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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 487 records · Page 27Linked to original sources

E-series prostaglandins are potent growth inhibitors for some B lymphomas.

The ability of prostaglandins (PG) to inhibit the growth of B cell lymphomas was investigated. Macrophage-secreted PGE2 was previously shown to promote unresponsiveness to antigen in normal B lymphocytes. This observation suggested that B lymphomas might also be regulated by prostanoids. Five non-PG-secreting Ly-1+ B lymphomas (CH12, CH31, CH33, NBL and WEHI-231) were incubated for 24-72 h with PGE2, PGE1 or PGF2 alpha. The level of lymphoma growth at the end of culture was determined using a colorimetric assay which detects only viable cells. A marked heterogeneity was observed with respect to the sensitivity of these lymphomas to PGE2 and PGE1. CH31 was very sensitive, being growth inhibited by as little as 10(-8) M PGE. In contrast, CH12, a more mature lymphoma, was highly resistant, whereas CH33, NBL and WEHI-231 were of intermediate resistance. All five lymphomas demonstrated little or no growth inhibition when cultured with PGF2 alpha. Moreover, unlike PGE2, PGF2 alpha failed to elevate intracellular cAMP levels. It was previously shown that CH31, CH33 and WEHI-231 could be growth inhibited by anti-immunoglobulin antibodies which cross-link surface immunoglobulin. Interestingly, these three lymphomas were rendered more sensitive to this treatment if PGE2 was present. For example, 10(-8) M PGE2 alone had little effect on CH33, but significantly augmented growth inhibition induced by suboptimal quantities of anti-immunoglobulin antibody. Cholera toxin, another agent which was found to rapidly elevate intracellular cAMP levels, also synergized with suboptimal doses of anti-immunoglobulin to induce growth inhibition. Overall these data suggest that, in vivo, macrophage-secreted prostanoids may slow the growth of some lymphomas and that anti-immunoglobulin or anti-idiotype treatment may be more effective in the presence of agents which elevate cAMP such as E-series PG.

Animals↗

Life stress and lymphocyte alterations among patients with rheumatoid arthritis.

The relation between life stress and immune parameters was investigated for 33 female rheumatoid arthritis (RA) patients interviewed during three routine monthly clinic checkups. Life stress from major and minor events, coping efficacy, and self-reported psychological distress were assessed, and immunofluorescence of T-cells and B-cells was performed on the blood drawn during each visit. Small stressful events were positively related to the proportion of circulating B-cells, psychological distress was inversely related to proportion of circulating T-cells, and major life events were associated with lower T-helper/T-suppressor cell ratios.

Adaptation, Psychological↗

Costs associated with ambulatory care and education.

The adoption of an ambulatory care classification system by the Health Care Financing Administration in 1991 may have significant implications for medical education programs in the Department of Veterans Affairs (VA) ambulatory care setting. Presently there is not adequate methodology in the VA to determine costs in ambulatory care and education. (Experience with the VA allocation model suggests that selected characteristics of reimbursement systems are incompatible with educational goals.) Barriers that inhibit the cost-effective delivery of ambulatory care in many VA hospitals must be eliminated so that effective patient care and training care can take place. These barriers include inadequacies of information systems, physical layouts, and staffing. Despite the perception that outpatient care is less costly than inpatient care, the transition from an inpatient-based education model to an ambulatory care model will require an infusion of resources to improve the ambulatory care environment in the VA.

Ambulatory Care↗

The comparative effects of tumor necrosis factor on tumor cells growing anchorage dependently and independently.

Tumor necrosis factor (TNF) is a macrophage-derived cytokine that has been shown to exert differential cytotoxic and/or cytostatic effects on many human and animal tumor cells. In vitro assays of TNF effects have been performed mainly on cultured tumor cells growing as a monolayer. However, tumor cells may respond differently to the effects of growth factors depending on whether they grow in two-dimensional monolayer cultures or in three-dimensional colonies in soft agar. We have tested the effect of TNF on the anchorage-dependent (monolayer) and anchorage-independent (soft agar) growth of five rat, two mouse, and one human tumor cell lines. The results indicate that tumor cells may demonstrate different growth responses in these two culture conditions, and that some tumor cells that are resistant to the cytostatic effect of TNF in monolayer cultures may demonstrate significant sensitivity when growing in soft agar medium. One of the rat tumor cell lines unaffected by TNF in monolayer culture was actually stimulated in their colony growth in soft agar medium. The clonogenic techniques of cultivating human tumor cells in soft agar may be suitable for the screening of TNF-sensitive tumors for therapeutic consideration with this substance.

Agar↗

Expression and processing of biologically active fibroblast growth factors in the yeast Saccharomyces cerevisiae.

Chemically synthesized genes for bovine and human fibroblast growth factors (FGFs) were expressed in heterologous microorganisms. Although the intracellular expression or secretion of acidic and basic FGFs in Escherichia coli or Saccharomyces cerevisiae yielded recombinant growth factors with high biological activity, the resulting proteins had structural microheterogeneity due to modified amino termini. Expression of amino-terminal extended forms of human acidic and basic FGFs in S. cerevisiae gave rise to soluble, but cell-associated polypeptides, with potent biological activity. These yeast-derived proteins were processed in vivo by removal of initiation codon-derived methionine residues and by amino-terminal acetylation. Both of these processes have been observed in mammalian tissues. The yeast systems described here, therefore, provide a good model system for the expression of FGFs as intracellular proteins, but more importantly they give high levels of authentically processed human FGFs with many potential medical applications. Since the recombinant proteins have all the biological activities of their native counterparts, their possible applications in wound healing, tissue grafting, nerve regeneration, and treatment of ischemia are discussed.

Amino Acid Sequence↗

Selective regulation of S-adenosylmethionine decarboxylase activity by the spermine analogue 6-spermyne.

Polyamine-biosynthesis activity is known to be negatively regulated by intracellular polyamine pools. Accordingly, treatment of cultured L1210 cells with 10 microM-spermine rapidly and significantly lowered ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities in a sequential manner. By contrast, treatment for 48 h with 10 microM of the unsaturated spermine analogue 6-spermyne lowered AdoMetDC activity, but not ODC activity. An initial decrease in ODC activity at 2 h was attributed to a transient increase in free intracellular spermidine and spermine brought about through their displacement by the analogue. Thereafter, ODC activity recovered steadily to control values as 6-spermyne pools increased and spermidine and spermine pools decreased owing to analogue suppression of AdoMetDC activity. The apparent ability of 6-spermyne to regulate AdoMetDC, but not ODC, activity suggests an interesting structure-function correlation and demonstrates that the typical co-regulation of these enzyme activities can be dissociated. This, in turn, may reflect the existence of independent regulatory binding sites for the two enzymes.

Adenosylmethionine Decarboxylase↗

Productivity of sustained research funded by the Medical Research Council of New Zealand during the period 1973-84.

From 1973-81, Medical Research Council funding for sustained research rose from $1.6 to $4.4 million per year but, during 1982-84 fell to $3.8 million. Corrected for inflation, this funding was constant until 1982-84 when it fell by one-third. Publications increased from about 190 in 1974 to a peak of about 310 in 1980 but fell to 200 during 1982-4. Grantees who failed to publish took about 16% of sustained project grants and 10% of such funding. The average cost of an article rose from $5500 in 1973 to $20,000 in 1983/4 but, in real terms, the cost in 1984 was two-thirds of that in the mid-1970's. Cost of publications from Auckland increased steadily from 1973-84. Those for Dunedin remained constant from 1974-80, but increased to exceed $20,000 in 1982-84. From 1973-78, articles from Wellington cost $12,000 but this rose to $20,000 thereafter. Costs in Christchurch increased from $2500 in 1973 to $12,000 in 1984. Inflation-corrected costs per publication from Auckland, Wellington and Dunedin have shown a downward trend while those from Christchurch showed a slight increase.

Costs and Cost Analysis↗

5S rRNA genes in Pisum: sequence, long range and chromosomal organization.

We have employed a combination of techniques to examine the organization of pea 5S rRNA genes. These include the analysis of length variant interspersion patterns in cosmid clones, sequence analysis, Southern analysis of both conventional gels and field inversion gels and in situ hybridization. From these analyses we conclude that the 5S rRNA genes of pea are arranged in three major tandem arrays which are represented by three large EcoRI fragments and that these correspond to the three sites of in situ hybridization in the haploid pea complement.

Base Sequence↗

Is rhodopsin the ligand for receptor-mediated phagocytosis of rod outer segments by retinal pigment epithelium?

It has been suggested that rhodopsin may have a direct role in the attachment of shed rod outer segments (ROS) to retinal pigmented epithelial (RPE) cells initiating the events which lead to engulfment. We isolated the soluble tryptic glycopeptide from rhodopsin (GP-T1) and used it as a probe to test this hypothesis. In phagocytic assays using both cultured chick and cat RPE cells, GP-T1 did not inhibit the phagocytosis of ROS. Additionally, mannose glycoconjugates were not effective inhibitors of phagocytosis. However, glycopeptides released by tryptic digestion of intact ROS did inhibit ROS uptake by the RPE cells. The results suggest that phagocytosis of ROS is not mediated through a simple carbohydrate recognition system and that rhodopsin is not the ligand recognized by RPE cells.

Animals↗

The oxidative metabolism of sparteine in the Cuna Amerindians of Panama: absence of evidence for deficient metabolizers.

Sparteine sulfate (50 mg) was administered to 170 Cuna Amerindians, 142 of whom were unrelated, and the drug and its dehydrometabolites were determined in the 0- to 12-hour urine samples. The log10 of the metabolic ratio was unimodally, but not normally, distributed and showed the following values: mean -0.21 +/- 0.26, median -0.24, limits -0.73 and 0.76, skewness 1.00, and kurtosis 4.95. On the basis of these results, it can be concluded that there are no deficient metabolizers in the Cuna sample population studied. However, the similarity of the skewness found between the Cuna sample population studied and the extensive Canadian white group, as well as an inflection point at 6.3 U in the former's probit plot, suggests the existence of at least two subgroups congregating within the same single mode in the frequency distribution curve. The use of the inflection point is discussed thoroughly, concluding that although it does not allow exclusion of the existence of genotypically different subgroups, the limitations of the data do not permit its use to determine the number of heterozygotes and thus the existence of polymorphism. The possibility of an isozyme variant, consistent with the general genetic structure of Amerindians, as suggested by the coexistence of two subgroups within the unimodal curve, is entertained.

Adolescent↗

Evaluating soft contact lens quality: a manufacturer's perspective.

This study was designed to compare quality control between six aphakic contact lens brands. The methodology eliminates the sampling and experimental variables of previous studies. The lenses were all purchased new at +13.00 D power, with the same number of lenses and distribution of manufacturing batch/lots per brand. We measured or assessed 120 study lenses (20 per brand) for diameter, front sagittal height, power and image quality, center thickness, surface and edge quality, and edge design. The base curve radius was calculated accurately using lens cross-sectioning techniques. The reproducibility of measured lens parameters (precision) and conformance to label claims (accuracy) were tabulated separately and the lens brands were ranked and grouped statistically. The tabulated results are represented graphically in one spread sheet where selected American National Standards Institute (ANSI) tolerances were used as a standard to which all lens brands were compared. Lens brands coded as Brand A and Brand B rated the highest using our criterion for ranking overall quality control.

Calibration↗