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D L Brown

Publications and source records attributed to D L Brown.

At least 253 records · Page 14Linked to original sources
PubMed1988

Vancomycin dosing chart for use in patients with renal impairment.

A new vancomycin dosing chart for use in patients with impaired renal function is described. The chart has been adapted from a previously published nomogram, based on a linear relationship between vancomycin clearance and creatinine clearance. Doses are designed to achieve an average steady-state serum concentration of approximately 15 mg/L. Use of the chart necessitates first measuring or estimating the patient's body weight and creatinine clearance. The chart provides the advantages of generating an exact dose and dosing interval, as well as being somewhat easier to use than the original nomogram. Predicted average steady-state serum concentrations resulting from the dosing chart range from 12.1 to 18.2 mg/L, with a mean of 15.0 mg/L.

Body Weight↗
PubMed1988

Total-body electrical conductivity method for estimating body composition: validation by direct carcass analysis of pigs.

Determination of body composition by measuring total-body electrical conductivity (TOBEC) is based on the principle that body fat and fat-free mass (FFM) differ in electrical properties. In humans, we are able to estimate body composition only by indirect methods, which have been used to validate the TOBEC instrument. Relationships between TOBEC and body composition were examined using direct carcass analysis of 24 pigs differing widely in body weight and composition (48-137 kg and 14-45% fat, respectively). Highly significant correlations (p less than 0.0001) were found between body conductivity and empty-body water (H2O) (r = 0.979), empty-body FFM (r = 0.980), empty-body crude protein (r = 0.962), and empty-body potassium (r = 0.949). Prediction of empty-body H2O or FFM from TOBEC had a SEE of 2.1 or 2.8 kg, respectively. Thus, the TOBEC method can predict body H2O and FFM over a wide range of body weight and fatness.

Adipose Tissue↗
PubMed1988

Changes in structure and protein composition of bovine lymphocyte nuclear matrix during concanavalin-A-induced mitogenesis.

A major component of nuclear change in concanavalin-A-stimulated bovine lymphocytes is a severalfold increase in interchromatinic volume, which coincides with nuclear swelling and extensive structural remodelling. Large-scale ultrastructural changes in isolated nuclei and nuclear matrices (NM) reflect those occurring within nuclei in situ during mitogenesis. While nonchromatinic nuclear material embedded within nuclease- and salt-extracted whole cells closely resembled in situ interchromatinic matrices, large NM isolated in solution shrank after chromatin was extracted. Numerous perinuclear filaments persisted throughout NM isolation and cytoskeletal proteins were identified in two-dimensional (2-D) gels of such preparations. Taken together these data indicated that the lymphocyte cytoskeleton is likely continuous with the nuclear matrix and could play a role in maintaining nuclear organization. A wide range of lymphocyte NM proteins were resolved in 2-D gels. Significant changes in protein composition coincided with nuclear structural remodelling. Lamin B was prominent at each stage of nuclear development, whereas lamins A and C were only found in stimulated lymphocyte matrices. Lymphoblast NM contained more large basic proteins. Progressively increasing polypeptide complexity of these NM arose by de novo protein synthesis and posttranslational modifications throughout concanavalin A stimulation. NM from stimulated lymphocytes also contained more ribonucleoproteins, possibly indicating the presence of significant amounts of transcriptional material.

Animals↗
PubMed1988

Taxol-induced reorganization of the microtubule system in murine splenic lymphocytes inhibits response to allogeneic cells but not to concanavalin A.

The exposure of mouse splenic lymphocytes to the microtubule assembly-promoting drug taxol (10 microM for 4 h) results in an extensive reorganization of the microtubule system to form one to a few large bundles of microtubules, which extend from the centrosome. Lymphocytes pretreated with taxol for 4 h, or cultured in the continued presence of taxol, respond normally to the mitogen concanavalin A up to, and including, the stage of DNA replication. In contrast, the induction of DNA synthesis during the alloactivation of lymphocytes is inhibited when taxol is present in the mixed leukocyte culture. If the stimulators are pretreated with this drug, the mixed leukocyte reaction occurs normally, but pretreatment of the responders inhibits the proliferative response markedly. Microscopic observations of nuclear morphologies in these populations and autoradiography indicate that taxol inhibition occurs early in alloactivation, prior to DNA replication. The responding ability of taxol-treated lymphocytes is not restored to control levels by the addition of interleukin 2, leading to the suggestion that interleukin 2 receptors do not emerge or function normally in these cells. We conclude that the capacity to respond to allogeneic cells, but not to a mitogen, is dependent on the presence of the normal submembranous organization of the microtubule system.

Alkaloids↗
PubMed1988

Improved prediction of intrauterine growth retardation with use of multiple parameters.

Several sonographic parameters have been proposed for predicting intrauterine growth retardation (IUGR), but each has been shown to have a low positive predictive value. To predict IUGR more reliably, the authors developed a multiparameter approach based on sonographic and clinical data from 62 fetuses with IUGR and 91 normal fetuses. Logistic regression analysis revealed that the combination of sonographically estimated fetal weight, amniotic fluid volume, and maternal blood pressure status best correlates with the presence or absence of IUGR and produced an IUGR scoring system based on these three parameters. The scoring system, which has a range of 0-100, was tested on a second set of fetuses (47 with IUGR, 81 normal) to determine its performance characteristics. An IUGR score below 50 virtually excludes the diagnosis of IUGR (0.9% likelihood of IUGR, or negative predictive value of 99.1%). A score above 75 allows confident diagnosis of IUGR (positive predictive value, 82%). A score of 50-75 is equivocal, in that it is associated with an intermediate (24%) likelihood of IUGR. The IUGR score is a practical tool that can be easily used in any ultrasound facility.

Amniotic Fluid↗
PubMed1988

Brain stem extracellular fluid pH and respiratory drive during hypoxia in newborn pigs.

In response to moderate hypoxia many newborn animals are capable of increasing ventilation only transiently. To examine the hypothesis that changes in brain stem extracellular fluid (ECF) pH explain this transient ventilatory response, we measured brain stem ECF pH and respiratory drive during hypoxia in newborn pigs. The animals were anesthetized with alpha-chloralose-urethan, paralyzed, vagotomized, and mechanically ventilated with a servo-controlled ventilator to regulate end-tidal CO2. Hypoxic ventilation for 6 min was achieved by changing inspired gas from 100% to 10-15% O2. Respiration, measured as integrated phrenic nerve activity, showed a range of responses. In 13 trials increased phrenic activity early in the hypoxic period was sustained or further augmented for the duration of the period. In contrast, in eight other trials phrenic activity increased and then declined. Regardless of the respiratory response, ECF pH (measured with a flat-surface electrode) increased slightly (0.009 +/- 0.002 U) during the first 2.5 min of hypoxia and then declined 0.061 +/- 0.017 U by the 6th min. This acidotic shift in ECF pH is inconsistent with the hypothesis that an alkalotic shift causes the nonsustained respiratory response of newborn pigs.

Animals↗
PubMed1988

The prometaphase configuration and chromosome order in early mitosis.

We have examined early mitotic stages in HeLa cells, mouse 3T3 fibroblasts and mitogen-activated mouse lymphocytes by immunofluorescence labelling with anti-tubulin and anti-centromere. Chromatin organization was monitored with the DNA-specific fluorochrome Hoechst 33258. This approach has led us to identify a modified Rabl array of chromosomes and spindle microtubules early in mitosis that is distinct from that at metaphase, and which we have called 'the prometaphase configuration'. In the configuration, chromosomes are oriented so that telomeres are clustered at the outer surface, whereas centromeres are clustered inside the configuration, at the surface of a hollow spindle. Observations on cells earlier in mitosis indicate that the configuration is presaged by the spatial relationship between chromosomes and cytoplasmic microtubules in prophase and early prometaphase. We propose a model in which the prometaphase configuration represents an important step linking prophase and metaphase, serving to translate interphase spatial and intragenomic order into order at the metaphase plate.

Animals↗
PubMed1988

Warthin's tumor: an ultrastructural and immunohistochemical study of basilar epithelium.

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.

Adenolymphoma↗
PubMed1988

Effects of caffeine and 3-isobutyl 1-methyl xanthine on caprine milk secretion.

The objective of these studies was to determine if methyl xanthines can be used to alter milk production or composition in ruminants by enhancing adipose tissue mobilization. Three trials were conducted, one with intravenous caffeine infusions, one with intramuscular caffeine injections, and one with intramuscular injections of 3-isobutyl 1-methyl xanthine. Results indicate that: 1) continuous intravenous infusions of caffeine (720 mg/d) may reverse the milk fat depression of intravenously infused glucose in dairy goats; 2) intramuscular injections of caffeine (200 mg twice daily) do not reverse the milk fat-depressing effects of pelleted dairy goat diets during the 4th mo of lactation; and 3) intramuscular injections of 3-isobutyl 1-methyl xanthine (50 mg twice daily) do not consistently affect milk production of early lactation dairy goats.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Almond hulls in diets for lactating goats: effects on yield and composition of milk, feed intake, and digestibility.

Four cubed rations of similar chemical composition were fed ad libitum to 16 lactating yearling Alpine goats. The rations contained 0, 15, 25, and 35% almond hulls; 0, .5, 1, and 1% urea; and 58.4, 42.5, 32.0, and 22.0% alfalfa hay (DM basis). Chromic oxide was added as a digestibility marker. Average nutrient composition of diets was 91% DM, 20% CP, 32% NDF, 9% ash, and 4.39 Mcal gross energy/kg. Goats were randomly assigned to one of four diet orders in four replications of a 4 X 4 Latin square, blocked by goat and period. Data were collected in the 3rd wk of each period. Diets containing 25 and 35% almond hulls increased DM intake and reduced milk protein percent and digestibilities of DM, organic matter, ash, and NDF. Dry matter intake and weight gain were highest for the diet containing 35% almond hulls and 1% urea. Results indicate that almond hulls and urea can be fed to lactating goats up to these amounts without adversely affecting lactation.

Animal Feed↗
PubMed1988

Modulation of lymphocyte nuclear matrix organization in vivo by 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole: an autoradiographic and immunofluorescence study.

Assembly of active nuclei in lymphocytes stimulated by mitogen is paralleled by the elaboration of a structurally and biochemically complex nuclear matrix (NM). To examine the dynamics of individual NM polypeptide components during blastogenesis, we have applied immunofluorescence labelling with anti-NM antibodies to concanavalin A-stimulated mouse splenocytes. Whereas peripherin and PI2 antigens did not reorganize during stimulation, labelling of PI1 and small nuclear ribonucleoprotein (snRNP) antigens increased markedly in intensity and redistributed in concert with the previously reported NM restructuring. Double-labelling showed, furthermore, that snRNPs and the internal staining component of PI1 were largely co-localized. As an approach to studying the role of RNA and RNA synthesis in NM organization, we have further examined the effects of the inhibitor of RNA synthesis, 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), on NM antigen distribution. The rapid inhibition of 3H-uridine incorporation by DRB was accompanied by coordinate aggregation of snRNPs and of the internal PI1 component into large, brightly stained patches. Both 3H-uridine incorporation levels and antigen localization were readily reversed upon removal of DRB. We conclude that NM antigens behave independently during nuclear and NM assembly and that NM organization, as reflected by NM antigen distribution, is modulated by con A- and DRB-induced alterations in RNA synthesis. We propose, furthermore, that the PI1 antigen plays a role in RNA metabolism, and is possibly involved in RNA transport to the nuclear periphery.

Animals↗
PubMed1988

Double-blind comparison of butorphanol and morphine in patient-controlled analgesia.

In this study, the patient-controlled analgesia (PCA) technique was used to compare the suitability of butorphanol with that of morphine in relieving postoperative pain. Twelve patients, 19-77 years old, who had abdominal surgery, used the PCA device through the first 24-hour postoperative period. Results showed that all patients expressed satisfaction with the PCA technique. Analysis of the degree of discomfort according to the verbal description scale, recordings of respiratory rate, and assessment of sedation status showed no significant differences between patients who received butorphanol and those who received morphine. Patients were able to maintain acceptable analgesia with minimal sedation. There were no adverse side effects reported with butorphanol.

Adult↗
PubMed1987

Vimentin dynamics during the mitogenic stimulation of mouse splenic lymphocytes.

We have used double immunofluorescence and electron microscopy to examine the distribution of tubulin and vimentin during the stimulation of mouse splenic lymphocytes by the mitogen concanavalin A. In unstimulated cells, vimentin forms a filamentous network partially coincident with the radial pattern of microtubules. In stimulated cells, the numbers of microtubules assembled from the centrosome have increased and vimentin is organized as an aggregate located near the centrosome. When these cells enter mitosis, vimentin is arranged into a filamentous cage enclosing the mitotic apparatus. During cytokinesis, the polar centrosomes are observed at a position adjacent to the midbody and vimentin is detected as an aggregate, similar to that seen prior to mitosis, close to the centrosome in each daughter cell. Using several agents, such as colchicine, colcemid, nocodazole, and taxol, which affect microtubule assembly, we have observed that the vimentin system, although closely related spatially to the microtubule complex in lymphocytes, can still reorganize independently as these cells progress through the cell cycle. Throughout mitogenic stimulation in the continued presence of taxol, microtubules are reorganized into a few thick bundles while the vimentin system undergoes a sequence of rearrangements similar to those observed during normal stimulation. These data suggest that vimentin dynamics may be important in the progression of lymphocytes through the cell cycle in response to mitogen.

Animals↗
PubMed1987

Structural and evolutionary implications of the packaging of DNA for differentiation and proliferation in the lymphocyte.

During the differentiation of the clonally distributed lymphocytes of mouse and man into mature resting B and T cells, their DNA becomes tightly packed into dense heterochromatin masses and exhibits very little transcriptional activity; it also becomes extensively nicked, containing some 3000-4000 single-strand breaks per diploid genome. The nuclear matrix is sparse and poorly organized and there are but trace amounts of the matrix-linked enzyme DNA topoisomerase II; the nucleus of these small cells is surrounded by a thin rim of cytoplasm. The resting cell can thus be considered (by analogy to a sperm cell) as a vector for transporting tightly packed and relatively inert genetic information to all parts of the body. When the lymphocyte is stimulated to enter a proliferative cycle by binding of appropriately presented antigen or mitogen to relevant membrane receptors, the cell enlarges, due to increased synthesis of protein; the dense heterochromatin is pulled out into very small clumps, as a result of an enormous growth in size as well as complexity of the nuclear matrix, and a great increase in transcriptional activity occurs. We have identified four nuclear matrix antigens that are very widely conserved in the evolution of eucaryotes and that occupy distinctive domains in interphase nuclei. Of particular interest is antigen P1, detected in organisms ranging from algae to mammals. By virtue of its location at the interface between nuclear envelope and chromatin, we propose that it plays a major and evolutionarily conserved role in chromatin organization and orientation in all eucaryotic cell types.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Organizational fate of vimentin during redistribution of surface immunoglobulin in mouse splenic lymphocytes.

We have used immunofluorescence to examine the organizational fate of vimentin and its spatial relationship to the microtubule system during antibody-induced redistribution of surface immunoglobulin (sIg) in control and drug-treated mouse splenic lymphocytes. In control cells, vimentin is relocalized as a diffuse accumulation underneath the site of the cap during sIg redistribution. Observations on cells that were treated with colcemid or taxol prior to induction of sIg redistribution have further shown that vimentin accumulation corresponds to a dynamic rearrangement of this filamentous system which is related to, but is not required for, the energy-dependent translocation of sIg.

Actin Cytoskeleton↗
PubMed1987

Enhancement of phenytoin elimination by multiple-dose activated charcoal.

The effect of multiple-dose activated charcoal on the elimination of intravenously administered phenytoin was studied. Seven normal volunteers received phenytoin sodium 15 mg/kg IV with and without activated charcoal. During the charcoal phase, a total dose of 300 g was administered in repeated doses over 48 hours with sufficient sorbitol to produce one to two bowel movements per day. Serum phenytoin concentrations were determined from one to 72 hours after the infusions and were fitted to a one-compartment linear elimination model. The administration of multiple-dose activated charcoal reduced the phenytoin half-life from 44.5 to 22.3 hours. In addition, phenytoin area under the curve was decreased and the elimination rate was increased. Multiple-dose activated charcoal is effective in enhancing the elimination of phenytoin in normal volunteers. Although future studies are needed to determine its role in treating patients with phenytoin toxicity, multiple-dose activated charcoal may provide a readily available, inexpensive therapeutic intervention.

Adult↗