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Biomedical subjects

T Wong

Publications and source records attributed to T Wong.

At least 127 records · Page 7Linked to original sources
PubMed1993

Immunogenicity of synthetic peptides related to the core peptide sequence encoded by the human MUC1 mucin gene: effect of immunization on the growth of murine mammary adenocarcinoma cells transfected with the human MUC1 gene.

The immune response of CAF1 mice to various synthetic peptides (SP) related to the amino acid sequence (PDTRPAPGSTAPPAHGVTSA) of the tandem repeat of the MUC1 human breast mucin core peptide was evaluated. The most immunogenic preparations of the synthetic peptides were those conjugated to keyhole limpet hemocyanin (KLH) or clustered in a dendritic multiple antigenic peptide (MAP-4) configuration. The mice were immunized subcutaneously with synthetic peptides emulsified in RIBI adjuvant, employing various immunization protocols. Equivalently high IgG responses were induced using SP-KLH conjugates (GVTSAPDTRPAPGSTA-KLH) or an SP--MAP-4 chimeric configuration (SP1-6), which also included a universal malarial CST-3 T-helper epitope (SP1-6 = SAPDTRPAEKKIAKMEKASSVFNVVNS--MAP-4). These IgG antibodies bound both the appropriate MUC1 synthetic peptides and the cell surface expressed MUC1 mucin on murine mammary cells that had been transfected with the human MUC1 gene and a human breast cancer cell line that expresses cell-surface MUC1. A MAP-4 molecule, which included the entire 20-amino-acid sequence of the MUC1 tandem repeat (SP1-5 = PDTRPAPGSTAPPAHGVTSA-MAP-4) induced a poor IgG response. In contrast, all three types of molecule: SP-KLH, SP1-6 and SP1-5, were found to be good immunogens for the induction of specific delayed-type hypersensitivity (DTH) reactions measured using either synthetic peptides or MUC1-transfected cells. In addition, immunization with irradiated MUC1-transfected cells induced strong DTH reactions measured using synthetic peptides that expressed the PDTRP sequence, which has been shown to be, or to overlap, a T cell epitope in humans and a B cell epitope in mice. Finally, it was demonstrated that synthetic MUC1 peptide "vaccines" could be used both prophylactically and therapeutically to inhibit the growth of MUC1-transfected tumor cells and prolong the survival of tumor-bearing mice.

Adenocarcinoma↗
PubMed1993

The effects of phonophoresis with corticosteroids: a controlled pilot study.

Although physical therapists and physicians often treat patients with local musculoskeletal inflammation using topically applied steroids enhanced with ultrasound, there is a paucity of research confirming that phonophoresis significantly enhances drug diffusion. The purpose of this study was to determine if ultrasound enhances the diffusion of transdermally applied corticosteroids. Diffusion was measured secondarily in terms of collagen deposition [estimated by levels of hydroxyproline in polytetrafluroethylene (ePTFE) tubing] and cellular activity (measured by levels of DNA). Sixteen pieces of ePTFE tubing were subcutaneously implanted on the dorsum of five mini Yucatan pigs. Pairs of tubing were randomly assigned to sham control or treatment groups. Over the paired ePTFE tubes in the treatment groups, a single transdermal application of hydrocortisone acetate (HC) or dexamethasone (DX) was applied to the skin by rubbing, sonating with the drug mixed in the acoustic gel (1.5 W/cm2, 1 MHz, 5 minutes), or injecting the drug into the tubing. Four additional ePTFE tubes were threaded in the extremities, two submuscularly and two subtendinously, with random assignment to a sham control or a DX sonation treatment group. At the end of a week, the mean hydroxyproline levels in the swine were lower than expected (mean = 9.3 micrograms/cm compared to an expected mean = 22.2 micrograms/cm). Comparing the control and skin-applied groups with the injected and sonated treatment groups, the hydroxyproline was found to be 50% lower in the DX-injected, DX-sonated, and HC-injected sites. However, statistically there were no significant differences in DNA or hydroxyproline levels between the HC subcutaneous control and treatment groups or the DX submuscular and subtendinous groups. There was a significant main effect of group on hydroxyproline levels in the group of DX-treated, subcutaneously implanted ePTFE tubes (p = 0.001). Post hoc testing revealed a significant difference between the skin-rubbed and control groups together compared to the DX-injected and DX-sonated groups together (p = 0.001). These findings indicate that the effects of phonophoresed DX can be measured in terms of reduced collagen deposition as far down as the subcutaneous tissue but not in the submuscular or subtendinous tissue. However, a single application may not have a measurable effect on cellular activity after 7 days of healing. The unusually low level of hydroxyproline across all groups suggests that phonophoresis with steroids may have had a systemic as well as a local effect.

Administration, Cutaneous↗
PubMed1993

Incisional wound healing: a controlled study of low and high dose ultrasound.

Ultrasound is commonly used by physical therapists, but there is no consensus regarding the most effective therapeutic dose for accelerating healing of open or closed wounds. A controlled, single-blind, posttest experimental study was carried out to compare differences in wound breaking strength and collagen deposition [hydroxyproline (HoPro)]. Forty-eight incisions were surgically induced in three mini Yucatan pigs. Each incision was randomly assigned to a control or an ultrasound treatment group with the sonated incisions further randomly assigned to 5 or 10 days of ultrasound treatment with either high dose ultrasound (HUS) (1.5 W/cm2, continuous mode, 1 MHz, 5 minutes) or low dose ultrasound (LUS) (0.5 W/cm2, pulsed mode, 20% duty cycle, 1 MHz, 5 minutes). Using the nonparametric two-sample Wilcoxon test, the breaking strength was found to be significantly higher in the sonated incisions compared with the control incisions (p < or = 0.02), but there were no significant differences in HoPro. For all groups, the level of HoPro measured the second week was significantly higher (an average of 60%) than measured the first week (p < or = 0.001). A significant interaction was found between the number of days of treatment and the dose of ultrasound. Hydroxyproline was significantly higher in the LUS group compared with the HUS group after 5 days of ultrasound. Both the wound breaking strength and the HoPro levels were significantly higher in the LUS group compared with the HUS group after 10 days of treatment (p < or = 0.02 and 0.01, respectively). The findings from this study suggest that physical therapists can use either LUS or HUS for approximately 1 week to enhance wound breaking strength in an acute incisional wound. However, if the goal is to continue to facilitate collagen deposition and wound strength, then a low dose of ultrasound should be used when treatment is continued for 2 weeks or more.

Animals↗
PubMed1993

Readout of thermoluminescence dosimetry chips using a contact planchet heater.

Thermoluminescence dosimetry (TLD) is performed in many radiotherapy departments using LiF chips which are evaluated by means of a contact heater. The aim of the present study was to investigate the influence of the TL chip position on the heating planchet and to study the self absorption of light in the chips during readout. Experiments were performed using standard LiF chips (3.1 x 3.1 x 0.89 mm3) on a circular heating planchet with a diameter of 13 mm. A two step readout cycle (10s 160 degrees C, 10s 300 degrees C) was used and the integral under the luminescence curve during the second step evaluated. Moving the chip away from the centre of the planchet without adjusting the temperature cycle leads to a peak broadening which can result in a signal loss of up to 40%. The use of a purpose build positioning device tended to improve the reproducibility of the readings. Self absorption of light in a normal chip on the heating planchet was studied by exposing chips in the strong dose gradient of the build up region of a 18 MV X-ray beam. The dose throughout the chip was investigated using a stack of 0.14 mm thick chips. In a 5 x 5 cm2 field the dose varied from 7% at the surface facing the beam to 23% at the opposite side of the chip. Reading the chips with the side facing the beam up in the reader resulted in a 1.9% smaller dose reading than with the chips upside down.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermoluminescent Dosimetry↗
PubMed1993

Beta 2-microglobulin metabolism in uremic patients who are undergoing dialysis.

Plasma beta 2-microglobulin (beta 2m) is increased in chronically hemodialyzed patients and remains in a steady range once residual diuresis has stopped. Factors controlling such a steady state are unknown. We undertook metabolic studies to define whether plasma beta 2m is regulated by extrarenal proteolysis of the protein or by storage in a captation pool, a condition which may precede beta 2m-derived amyloidogenesis. Seventeen uremic patients on supportive therapy and five healthy controls were enrolled into the 6 to 10 day study. Using trace amounts of 131I-beta 2m and total body counting, half-life was between 2.4 and 8 days. 125I-beta 2m plasma kinetics was more suitable to calculate fractional catabolic rate and synthetic rate. A three compartment model was chosen to calculate turnover parameters in dialysis patients, whereas the regular two compartment model fitted best for healthy controls. beta 2m synthesis rate was increased in uremic patients when compared with controls (4.49 +/- 2.60 vs. 3.68 +/- 1.43 mg/kg/day, NS). The three compartment model did not integrate all the experimental data, since it was possible to calculate a captation compartment which accumulated beta 2m without fast proteolysis. The captation pool was positively correlated with plasma beta 2m concentration and comprised between 23% and 59% of the amount of the beta 2m disappearing from plasma per day. In conclusion, metabolic studies with radioiodinated beta 2m indicate a slight increase in beta 2m synthesis rate in uremic patients on supportive therapy, irrespective of the technique in use. Kinetic analysis requires a model taking into account a storage compartment which is more complex than the three compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Tracing patients from acute psychiatric wards.

A random sample of those admitted to acute psychiatric wards in Sheffield in 1985 was traced to establish whether or not the patients were homeless 5 years later. Contrary to expectations none were found to be homeless. Although the proportion of mentally ill amongst the homeless may be significantly high, the number discharged from psychiatric hospital, at least in Sheffield, living consistently 'on the streets' or staying regularly in night shelters seems small as a proportion of all discharges.

Adolescent↗
PubMed1992

Preoperative cardiac risk assessment for patients having peripheral vascular surgery.

PURPOSE: To review the methods used for preoperative cardiac risk stratification of patients having peripheral vascular surgery. DATA SOURCES: Relevant studies published before August 1991 were identified using a MEDLINE search of the English-language literature, followed by a manual search of the references of all identified articles. STUDY SELECTION: All clinical studies evaluating methods used for preoperative cardiac risk stratification of patients having peripheral vascular surgery. DATA EXTRACTION: The key data extracted from each article included the inclusion and exclusion criteria of the study patients, the techniques used for testing and the corresponding definitions of positive test results, and the clinical outcomes of the tested patients. Data were analyzed using a Bayesian conceptual framework, and pretest probabilities were converted to post-test probabilities using calculation of likelihood ratios. RESULTS: Patients with high scores on clinical cardiac risk indexes (Goldman index greater than 12 or Detsky index greater than 15), or more than three of the criteria identified by Eagle (age greater than 70 years, diabetes, angina, Q waves on electrocardiogram, or ventricular arrhythmias) are likely to be at higher risk for cardiac death and myocardial infarction after vascular surgery. Those with both low scores and none of Eagle's criteria may be at lower risk, but this result has not been reproduced by independent studies. Neither group of patients would benefit from further investigation for cardiac risk stratification. Patients with one or two of these criteria may be at intermediate risk and would benefit most from further testing for the purposes of risk stratification. Most of the published evidence shows that the absence of redistribution on dipyridamole-thallium scanning identifies a low risk for postoperative cardiac complications, whereas the presence of redistribution predicts a high risk. Preliminary reports suggest that preoperative monitoring for silent myocardial ischemia may also be useful in identifying a high-risk subset of patients. CONCLUSIONS: Patients identified clinically to be at either very low or high risk for cardiac complications after peripheral vascular surgery are unlikely to benefit from further risk stratification. Dipyridamole-thallium scanning is the test of choice for further evaluation of patients at intermediate clinical risk because studies have shown that it is sensitive enough to rule out a high-risk status for patients who do not have redistribution.

Bayes Theorem↗
PubMed1992

Septicemia due to Yersinia enterocolitica in a hemodialyzed, iron-depleted patient receiving omeprazole and oral iron supplementation.

Septicemia occurred in a long-term hemodialysis patient on oral iron supplementation who had been treated for esophageal ulcer by omeprazole, an ulcer-healing drug. Yersinia enterocolitica serotype 0:3 was recovered from blood cultures. A raised intraintestinal pH and an increased intraluminal iron load may have been contributing factors for the enhanced proliferation and generalized infection of Y enterocolitica.

Aged↗
PubMed1992

Kinetics of 125I-beta 2-microglobulin turnover in dialyzed patients.

The kinetics of beta 2-microglobulin (beta 2m) were studied in 17 anephric or functionally anephric hemodialyzed patients and five healthy subjects as controls. Highly purified beta 2m was radiolabeled with 125I and infused into patients. The radioactivity in plasma and dialysis fluids was measured during a week including two or three dialysis sessions. Patients were classified in four groups according to treatment: hemodialysis on Cuprophan (N = 5) or on AN69 membranes (N = 5), hemofiltration (N = 4) and CAPD (N = 3). Plasma activity was fitted to a three compartment model. In controls almost 100% of the radioactivity was recovered in urine within 96 hours and there was no extrarenal catabolism. In patients the fractional catabolic rate ranged from 0.0008 to 0.0022 min-1 versus 0.026 to 0.047 min-1 in controls. The synthetic rate was within the range of values from controls in 10 patients but higher in the seven others. It was correlated with plasma beta 2m concentration. Kinetic data indicate a retention of intact beta 2m. The original model was therefore modified with an additional compartment representing beta 2m captation. The amount of capted beta 2m was more elevated in hemodialyzed patients than in patients treated by hemofiltration or CAPD, in whom it could reach 5 mg/kg/day. Hemofiltration or CAPD may eliminate about 30 to 100% of beta 2m produced and therefore contribute to the low captation amount of these patients, as compared with that of patients treated by hemodialysis.

Adult↗
PubMed1992

Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen.

In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Platelet plasma membrane is equally distributed between surface and osmotically-evaginable surface-connecting membrane, independent of size, subpopulation or species.

Osmotic swelling can double the external plasma membrane surface area of normal human platelets. The surface-connected open canalicular system (SCCS) has been proposed as the major source for this additional membrane. As bovine (B) platelets have been reported to lack SCCS, we compared osmotic swelling for B and human (H) cells. Addition of water to platelet-rich-plasma (10-90% v/v) caused sequential shape change and osmotic spherocyte (OS) formation, analyzed for size and surface area changes from time-dependent phase-contrast videomicroscopic images. Selected samples were fixed and stained with tannic acid prior to osmic acid fixation for visualization of open SCCS by transmission electron microscopy. Bovine platelets required 3-4x less water dilution of PRP than human platelets, with significant OS forming at 20% water addition. Continued water dilution converted 50% of platelets to OS, with maximally stable swelling and no significant lysis for bovine OS up to 60% dilution. Electron micrographs of unactivated discocytes (D) and of optimally-swollen OS showed open SCCS in human D not detectable in any of the swollen platelets, though granules, mitochondria and a small number of vesicles and vacuoles persisted. No evidence for any open SCCS was found for bovine D or OS, though the OS otherwise appeared similar to human OS. Geometric measurements of D and nonlysed OS showed a stable, maximal 2.1 +/- 0.1 fold increase in external plasma membrane surface area with osmotic swelling, identical for different-sized normal human platelets (mean volume V = 2.8-6.8 fl), for abnormally-large platelets (V = 8.7-11.6 fl), or for bovine or rabbit platelets (V = 3-4 fl). As osmotic swelling appears to primarily externalize SCCS in human platelets, the identical relative amounts of internal membrane externalized for bovine platelets is hypothesized to arise from an osmotically more labile, "closed", and structurally simpler SCCS or from a distinct membrane source than in human platelets. It appears that the surface to invaginated ("SCCS") plasma membrane is kept constant for human, bovine and rabbit platelets, independently of platelet production, size-dependent subpopulations, or of platelet ageing.

Animals↗
PubMed1992

Identification of the steroids in neonatal plasma that interfere with 17 alpha-hydroxyprogesterone radioimmunoassays.

Neonatal plasma contains interferents that increase the apparent 17 alpha-hydroxyprogesterone (17-OHP) content measured by direct (no-extraction) radioimmunoassay. We fractionated extracts from neonatal plasma pools by liquid chromatography with a Sephadex LH-20 column and measured 17-OHP immunoreactivity by a direct test kit. We found immunoreactivity in the free steroid and glucuronide fraction and also in the monosulfate fraction. We analyzed these two fractions by reversed-phase high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry. We collected fractions and assayed for 17-OHP immunoreactivity. The HPLC fractions containing the interfering steroid monosulfates were analyzed by ion-spray mass spectrometry and, after solvolysis, by gas chromatography-mass spectrometry. Several monosulfates were identified, including those of 17 alpha-hydroxy-pregnenolone, 16 alpha-hydroxypregnenolone, pregnenolone, and several pregnenetriols. 17 alpha-Hydroxypregnenolone sulfate was the most significant interferent. Other commercially available 17-OHP assays showed similar interference when used without an extraction step. Kit manufacturers should select antibodies and protocols to minimize cross-reaction with sulfates, especially 17 alpha-hydroxypregnenolone sulfate.

17-alpha-Hydroxyprogesterone↗
PubMed1991

Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations.

We recently have devised a method for the derivation of OVA-specific Th1 and Th2 clones from the same primed lymph node cell preparation. Using a panel of such cells, we have examined the ability of distinct APC populations to stimulate proliferation of Th1 and Th2 clones. Both subsets proliferated well in response to OVA in the presence of whole spleen cells. However, purified B cells stimulated optimal proliferation of Th2 clones, whereas adherent cells stimulated optimal proliferation of Th1 clones. The proliferative response of Th2 cells stimulated with spleen cells irradiated with 3300 rad was dramatically less than that observed in response to spleen cells treated with 1000 rad; Th1 clones responded similarly to spleen cells exposed to either irradiation dose. Differential activation of Th1 and Th2 clones did not correlate with MHC-restricting element, or susceptibility to inhibition by mAb directed against CD4 or LFA-1. Lymphokine production by each subset still occurred under conditions of suboptimal proliferation, suggesting that the appropriate Ag processing and presentation events had transpired. The same pattern of response was observed using a specific OVA peptide that does not require processing, suggesting that differential responsiveness of Th1 and Th2 clones to different APC populations is not a result of defective Ag processing. Neither rIL-1 nor rIL-6 restored optimal proliferation of either subset. Our results suggest that unique cofactors are necessary for the optimal proliferation of Th1 and Th2 clones, and that these cofactors are produced by specialized APC populations.

Animals↗
PubMed1991

[Treatment of legionellosis with ofloxacin in kidney transplanted patients. Lack of interaction with cyclosporin A].

Seven cases of legionellosis were observed in a series of 81 renal transplant recipients. In the 6 patients with functional graft, pneumonia occurred 17 days on average after the beginning of transplant rejection treatment. The diagnosis was made by bronchoalveolar lavage: the direct immunofluorescence antigen technique was positive in 5 cases and culture in 6 cases. Legionella pneumophila sero-groups 5 and 1 were identified in one and 5 patients respectively. Six of the 7 patients were treated with ofloxacin. This fluoroquinolone was effective in all cases. It was administered as single therapy in 3 patients and did not interfere with ciclosporin A metabolism. Ofloxacin given in mean doses of 400 mg per day adjusted to renal function proved to be a simple, effective and well tolerated treatment of legionellosis in transplant recipients receiving ciclosporin A.

Adult↗