Hospital outbreak of hepatitis E.
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Adult↗
Biomedical subjects
D Bradley
Publications and source records attributed to D Bradley.
Presence of Langerhans cells in the central cornea linked to the development of ocular herpes in mice.
Recurrences of herpetic stromal keratitis are believed to be initiated by reactivation of herpes simplex virus infection, probably in the trigeminal ganglion. Genetic features of the virus and the host as well as the immune status of the host influence the outcome of infection. Following infection on the snout with HSV-1, mice with normal corneas usually develop mild anterior segment disease. We studied the induction of herpetic infection in mice that had abnormal corneas, containing center due to trauma or a spontaneous dystrophy. The corneal abnormality led to more frequent herpetic stromal keratitis and more severe anterior chamber reaction. In addition, we found that snout-infected mice with dystrophic corneas had an increased risk of dying from viral infection. Our data suggest that not only the strain of virus and the genetic background of the mouse, but also the state of the cornea itself, can contribute to susceptibility to ocular herpes infection.
Animals↗
An atlas of the rat subpostremal nucleus tractus solitarius.
The nucleus tractus solitarius (NTS) in the dorsal medulla is the principal visceral sensory relay nucleus in the brain. In the rat, numerous lines of evidence indicate that the caudal NTS at the level of the area postrema serves as a major integrating site for coordinating cardiorespiratory reflexes and viscerobehavioral responses. This region of the caudal NTS not only exhibits high densities of binding sites for an impressive array of transmitters and modulators but microinjections of many of these same neuroactive substances into the rat subpostremal NTS elicit pronounced cardiorespiratory and visceral response patterns. This report provides an abbreviated atlas of the rat subpostremal NTS consisting of a series of transverse, sagittal, and horizontal plates. Photomicrographs, together with their corresponding schematic drawings, are provided for the serial sections generated from each reference plane.
Animals↗
Identification of the major, parenteral non-A, non-B hepatitis agent (hepatitis C virus) using a recombinant cDNA approach.
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DNA, Recombinant↗
Legionnaires' disease in elderly people: the first sign of an outbreak in the community?
Legionella pneumophila is responsible for up to 5% of cases of community-acquired pneumonia and mainly affects people aged over 50 years. The confirmation of legionellosis in two elderly patients living close to each other prompted a search for other cases. A total of eleven subjects with legionnaires' disease was recognized. The clinical findings are described and the diagnosis of legionellosis is discussed. Environmental investigations pointed to a cooling tower in the local town centre as the probable source of infection.
Aged↗
Effect of intraocular gamma-interferon on immunoregulatory properties of iris and ciliary body cells.
Resistance of the anterior chamber (AC) of mouse eyes to expression of cell-mediated immunity can be overcome by pre-treating the eye with a dose of recombinant rat gamma-interferon (gamma IFN) that is of itself noninflammatory. To study the mechanism of this form of intraocular inflammation, cells of the tissues surrounding the AC (iris, ciliary body, cornea) were studied in vivo for alterations in phenotype and in vitro regarding their effects on antigen-driven T cell activation. The results indicate that gamma IFN: (1) induced class II major histocompatibility complex (MHC) expression on resident bone marrow-derived cells of iris and ciliary body (I/CB), but not the cornea; (2) led to recruitment of bone marrow-derived cells into the I/CB stroma; and (3) failed to induce class II MHC expression on ocular epithelial cells. Cell suspensions prepared from gamma IFN-treated I/CB superficially resembled normal I/CB cells in that neither were able to activate allogeneic T cells and both were able to suppress antigen-driven T cell activation in vitro. However, unlike cells from normal eyes, I/CB cells from gamma IFN-treated eyes suppressed T cell activation primarily through the secretion of prostaglandins. These results indicate that the ability of gamma IFN-treated eyes to display immunogenic inflammation probably does not result merely from the restoration of conventional antigen presenting cells to this environment, but appears to correlate with a critical change in the molecular mediators of immunosuppression. The findings are discussed in terms of the possibility that the eye may be able to respond to abrogation of its primary immunosuppressive microenvironment by erecting a secondary microenvironment that also is capable of suppressing immunogenic inflammation with a different set of antiinflammatory mediators.
Animals↗
Dr Marion Souchon. Physician and artist.
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History, 19th Century↗
Scales modified for dose determination in population-based chemotherapy.
Integration of schistosomiasis control into primary health care services in The Gambia required semiliterate health workers to administer praziquantel and metrifonate to the community in doses based on weight. Special scales to weigh people with a direct readout in the form of numbers of tablets obviated the need to read figures or make calculations at the scene. The scales were used with a simple record system. Coverage of up to 97% was achieved with single dose praziquantel; for three doses of metrifonate spread over 2 months, coverage reached 82.4%. The tablet scale was easy to devise and fit to commercial scales.
Adult↗
Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose.
Physicochemical and molecular characterization studies of hepatitis C virus (HCV), the major causative agent of parenterally transmitted non-A, non-B hepatitis (PT-NANBH), strongly suggest that it is a pesti-/flavivirus-like virus. Additional studies show that the buoyant density of plasma-derived HCV in sucrose is significantly lower than that of most tissue culture-derived flaviviruses (1.20 g/cm3). Our finding suggests, but does not prove, that at least one physicochemical property of HCV is more similar to that of the pestiviruses, bovine viral diarrhea virus (BVDV) and hog cholera virus (HogCV), than that of the flaviviruses.
Animals↗
Herpetic stromal keratitis in mice: less reversibility in the presence of Langerhans cells in the central cornea.
Infection on the snout with HSV-1 in mice with normal corneas produced a mild ocular disease, characterized by a zosteriform skin lesion around the eye, enlargement of the pupil, hyperemia of the iris and, sporadically, transient keratitis. By contrast, snout infection after prior cauterization of the cornea induced significantly more frequent and more severe corneal disease, in which keratitis was usually permanent. Corneal cauterization also produced increased numbers of Langerhans cells in the central cornea. We speculate that the combination of virus and increased numbers of Langerhans cells within the cornea may lead to an exaggerated ocular immune response that is destructive to the cornea.
Animals↗
Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products.
The anterior chamber of the eye is an immunosuppressive microenvironment as shown experimentally by immune privilege, anterior chamber-associated immune deviation, and inability to display local delayed-type hypersensitivity responses. It recently was reported that both the aqueous humor and the cells of the iris and ciliary body (I-CB) have immune inhibitory properties in vitro, suggesting that these components of the anterior segment might contribute to the unique properties of this microenvironment. To explore the cellular sources of immunosuppressive factors in the anterior chamber, cultures of I-CB cells were established from normal eyes of BALB/c mice. Supernatants were harvested from these cultures and assayed in vitro for their ability to inhibit T-lymphocyte activation. It was found that I-CB cell-derived supernatants profoundly suppressed alloantigen-driven T-cell proliferation (mixed lymphocyte response) and interleukin-2 production by a T-cell hybridoma that responds to stimulator cells bearing I-Ad. The inhibitory activity of I-CB supernatants did not appear to be related to prostaglandins; supernatants of I-CB cells cultured with indomethacin retained their suppressive properties, as did supernatants to which neutralizing antiprostaglandin E2 antibodies had been added. Moreover, suppression by I-CB supernatants was not relieved by antibodies specific for transforming growth factor-beta, even though this cytokine is known to be present in normal aqueous humor. Thus, the identity of the suppressive factor(s) in cultured I-CB cell supernatants remains elusive. Finally, by separating I-CB cell suspensions into bone marrow-derived (T-200-positive) and those not derived from bone marrow (parenchymal) subpopulations with a fluorescence-activated cell sorter, it was determined that the inhibitory activity of I-CB cell suspensions was produced by parenchymal, rather than hematogenous, cells. It is proposed and discussed that inhibitory factors and cytokines secreted by parenchymal I-CB cells contribute to the immunosuppressive qualities of the anterior chamber.
Animals↗
A double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine in the treatment of pediatric mastocytosis.
To asses the efficacy of ketotifen (Zaditen; Sandoz Pharmaceuticals, Basel, Switzerland) for the treatment of pediatric mastocytosis, eight children who exhibited symptoms as a result of mastocytosis were enrolled in a 12-week, double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine (Atarax; Roerig, New York, N.Y.). Efficacy of each drug was assessed by daily symptom scores and plasma- and 24-hour urine-histamine levels. After completion of the study, symptom scores revealed that seven of the eight children exhibited a greater reduction in symptoms while they were receiving hydroxyzine (p less than 0.05). The symptoms most likely to improve with treatment with hydroxyzine were flushing and abdominal pain. Analysis of plasma- and 24-hour urine-histamine levels at the beginning and end of each trial period of each drug revealed no significant differences (p greater than 0.20). Changes in 24-hour urine-histamine levels, but not plasma-histamine levels, correlated with changes in symptom scores. We conclude that ketotifen offers no advantage over hydroxyzine in the treatment of pediatric mastocytosis.
Child↗
Use of plasma histamine levels to monitor cutaneous mast cell degranulation.
A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 microgram intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml (n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml (n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergens↗
Linkage analysis of human chromosome 4: exclusion of autosomal dominant retinitis pigmentosa (ADRP) and detection of new linkage groups.
As part of our ongoing linkage studies of degenerative retinal diseases, we tested seven DNA markers and two classical genetic markers from chromosome 4 in two extended families with autosomal dominant retinitis pigmentosa (ADRP). Our goals were (1) to detect or exclude linkage of ADRP to markers spanning most of chromosome 4 and (2) to contribute useful new information regarding the linkage map of this chromosome. Our results exclude linkage of ADRP from more than 82% of chromosome 4. We detected four new linkage relationships: loose linkage of K082 (D4S10) and G1E5 (D4S21) at a distance of 21 cM; loose linkage of 4F2 (D4S18) and GC protein at a distance of 19 cM; tight linkage (i.e., no recombinants) between B3D (D4S44), B5A (D4S40), and the MNS blood group; and tight linkage between 4F2 and GDS5 (D4S23). These data, combined with previously reported data, exclude ADRP from approximately 35% of the human genome.
Adolescent↗
Immunoregulatory properties of bone marrow-derived cells in the iris and ciliary body.
Iris and ciliary body of mouse eyes have been examined for the presence of bone marrow-derived cells possessing the capability of functioning as antigen-presenting cells (APC). We have determined that iris and ciliary body contain significant numbers of cells bearing T200, indicating their bone marrow origin. Most of these express the F4/80 marker typically found on mature macrophages. However, approximately one-third of the cells express Ia and a similar number express Mac-1 markers. Virtually none of the cells express Thy-1 or surface immunoglobulin. Whole preparations of excised iris/ciliary body, or single cell suspensions prepared from these tissues were then assayed for their capacity to induce proliferation among allogeneic lymphocytes. It was discovered that iris/ciliary body tissues or cells did not function as alloantigen-presenting cells, although tissue and cells derived from the corneal limbus were allostimulatory. In addition, iris/ciliary body tissues and cells displayed the ability to suppress mixed lymphocyte reactions to which they had been added as regulatory cells. We conclude that normal iris and ciliary body contain bone marrow-derived cells that fail to function as alloantigen-presenting cells. However, cells were present that have the capacity to inhibit alloimmune lymphocyte proliferation. The strategic location of inhibitory cells in the tissues that line the anterior chamber of the eye raises the possibility that these cells may play a role in the phenomenon of immunological privilege that is characteristic of this site.
Animals↗
The Commission on Health Research for Development.
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Developing Countries↗
Chloroplast fructose-1,6-bisphosphatase: the product of a mosaic gene.
We show here that light stimulates the expression of nuclear genes in wheat leaves for chloroplast fructose-1,6-bisphosphatase (FBPase) and describe a sequence of amino acids in this enzyme which may be responsible, via thioredoxin, for the light regulation of its activity. This data results from (a) our isolation and characterization of a cDNA of this enzyme which contains its entire coding sequence, and (b) our use of this cDNA as a probe to detect mRNA levels in wheat plants subjected to different light regimes. The similarity in amino acid sequence of the encoded enzyme from diverse sources suggests that the FBPase genes all had a common origin. However, their control sequences have been adjusted so that they are appropriately expressed and their coding sequences modified so that the enzymic activity of their products are suitably regulated in the particular cellular environment in which they must function. The light-activated regulatory sequences in the gene for the chloroplast protein have probably come together by a shuffling of DNA segments.
Amino Acid Sequence↗
Evaluation of a radioimmunoassay for histamine measurement in biologic fluids.
A new radioimmunoassay for the measurement of histamine in biologic fluids was evaluated. Assay selectivity and specificity were achieved by "succinyl-glycinamide derivatization" of histamine in samples to mimic the immunogen used to generate the monoclonal antibody. The assay exhibits a linear response from 0.1 to 5.0 ng/ml of histamine and the monoclonal antibody used has partial recognition of only N-methylhistamine (other than histamine). With minimal modifications, the assay can accurately measure histamine in plasma, urine, and buffer. Normal ranges for human subjects were established: plasma levels are 0.193 +/- 0.08 ng/ml (n = 40) and urine levels are 20.9 +/- 11.2 micrograms histamine/gm creatinine (n = 10).
Body Fluids↗