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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 451 records · Page 25Linked to original sources

Cytomegalovirus excretion after bone marrow transplantation cannot be predicted from the pre-transplant level of IgG antibodies.

The relationship of pre-bone-marrow transplant recipient and donor cytomegalovirus (CMV) antibody level to post-transplant recipient CMV excretion was investigated. CMV excretion was found to be related to pre-transplant recipient serological status, but not to level of antibody. This therefore contrasts with herpes simplex virus (HSV), for which pre-transplant antibody level in recipients predicts post-transplant HSV excretion.

Adolescent↗

A scanning electron microscope study of microcorrosion casts of the microvasculature of the marmoset palate, gingiva and periodontal ligament.

In the hard palate, sagittally oriented capillary loops, 8-10 microns in diameter and 70-250 microns high, extended perpendicularly from a subcapillary plexus to the connective tissue papillae. These loops formed a well-delineated vascular spine beneath the rugal crests. Capillary loop density was estimated to be 200-270/mm2 on the rugal crest, 75-160/mm2 on the rugal slopes and 70-140/mm2 in the trough. In the gingiva, the crevicular loop system was separated by a gap from the vestibular, palatal and col loop systems. Anastomoses occurred between these systems at a deeper level. The crevicular circular plexus varied from 1 to 4 vessels. Apical to the gingival margin the buccal vasculature was composed of occluso-apically orientated loops draining towards the vestibular sulcus. The capillary loops were 60-120 microns high near the gingival margin, compared with 40-60 microns near the mucogingival junction. The mucogingival margin was demarcated by a change in capillary orientation. The periodontal ligament contained mainly postcapillary-sized venules, 10-25 microns in diameter, orientated occluso-apically. Capillary loops, 50-100 microns long and directed at right angles to the root surface, occurred in the cervical third. These microvascular patterns of the marmoset are different from those of the mouse and rat.

Animals↗

Drug utilization in Panama.

The availability and use of therapeutic agents in Panama is critically reviewed. Of the 3800 drug products on the market, 50% are vitamins, tonics and fixed ratio combination products. Many drugs are of unproven efficacy and safety, not marketed in more developed countries. Hospital and outpatient studies have documented inappropriate prescribing habits. To improve drug utilization, regulatory and educational strategies have been implemented in the Panama Social Security Institute. Drugs of doubtful or no value and unnecessary duplications have been withdrawn from its therapeutic formulatory. Outreach services provided by the Panama Social Security Institute include the distribution of a drug bulletin, workshops, seminars and person to person drug information (counterdetailing) to health personnel. Drug information to patients is also included in the overall strategy to promote the rational use of drugs. Nevertheless, much work is still needed to formulate and implement an essential drugs and health policy in Panama.

Drug Utilization↗

Taxonomic relationships among strains of the anaerobic bacterium Bacteroides ruminicola determined by DNA and extracellular polysaccharide analysis.

DNA and extracellular polysaccharide (EPS) analyses were performed on 14 strains of Bacteroides ruminicola. The guanine-plus-cytosine (G+C) base contents, determined from the buoyant densities of chromosomal DNAs, showed a broad range of values, from 37.6 to 50.9 mol%. DNA hybridization showed generally low DNA relatedness among the strains. Seven strains formed two groups of closely related bacteria consisting of five (group 1) and two (group 2) strains, and another strain, E42g, showed moderate relatedness to group 1 strains. However, the remaining six strains were not related to any of the other strains. DNA reassociation indicates that the strains constitute a genetically diverse group representing as many as nine separate species. EPS analysis showed that the strains produced EPS with rather uniform sugar compositions, which did not correlate with strain relationships determined by DNA analysis. Four strains had EPS with acidic sugars or unknown compounds. The EPS of strain 20-63 contained the unusual acidic sugar 4-O-(1-carboxyethyl)-rhamnose. This monosaccharide has been shown to occur in nature in only one other bacterial species.

Animals↗

Evidence for atrial natriuretic peptide-(5-28) production by macrophages of the rat spleen: an immunochemical and nonradioactive in situ hybridization approach.

Atrial natriuretic peptide (ANP), a 28-amino acid peptide, is produced and secreted by cardiac atriocytes to modulate cardiovascular functions. Recently, biologically active receptors for ANP have been demonstrated in the spleen; we report here the production of ANP-(5-28) and its 15-kDa (K) mol wt (Mr) presumptive precursors by macrophages of rat splenic tissues. Splenic, hypothalamic, and heart tissues were collected from adult male Sprague-Dawley rats and acid extracted for ANP assay. The splenic content of immunoreactive (ir) ANP (mean +/- SEM, 428 +/- 68 pg/tissue; n = 7) was approximately a fifth of that found in the hypothalamus and about 4 orders of magnitude lower than that in the heart of the same animals. The Sephadex G-50 column profile of splenic extracts revealed two immunoreactive peaks; the major peak eluted in positions consistent with 15K Mr, while a minor peak coeluted with synthetic rat ANP-(1-28) of 3K Mr. HPLC analysis of the 3K Mr species showed a single peak of immunoreactivity, which eluted with a retention time similar to that of ANP-(5-28). In rat splenic sections, immunoperoxidase localization of ir-ANP revealed positive cells sparsely distributed in marginal sinuses and the red pulp of the tissue; employing a double staining technique, S22, a surface marker for macrophages, was colocalized on the same splenocytes. Furthermore, colorimetric in situ hybridization with antisense oligonucleotide probes labeled with digoxigenin, identified specific signals for pro-ANP mRNA in splenocytes of tissue sections. In monolayer cultures of vehicle-treated splenocytes, approximately 87% of the adherent cells stained positive for S22; this marker was colocalized with ir-ANP in approximately 15% of the cells. Twenty-four-hour treatment with lipopolysaccharide (50 micrograms/ml), a bacterial endotoxin, tripled the proportion of adherent cells (32 +/- 4%; P less than 0.01) staining positive for ir-ANP over that in control cultures (mean +/- SEM, 11 +/- 3%; 10(4) cells/sample; n = 5). Furthermore, an equivalent dose of lipopolysaccharide, but not Concanavalin-A (50 micrograms/ml), quadrupled ir-ANP content compared to that in vehicle-treated cultures (less than 5 pg/well). Thus, our findings suggest that ANP-(5-28) is produced by a small population of splenic macrophages and raise the possibility that the peptide may play a signalling role at the tissue level.

Animals↗

Tender shins and steroid therapy.

To quantify previously described shin tenderness in patients receiving chronic steroid therapy, we studied 54 patients, 26 treated with steroid, by dolorimetry at 4 control, 4 "fibrositic," and 4 shin sites. To measure observer variation, assessments were done by 2 or 3 of 10 observers, one of whom examined each subject. The specific increase of tenderness at shin sites associated with steroid therapy was confirmed, with a mean (SD) threshold in the steroid group of 3.0 (1.7) kg, and in the control group 5.6 (2.4). Other effects which were not site specific were found. There was a 2.0 kg increase in control site tenderness associated with steroid therapy, and a similar general increase in tenderness in patients with lupus and in women, independent of steroid therapy, affecting control as well as fibrositic sites. Underlying mechanisms must act generally as well as being site specific.

Adult↗

Predictors of side effects associated with lithium administration in children.

Data were pooled from three controlled and double-blind studies of lithium carbonate involving a total of 48 hospitalized children, and secondary data analyses were conducted. The objective was to assess whether there is a relationship between a child's chronological age and side effects associated with lithium administration. Two dependent measures of side effects were investigated: number of side effects per child and number of episodes of side effects per child. The children were diagnosed as having conduct disorder with a profile of severe aggressive and explosive behavior; their ages ranged from 5.08 to 12.92 yrs (mean, 9.23 yrs). For the entire sample of 48 children, the effect of age on side effects was statistically significant (p = .057); younger children had more side effects than older children. This relationship continued to hold after adjustment for weight, serum lithium levels, optimal dose, and duration of optimal dose.

Child↗

Healing of digital flexor tendons: importance of the interval from injury to repair. A biomechanical, biochemical, and morphological study in dogs.

The effect of an elapsed interval of time between injury and operative repair of the flexor tendons was investigated in a canine model. Transected intrasynovial flexor tendons were repaired either immediately or after a delay of seven or twenty-one days. The biomechanical, biochemical, and morphological characteristics were compared at three and six weeks. The values for angular rotation, linear excursion, ultimate load, and linear slope were determined; concentrations of collagen and reducible collagen cross-links, an index of newly synthesized collagen, were measured; and the ultrastructural morphology of the tendons was examined by high-voltage electron microscopy. For the tendons that were repaired immediately, the values for angular rotation were 9.4 +/- 3.2 and 13.0 +/- 3.7 degrees at three and six weeks; for those that were repaired at seven days, 4.1 +/- 1.3 and 2.5 +/- 1.4 degrees; and for those that were repaired at twenty-one days, 2.7 +/- 0.8 and 4.7 +/- 0.7 degrees. There was a significant effect of the delay until repair on the angular rotation and linear excursion in all three groups (p less than 0.005 for both). Tensile testing of the bone-tendon complex revealed no significant effect of the delay on the values for ultimate load (p greater than 0.05). There were no significant differences in total concentration of collagen at the sites of repair or in the levels of reducible Schiff-base cross-links (indicators of newly synthesized cross-links) in tendons from the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells.

The combined use of 2'-deoxy-5-azacytidine with cisplatin or 4-hydroperoxycyclophosphamide in vitro frequently resulted in synergistic cytotoxicity against a panel of six human cell lines. This enhanced cell killing occurred at drug concentrations that are clinically achievable. Synergy was also seen if the sequence of drug administration was altered, implying that a temporal overlap between the drugs was necessary, but that the actual biochemical lesions induced by each agent were probably unique, and interacted in an as yet undefined manner. Of further interest was the observation that at least one of the synergistic pairs was active against five of the six cell lines tested. 2'-Deoxy-5-azacytidine incorporation as assessed by the level of gross genomic DNA methylation did not appear to correlate with the synergistic cytotoxicity observed. Thus, we could not discern a clear relationship between the degree of DNA hypomethylation and the observed synergies, although DNA hypomethylation frequently occurred when synergy was demonstrated. The practical usefulness of these drug combinations has not yet been tested and awaits appropriate clinical trials both to assess the tumoricidal effects and possible increased toxicity.

Antineoplastic Agents↗