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J S Lim

Publications and source records attributed to J S Lim.

At least 55 records · Page 3Linked to original sources

Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils.

Trans-tamoxifen (TAM) has been used successfully in therapy for estrogen-dependent human breast tumors and prevention of their recurrence. The mechanism of this prevention was thought to be due to the interference of TAM with estrogen promotion. TAM has a wider anticarcinogenic action that is similar to other chemopreventive agents in that it suppresses tumor promotion in 2-stage carcinogenesis by interfering with the action of protein kinase C. We report that TAM (5 microM) totally inhibits hydrogen peroxide (H2O2) formation by 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-treated human neutrophils. Interestingly, beta-estradiol (10 microM) also slightly inhibits the oxidative burst of neutrophils. Pretreatment of neutrophils with varying amounts of TAM and beta-estradiol caused additive inhibition of H2O2 formation by the 2 agents. 4-Hydroxy-tamoxifen, a metabolite with the highest affinity for the estrogen receptor, was only as inhibitory as beta-estradiol. Other derivatives (cis-, N-desmethyl-, and N-desdimethyl-tamoxifen) with low biological activities had a smaller effect on H2O2 formation. TPA-treated neutrophils were shown to contain 5-hydroxymethyl uracil (HMU). TAM prevented the TPA-induced formation of HMU in other cells. Like TPA, dietary fat, which is a risk factor for breast cancer, induces formation of HMU in the DNA of human white blood cells. TAM may suppress the dietary fat-induced HMU in the same manner at it does in TPA-induced neutrophils.

Estradiol↗

Expression of increased immunogenicity by thiol-releasing tumor variants.

Even moderate variations of the extracellular cysteine concentration were previously shown to affect T cell functions in vitro despite high concentrations of cystine. We therefore analyzed the membrane transport activities of T cells for cysteine and cystine, and the role of low molecular weight thiol in T cell-mediated host responses against a T cell tumor in vivo. A series of T cell clones and tumors including the highly malignant lymphoma L5178Y ESb and its strongly immunogenic variant ESb-D was found to express extremely weak transport activity for cystine but strong transport activity for cysteine. However, not all cells showed the expected requirement for cysteine (or 2-mercaptoethanol (2-ME)) in the culture medium. One group of clones and tumors including the malignant ESb-lymphoma did not respond to changes of extracellular cystine concentrations and was strongly thiol dependent. This group released only little acid soluble thiol (cysteine) if grown in cystine-containing cultures. The other T cell lines, in contrast, were able to maintain high intracellular GSH levels and DNA synthesis activity in cystine-containing culture medium without cystein or 2-ME and released substantial amounts of thiol. This group included the immunogenic ESb-D line. Additional thiol-releasing ESb variants were obtained by culturing large numbers of L5178Y ESb tumor cells in cultures without cysteine or 2-ME. All of these ESb variants showed a significantly decreased tumorigenicity and some of them induced cytotoxic and protective host responses even against the malignant ESb parent tumor. Taken together, our experiments suggest that the host response against a tumor may be limited in certain cases by the failure of the stimulator (i.e., the tumor) cell to deliver sufficient amounts of cysteine to the responding T cells.

Amino Acids↗

Suprasellar and intraventricular blood predict elevated plasma atrial natriuretic factor in subarachnoid hemorrhage.

Following subarachnoid hemorrhage, the plasma concentration of atrial natriuretic factor is elevated and appears to be independent of atrial stretch. While the hypothalamus and circumventricular organs contribute to sodium and intravascular volume regulation, their influence on atrial natriuretic factor is not known. We tested the hypothesis that, following subarachnoid hemorrhage, suprasellar cisternal blood, intraventricular blood, or ventricular enlargement would be associated with elevated plasma levels of atrial natriuretic factor. Computed tomograms of 26 patients performed less than or equal to 3 days after hemorrhage were analyzed to determine the presence of suprasellar or intraventricular blood and enlargement of the third or lateral ventricle. These results were correlated with the plasma atrial natriuretic factor and serum sodium concentrations. The initial atrial natriuretic factor concentration was elevated and was higher in patients with suprasellar or intraventricular blood than in those without (suprasellar: 131 +/- 20 and 54 +/- 10 pg/ml, respectively; intraventricular: 137 +/- 25 and 84 +/- 31 pg/ml, respectively). The atrial natriuretic factor concentration remained higher over the week following hemorrhage in patients with suprasellar blood than in those without (127 +/- 16 and 68 +/- 12 pg/ml, respectively). The atrial natriuretic factor concentration was not correlated with hyponatremia (125-134 meq/l) or age-corrected ventricular size. Hyponatremia did not correlate with the presence of intraventricular or suprasellar blood. Our data suggest that suprasellar and intraventricular blood disturb hypothalamic function, resulting in an elevated plasma atrial natriuretic factor concentration. The presence of a direct relation between atrial natriuretic factor and hyponatremia remains unclear.

Adult↗

Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. II. Sandhoff disease gene frequencies in American Jewish and non-Jewish populations.

Carrier frequencies for the allele(s) causing Sandhoff disease have been estimated for the U.S. Jewish and non-Jewish populations. The estimates have been made directly, with data from 22,043 Jewish and 32,342 non-Jewish individuals measured for total serum hexosaminidase activity and the heat-labile fraction. These values have been shown to identify potential carriers of the Sandhoff allele(s) with 95% sensitivity. Subsequent leukocyte assays of total hexosaminidase activity and the heat-labile fraction in those identified in serum tests have been shown to provide a much finer discrimination between those who carry the allele(s) and those who do not. Results from such assays were used to generate these carrier frequency estimates. Carrier frequency estimates have also been made indirectly from Sandhoff disease incidence data collected during the period 1979-84. These estimates are in agreement with data for the Jewish population under analysis, but in the non-Jewish population the estimate derived from data on screened individuals is greater than the estimate derived from incidence figures. The possible causes for such a difference are discussed. In a study of non-Jewish individuals each of whose grandparents derives from a single country of origin, the distribution of countries among Sandhoff disease carriers differs significantly from that in the non-Jewish sample under analysis, indicating possible ethnic groups with increased or decreased carrier frequencies. These analyses suggest an increased Sandhoff disease carrier frequency among Mexican and Central-American populations and a decreased carrier frequency among non-Jewish German populations.

Gene Frequency↗

Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. I. Statistical methods.

Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers of the allele(s) for SHD among individuals screened in a TSD heterozygote identification program. Using multivariate statistical methods of cluster analysis and discriminant analysis on serum and leukocyte hexosaminidase profiles from 102 potential SHD carriers, a linear discriminant function to classify individuals as SHD carriers or SHD noncarriers was constructed. This function classifies the serum and leukocyte profiles from all 15 obligate SHD heterozygotes studied, as those of SHD carriers. A 95% isodensity ellipse derived from only the serum hexosaminidase profiles of the 15 SHD obligate carriers has been applied to a TSD screened sample of 37,843 Jewish and non-Jewish individuals. A potential recall rate of screened individuals for serum retests and leukocyte assays of 2.01% has been estimated. These statistical methods enhance the TSD heterozygote screening program by permitting one to detect SHD heterozygotes within the screened population.

Genetic Carrier Screening↗

Intensity perception. XIII. Perceptual anchor model of context-coding.

In our preliminary theory of intensity resolution [e.g., see N. I. Durlach and L. D. Braida, J. Acoust. Soc. Am. 46, 372-383 (1969)], two modes of memory operation are postulated: the trace mode and the context-coding mode. In this paper, we present a revised model of the context-coding mode which describes explicitly a process by which sensations are coded relative to the context and which predicts a resolution edge effect [L. D. Braida and N. I. Durlach, J. Acoust. Soc. Am. 51, 483-502 (1972); J. E. Berliner, L. D. Braida, and N. I. Durlach, J. Acoust. Soc. Am. 61, 1256-1267 (1977)]. The sensation arising from a given stimulus presentation is coded by determining its distance from internal references or perceptual anchors. The noise in this process, combined with the sensation noise, constitutes the limitation on resolution in the model. In the revised model the probability density functions of the decision variable are not precisely Gaussian (and cannot be expressed analytically in closed form). This paper outlines the predictions of the model for one-interval paradigms and for fixed-level two-interval paradigms and derives estimates of the values of model parameters.

Discrimination Learning↗

The Tay-Sachs disease gene in North American Jewish populations: geographic variations and origin.

From data collected in a North American Tay-Sachs disease (TSD) heterozygote screening program, the TSD carrier frequency among 46,304 Jewish individuals was found to be .0324 (1 in 31 individuals). This frequency is consistent with earlier estimates based on TSD incidence data. TSD carrier frequencies were then examined by single country and single region of origin in 28,029 Jews within this sample for whom such data were available for analysis. Jews with Polish and/or Russian ancestry constituted 88% of this sample and had a TSD carrier frequency of .0327. No TSD carriers were observed among the 166 Jews of Near Eastern origins. Relative to Jews of Polish and Russian origins, there was at least a twofold increase in the TSD carrier frequency in Jews of Austrian, Hungarian, and Czechoslovakian origins (P less than .005). These findings suggest that the TSD gene proliferated among the antecedents of modern Ashkenazi Jewry after the Second Diaspora (70 A.D.) and before their major migrations to regions of Poland and Russia (before 1100 A.D.).

Female↗

Intensity perception. VIII. Loudness comparisons between different types of stimuli.

In this paper, we describe an extension of our preliminary theory of intensity resolution [Durlach and Braida, J. Acoust. Soc. Am. 46, 372-383 (1969)] to include loudness comparisons among different types of stimuli. The extended theory relates mean loudness matches to discrimination and provides a framework for the interpretation of results on the intrasubject variability of loudness comparisons. The predicted relation between mean loudness matches and discrimination is essentially the same as that proposed by Riesz [J. Acoust. Soc. Am. 5, 211-216 (1933)]. With regard to the variability of loudness comparisons, the extended model is essentially the same as the preliminary model except that a new term is included in the trace-mode memory variance to account for the dissimilarity of the stimuli being compared. The model is compared to some published data on loudness matching and discrimination and to some new data of our own on the variability of loudness comparisons obtained in a two-interval, roving-level, loudness-discrimination experiment.

Acoustic Stimulation↗

Left main coronary arterial obstruction: Long-term follow-up of 141 nonsurgical cases.

The prognosis of 141 patients with obstructive left main coronary artery disease was studied. The patients were followed up for 5 to 10 years from the date of coronary arteriography. The 5 year cardiac mortality rate was 51 percent. During the first 3 years after diagnosis, the mortality rate was especially high, 21.9, 34.7 and 43 percent, respectively. Among patients who died in the 1st year after diagnosis, evidence of left ventricular hypertrophy or conduction delay in the electrocardiogram and multiple vessel involvement indicated poor prognosis. Severe angina pectoris, evidence of congestive heart failure and generalized decrease in left ventricular contractility increased the 5 year mortality rate. More than 97 percent of the total patient population had additional lesions elsewhere in the coronary arteries.

Angina Pectoris↗

The spectrum of exercise test and angiographic correlations in myocardial revascularization surgery.

Maximal exercise tests and angiographic evaluations were obtained in a group of patients before and after myocardial revascularization. Patients were classified on the basis of angiography and operative records. Two primary groups of 33 patients with complete revascularization and 95 patients with postoperative residual ischemia were studied. The residual ischemia subgroups included patients with partial revascularization, progressive coronary atherosclerosis, or graft failure. Patients with complete revascularization had statistically significant improvements in work capacity, maximal heart rate, maximal rate-pressure products, abnormal exercise electrocardiograms, exercise-induced angina pectoris, and atrial gallop sounds. A spectrum of lesser improvements in these measurements was observed in the subgroups with residual ischemia. Total graft failure resulted in no significant improvements in exercise-test parameters. Maximal stress tests provide a useful adjunct to routine clinical follow-up of myocardial revascularization patients. Myocardial revascularization is associated with significant patient palliation as determined by serial stress testing.

Angina Pectoris↗