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Biomedical subjects

A Sanderson

Publications and source records attributed to A Sanderson.

At least 19 recordsLinked to original sources
PubMed2002

Cerebral metastasis and other cerebral events in women with ovarian cancer.

AIM: To determine the incidence, imaging findings and prognostic significance of cerebral metastases and other cerebral events in women with ovarian cancer. METHOD: A 5-year retrospective review of all women with ovarian cancer who had cranial imaging was undertaken at two major gynaecological oncology centers. RESULTS: Of 1222 women under clinical review, 78 underwent cranial imaging and 13 (1.1%) had cerebral metastasis. Computed tomography (CT) was diagnostic of parenchymal disease in 12 and magnetic resonance imaging (MRI) showed leptomeningeal disease in two. The women were aged between 23 and 73 years and all had stage III or IV disease at presentation. Cerebral metastasis occurred at 6-60 months from initial diagnosis, with death occurring predominantly within 12 months, but with five survivors at 4-45 months. Of the remaining 65 women, 10 had cerebrovascular disease and three had unrelated lesions. CONCLUSION: Cerebral metastasis remains a rare event in women with ovarian cancer but may be an isolated late event associated with survival beyond a year after neurosurgery and chemotherapy. CT should be the first investigation as the incidence of cerebrovascular disease is similar to that of metastatic disease.

Adult↗
PubMed2001

Theileria annulata: attenuation of a schizont-infected cell line by prolonged in vitro culture is not caused by the preferential growth of particular host cell types.

Flow cytometry and monoclonal antibodies to bovine leucocyte surface antigens were used to identify the types of host cells that the sporozoites of Theileria annulata infect in cattle, to determine whether virulent schizont-infected cell lines (lines) differed phenotypically from avirulent lines, and to establish whether attenuation in vitro was accompanied by the preferential growth of particular host cell types. The surface antigens of four pairs of T. annulata (Ta) (Hisar) lines derived ex vivo and in vitro, including the virulent ex vivo-derived Ta Hisar S45 line, were consistent with a myeloid origin for all lines, irrespective of their derivation. The profiles of lines derived from cattle inoculated with a virulent line showed that the schizonts liberated from inoculated cells had transferred to myeloid cells. A number of other lines infected with different stocks of T. annulata expressed myeloid markers; a single line expressed CD21, a B cell marker. During prolonged in vitro culture, the parasites in the ex vivo (virulent)- and in vitro (avirulent)-derived Ta Hisar S45 myeloid lines became clonal, as defined by glucose phosphate isomerase (GPI) polymorphism, and the virulent line became attenuated. The two lines retained phenotypic profiles indicative of a myeloid origin but coexpressed some lymphoid antigens (CD2, CD4, CD8), although not CD3. Cloned schizont-infected lines, representing the three parasite GPI isotypes which constituted the virulent line, expressed similar patterns of myeloid and lymphoid markers to the virulent parent line. Some schizont-infected clones failed to establish as lines during the early weeks of culture because the cells died as the parasites differentiated into merozoites at 37 degrees C, the temperature at which schizont-infected cells normally grow exponentially. These results provided no evidence that prolonged culture induces preferential growth or loss of particular host cell types. However, a number of the alterations in host cell surface antigens induced by prolonged culture were shown to be linked to permanent changes in the parasite genome.

Animals↗
PubMed1998

Theileria annulata: the expression of two novel macroschizont antigens on the surface of infected mononuclear cells differs during in vitro attenuation of a virulent cell line.

The first part of this study of the biological mechanisms underlying attenuation of virulent Theileria annulata macroschizont-infected cell lines screened four pairs of T. annulata (Hisar) in vivo- and in vitro-derived macroschizont-infected cell lines (lines) and identified a single in vivo-derived line, which induced lethal tropical theileriosis. The other seven lines were relatively avirulent. Analysis of the clinical, hematological, and parasitological responses of cattle immunized with different passages of the virulent line after in vitro culture showed that it was partly attenuated by passage (p) 50 and avirulent by p130. Clones representing the three glucose phosphate isomerase (GPI) isotypes, which constituted the newly isolated virulent culture, were obtained from p3 by limiting dilution; p50 and p130 consisted of one isotype. The second part of the study raised monoclonal antibodies (MAbs) against macroschizont-infected cells, as reagents for detecting antigenic differences between virulent and avirulent parasites, and identified two MAbs that recognized the surface of infected cells as well as macroschizonts. MAb EU1 recognized an antigen expressed by all the lines tested, whether in vitro- or in vivo-derived, whether uncloned or cloned, and irrespective of extent of subpassage in culture. MAb EU106 recognized an antigen whose expression by the virulent line and its clones disappeared on passage in culture. This antigen was not expressed at all by the avirulent in vitro-derived line prepared with cells from the same calf. Both antigens were expressed by lines infected with other stocks of T. annulata, including two lines known to induce lethal disease. The different profiles of expression of the two novel antigens, recognized by MAbs EU1 and EU106, by the line undergoing attenuation suggest (1) that the two antigens interact differently with the bovine immune system; and (2) that there are two, very different, potential roles for these antibodies in the development of vaccines against T. annulata infections.

Animals↗
PubMed1997

Bovine cells infected in vivo with Theileria annulata express CD11b, the C3bi complement receptor.

Bovine cells from cattle infected with Theileria annulata were phenotyped with monoclonal antibodies recognizing bovine leukocyte antigens. Macroschizont-infected, transformed cell lines prepared from peripheral blood mononuclear cells of cattle, infected with sporozoites, were assessed by flow cytometry; parasitized cells in tissues from infected cattle were examined by immunocytochemical techniques. Co-expression of markers for different cell lineages by the cell lines precluded a definite conclusion as to their phenotypic origins. For, while the pattern of leukocyte antigens expressed by these in vivo-derived schizont-infected cells, which included CD11b, was indicative of a myeloid origin, the possibility that they were NK cells could not be excluded. The monoclonal antibody (MAb) IL-A15, which recognizes CD11b, reacted with a high proportion of parasitized cells in sections of tissues from infected cattle at all stages of acute disease. Mononuclear cells infected with parasites at all stages of differentiation, from macroschizont to microschizont, expressed CD11b. Such parasitized cells occurred throughout the lymphoid tissues, being found in the thymus, spleen and lymph nodes, particularly the prescapular node draining the site of infection, the hepatic, mesenteric and precrural nodes, as well as in the reticulo-endothelial tissue of the liver, kidney, lung, abomasum, adrenal and pituitary glands. These observations provided the first evidence for a myeloid origin for the parasitized T. annulata cells found in infected bovine tissues and blood and suggested a mechanism whereby schizonts could transfer from cell to cell during mechanical infection with schizont-infected cells.

Animals↗
PubMed1996

Effect of cisapride on gallbladder emptying and plasma CCK in normal and vagotomized human subjects.

Previous studies have provided conflicting results of cisapride on gallbladder emptying in response to a meal. We studied six volunteers and six patients after a truncal vagotomy in a double-blind, placebo-controlled, prospectively randomized study using 10 mg cisapride four times a day for three days. Gallbladder volume was quantitated using ultrasonography, and plasma CCK levels were measured with a sensitive and specific radioimmunoassay using the DINO antibody before and for 90 min after a fatty, mixed meal. Plasma effect was observed on the gallbladder either in normal subjects or vagotomized patients. Paradoxically, residual volume (RV) was increased in the vagotomized patients after treatment with cisapride: RV cisapride 7.1 (4.1-15.9) ml, RV placebo 5.1 (3.8-14) ml, P < 0.05. Further work is required to clarify the mechanisms of action of cisapride on the gallbladder and the sphincter of Oddi. The use of cisapride during litholytic therapy may impair gallbladder emptying and delay stone clearance.

Adult↗
PubMed1995

Induction of CD4+ and CD8+ T cell responses in efferent lymph responding to Toxoplasma gondii infection: analysis of phenotype and function.

The kinetics of induction of T cell responses were examined in efferent lymph from a node draining the site of a primary inoculation of Toxoplasma gondii. The numbers of T cells increased after infection, due initially to an expansion of the CD4+ T cell population followed by an increase in the number of CD8+ T cells which coincided with the peak lymphoblast response. Proliferative responses of CD4+ T cells to T. gondii antigen were detectable from day six after infection and immune efferent lymph cells inhibited the intracellular multiplication of T. gondii in vitro. Optimum inhibition was achieved using CD8+ T cells restimulated in vitro, and the effector function appeared to be directed preferentially against the autologous rather than the allogeneic infected target cell. The results provide unique information on the induction of immune responses to T. gondii in vivo and provide evidence that both CD4+ and CD8+ T cells are necessary for the development of protective immunity induced by the S48 strain of T. gondii which is used as a live vaccine in sheep.

Acute Disease↗
PubMed1993

Alternative pathways of apoptosis induced by methylprednisolone and valinomycin analyzed by flow cytometry.

Apoptosis of murine thymocytes induced by either methylprednisolone or valinomycin was studied by flow cytometry. The apoptosis induced by methylprednisolone followed three stages: an initial decrease in cell volume, indicated by a fall in forward scatter accompanied by faint ethidium bromide staining, a second stage in which the cells became brightly stained by ethidium bromide, and a final stage when the cells were apparently less fluorescent as the nuclei disintegrated into apoptotic bodies. As the forward scatter of cells decreased there was a simultaneous depolarization of the cells and an elevation of intracellular calcium. These early changes preceded the fragmentation of the DNA which also preceded the intense staining of the cells by ethidium bromide. Methylprednisolone-induced apoptosis was inhibited by low concentrations (1 x 10(-7) M) of valinomycin and nonactin, neither of which could themselves induce apoptosis at these low concentrations. Cadmidazolium and cycloheximide arrested the program at an early stage. Okadaic acid allowed volume loss and ethidium bromide staining to proceed in the absence of DNA fragmentation. At high concentrations (1 x 10(-5) M) valinomycin induced a form of apoptosis, but nonactin only caused the cells to fragment. The valinomycin-induced apoptosis, although it involved the degradation of DNA and the disintegration of the nuclei into apoptotic bodies, differed from the methylprednisolone apoptosis as it did not involve a decrease of cell volume and was not inhibited by cycloheximide or affected by okadaic acid.

Animals↗
PubMed1992

Simultaneous analysis of immunophenotype and apoptosis of murine thymocytes by single laser flow cytometry.

The study of the role of apoptosis in thymocyte development has been hampered by the lack of a means of directly immunophenotyping cells undergoing the early phase of apoptosis. This restriction has been overcome by single laser flow cytometry in which apoptosis is detected by Ethidium Bromide (EBr) staining and cell phenotype by binding of FITC-labelled antibody. The initial phase of apoptosis is observed as a cell population that stains faintly with EBr preceding the characteristically bright EBr-staining normally associated with cell death. Here we directly demonstrate using single laser flow cytometry that CD4+ CD8+ CD3low/CD3intermediate thymocytes undergo apoptosis in vitro in response to glucocorticoid treatment.

Animals↗
PubMed1992

Eye movement desensitization versus image confrontation: a single-session crossover study of 58 phobic subjects.

Eye movement desensitization (EMD) and a control procedure, image confrontation (IC) were compared in a group of 58 phobics, 31 of them arachnophobes. Subjects confronted disturbing images in a single-session crossover trial. Anxiety levels were recorded on the SUD Scale. Whenever practicable, SUDs to feared objects were also recorded. EMD and IC were equally effective in reducing anxiety levels. After 1 month, during which subjects were encouraged to use IC daily, improvement was maintained. Since exposure to the disturbing image is common to both methods it must be presumed to be the basis of change when EMD is used in cases of phobia.

Adult↗
PubMed1992

Tropical theileriosis in Bos taurus and Bos taurus cross Bos indicus calves: response to infection with graded doses of sporozoites of Theileria annulata.

This work extends basic knowledge of tropical theileriosis in taurine and crossbred cattle. Infection of Bos taurus and Bos taurus cross Bos indicus (Sahiwal) calves with graded doses of sporozoites of Theileria annulata (Hissar), an Indian stock of the parasite, showed the following to be dose dependent in both cattle types: the time to appearance and population size of macroschizonts, microschizonts and piroplasms, time and severity of pyrexia, anaemia manifested by erythrocyte counts and haematocrit. All infections were accompanied by a prompt and severe panleucopenia. This effect was dose related in both the taurine and the Sahiwal crossbred calves. Lymphocyte counts returned to preinfection levels in the blood of animals which recovered, but death from theileriosis was characteristically accompanied by a persistent and severe lymphocytopenia. Flow cytometry using monoclonal antibodies to bovine mononuclear cells was used to identify the lymphocyte subsets involved in lymphocytopenia. The outcome of infection was dose dependent in the crossbred calves but not in taurine calves. Although the results obtained did not differ qualitatively between the two cattle types, they provided some preliminary evidence for resistance to tropical theileriosis in Sahiwal crossbred calves.

Animals↗
PubMed1992

Acute effects of intravenous phosphodiesterase inhibition in chronic heart failure: simultaneous pre- and afterload reduction with a single agent.

Intravenous phosphodiesterase inhibition with milrinone is known to have a beneficial effect on haemodynamics in chronic heart failure. Its effect on lower limb capacitance vessels has not been previously investigated. We have studied the effect of intravenous milrinone in 10 patients with severe chronic heart failure. Thirty minutes after commencement of treatment mean cardiac index had risen by 26% and pulmonary artery wedge pressure, systemic vascular resistance and right atrial pressure had fallen by 51, 24 and 89%, respectively (p less than 0.05 for all changes). These changes were maintained for the 2 h observation period with no evidence of tolerance and were accompanied by a 17% increase in venous volume (p less than 0.01) and a 42% increase in ejection fraction (p less than 0.001) at 30 min; at 120 min the improvement in ejection fraction had been maintained and a further increase in venous volume to 38% above baseline was evident. The increase in venous volume was strongly correlated with the decrease in mean pulmonary artery wedge pressure and mean right atrial pressure at 30 min and 2 h (r = -0.80 and -0.69 for mean pulmonary artery wedge pressure, r = -0.88 and -0.56 for mean right atrial pressure). Milrinone therefore has clinically important venodilating properties, in addition to its known effects as an arterial vasodilator and a positive inotrope.

Aged↗
PubMed1991

Discrete subpopulations, defined by CD45 isoforms, coexist within the leukaemic cells of B-chronic lymphocytic leukaemia patients.

The expression of CD45 isoforms by B-CLL leukaemic lymphocytes has been analysed by 2 colour flow cytometry and vectorial iodination. The cytometry has demonstrated the presence of cells with different CD45 phenotypes which vary in the relative expression of the CD45RA and CD45RO determinants. Discrete populations have been detected which can coexist within an individual patient. One of these populations which is CD45RO-negative consists of cells expressing only the 230 kD isoform, in the others the smaller isoforms are expressed, the appearance of the CD45RO determinant of 180 kD being accompanied by the appearance of the 190 kD isoform. The relative proportion of cell populations is stable within patients but can be altered by phorbol ester which enhances CD45RO expression and diminishes CD45RA expression. The populations may be partially resolved by the density gradient fractionation.

Antigens, CD↗
PubMed1989

The role of cell maturation in the generation of phenotypic heterogeneity in B-cell chronic lymphocytic leukaemia.

B-chronic lymphocytic leukaemia (B-CLL) patients can be ranked along a progression of phenotypes characterized by a decreasing surface expression of CD20, CD21, CD22 and membrane immunoglobulin and a gradual replacement of the high molecular weight (MW) glycoproteins of the leucocyte-common antigen (LC) CD45RA by the lower MW components, including the CD45RO determinant. As CD20, CD21, CD22 and membrane immunoglobulin change during or after B-cell activation, and the CD45RA/CD45RO inversion is implicated in T-cell maturation, the possibility that the phenotypic differences are generated by a maturational diversity of the CLL clones has been investigated by testing the effects of TPA treatment of the leukaemic cells. TPA reduces the level of expression of CD20, CD21, mIg and CD45RA and increases CD45RO binding, thereby minimizing the phenotypic heterogeneity of the CLL clones and causing them to converge towards one end of the natural range. We propose that the phenotypic diversity in CLL is, at least in part, a consequence of maturational diversity where lymphocyte development is disrupted at different stages in different patients.

Antigens, CD↗
PubMed1987

Immunophenotyping of the cutaneous infiltrate and of the mononuclear cells in the peripheral blood in patients with atopic dermatitis.

Fourteen adult patients with chronic atopic dermatitis and active skin lesions had a skin biopsy and venous blood sample taken on the same day. Absolute numbers of circulating lymphocytes were normal in all patients. Fluorescence-activated cell sorter (FACS) analysis revealed normal numbers of total T lymphocytes and T-helper and T-suppressor subsets (helper:suppressor ratio, 2:1) in the atopic patients' peripheral blood, but an increase in circulating B lymphocytes and in HLA-D-related antigen-bearing cells. The skin biopsy showed a dermal infiltrate of predominantly T-helper lymphocytes (helper:suppressor ratio, 7:1). These cells showed strong HLA-DR plasma membrane staining. There was no HLA-DR staining in the membranes of epidermal keratinocytes. Using a monoclonal antihuman IgE, positive staining was observed in the dermis, though none was identified in the epidermis. The dermal anti-IgE staining was concentrated around clusters of T lymphocytes.

Adolescent↗
PubMed1985

Enzyme variation in T. brucei ssp. II. Evidence for T. b. rhodesiense being a set of variants of T. b. brucei.

A collection of stocks of Trypanosoma brucei rhodesiense isolated in Kenya have been examined for electrophoretic variation in 20 enzymes. The results obtained have been analysed in order to determine whether these trypanosomes are diploid and undergo mating and to determine the genetic distance between T. b. rhodesiense, T. b. brucei and T. b. gambiense. The enzyme electrophoretic markers were further used in experiments involving cyclically transmitted mixtures of stocks aimed at detecting genetic exchange in the laboratory. No genetic exchange was detected. Two novel features of the enzyme electrophoretic results were found. Firstly, the stocks of T. b. rhodesiense were considerably more homogeneous than equivalent collections of stocks of T. b. brucei and secondly, all the stocks examined were heterozygous for two alleles of alkaline phosphatase and showed an excess of heterozygotes at the phosphoglucomutase locus. The degree to which these features are typical of T. b. rhodesiense has been examined in relation to previously published data. The results obtained strongly support the view that T. b. rhodesiense is a set of variants of T. b. brucei rather than a subspecies and a working hypothesis as to the relationship between T. b. brucei and T. b. rhodesiense is proposed to explain the enzyme electrophoretic data obtained.

Animals↗