Biomedical subjects

E Chan

Publications and source records attributed to E Chan.

At least 127 records · Page 7Linked to original sources

PubMed1991

Variant surface glycoprotein from Trypanosoma brucei clone YTat 1.1 contains a latent calmodulin-binding domain.

Calmodulin affinity chromatography and chromatofocusing were used to purify calmodulin-binding proteins of 32-40-kDa from homogenates of Trypanosoma brucei clone YTat1.1. The trypanosome proteins associated with calmodulins from different sources and reversibly inhibited calmodulin-dependent bovine brain phosphodiesterase. Purified 32-kDa protein bound to calmodulin with an approximate Kd of 1.3 nM. Polyclonal antibodies directed against purified 32-kDa protein and monoclonal antibody ECA6 recognized each of the 32-40-kDa proteins. Immunoprecipitation with biotinylated monoclonal antibody ECA6 (Bio-ECA6) or biotinylated calmodulin (Bio-CaM) identified the 32-40-kDa proteins in phenylmethylsulfonyl fluoride-treated lysates of slender forms of YTat1.1, but not procyclic forms of YTat1.1 or slender forms of EATRO110. In the presence of leupeptin, lysates of slender YTat1.1 contained a single protein of 58 kDa that immunoprecipitated with Bio-ECA6. The 58-kDa protein was exposed to the extracellular space as demonstrated by immunolocalization and sensitivity to pronase treatment in intact cells. The protein was identified as variant surface glycoprotein (VSG) based upon immunolocalization, pattern of expression and cross-reactivity of ECA6 with authentic VSG. The amino-terminal 17 residues of 32-kDa protein were identical with the amino-terminus of YTat1.1 VSG. Putative calmodulin-binding domains were identified in other VSGs by computer modeling. The model was tested with CNBr fragments of VSG 117. The fragments reversibly inhibited calmodulin-dependent activation of phosphodiesterase with approximate Kd of 11 nM. We conclude that endogenously generated proteolytic fragments of VSG from clone YTat1.1, and CNBr fragments of VSG 117 bind with high affinity to calmodulin.

Amino Acid Sequence↗

PubMed1991

Epidemiologic investigation of a cancer cluster in professional football players.

In 1976, the New York Giants professional football team relocated to the newly constructed Meadowlands Sports Complex (MSC) in East Rutherford, NJ. Between 1980 and 1987 four team members developed cancer: one case each of non-Hodgkin's lymphoma, glioblastoma, angiosarcoma, and Hodgkin's disease. Because the surrounding area contains three superfund sites, concern was widespread that the cancers were related to environmental contamination. To assess for a possible environmental etiology, we conducted clinical, environmental, and epidemiologic studies at the MSC. Measurements of volatile organic compounds were all below occupational exposure limits and were similar to ambient levels in nearby Lyndhurst, NJ. Outdoor AM radio broadcast field strengths were in the uppermost 0.1% of field strengths measured in urban areas of the United States. Proportionate mortality ratio and proportional cancer incidence ratio studies of the MSC workforce found no excesses of cancer deaths or of incident cancer cases either for all sites combined or for any specific site. No significant differences in cancer incidence or mortality were found between indoor and nonindoor workers. Based on examination of all available data, the four cancer cases were judged most likely to have been clustered by chance and not to have been caused by environmental conditions at the MSC.

Adult↗

PubMed1991

Successful immunization of infants at 6 months of age with high dose Edmonston-Zagreb measles vaccine. Cite Soleil/JHU Project Team.

A group of 2097 Haitian infants 6 to 11 months of age were randomized to receive Schwarz or Edmonston-Zagreb strain measles vaccines containing 10- to 500-fold more vaccine viral particles than standard potency vaccines. No unusual adverse reactions were noted. Edmonston-Zagreb vaccines were more effective than equivalent doses of Schwarz vaccines as measured by the proportion of vaccinated children with measles antibody concentrations greater than or equal to 200 mIU/ml 2 months after vaccination and the persistence of antibody at 18 to 24 months of age. High titer Edmonston-Zagreb vaccine administered at 6 months of age induced antibody concentrations greater than or equal to 200 mIU/ml in 83% of infants by plaque reduction neutralization and 93% of infants by enzyme-linked immunosorbent assay with high rates of antibody persistence at 12 to 24 months of age. The World Health Organization recommends high titer Edmonston-Zagreb measles vaccines for routine use at 6 months of age in areas where measles is an important cause of mortality in young infants.

Antibodies, Viral↗

PubMed1990

Two decades of increasing mortality from Parkinson's disease among the US elderly.

To examine the possible role of environmental factors in the cause of Parkinson's disease (PD), we reviewed mortality trends for PD in the United States from 1962 through 1984. We found that age-specific mortality for PD in all demographic groups had changed notably during this 23-year interval. Among whites of both sexes, substantial declines were observed among the middle-aged, while notable increases were seen in the geriatric age groups. Similar changes were found in nonwhites; among nonwhites in the geriatric age range, increases of 22% to 553% were observed among women. Men generally had a 100% higher risk of death due to PD than did women. Whites were at three times the risk of nonwhites. The observed temporal changes appear to reflect improved treatment, better case ascertainment, and a true rise in the incidence of PD, particularly among the elderly. This rise may be due to preventable environmental causes and will require further investigation.

Aged↗

PubMed1990

Population pharmacokinetics of phenytoin in Singapore Chinese.

The pharmacokinetics of phenytoin was studied in 66 epileptic Chinese children and adults. The data were analysed by the population approach, using the non-linear mixed effect model, in the MULTI (ELS) program. There was no age or gender-related effect on either the apparent maximum elimination rate (kmax) or Michaelis-Menten constant (KM). Kmax was related to body weight 0.656. The population pharmacokinetics was similar in children and adults. Kmax and KM were estimated to be 30.72 mg.kg-0.656 day-1 and 2.307 mg.l-1, respectively. Kmax was higher than reported values, and KM was comparable to that reported in a study in Japanese, but was much lower than that reported in studies of European patients. The inter-individual variability of KM (CV 65.58%) was substantially higher than that of kmax (CV 28.49%), and the residual (intra-individual) variability was found 21.33% (CV).

Adolescent↗

PubMed1990

Role of prolactin in lactation-induced changes in brown adipose tissue.

During lactation the efficiency of energy utilization is increased and brown adipose tissue (BAT) thermogenesis is suppressed. We have examined the role of prolactin in the suppression of BAT during lactation in the rat. Changes in BAT were studied using an enzyme-linked immunosorbent assay for the uncoupling protein (UCP). In the first experiment BAT from pregnant and lactating rats was examined at various times. Total UPC content of BAT decreased from 364 +/- 34 to 32 +/- 9 micrograms during late lactation (20 days). Serum prolactin (PRL) concentration was elevated during lactation and was highest at 10 days. When endogenous PRL was stimulated by injection of metoclopramide (1.67 mg/kg) for 5 days, UCP content of BAT decreased by 50%. This action of metoclopramide could be blocked by simultaneous administration of bromocriptine, an inhibitor of PRL secretion. Serum PRL concentration was elevated during metoclopramide administration but not when metoclopramide and bromocriptine were given together. We conclude that PRL is a possible mediator of the suppression of BAT during lactation.

Adipose Tissue, Brown↗

PubMed1990

Parkinsonism death rates by race, sex and geography: a 1980s update.

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups. The patterns were different from those reported during 1959-1961. Changing geographic patterns in mortality provide evidence for an environmental etiology for PD.

Cause of Death↗

PubMed1990

Mortality from pulmonary embolism in the United States: 1962 to 1984.

To examine the effect of advances in the prevention of and therapy for PE, we reviewed mortality for PE in the United States from 1962 to 1984. Age-adjusted PE mortality increased by 67 to 100 percent between 1962 and 1974 for white and non-white men and women. From 1975 to 1984, these rates declined by 20 to 28 percent. Non-white PE mortality was greater than white PE mortality; men had a greater risk of PE death than women. Age-specific patterns (more than 40 years of age) of PE mortality followed those of the age-adjusted death rates, with increases noted in all groups between 1962 and 1974 and declines during the 1975-1984 period. These patterns might reflect improved ascertainment of cases and better prevention of disease. The magnitude of the rates suggests that the list of indications for prophylactic anticoagulation should be re-examined for possible expansion.

Adult↗

PubMed1989

Rising mortality from motoneuron disease in the USA, 1962-84.

From 1962 to 1984, age-specific mortality for motoneuron disease (MND) in the United States rose in all demographic groups over the age of 40. The increase was seen in both men and women, and both whites and non-whites, and was most pronounced in the elderly (eg, 378% in white women aged 80-84 years). Men were at 50% higher risk than women, and whites had twice the risk of non-whites. These increases may reflect an improvement in case ascertainment, but they also seem to show a true rise in the incidence of MND, particularly among the elderly. Such an increase suggests an environmental aetiology.

Adult↗

PubMed1989

Structure of the hepatitis A virion: identification of potential surface-exposed regions.

Iodination of highly purified hepatitis A (HAV) virus results in the selective labeling of two viral polypeptides, which are identified as the the VP 1 and VP 2 capsid polypeptides. Based upon the kinetics of labeling, the exposed region of VP 1 appears to be more accessible to iodination, although the ultimate proportion of label present within VP 1 and VP 2 is approximately equal. By utilizing iodinated whole virions, isolated VP 1, VP 2, and the tryptic digest derived from VP 1 and VP 2, binding by heterologous anti-160 S antibody indicated that a significant portion of the antibodies was directed against an epitope on VP 2 that was not affected by denaturation. Identification of the regions exposed for iodination on these two polypeptides was accomplished by tryptic digestion of the isolated polypeptides followed by characterization of the iodinated tryptic peptide by gel filtration and reverse-phase chromatography. The results indicate that tyrosine 100 on VP 2 and a large tryptic peptide composed of amino acids 222 through 260 on VP 1 which contains four tyrosine residues are two regions that are surface-exposed on these molecules.

Amino Acid Sequence↗

PubMed1989

Comparison of intraperitoneal and subcutaneous insulin administration on lipids, apolipoproteins, fuel metabolites, and hormones in type I diabetes mellitus.

The relative biologic efficacy of intraperitoneal (IP) insulin administration over peripheral routes of insulin infusion for artificial delivery devices is still poorly documented. Thus, the effects of IP insulin administration have been compared with the effects of subcutaneous (SC) insulin administration upon circulating fuel metabolites, hormones and lipoproteins. In a longitudinal study, seven type I diabetic patients, aged 33 +/- 3 years, duration 16 +/- 4 years, were studied. SC intensive insulin therapy was used for 3 months, then insulin was infused IP via an implantable pump for 6 months with a similar good blood glucose control. Lipids including high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol, apolipoproteins A-I, A-II, and B were measured every 3 months. Although all values remained in the normal range, significant changes occurred in plasma triglycerides (63 +/- 9 SC v 88 +/- 12 mg/dL IP, P less than .05) and HDL-cholesterol (57 +/- 4 SC v 42 +/- 4 mg/dL IP, P less than .05) without concomitant changes in apolipoprotein levels. In another cross-sectional study, six of the patients consumed a standardized 400 kcal breakfast after 0.15 U/kg insulin. Eight SC insulin infused age-, glucose control- and weight-matched diabetic patients also underwent the same test using SC insulin. Six normal subjects consumed the same breakfast and served as controls. Plasma glucose, B-hydroxybutyrate, lactate, alanine, free fatty acids, free insulin and glucagon were measured for five hours after the meal. All measured parameters were comparable in both groups except free insulin and lactate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Treatment of primary Sjögren's syndrome with hydroxychloroquine.

Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary/lacrimal glands, autoantibody production, and polyclonal hyperglobulinemia. In view of the efficacy and relative safety of hydroxychloroquine in other autoimmune disorders, the potential benefit of hydroxychloroquine (200 mg per day for 12 months) in 10 patients with Sjögren's syndrome was evaluated. Changes in levels of total immunoglobulin, antibody against Sjögren's syndrome-associated antigen B, rheumatoid factor, and in vitro production of immunoglobulin in the serum were evaluated. For comparison, 10 patients matched according to age and sex, who did not receive hydroxychloroquine were studied. In the hydroxychloroquine-treated group, the following observations were made: (1) significantly decreased total immunoglobulin G (IgG) and IgA levels with little change in IgM levels; (2) significant decrease in IgA-rheumatoid factor with a smaller decrease in IgM-rheumatoid factor; (3) decreased IgG anti-Sjögren's syndrome-associated antigen B autoantibody; and (4) decreased erythrocyte sedimentation rate and increased hemoglobin level. Further, a specific idiotype present on their rheumatoid factor (defined by monoclonal antibody 17-109) was significantly decreased, with disappearance of detectable circulating paraprotein in two hydroxychloroquine-treated patients. Finally, rheumatoid factor production in vitro by lymphocytes from hydroxychloroquine-treated patients using a T cell-dependent mitogen was significantly decreased. These results suggest that hydroxychloroquine modulates lymphoproliferation in patients with Sjögren's syndrome and may prevent progression to extraglandular sites of neoplastic transformation.

Autoantibodies↗

PubMed1988

Monovision contact lens wear and occupational task performance.

The effects of monovision (MV) contact lens wear on the performance of occupational-type nearpoint tasks was evaluated on 18 presbyopic subjects (ages 44 to 67 years) by comparing MV performance (MV condition) to that with distance contact lenses with reading glasses (BV condition). Each subject had correctable distance visual acuity of 6/6 (20/20) in each eye, at least 60 sec arc of near stereopsis, good ocular health, and no previous MV experience. Time performance and error performance for 3 nearpoint occupational tasks (pointers and straws, card filing, and letter editing) were measured with the MV correction and BV correction. Measurements were taken at dispensing and at 2 weeks and 8 weeks after dispensing. Subjects were instructed to wear the MV soft spherical contact lenses at least 8 h per day. We measured BV time performance to be better than MV time performance by 2.8 to 5.7% and also measured an increased number of errors with MV.

Aged↗

PubMed1988

Comparison of criteria for assigning germ cell tumor patients to "good risk" and "poor risk" studies.

To evaluate the potential effect of patient selection on chemotherapy trials for patients with advanced germ cell tumors (GCT), four sets of eligibility criteria for poor risk trials were compared in 118 patients. A significant difference was found in the number of patients designated poor risk by the various criteria (P less than .005). Disagreement in the risk assignment by the various selection criteria was seen in 44% of patients. Initial complete response (CR) rates in patients designated poor risk by the various criteria ranged from 38% to 62%. Initial CR rates as high as 94% were seen in patients considered to be poor risk by one set of criteria, but good risk by another. Substantial differences in sensitivity, specificity, overall predictive value, and survival distributions were observed for the various selection criteria. Randomized trials will be necessary to reduce the influence of eligibility criteria on trial outcome and conclusions.

Adolescent↗

PubMed1988

Pharmacokinetics of recombinant human interferon-gamma in the rhesus monkey after intravenous, intramuscular, and subcutaneous administration.

The pharmacokinetics of recombinant human interferon-gamma (rIFN-gamma) were studied in rhesus monkeys. Intravenous administration of 0.1 mg/kg yielded half-lives of 12.3-13.4 min and 130 min. Clearance after intravenous administration was 18.7 ml/min/kg, and the steady-state volume of distribution (Vdss) was 510 ml/kg. The peak serum concentrations after intramuscular and subcutaneous administration of 0.25 mg/kg rIFN-gamma were 50.7 and 52.3 ng/ml, respectively. The time to reach the peak serum concentration was 480 min for both routes. The mean bioavailabilities after intramuscular and subcutaneous administration were 109 and 90%, respectively. Intravenous administration of 0.25 mg/kg rIFN-gamma resulted in no significant change in the clearance, half-life, or Vdss, suggesting that the kinetics of rIFN-gamma are linear over the range of doses tested. Nearly all of the animals developed antibodies to rIFN-gamma after three doses. The presence of nonneutralizing antibodies to rIFN-gamma had no discernible effect on the calculated pharmacokinetic parameters.

Animals↗

PubMed1987

Induction of integrated adenovirus E1A and E1B genes in transformed human cells by phorbol ester tumor promoters.

The effect of phorbol esters on transcription of human type 5 adenovirus (Ad5) early region 1 (E1) genes was studied in two human cell lines (293 and KB16) that contain integrated viral DNA. In 293 cells 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol 12,13-dibutyrate and phorbol 12,13-didecanoate caused a 2- to 3-fold increase in cytoplasmic levels of E1 RNA within 90 min, whereas the nonpromoting TPA analogues 4-alpha-phorbol 12,13-didecanoate and phorbol, or the addition of serum to serum-starved cells, had no effect on E1 RNA. Stimulation by TPA was transient, and the concentrations of all E1 RNA species returned to basal levels by 5 h. The kinetics of E1 RNA accumulation in the presence of TPA were unaffected by cycloheximide, although levels of E1 RNA remained elevated in these conditions. The apparent molecular sizes of major RNA species synthesized from the E1A and E1B regions in 293 cells were the same as those seen early in productive infection by Ad5, and were not changed after induction by TPA. Nuclear run-on assays showed that E1 transcription, as well as transcription of c-fos, c-myc, and beta-actin was stimulated in 293 cells within 30 min of TPA exposure and returned to basal levels by 60 min. In contrast to the 293 cells, expression of Ad5 E1 genes in a second transformed human cell line, KB16, was not altered by TPA. These results show that the induction of Ad5 E1 genes by TPA does not require their presence on infecting genomes, but suggest that inducibility of integrated, functionally expressed E1 genes can be influenced by factors other than their primary sequence.

Adenovirus Early Proteins↗

PubMed1987

Endonuclease IV of Escherichia coli is induced by paraquat.

The addition of paraquat (methyl viologen) to a growing culture of Escherichia coli K-12 led within 1 hr to a 10- to 20-fold increase in the level of endonuclease IV, a DNase for apurinic/apyrimidinic sites. The induction was blocked by chloramphenicol. Increases of 3-fold or more were also seen with plumbagin, menadione, and phenazine methosulfate. H2O2 produced no more than a 2-fold increase in endonuclease IV activity. The following agents had no significant effect: streptonigrin, nitrofurantoin, tert-butyl hydroperoxide, gamma rays, 260-nm UV radiation, methyl methanesulfonate, mitomycin C, and ascorbate. Paraquat, plumbagin, menadione, and phenazine methosulfate are known to generate superoxide radical anions via redox cycling in vivo. A mutant lacking superoxide dismutase was unusually sensitive to induction by paraquat. In addition, endonuclease IV could be induced by merely growing the mutant in pure O2. The levels of endonuclease IV in uninduced or paraquat-treated cells were unaffected by mutations of oxyR, a H2O2-inducible gene that governs an oxidative-stress regulon. The results indicate that endonuclease IV is an inducible DNA-repair enzyme and that its induction can be mediated via the production of superoxide radicals.

Anaerobiosis↗

PubMed1987

Inter-relationship among individual vitamin K-dependent clotting factors at different levels of anticoagulation.

1. The effect of subtherapeutic doses of warfarin on the activities of the four vitamin K-dependent clotting factors was studied at steady state in five patients each of whom had completed a therapeutic course of anticoagulation. 2. The four clotting factor activities were shown to be depressed to a similar extent for a given dose of warfarin. 3. The prothrombin complex activity was significantly lower than that of any of the clotting factors.

Aged↗