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C Burger

Publications and source records attributed to C Burger.

At least 19 recordsLinked to original sources

The impact of the ISIS experiment order on spatial contamination.

When performing volume-localized spectroscopy measurements, the amount of spatial contamination is an important quality criterion. With the ISIS localization technique contamination cannot only arise from the transition regions around the volume of interest, but also from remote regions of the sample. The latter contamination component is a consequence of inhomogeneous excitation pulses, if short repetition times TR are used. Its severity depends both on the order of the eight phase cycling experiments needed for an ISIS measurement, and on the ratio TR/T1. Here it is theoretically discussed from which regions of the sample contamination can arise for a specific phase cycling order. For the worst orders the contaminating regions are almost three times as large as for the optimal orders. The ratio for the effectively measured contamination, however, can be moderated in real experiments, because cancellation effects occur due to the phase distribution of the contaminating signals. 31P phantom experiments clearly demonstrate that contamination is present even if adiabatic excitation pulses are applied and that spatial contamination can be reduced to about a third by an optimal choice of the phase cycling order.

Brain

Demethylation of the constant region genes of immunoglobulins reflects the differentiation state of the B cell.

Previous results showed a developmentally regulated, strong linkage between demethylation and transcriptional activity for the light chain kappa locus in the mouse (Kelley et al., Molec. cell. Biol. 8, 930-937, 1988). These results indicate the existence of a stage of development of the B cell in which permanent expression (which may be enhancer independent) of a gene is associated with its demethylation. According to this result, demethylation could mirror terminal differentiation of a cell. We tested this hypothesis by analyzing the methylation status of immunoglobulin (Ig) genes in normal B cells before and after their activation with lipopolysaccharide (LPS) to induce IgM secretion and an immunoglobulin class switch. This pattern of methylation has been compared with that of Ig genes in nonlymphoid tissues and in transformed cell lines. In general, transformed cells are terminally differentiated cells. Our results show, that in normal splenic B cells only regions proximal to the heavy chain enhancer are demethylated. The coding regions of the c mu, c delta and the c gamma 1 genes remain methylated regardless of transcription. Demethylation of the coding regions is only detectable in transformed cell lines. Hence demethylation of immunoglobulin genes may reflect a stage of terminal differentiation in which the transcription pattern of the cell is fixed. Methylation of the genes before terminal differentiation may be necessary to allow controlled expression of genes on the transcriptional level, such as by splicing and differential termination.

Animals

Toward fully automatic estimation of in vivo 31P spectra.

Fitting a model to an experimental spectrum is a difficult nonlinear estimation problem. The solution presented here is to start an iterative search procedure sufficiently close to the optimal model parameter set. This is achieved by providing tissue-dependent a priori peak information and by a novel correlation method to get good primary estimates of the resonance and phase offset parameters. The resulting estimation procedure is fully automatic and has proven to be robust for 31P data.

Brain

The response of B cells in spleen, Peyer's patches, and lymph nodes to LPS and IL-4.

The vast majority of B lymphocytes in the Peyer's patches (PP) and lymph nodes (LN) are memory cells or activated cells. Hence, in comparison to B lymphocytes in the spleen (SP), most B cells in these lymphoid organs have already encountered antigen. To further examine the ability of B cells in these peripheral lymphoid organs to respond to mitogens and interleukins in vitro, we have analyzed the ability of these cells (as compared to splenic B cells) to respond to LPS and LPS plus IL-4. Our results indicate that B cells from PPs and LNs proliferate poorly to LPS during the first 3 days of culture. In contrast, at later times, PP and LN B cells show enhanced proliferation as compared to splenic B cells. Furthermore, the addition of Interleukin-4 (IL-4) changes the proliferative activity of B cells from PPs and LNs, had only a minimal effect on splenic B cells. Hence, high doses of IL-4 (100 units/ml) enhance the proliferative rate of B cells from PPs and LNs early after activation, and have a suppressive effect at later times. The enhanced response of cells in PPs and LNs is further manifested by the presence of larger numbers of sIgG1+ cells 4 days after activation with LPS plus IL-4 and at 5 days these cells also secrete proportionally more IgG1 than splenic B cells. Enhanced IgG1 secretion is reflected in the methylation pattern of the s gamma 1 switch region of these cells. In cells from PP and LN cultured with LPS plus IL-4, most alleles containing the s gamma 1 region are demethylated or partly deleted, reflecting activation of this region of the Ig gene complex. In contrast, in splenic B cells, half the alleles remain in germline configuration. Our results suggest the presence of larger numbers of "preactivated" B cells in PPs and LNs as compared to spleen. These cells more rapidly secrete Ig following stimulation with LPS plus IL-4 in the absence of significant proliferation.

Animals

Memory B and T cells.

Three remarkable and unique features of the immune system are specificity, diversity, and memory. Immunological memory involves both T and B cells and results in a secondary antibody response that is faster, of higher affinity, and results in the secretion of non-IgM isotypes of Ig. In this review we discuss the properties of memory T and B cells, their specific receptors, and the events which occur both in the nucleus and on the cell surface during generation and activation of these cells. Although memory T and B cells use different mechanisms to elaborate memory, there are a number of interesting analogies: lymphokines vs antibodies and affinity maturation of B cell antigen receptors vs upregulation of adhesion molecules on T cells. Finally, we discuss the importance of these cells in health and disease and suggest what impact additional information about these cells might have on the manipulation of the immune response.

Animals

Protective methylation of immunoglobulin and T cell receptor (TcR) gene loci prior to induction of class switch and TcR recombination.

Methylation of the S gamma 1 switch region and C gamma 1 constant region gene from the immunoglobulin heavy chain locus and of the J beta 2 and C beta regions from the T cell receptor beta chain (TcR beta) locus is compared here in murine germ-line cells, nonlymphoid cells and lymphocytes. In germ-line cells and in lymphocytes prior to recombination all four regions show strong methylation, i.e. most Msp I sites are methylated. After activation of lymphocytes, demethylation is observed for those regions which are activated for recombination, at specific sites 5' of S gamma 1 in B cells activated with bacterial lipopolysaccharide and interleukin 4, and for J beta 2 in thymocytes. In nonlymphoid cells, where these regions cannot be used for recombination, considerable demethylation is observed for all four regions analyzed as compared to lymphocytes. The result implies an important role for methylation of recombinatorial regions. Methylation may be involved in protecting them from uninduced recombination, thus allowing regulated expression of distinct genes in lymphocyte ontogeny.

Animals

Spectral baseline correction using CLEAN.

Baseline distortion in NMR spectroscopy, caused by the "dead time" between signal excitation and detection, makes quantitative interpretation difficult and is aesthetically displeasing. Here the use of the CLEAN algorithm for deconvolving the effect of signal dead time to produce a distortionless baseline is discussed. Unlike other nonlinear spectral estimation techniques, CLEAN is easy to program, easy to use, quite robust, and fast.

Algorithms

The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension.

The study objective was to determine the effects of monotherapy with clonidine and atenolol versus placebo on serum lipids, apolipoproteins, and blood pressure in patients with mild primary hypertension. The protocol comprised a double blind, randomized, placebo-controlled 5-month prospective study carried out in an outpatient general internal medicine clinic in a university medical center. There were 92 patients ages 18 to 70, with mild primary hypertension (sitting diastolic blood pressure of greater than 90 mm Hg and less than 105 mm Hg) without significant cardiac, renal, cerebrovascular, hepatic, neoplastic, or hematologic disorders. Patients with severe hyperlipidemia or peripheral vascular disease were also excluded. All factors known to effect serum lipids were held constant throughout the study (i.e., diet, weight, exercise, caffeine, tobacco). Atenolol and clonidine significantly reduced blood pressure when compared with placebo. Atenolol caused significant increases in serum triglycerides and apolipoprotein B (p less than 0.05) and significant reductions in high-density lipoprotein-cholesterol, apolipoproteins A-I and A-II (p less than 0.05). Atenolol also induced a significant adverse effect on all lipid ratios, increasing total cholesterol/high density lipoprotein-cholesterol, low density lipoprotein-cholesterol/high density lipoprotein-cholesterol, apolipoprotein B/apolipoprotein A-I and apolipoprotein B/apolipoprotein A-II ratios and decreasing low density lipoprotein-cholesterol/apolipoprotein-B ratio (p less than 0.05). Clonidine caused significant reductions in high-density lipoprotein-cholesterol, apolipoproteins AI and AII (p less than 0.05 but was neutral on all other lipids, lipid subfractions, and apolipoproteins. Clonidine did not significantly alter any of the lipid ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Assessment of nutritional status in noninstitutionalized elderly.

Aging may modify both the availability of and needs for certain nutrients. Our study was done to assess the contribution of age alone to micronutrient levels in older volunteers (aged 60 or more). One hundred two healthy elderly white subjects, 63 women and 39 men, carefully screened by history or chart review, were studied in the fasting state. All were noninstitutionalized without serious chronic or acute illness; their diets were nutritionally adequate, containing more than two thirds of the recommended dietary allowance (RDA) for all nutrients, and no subject was taking more than twice the RDA of fat-soluble vitamins. These subjects had higher levels of plasma and red blood cell carnitine, and vitamins A, E, and C. They had lower levels of albumin, transferrin, and zinc than younger laboratory reference subjects. Retinol-binding protein, serum and red blood cell folate, and copper levels were not different. With increasing age, levels of transferrin and vitamins C and E fell; all other measured micronutrient levels were similar. Albumin, vitamin C, and copper values were higher among elderly women, and plasma and red blood cell carnitine values and zinc levels were higher in elderly men. There was great variability in the micronutrient levels despite similar nutrient intakes.

Age Factors

Exercise and balance in aged women: a pilot controlled clinical trial.

A pilot controlled trial was conducted to determine the feasibility of testing an exercise program as a means of improving balance in aged women. A random sample of 50 women more than 65 years old was recruited from two apartment buildings. The buildings were randomized to serve as exercise and control sites. The 24 exercisers did not differ significantly from the 26 controls except that they were better educated and had better vision. The median compliance was 85% of requested sessions attended by the exercisers. Follow-up measures were obtained in 92% and 81% of the exercise and control groups, respectively. The outcome variables studied were changes in sway (areas and velocity of the center of force as measured using a biomechanics platform) in four stances with eyes open or closed, on two feet, or on one foot. After 16 weeks, in stances on one foot, exercisers had smaller areas compared to controls with eyes open, but larger areas with eyes closed. Subgroup analysis indicated that compliance with the exercise program was a determinant of degree of change in the area measures. The inconsistent effect of exercise on area measures of sway in this study may be due to (a) lack of statistical power to detect between-group differences, (b) inadequate compliance with the exercise program, (c) baseline differences between the two groups at randomization, and (d) ineffective or inadequate duration of the exercise program. We conclude that controlled clinical trials to study the effect of exercise on balance measures in community-dwelling elderly women are feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Comparing the quality of death for hospice and non-hospice cancer patients.

In this secondary analysis of data from the National Hospice Study (NHS), a new measure, quality of death (QOD), was developed by weighting reports of cancer patients' last 3 days of life by what patients wanted their last 3 days to be like. Using analysis of covariance, the QOD scores were higher for terminally ill patients in hospices (either home-care [HC] or hospital-based [HB]) than similar patients who received conventional care (CC). The results are discussed in terms of verification of the hospice philosophy and other uses for a quality of death measure.

Attitude to Death

Idiotypic selection of an antibody mutant with changed hapten binding specificity, resulting from a point mutation in position 50 of the heavy chain.

Somatic mutation occurs at a low rate in the rearranged antibody V region genes of the hybridoma line B1-8. delta 1 which expresses an antibody with specificity for the hapten 4-hydroxy-3-nitro-5-iodo-phenylacetyl (NIP). A mutant was selected which had lost a binding site-related idiotope but retained most of its other idiotypic determinants. The mutant had concomitantly lost NIP binding and acquired specificity for dinitrophenylated bovine serum albumin. It carried a single point mutation in position 50 of the heavy chain, resulting in the replacement of an arginine by a glycine.

Amino Acid Sequence

A teaching nursing home: the Vanderbilt experience.

A program to provide exposure to geriatrics as a teaching nursing home project was initiated at a large urban university medical center. Positive experiences, changes of attitude, and personal growth were noted among those involved in teaching, learning, and care of patients. A description of the program, its expansion, and plans for the future are detailed.

Academic Medical Centers

Control of immunoglobulin class switch recombination.

The comparative analysis of Ig class switch recombination in a priori IgG/IgA-expressing myelomas and hybridomas, in switch variants and in activated normal B cells shows the following characteristics of class switch recombination in activated B cells: It is prevented during most of B cell ontogeny. It happens on both IgH loci of activated and switched B cells. The recombination is programmed in that on both IgH loci of switched cells the same switch regions recombine with Smu. This is true at least for the IgG1 pathway. IgM-expressing cells show no class switch recombination on the inactive IgH locus. Thus, physiological class switch recombination is a programmed rather than a random event and is controlled as such. The initial stages of class switching and the molecules involved in these are largely unclear: What is the nature of the protection of switch regions and how is this protection abrogated? Do specific recombinases exist? What is the role of large transcription units? Is the specificity of class switch recombination a result of specific "opening" of the DNA for transcription? Do all B cells use the same switch mechanism? What is the role of switch factors (such as lymphokines)? These and more questions await answers and although a variety of switch scenarios could be discussed at present a detailed speculation seems premature.

Animals

Identification and biochemical analysis of DNA replication-defective large T antigens from SV40-transformed cells.

Nine commonly studied Simian virus 40 (SV40)-transformed rodent cell lines were screened for tumor (T) antigens defective in SV40 DNA replication using a simple polyethylene glycol-mediated cell fusion assay. Each line contained a functional origin of SV40 DNA replication, as shown by fusion with Cos 1 cells. Fusion with uninfected monkey cells revealed that T antigens from two lines lacked detectable replicative activity, while T antigens from five other lines exhibited only very weak replicative activity. One line, and a tumor cell line derived from it, expressed T antigen with wild-type replication activity. Biochemical analysis of these proteins revealed defects in DNA binding activity and ATPase activity. One line expressed large T antigen defective in both activities. All of the lines contained complexes of T antigen with the cellular protein p53 and all of the T antigens exhibited nucleotide-binding activity. The results indicate that some of these lines may constitute a useful source of new replication-defective T antigens.

Adenosine Triphosphatases

Platelet aggregation studies in coronary artery disease. Past 4. Effect of aspirin.

We evaluated platelet aggregation in vitro in blood samples drawn simultaneously from aorta and coronary sinus. Platelet aggregation was significantly lower in the coronary venous blood than in the aortic blood in patients with coronary artery disease. Lower platelet counts were also observed in coronary venous blood. No such differences were seen in subjects with normal coronary arteries. Oral administration of aspirin eliminated the differences in platelet aggregation and counts across the myocardial vascular bed. These observations suggest that platelet sequestration in the myocardial vasculature may be related to the presence of disease in the coronary arteries.

Adult