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Biomedical subjects

C C Wong

Publications and source records attributed to C C Wong.

At least 37 records · Page 2Linked to original sources

Effect of beta-adrenergic blocking agents on mortality rate in patients not revascularized after myocardial infarction: data from a large HMO.

We investigated whether patients who do not undergo coronary angiography and therefore any form of revascularization after a myocardial infarction derive greater benefit from chronic beta-blocker therapy than patients who undergo coronary angiography. With multivariate analyses, treatment with beta-blockers was a much stronger predictor of survival in patients who did not undergo coronary angiography (relative risk = 0.38, p = 0.005) than in those patients who did undergo catheterization (p < 0.05 for interaction). Our findings provide direct support for the recommendation by the American College of Cardiology/American Heart Association task force that beta-blocker therapy should be initiated for all infarct survivors who do not undergo revascularization and who have no contraindications.

Adrenergic beta-Antagonists↗

The antigenic sites of trichosanthin, a ribosome-inactivating protein with multiple pharmacological properties.

Trichosanthin (TCS) fragments were produced by Tn1000 deletion mutagenesis and by cyanogen bromide (CNBr) cleavage and their immunoreactivity was examined by incubating with various antibodies. Twelve C-terminally truncated TCS variants were successfully synthesized under the control of a T7 RNA driven promoter. The smallest antigenic fragment mapped corresponded to the N-terminal 20 amino acids (aa). Six CNBr fragments of TCS were created and identified by electrospray mass spectrometry and N-terminal sequencing. Three antigenic fragments corresponding to aa 1-72, 101-152 and 153-246, respectively were mapped. Fragments corresponding to aa 1-72 and 153-246 were immunoreactive to the same monoclonal antibody showing they are components of a discontinuous epitope. On the other hand, the fragment containing aa 73-100 was not detected by any of the antibodies used.

Animals↗

Variation among hospitals in coronary-angiography practices and outcomes after myocardial infarction in a large health maintenance organization.

BACKGROUND: Wide geographic variation in the use of coronary angiography after myocardial infarction has been documented internationally and within the United States. An associated variation in clinical outcomes has not been consistently demonstrated. METHODS: We assessed the risk of death from heart disease and of any heart disease event (death, reinfarction, or rehospitalization) over a follow-up period of one to four years in 6851 patients hospitalized with acute myocardial infarction at 16 Kaiser Permanente hospitals from 1990 through 1992. The percentage of patients who underwent angiography within three months after infarction ranged from 30 to 77 percent. We selected a subcohort of 1109 patients from three hospitals with higher rates of angiography and four with lower rates for a record review to assess the severity of infarction, the number of coexisting conditions, treatments received, and the appropriateness and necessity of angiography, using established criteria. RESULTS: The rates of angiography were inversely related to the risk of death from heart disease (P= 0.03) and the risk of heart disease events (P<0.001) among the 16 hospitals after adjustment for age, sex, race, coexisting conditions, and the location of the infarction (subendocardial vs. transmural). In the subcohort, 440 patients met criteria indicating that angiography was necessary and 669 did not. Among the former, patients treated at hospitals with higher rates of angiography had a lower risk of death and of any heart disease event than those treated at hospitals with lower rates (hazard ratios, 0.67 and 0.72, respectively). Among the latter, the apparent benefits of being treated at hospitals with higher angiography rates were smaller (hazard ratios, 0.85 to 0.90 for death and any heart disease event, respectively). CONCLUSIONS: During the one to four years after myocardial infarction, patients treated at hospitals with higher rates of angiography had more favorable outcomes than those treated at hospitals with lower rates. This association was stronger among patients for whom published criteria indicated that angiography was necessary.

Aged↗

Effect of thyroid deficiency on Go alpha-subunit isoforms in developing rat cerebral cortex.

Postnatal development of G alpha o isoforms in rat cerebral cortex was studied by SDS-PAGE and immunoblotting. When rat cerebral cortical membranes were resolved on separating gels containing 9% acrylamide and 8 M urea, three electrophoretically distinct G alpha o-immunoreactive proteins were evident. Comparison of their electrophoretic mobilities and partial tryptic digest pattern with recombinant G alpha o1 or G alpha o1-specific antibody revealed that the slowest and intermediate-migrating bands represent unmodified and fatty acylated forms of G alpha o1 protein, respectively. The fastest-migrating band corresponds to G alpha o2. While the fatty acylated form of G alpha o1 is the predominant species, its appearance paralleled that observed for G alpha o2 in developing rat cortex. Perinatal hypothyroidism induced by methimazole treatment did not significantly alter the appearance of cerebral cortical G alpha o1 and G alpha o2 between days 1 and 22 postpartum. Our findings support the earlier idea that heterogeneity of G alpha o proteins in mammalian brain is likely the result of different co- or post-translational processings of each splice variant of G alpha o. While the appearance of G alpha o isoforms is developmentally regulated, they likely do not play an obligatory role in neonatal brain development. Alternatively, the expression of G alpha o isoforms in developing rat cortex may be controlled by an intrinsic signal(s) that is independent of the thyroid status.

Amino Acid Sequence↗

Differential ontogenetic appearance and regulation of stimulatory G protein isoforms in rat cerebral cortex by thyroid hormone deficiency.

We have examined the effects of perinatal hypothyroidism on the levels of several G protein subunits in developing rat cerebral cortex. Thyroid deficiency significantly reduced the levels of the short form of G alpha s (G alpha s-s) by 70% and 83%, on P17 and P22, respectively, but had no effect on the long form of G alpha s (G alpha s-1), except that the G alpha s-1 levels were moderately increased on P22. Compared with age-matched controls, no significant differences were observed for G alpha i-1, G alpha i-2, G alpha o, G alpha q/11, G beta 1 and G beta 2 immunoreactivity in the cerebral cortex of the 22-day-old hypothyroid pups. These findings suggest that thyroid hormones may play an important role in controlling the pattern of expression of G alpha s isoforms during neonatal brain development and the reduced levels of G alpha s-s may contribute to some of the developmental abnormalities seen with perinatal hypothyroidism by altering signal transduction and intercellular communication.

Aging↗

Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract.

Recent studies have suggested a probable etiologic association between Epstein-Barr virus (EBV) and nasal lymphomas, irrespective of geographic location. This study was performed to investigate the strength of association of EBV with non-Hodgkin's lymphomas of the upper aerodigestive tract, based on a large series of cases that have been thoroughly immunophenotyped on frozen tissues. A sensitive in situ hybridization technique was used to detect EBV encoded RNA (EBER) in paraffin sections. Among 30 cases of nasal/nasopharyngeal T-cell lymphoma, 25 (83.3%) were EBER-positive. In the positive cases, most of the neoplastic cells showed strong nuclear signals. Further analysis of this group of tumors showed that all 21 cases (100%) with a CD56+ CD3-phenotype were EBER positive, whereas four of nine cases (44.4%) with a CD56-negative immunophenotype were positive. Only one of 10 cases (10%) of nasal/nasopharyngeal B-cell lymphoma was EBER positive; the positive case was a diffuse mixed-cell lymphoma and could not be distinguished morphologically from the negative cases. Among the 21 cases of lymphoma of the tonsils and back of the tongue (20 B-lineage and one T-lineage), none was EBER positive. In the normal mucosa of the nose/nasopharynx or tonsil (20 cases studied), only very rare EBER-positive small lymphocytes were found in two cases. The almost exclusive detection of EBER in nasal/nasopharyngeal T-cell neoplasms among the lymphomas of the upper aerodigestive tract suggests that EBV probably plays an etiologic role in the pathogenesis of this group of tumors and is not simply a passenger virus, and neither is this merely a site-dependent phenomenon in view of the weak association with nasal/nasopharyngeal B-cell lymphoma.

Herpesvirus 4, Human↗

Repressed activity of peritoneal macrophages in methimazole-induced hypothyroid mice.

In this study we compared the functions of normal peritoneal macrophages with those from methimazole-induced hypothyroid C57BL/6 mice. Methimazole (MMI) suppressed the expression of the tumor necrosis factor (TNF) gene in peritoneal macrophages (MAM) at both transcriptional and translational levels. The kinetics of TNF synthesis by MAM following in vivo and in vitro lipopolysaccharide (LPS) challenge were different, but both treatments resulted in significant decreases (P < 0.05) in TNF mRNA and protein after 60 min. Similarly, the production of reactive nitrogen and oxygen intermediates by MAM were significantly (P < 0.05) lower compared with control macrophages (CAM). In addition, the serum TNF protein was significantly lower (P < 0.05) in MMI-treated mice following intravenous LPS challenge for 90 min. These data suggested that peritoneal macrophages were inactivated in MMI-induced hypothyroid mice.

Animals↗

Study on the purification of growth hormone-like substance from pituitaries of the snake Ptyas mucosa.

Extract from the snake (Ptyas mucosa) pituitaries was capable of inhibiting the binding of 125I-labelled bovine growth hormone to female rat liver membranes. The growth hormone-like substance was not adsorbed on Concanavalin A-Sepharose nor DEAE-cellulose, but could be purified by gel filtration on Sephadex G-50. It possessed a molecular weight of about 19,000 as judged by SDS-polyacrylamide gel electrophoresis. The iodinated snake growth hormone-like substance bound to membranes prepared from female rat and pregnant rabbit livers. The binding could be inhibited by unlabelled snake growth hormone-like substance as well as by bovine growth hormone.

Animals↗

Terminal loop cutaneous ureterostomy in renal transplantation.

Patients presenting for renal transplantation with urinary diversion abnormalities pose serious problems. The use of a terminal loop cutaneous ureterostomy (TLCU) in patients whose outcome was satisfactory was first described in 1977. Primary urinary drainage was achieved in 3 recipients of cadaver renal allografts by creating a TLCU. This method of drainage has been satisfactory in these patients with follow-up between four and thirty months. We suggest that this simple technique should be considered more frequently for selected patients who require supravesical urinary diversion.

Adult↗

Cervical disc calcification in children. A long-term review.

Four cases of symptomatic cervical disc calcification in children are presented. Three cases were followed for more than 10 years. In one case, persistent flattening of the adjacent vertebral body remained into adulthood. To quantify the deformity, the height and width of each vertebral body was measured. These permanent changes may be associated with early degenerative changes seen radiologically in young adults.

Calcinosis↗

Modulation of trichosanthin antigenicity by coupling to dextran.

Trichosanthin (TCS) is a plant-derived type I ribosome-inactivating protein with a wide spectrum of biological and pharmacological activities. Recently, it was covalently coupled to dextran in order to prolong its half-life in plasma. The major biological activities were generally retained but at lower potency. The immunogenicity of the dextran-trichosanthin (DX-TCS) was compared to that of TCS itself in this study. The results showed that mice immunized with TCS produced 8 times as much TCS-reactive IgE than those immunized with DX-TCS. However, both TCS and DX-TCS immunization produced similar titers of TCS-reactive IgG. A trace of dextran-reactive IgG was detected in mice immunized with DX-TCS. Thus, coupling of TCS to dextran reduced its antigenicity but slightly enhanced that of dextran, and the conjugate elicited less IgE than TCS.

Adjuvants, Immunologic↗

Increasing the plasma half-life of trichosanthin by coupling to dextran.

Trichosanthin (TCS) is a plant protein which has a wide spectrum of pharmacological activities. It was demonstrated recently that this compound suppressed the replication of human immunodeficiency virus (HIV-1) in vitro. The mechanism of action is believed to be inhibition of protein synthesis. Trichosanthin is a low molecular weight protein which is expected to be easily filtered and eliminated through the kidney. To minimize renal loss, the molecular size of trichosanthin can be increased by coupling to dextran. The larger complex will not undergo glomerular filtration and therefore renal loss can be prevented. This study investigates the kidney's role in trichosanthin elimination and the beneficial effect afforded by coupling to dextran in prolonging plasma half-life. For this purpose, a radioimmunoassay has been developed to determine the concentration of TCS in plasma and urine. The sensitivity of this assay is in the nanogram range. Trichosanthin was coupled to dextran T40 by a dialdehyde method and successful coupling was confirmed by gel filtration chromatography. The complex retained specific binding to trichosanthin antibodies with decreased affinity which can be partially reversed after incubation with dextranase; an enzyme that digested dextran. The pharmacokinetics of intravenously administered trichosanthin (0.75 mg/kg) was compared between two groups of rats with normal and impaired renal function (bilateral renal arterial ligation). Rats with ligation showed a decrease in plasma clearance from 4780 +/- 570 to 220 +/- 20 microL/min and an increase in the mean residence time from 9 +/- 1 to 145 +/- 16 min. Despite the several-fold difference in these parameters, recovery of trichosanthin from normal rat urine was only 0.38 +/- 0.05%. This value can be increased by using higher injection doses. The data indicate that the kidney is an important organ for the elimination of trichosanthin. When the dextran-trichosanthin complex was injected into normal rats trichosanthin activity was not detected in the urine. All the pharmacokinetic parameters suggest that the dextran-trichosanthin complex stayed longer in the body and maintained a much higher plasma concentration than trichosanthin.

Animals↗

Presence of prolactin receptors in kidney and large intestine of the snake Ptyas mucosa.

125I-labeled ovine prolactin was used to test for the presence of prolactin receptors in membranes prepared from tissues of the common rat snake Ptyas mucosa. High levels of specific binding were found in kidney and large intestine membranes prepared from snakes of both sexes. The binding was time, temperature, and protein dependent. The presence of Ca2+ in the incubation medium enhanced the binding, with optimal concentrations at 10-20 mM. Specificity of binding was established by employing different hormones as the displacing species in the radioreceptor assay. The results suggested the presence of lactogenic receptors in snake kidney and large intestine membranes. Scatchard analysis of the binding data indicated the presence of a single class of binding sites in snake kidney membranes with a dissociation constant of 0.83 nM. The present study is the first report of the presence of prolactin receptors in snake kidney and large intestine membranes.

Animals↗

Partial purification of prolactin-like substance from snake (Ptyas mucosa) pituitaries.

Pituitary extract of the common rat snake (Ptyas mucosa) was found to be capable of displacing the binding of 125I-labelled ovine prolactin to female rat liver membranes, suggesting the presence of prolactin-like substance in snake pituitary. The snake prolactin-like substance was unadsorbed on Concanavalin A-Sepharose, but adsorbed on DEAE-cellulose. The partially purified snake prolactin-like substance was also capable of displacing the binding of 125I-labelled ovine prolactin to snake kidney and large intestine membranes. Chromatographic fractions derived from snake pituitary and which possessed potent growth hormone receptor binding activity were devoid of prolactin receptor binding activity, suggesting the existence of distinct prolactin-like and growth hormone-like substances in snake pituitary.

Animals↗

beta-Endorphin-like and adrenocorticotropin-like hormones in the pituitary of the snake Ptyas mucosa.

Snake (Ptyas mucosa) pituitaries were heated, extracted with an acidic medium, and the extract subsequently chromatographed on carboxymethyl cellulose (CMC). Fractions were assayed for their abilities to displace D-ala2-D-leu5-[tyrosyl, 3,53H] enkephalin from binding to rat brain membranes and 125I-beta-endorphin from binding to its antibody, and to stimulate corticosterone production by isolated rat adrenal cells. The fraction unadsorbed on CMC (having the least basic character) had the lowest opiate receptor binding activity and beta-endorphin-like immunoreactivity. The highest steroidogenic activity, opiate receptor binding activity and beta-endorphin-like immunoreactivity were concentrated in a strongly adsorbed fraction. Snake pituitaries were also extracted with Tris-HCl buffer (pH 7.8). The extract from the second procedure was subsequently chromatographed on ConA-Sepharose, ultrafiltered and dialyzed to obtain a nonglycopeptide fraction with a molecular weight between 1,000 and 10,000. This fraction also exhibited steroidogenic and opiate receptor binding activities.

Adrenocorticotropic Hormone↗

Effects of neonatal capsaicin treatment and streptozotocin-induced diabetes on urinary bladder function in rats.

A significant increase in the size and weight of the urinary bladder was observed 2 weeks after streptozotocin treatment and 2 months after neonatal capsaicin treatment. Both treatments induced a significant increase in the level of [3H]quinuclidinyl benzilate binding to muscarinic cholinergic receptors in the urinary bladder membranes. However, contractile responses of urinary bladder muscle strips to carbachol (0.3-20 microM) were not significantly affected by either treatment. On the other hand, neonatal capsaicin treatment, but not streptozotocin treatment, significantly enhanced contractile responses of bladder strips to electric field stimulation.

Animals↗

Localization of thyroid hormone in subpopulations of rat alveolar macrophages.

Radioimmunoassay and immunocytochemical staining methods were used to study the distribution of thyroid hormone in rat alveolar macrophages. The cells were fractionated into six subpopulations by Percoll density gradient. Positive immunoreactive tri-iodothyronine (T3) was observed in all subpopulations of macrophages, especially in low-density (1.040 and 1.050 g cm-3) groups, by avidin-biotin-peroxidase immunostaining techniques. The macrophages also showed various patterns of cellular T3 stainability. Results from radioimmunoassay of macrophage extracts also demonstrated that macrophages of low density had a higher level of total T3 than those of higher densities (greater than or equal to 1.060 g cm-3).

Animals↗

Effects of neonatal monosodium-L-glutamate treatment on rat alveolar macrophages.

Treatment of neonatal rats with repeated doses of monosodium-L-glutamate resulted in changes of morphology and function of alveolar macrophages recovered from adult female rats. Numerous cellular lipid vacuoles and lamellar structures were observed in these alveolar macrophages under transmission electron microscopy. There was approximately 50% increase of cellular total lipid content measured by Oil-Red-O staining and colorimetric method. The yeast phagocytosis and intracellular killing ability, as well as the inhibitory effect on the growth of tumor cells were reduced in alveolar macrophages from neonatal MSG-treated rats.

Animals↗