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Biomedical subjects

A L Sullivan

Publications and source records attributed to A L Sullivan.

At least 19 recordsLinked to original sources

Suppression of false recognition in Alzheimer's disease and in patients with frontal lobe lesions.

Previous research has shown that patients with Alzheimer's disease show increasing levels of false recognition across five repeated study-test trials of semantic associates. The present study tested the hypotheses that (i) the increasing false recognition was partly due to the frontal lobe dysfunction of patients with Alzheimer's disease, and (ii) a failure of source monitoring was the central mechanism by which frontal lobe dysfunction led to increasing false recognition across trials. In Experiment 1, patients with frontal lobe lesions and controls were examined in the same repeated trials paradigm as that used previously in patients with Alzheimer's disease. Although controls were able to reduce their false recognition across trials, the patients with frontal lobe lesions were not, and instead showed a constant level of elevated false recognition across the study-test trials. In Experiment 2, two groups of patients with Alzheimer's disease and healthy older adult controls were studied: the first group was given a single study session followed by a recognition test, the second group was given five study sessions followed by a single recognition test. Older adults who were exposed to five study lists demonstrated lower levels of false relative to true recognition, whereas patients with Alzheimer's disease in this condition exhibited levels of false recognition elevated to that of their true recognition, even with the source memory confusion of intervening tests eliminated. The authors suggest that impairment in aspects of frontal lobe function, such as verification-inhibition mechanisms, probably contributes to the inability of patients with Alzheimer's disease to suppress their false recognition across repeated trials. Lastly, it is speculated that one way in which the frontal lobes enable normal episodic memory function is by facilitating the suppression of false recognition and other distortions of memory.

Adult↗

Shortcomings in psychosocial history taking in a paediatric emergency department.

OBJECTIVE: To assess the quality of documentation of the psychosocial history taken from parents who repeatedly bring their infants and young children to an emergency department. METHODOLOGY: We prepared a list of 26 psychosocial items, indicated by the literature to be important elements of a history taken in this setting. We then reviewed subjects' casenotes, and compared each history to this ideal list. PARTICIPANTS/SETTING: Case note review of 104 children under 2 years who had presented to a paediatric emergency department at least five times in 1 year. RESULTS: Documentation of psychosocial history for these subjects was very poor, with a mean of only 5 of the 26 possible psychosocial items mentioned per set of casenotes. The majority of records lacked important information, including basic demographic data. CONCLUSIONS: We canvass possible reasons for poor psychosocial history taking, and argue for changes in medical education, the development of techniques to efficiently identify at risk children and families, and improved resources for referral.

Australia↗

Corneal donor infection by herpes simplex virus: herpes simplex virus DNA in donor corneas.

Three corneoscleral discs (from two donors) underwent subtotal endothelial loss during routine "long-term" organ culture storage. Laboratory studies of these corneas revealed evidence of herpes simplex virus (HSV) infection. The fellow cornea from one of the donors had been issued for transplant to a patient with keratoconus. Deterioration of the graft was noted 5 days after surgery; the disc was removed at 2 months and was shown to be infected with HSV. In an experiment designed to simulate initial "cleansing" of donor globes, 0.1% polyvinylpyrolidone-iodine protected cells from infection with HSV. It was concluded that the detection of HSV in these corneas could not be explained by external contamination of the ocular surface. Furthermore, culture of conjunctival and pharangeal swabs taken from 47 consecutive donors confirmed that HSV is rarely isolated at or around the time of death. Five pairs of donor corneas destined for use in transplantation were selected at random and investigated for the presence of HSV. HSV DNA was detected by polymerase chain reaction (PCR) in tissue from two of the corneal donors. Sequential stepwise sectioning suggested that HSV DNA when present was distributed in discrete foci within the cornea. These observations suggest that HSV infection may be a cause of severe endothelial loss during corneal organ culture and possibly provide an explanation for some "failures" of corneal grafting.

Adult↗

Energy-dispersive X-ray analysis of the mitochondria of sideroblastic anaemia.

Energy-dispersive X-ray analysis has been performed on marrow sideroblasts obtained from 10 patients with sideroblastic anaemias or erythroleukaemia (six primary refractory sideroblastic anaemia, two pyridoxine-responsive, one secondary sideroblastic anaemia, two erythroleukaemia). Irrespective of the nature of the disorder associated with the presence of sideroblasts, X-ray analysis of siderotic mitochondria consistently revealed the presence of iron and phosphorus with the average Fe/P intensity ratio measuring 1.4-1.5. Other elements variably detected within siderotic mitochondria included calcium, lead, potassium and zinc. Variation in the presence of these latter elements was detected not only between different patients, but also within different samples taken at different times from a single patient and even among different cells of the same sample. Despite the detection of lead in siderotic mitochondria of a significant number of patients (five out of seven), there was no clinical evidence of lead toxicity. The elemental composition of the intramitochondrial deposits in sideroblasts was distinct from that of ferritin or haemosiderin and probably consists of ferric phosphate, possibly, ferric orthophosphate (FePO4).

Anemia, Sideroblastic↗

Defective delivery of iron to the developing red cell of the Belgrade laboratory rat.

Erythroid cell iron and transferrin uptake and release was studied in the anemia of the Belgrade laboratory rat (gene symbol, b), an autosomal recessive trait characterized by hypochromia and hyperferrinemia. When reticulocyte-rich red cells were incubated in vitro with doubly (59Fe, 125I) labeled transferrin, b/b cells demonstrated a significantly higher uptake of transferrin (164% of control at 60 min), and a significantly lower uptake of iron (21% of control at 60 min) than control cells. These findings with b/b cells were simulated by sodium-fluoride-treated control cells, but not by trypsin-treated control cells. When reticulocytes exposed to doubly labeled transferrin were incubated in normal rat plasma, there was a substantial loss of 125I from both the b/b cells (mean 71%) and control cells (mean 49%), but only a loss of 59Fe from the b/b cells (mean 21%). These findings suggest a defect in the delivery of iron to the b/b reticulocyte, which is distal to the binding of transferrin to its cell surface receptor.

Anemia, Hypochromic↗

Malignant lymphoma simulating leukemic reticuloendotheliosis: a clinicopathologic study of ten cases.

We have studied ten patients with a lymphoproliferative disorder characterized by massive splenomegaly; minimal lymphadenopathy; varying degrees of blood cytopenias; circulating atypical lymphoid cells frequently with "hairy" cytoplasm; monoclonal serum paraprotein; and tartrate-resistant acid phosphatase reactivity in the tumor cells of five patients tested. Although the clinical and laboratory features in most cases prompted a clinical diagnosis of "hairy cell leukemia" (HCL), histologic, ultrastructural and immunohistologic studies of multiple organs revealed distinctive features recognizably different from leukemic reticuloendotheliosis (LRE). Because this B lymphocyte proliferation may be mistaken for LRE in cases where careful histologic study is not performed, it may be responsible in part for the conflicting data in attempts to characterize the cell of origin of the latter disease. Clinical and experimental data in HCL must be questioned if they do not include histopathologic confirmation of the diagnosis.

Acid Phosphatase↗

Studies of the endoplasmic reticulum and plasma membrane-bound ribosomes in erythropoietic cells.

Erythropoietic cells of 5 species, including man, contain endoplasmic reticulum present as individual cisternae or tubules scattered throughout the cytoplasm of all stages except mature RBCs. The endoplasmic reticulum is mainly agranular but occurs frequently as a variant of granular ER which is characterized by an asymmetrical and irregular distribution of ribosomes along one cytoplasmic face. In most cells, the endoplasmic reticulum occurs in close proximity to mitochondria or the plasma membrane , suggesting that the organelle may be involved in functions related to these structures, e.g. haem biosynthesis. Endoplasmic reticulum is more abundant in early than in late erythroid cells. Its exact role in RBC development is unclear. Since endoplasmic reticulum could account for 'plasma membrane-bound ribosomes' reported in lysed reticulocytes, studies were performed which ruled out this possibility and which suggested that such ribosomes were an artifact of the lysing conditions. Hypotonic lysis in less than 20 vol. of magnesium-containing buffers yielded ghosts variably contaminated by ribosomes and other structures. Lysis of reticulocytes in 20-30 vol. of magnesium-free buffer or homogenization of whole cells or crude membrane fractions in hypotonic buffer removed virtually all contaminating ribosomes from the purified membrane fraction.

Animals↗

The heterogeneity of leukemic reticuloendotheliosis, "hairy cell leukemia". Evidence for its monocytic origin.

The presence of B, T, and monocyte markers were studied on the spleen and peripheral blood mononuclear cells from two patients with leukemic reticuloendotheliosis. A high proportion of cells from both patients bore a receptor for cytophilic antibody, both in suspension and frozen tissue section. Cells in suspension lacked surface immunoglobulins or a receptor for sheep red blood cells. These results favor the evidence that "hairy cells" are monocytic in origin.

Animals↗

Micropinocytosis of transferrin by developing red cells: an electron-microscopic study utilizing ferritin-conjugated transferrin and ferritin-conjugated antibodies to transferrin.

Electron-microscopic examination of rat reticulocytes and normoblasts incubated with transferrin conjugated to ferritin or ferritin-labeled antitransferrin revealed binding of ferritin conjugates to the surface membrane, and uptake of ferritin conjugates in micropinocytotic vesicles. No binding or endocytosis of ferritin was visualized when rat reticulocytes or normoblasts were incubated with ferritin alone or ferritin conjugated to nonspecific rabbit IgG. These observations support the concept that transferrin binds to a surface membrane receptor and is subsequently internalized by the developing red cell. Time course and temperature dependence studies suggest the endocytosis of transferrin may be an important mechanism in delivery of iron to the developing red cell.

Animals↗

Ultrastructural studies of the bone marrow in sickle cell anaemia. I. The structure of sickled erythrocytes and reticulocytes and their phagocytic destruction.

Marrow aspirates from sickle cell patients were examined without prior deoxygenation and revealed the presence of a variable proportion (10-30%) of sickled red cells and reticulocytes. The main feature of sickled red cells was the presence of 17.6 nm fibres arranged in hexagonal order, and to a lesser extent in square or rectangular array, to form bundles of varying size and compactness which occupied the entire cytoplasm. The sickling pattern in reticulocytes was more variable. Some reticulocytes contained highly-ordered bundles of 17.6 nm fibres whose structure and distribution was identical to that in red cells from whiich they could be distinguished only by their content of organelles. Many reticulocytes exhibited less-organized fibre patterns ranging from localized aggregates to poorly-ordered regions of short fibres and filaments lacking apparent preferential orientation. In these cells, the bulk of the cytoplasm was not polymerized. Haemoglobin polymerization in reticulocytes led to entrapment of ribosomes in concentrated foci among the fibres. Frequently, iron-laden mitochondria were associated with sickled reticulocytes. The variation in pattern of sickling seen in reticulocytes is attributed to possible differences in concentration of Hb S. Correlative studies have shown that fibres were not induced by fixation procedures. Marked phagocytic degradation of sickled cells by macrophages was observed. The results are interpreted to indicate the possible intramedullary phagocytosis of red cells and reticulocytes, predisposed to sickling in the marrow. However, the data are also consistent with the removal of sickled elements from the circulating blood.

Anemia, Sickle Cell↗

Ultrastructural studies of the bone marrow in sickle cell anaemia. II. The morphology of erythropoietic cells and their response to deoxygenation in vitro.

Electron microscopic studies of bone marrow aspirates obtained from patients with homozygous sickle cell anaemia (HbSS) were fixed immediately without attempts to deoxygenate the samples. Erythroblasts and normoblasts in these preparations were devoid of haemoglobin polymers or other indications of sickling. Furthermore, the nucleated erythroid cells from sickle-cell patients presented an ultrastructural morphology indistinguishable from that of identically-processed erythroid cells in marrow samples from normal human volunteers. This report presents a description of the ultrastructural features of pronormoblasts and normoblasts in normal and sickle-cell marrows and stresses the essentially normal appearance of nucleated erythroid elements in sickle cell anaemia. Exposure of sickle-cell marrow aspirates to nitrogen at 37 degrees C for 30 min resulted in haemoglobin polymerization in most erythrocytes and reticulocytes but only in 10-20% of the nucleated erythroid cells. Haemoglobin polymers in the form of intertwining fibre meshworks were observed in reticulocytes, orthochromatic and polychromatophilic normoblasts, but were absent in basophilic normoblasts and pronormoblasts. The results suggest that the concentration of haemoglobin in intramedullary normoblasts may be the limiting factor determining the predisposition of these cells to undergo sickling as well as the pattern of haemoglobin aggregation. Under the physiological conditions prevailing in the marrow, haemoglobin concentration in normoblasts may be insufficient to result in aggregation and polymerization.

Anemia, Sickle Cell↗

Electron microscopic localization of immunoglobulin E on the surface membrane of human basophils.

We have examined human leukocyte preparations for the presence of surface-bound IgE by electron microscopy. Basophil-enriched leukocytes were reacted with burro anti-IgE, a hybrid antibody to burro IgG and ferritin, and ferritin, with or without prior incubation of the cells with an IgE myeloma protein. In the absence of preincubation with IgE small amounts of ferritin were fixed to the surface of basophils but on no other cells. When cells were preincubated with IgE the amount of ferritin fixation on the basophils was markedly increased and a small amount of ferritin was also bound to platelets but again to no other leukocytes. The distribution of ferritin on the basophil surface appeared dependent upon the temperature at which the cells were kept during and after reaction with the various reagents. Basophil sections from cells kept at 0 degrees C had ferritin bound to the surface membrane in patches distributed around the entire circumference. Basophil sections from cells prepared at room temperature had ferritin distributed assymetrically covering a surface membrane segment one-fifth to one-half of the circumference. In control studies in which monomeric IgG was substituted for the IgE and burro anti-IgG was used instead of burro anti-IgE, no cellular fixation of ferritin was observed.

Animals↗