Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome

BACKGROUND: Fever is commonly observed in patients with human immunodeficiency virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow biopsy in the diagnosis of fever of unknown origin in patients infected with HIV remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive patients with 137 episodes of fever lasting 10 or more days without diagnosis after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS: Overall, a specific diagnosis was achieved in 52 episodes by means of culture and histopathological examination (diagnostic yield, 37.9%). Three types of disease were found: mycobacterial infections (n = 36, 69% of documented episodes), including 18 patients with disseminated tuberculosis and 14 with Mycobacterium avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more sensitive than microscopic examination with special stains for the diagnosis of mycobacterial infections, the pathological examination of bone marrow led to a more rapid diagnosis of disease. In addition, the histopathological examination of bone marrow alone led to the diagnosis of a specific condition in 43 episodes (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure for the diagnosis of fever in patients with advanced HIV disease, particularly in areas where tuberculosis and leishmaniasis are prevalent. Involvement of the marrow may be the first indication of the existence of extranodal non-Hodgkin lymphoma. For Mycobacterium avium-intracellulare complex infection, blood cultures were more sensitive than bone marrow biopsy.     

Finite element approach for the modal analysis of open-boundarywaveguides

A general finite element approach to computing the modes of open-boundary waveguides is presented. This efficient and robust scheme applies equally to situations with real and complex propagation constants. By using a localised boundary impedance condition, the approach preserves the sparsity of the global matrices. A comparison with the well established infinite element technique and the analysis of a 2-D leaky optical structure are given as examples     

Time courses of calcium and calcium-bound buffers following calcium influx in a model cell

Fixed and diffusible calcium (Ca) buffers shape the spatial and temporal distribution of free Ca following Ca entry through voltage-gated ion channels. This modeling study explores intracellular Ca levels achieved near the membrane and in deeper locations following typical Ca currents obtained with patch clamp experiments. Ca ion diffusion sets an upper limit on the maximal average Ca concentration achieved near the membrane. Fixed buffers restrict Ca elevation spatially to the outermost areas of the cell and slow Ca equilibration. Fixed buffer bound with Ca near the membrane can act as Ca source after termination of Ca influx. The relative contribution of fixed versus diffusible buffers to shaping the Ca transient is determined to a large extent by the binding rate of each buffer, with diffusible buffer dominating at equal binding rates. In the presence of fixed buffers, diffusible buffers speed Ca equilibration throughout the cell. The concentration profile of Ca-bound diffusible buffer differs from the concentration profile of free Ca, reflecting theoretical limits on the temporal resolution which can be achieved with commonly used diffusible Ca indicators. A Ca indicator which is fixed to an intracellular component might more accurately report local Ca concentrations.     

Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets

Adequacy of nutrient intakes of adolescents with and without phenylketonuria (PKU) and infants and children with and without maple syrup urine disease (MSUD) were assessed using 3-day diet records sorted by disease and by age of the subject. Mean intakes of all nutrients were greater than two-thirds of the Recommended Dietary Allowances (RDA) or Estimated Safe and Adequate Daily Dietary Intakes (ESADDI) for all adolescents studied, with the exception of selenium (Se) in PKU adolescents, which averaged 27.8 micrograms. For adolescents with PKU, > 50% of the RDA or ESADDI for all nutrients was provided by elemental or modified protein hydrolysate medical foods, except for vitamin A in children aged 11-15 years and Se in children 11-18 years. Mean nutrient intakes of all infants and children were greater than two-thirds of the RDA or ESADDI for all nutrients except Se in MSUD children aged 1-11 years, where intakes ranged from 6.4 to 13.2 micrograms (21-66% of the RDA). The medical foods provided for most of the RDA and ESADDI recommendations, with the exception of Se in MSUD children.     

Further characterization of the alpha-actinin-actin interface and comparison with filamin-binding sites on actin

The interaction between alpha-actinin and actin was further characterized using natural and synthetic peptides of actin together with anti-actin antibodies of known specificity. We demonstrated that two alpha-actinin binding sequences on actin are located within residues 112-125 and 360-372. Each peptide was shown to directly bind alpha-actinin and was able to dissociate the alpha-actinin-actin complex using solid phase binding assays and cosedimentation experiments. Taking into account the three-dimensional structure of actin (Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., and Holmes, K. C. (1990) Nature 347, 37-44), we postulate that these two segments, proximal in the actin structure, are part of the same site. In addition, we compared these two segments with those recently found for filamin (Méjean, C., Lebart, M. C., Boyer, M., Roustan, C., and Benyamin, Y. (1992) Eur. J. Biochem. 209, 555-562), Egan, S., Stewart, M., Stossel, T. P., Kwiatkowski, D. J., and Hartwig, J. H. (1990) J. Cell Biol. 111, 1089-1105), and concluded that the two actin-binding proteins interact with closely spaced or overlapping but not identical sequences of actin subdomain 1.     

The Appropriation of the Material of Places in the Landscape: the case of tufa and springs

Springs have long been recognized as being significant places in the landscape, and there is ample evidence of later-prehistoric and Roman activity at spring sites. The Christian appropriation of springs as 'places', either indirectly by assigning their origin to saints, or directly by building chapels and churches on spring-head sites, is also well evidenced. The possibility that the material of petrifying springs - tufa - was both transplanted and appropriated, and that the symbolic properties of the material may go back well into British prehistory, is explored.     

Effects of ketotifen on human lymphocytes in vitro and in vivo

The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen- and adenosine triphosphate stimulated increases in intracellular Ca2+ in lymphocytes and the U937 human monocyte precursor cell line, respectively; this involved inhibition of both Ca2+ influx and intracellular mobilization. In in vivo experiments, treatment of healthy volunteers with 1 mg ketotifen b.i.d. for 7 d did not alter the number or subset composition of circulating lymphocytes. Moreover, the mitogen-stimulated in vitro proliferation of lymphocytes obtained before and after ketotifen treatment in vivo was similar. It is concluded that high ketotifen concentrations can inhibit the activation of resting lymphocytes in vitro but standard ketotifen treatment does not notably affect the number of function of circulating lymphocytes in vivo.     

Characterization of mutated transforming growth factor-beta s which possess unique biological properties

Transforming growth factor-beta (TGF-beta) is a potent regulator of cell growth and differentiation. On the basis of the crystal structure of TGF-beta 2, we have designed and synthesized two mutant TGF-beta s, TGF-beta 1 (71 Trp) and TGF-beta 1 (delta 69-73). Although both of these molecules inhibited the growth of Mv1Lu mink lung epithelial cells and LS1034 colorectal cancer cells, which are affected equally by TGF-beta 1 and TGF-beta 2, TGF-beta 1 (delta 69-73) was much less potent than TGF-beta 1 or TGF-beta 1 (71 Trp) at inhibiting the growth of LS513 colorectal cancer cells which are growth-inhibited by TGF-beta 1 but not TGF-beta 2. Both TGF-beta 1 (71 Trp) and TGF-beta 1 (delta 69-73) increased levels of mRNAs for fibronectin and plasminogen activator inhibitor with Mv1Lu cells, whereas only TGF-beta 1 (71 Trp) and not TGF-beta 1 (delta 69-73) up-regulated the mRNA level of carcinoembryonic antigen in LS513 cells. The expression level of carcinoembryonic antigen mRNA in LS1034 cells was not altered by either wild-type or mutant TGF-beta s. Receptor labeling experiments demonstrated that TGF-beta 1 (71 Trp) bound with high affinity to the cell-surface receptors of Mv1Lu, LS1034, and LS513 cells while TGF-beta 1 (delta 69-73) bound effectively to the receptors of Mv1Lu and LS1034 cells but much less to the receptors on LS513 cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes. International Consortium for the Genetics of Autoimmune Thyroid Disease

Graves' and Hashimoto's diseases are autoimmune thyroid diseases in which the genetic contribution is complex. For this reason, identification of necessary susceptibility genes has been difficult. However, a number of immunoregulatory genes have been implicated by association studies, including: CTLA-4, a recently described protein involved in antigen presentation, located on chromosome 2q33; the T-cell receptor V alpha and V beta gene complexes, located on 14q11 and 7q35, respectively; and the Ig gene complex (IgH), located on 15q11. We used polymorphic microsatellite markers located within these genes, or gene complexes, to test for linkage (rather than association), to each of these candidates. Using markers within the loci allowed us to assume a fixed recombination fraction of 0.01 in the tested model. Three hundred eight subjects from 48 multiplex families were studied, with 142 affected subjects. Using this set of families, we have previously shown evidence of linkage with a major susceptibility locus for Graves' disease (GD-1) on 14q24.3-31, with a maximum lod (logarithm + odds) score of 2.1, at a penetrance of 80% and with a dominant mode of inheritance. In the present study, we obtained consistently negative lod scores for each of the candidate genes, assuming either dominant or recessive modes of inheritance. These data, therefore, showed evidence against linkage with all the candidate genes. Unlike association studies, linkage analyses detect major genetic influences on disease susceptibility exerted by the linked loci. The lack of linkage for the immunoregulatory genes that were studied indicated, therefore, that they were not major contributors to disease etiology.