time in nursing and generally had a more negative opinion about the influence of technology when compared to those from China (Beijing), Philippines, China (Hong Kong) and Singapore. The results are discussed in the light of the cultural differences in the sample and recommendations for future research are considered.

Adult↗

Verification of brachytherapy dosimetry with radiochromic film.

The aim of this work is to empirically validate the optimized dose distribution calculated by the Nucletron Brachytherapy Planning System (v. 13.3) at a distance of 1.0 cm from a stepping source of high-dose-rate-iridium 192 (192Ir). The longitudinal dose distribution at 1.0 cm from a straight pathway of multiple-source positions is measured using radiochromic film and compared with the planning system's calculated results. The optical density of the exposed films was determined with a modified Scanditronix film scanner, and the film was calibrated with 192Ir using manually calculated exposure times. A calibration equation was used to convert scanner output to dose. Our results illustrate the significance of exacting geometry in the experimental setup due to the inverse square law and the small distances involved. The dose distribution calculated by the Nucletron Brachytherapy Planning System (v. 13.3), at a distance of 1.0 cm, is validated to within +/-4% of the measured dose distribution. The advantages and limitations of radiochromic film as a dosimetry tool are also addressed in this work.

Brachytherapy↗

Epidemiology and predictors of post-concussive syndrome after minor head injury in an emergency population.

OBJECTIVE: To determine if clinical variables or neurobehavioural test (NBT) scores obtained in the ED within 24 hours of minor head injury (MHI) predict the development of postconcussive syndrome (PCS). METHODS: Prospective, observational study of 71 MHI patients and 60 orthopaedic controls. MHI defined as loss of consciousness < 10 minutes or amnesia, GCS 15, no skull fracture or new neurologic focality on PE, and no brain injury on CT (if done). All patients received a seven part NBT battery in the ED. Telephone follow-up was done at 1, 3 and 6 months to determine if patients met the DSM IV definition of PCS. ANALYSIS: Stepwise, multivariate, logistic regression. RESULTS: Predictors of PCS at 1 month were female gender (OR = 7.8; 95% CI = 41.6, 1.98), presence of both retrograde and anterograde amnesia (OR = 0.055; CI = 0.002, 0.47), Digit Span Forward Scores (OR = 0.748; CI = 0.52, 1.03) and Hopkins Verbal Learning A scores (OR = 0.786; CI = 0.65, 0.91); at 3 months, presence of both retrograde and anterograde amnesia (OR = 0.13; CI = 0.0, 0.93), Digit Span Forward Scores (OR = 0.744; CI = 0.58, 0.94). No variables fit the model at 6 months. 92% of males scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month, and 89% of females scoring < 9 on Digit Span Forward did have PCS at 1 month. CONCLUSIONS: Gender and two NBTs can help predict PCS after MHI.

Adult↗

Dose errors in the near field of an HDR brachytherapy stepping source.

The dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter with an active stepping source (Nucletron microSelectron HDR source) with a dwell length of 2 cm was calculated using Monte Carlo code MCNP 4.A. The source step sizes were 1 cm and 0.25 cm. The Monte Carlo (MC) results were used for comparison with the results calculated with the Nucletron brachytherapy planning system (BPS) formalism, first with BPS variants and then with its respective MC calculated radial dose function and anisotropy function. The dose differences at point P calculated using the BPS formalism and variants are +15.4% and +3.1% for the source step size of 1 cm and 0.25 cm respectively. This reduction in dose difference is caused by the increased importance of errors in the anisotropy function with the smaller step size, which counter the errors in the radial dose function. Using the MC calculated radial dose function and anisotropy function with the BPS formalism. 1% dose calculation accuracy can be achieved, even in the near field, with negligible extra demand on computation time.

Algorithms↗

Large ex vivo expansion of human umbilical cord blood CD4+ and CD8+ T cells.

The use of human umbilical cord (UC) blood as a source of transplantable hematopoietic stem cells and progenitor cells may present some advantages over the use of BM. For example, it has been suggested that the degree of HLA matching may be less stringent, and the risk of GvHD may be lower. We have been studying the ex vivo expansion of UC blood T lymphocytes with a view to their use in the adoptive immunotherapy of cancer, autoimmunity, and infectious disease. We have developed a new method involving the use of a conditioned medium (XLCM) that consistently results in levels of UC blood T cell expansion not hitherto possible. Primary cultures of unfractionated low-density MNC (LDMNC) derived from UC blood treated with 5% XLCM routinely show expansions greater than 10,000-fold within 4 weeks. By contrast, similar FBS-free cultures treated with IL-2 expand less than 10-fold and not after 1 week, and cultures treated with IL-2 and concanavalin A (ConA) expand to a maximum of only 300-500-fold over 2 weeks and fail to continue to proliferate thereafter. The MAb, OKT3, which, when combined with IL-2 and FBS, is known to stimulate proliferation of adult peripheral blood lymphocytes, permitted only a 17-fold expansion of UC blood lymphocytes under the same conditions. Thus, XLCM, which can also stimulate adult peripheral blood lymphocyte expansion to levels exceeding 100,000-fold in 3-4 weeks, is uniquely able to stimulate proliferation of UC blood lymphocytes to high levels. From initiation of the UC blood or adult peripheral blood LDMNC/XLCM cultures up to approximately 2 weeks, the cultures are dominated by CD4+ T lymphocytes. By 4 weeks, >80% of the cultured cells bear the CD8+ phenotype, whereas UC blood T lymphocytes cultured in the presence of IL-2 are predominantly CD8+. Thus, XLCM not only allows high levels of expansion of UC blood T lymphocytes not heretofore possible but also permits the selective expansion of different T lymphocyte subsets from a single source.

Adult↗

The selective expansion of functional T cell subsets.

Adoptive cellular immunotherapy is considered a potential treatment for a wide range of diseases, including cancer, infectious diseases, and autoimmune disorders. We have developed a method using a conditioned medium, XLCM, that selectively expands several different T cell subsets with a view to their use in cell therapy. Primary FBS-free suspension cultures of human peripheral blood low-density mononuclear cells treated with XLCM reproducibly expand over 100,000-fold within a period of 4 weeks. CD4+ T cells and CD8+ T cells expand sequentially in the unfractionated cultures, and relatively pure populations of CD4+ and CD8+ T cells may be expanded from populations first enriched in the respective T cell subset. CD4+ T cells cultured in XLCM produce cytokines consistent with the expansion of Th1, Th2, and Th0 subsets, whereas CD8+ T cells cultured in XLCM are cytolytically competent. An interesting feature of T cells cultured in XLCM is the persistence of 5%-10% CD4+CD8+ double-positive T cells in spite of substantial single-positive T cell expansion, suggesting that these cells also proliferate in XLCM. In addition to subsets of TCRalphabeta+ T cells, TCRgammadelta+ T cells are also significantly expanded by XLCM. These results demonstrate that XLCM efficiently expands several functional T cell subsets and provides a means of obtaining selected populations suitable for use in cellular immunotherapy.

Adoptive Transfer↗

Chemoprophylaxis of influenza A virus infections, with single doses of zanamivir, demonstrates that zanamivir is cleared slowly from the respiratory tract.

Zanamivir (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid; Relenza; GG167) is a potent and highly specific neuraminidase (sialidase) inhibitor with inhibitory activity in vivo against both influenza A and B viruses. This compound has been extensively tested in both mouse and ferret models of influenza and has recently been approved for the treatment of influenza in Europe and Australasia. The compound markedly reduces the clinical course of disease in humans when given therapeutically by inhalation directly into the respiratory tract. In addition, experimental influenza infections in phase I clinical trials have shown the benefit of giving a single prophylactic dose of zanamivir in addition to a therapeutic regime. The studies reported here were designed to determine the persistence of zanamivir, as assessed by its antiviral activity in vivo, in the respiratory tracts of infected animals. We have shown that the prophylactic administration of zanamivir, when the drug is given in a single dose by the intranasal route, can significantly reduce lung virus titers in the mouse and can reduce both viral titers and symptoms in the ferret. Whole-body autoradiographical analyses of mice have indicated a long retention time for this compound in respiratory tract tissues when it is given in a single dose by the intranasal route. These results indicate that zanamivir may have clinical value as a prophylactic agent in protecting at-risk groups from influenza virus infection. In addition, these data may be useful in the design of prophylactic protocols for humans, in that the dosing schedule may only need to be intermittent to provide protection.

Administration, Intranasal↗