The National Council on Patient Information and Education.
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Drug Labeling↗
Biomedical subjects
C Pearson
Publications and source records attributed to C Pearson.
Learning impairment induced by lesion of the CA1 field of the primate hippocampus: attempts to ameliorate the impairment by transplantation of fetal CA1 tissue.
Monkeys with bilateral excitotoxic lesion of the CA1 field of the hippocampus were severely impaired at learning visuospatial conditional tasks. This was not a general spatial impairment, because the animals were not impaired on serial spatial reversal, which requires response flexibility in the spatial domain; they were not impaired at learning to choose the position furthest away from a single stimulus, which requires analysis of spatial layout of the test area, and they were not impaired at discriminating between two patterns that differed only in orientation. CA1-lesioned monkeys were impaired at learning a visuospatial conditional task when trials of the two component types "if AA go left" and "if BB go right" were presented according to either a pseudorandom or alternating schedule; but they were not impaired if one component type of trial was presented until three consecutive correct responses were made, followed by the other type of trial, to three consecutive correct responses. In all cases testing continued until a criterion of 27 of 30 consecutive correct responses across both types of trial was achieved. Although this suggests that CA1-lesioned animals are particularly prone to interference effects, they had no difficulty in learning ten concurrent visual discriminations presented against either a uniform background or with each discrimination presented against its own distinctive background, a condition that might reduce interference in unoperated monkeys. Interference following hippocampal damage might occur at a deeper level than stimulus identification such that animals with hippocampal damage may be able to learn about many aspects of different stimuli in parallel but may be unable to learn about multiple related aspects of the same subject matter. Monkeys with grafts of fetal CA1 tissue in the lesioned CA1 field showed significant improvement relative to CA1-lesioned animals on those tasks on which CA1-lesioned animals were impaired, although they remained impaired relative to control animals. This suggests that the grafts had produced some improvement in performance. Grafted monkeys did not differ from unoperated control monkeys or from CA1-lesioned monkeys on those tasks that were not sensitive to CA1 damage. This demonstrates that the grafts did not have an additional deleterious effect on cognitive performance.
Animals↗
Nicotinic receptor distribution in the human thalamus: autoradiographical localization of [3H]nicotine and [125I] alpha-bungarotoxin binding.
The thalamus plays a major role in relaying and transforming information that is relayed to the cortex and in turn modulates cortical outputs. The reticular nucleus projects to the other thalamic nuclei, modulating and integrating their activity. The distribution of high affinity nicotine and alpha-bungarotoxin (alpha BTX) receptors in the human thalamus has been investigated by radioligand autoradiography in post mortem human tissue. [3H]nicotine binding in the human thalamus was high in most thalamic nuclei, especially in the lateral dorsal, the medial geniculate, lateral geniculate and anterior nuclei. The distribution of [125I] alpha BTX binding was quite distinct from [3H]nicotine binding. [125I] alpha BTX binding was generally lower (< 0.26-11.62 fmol/mg protein compared with 6.68-36.17 fmol/mg protein for nicotine binding) and concentrated in the reticular nucleus, with discrete groups of cells displaying higher binding in the latter. These results indicate differences between the distribution of nicotinic receptors in humans and those previously reported in mice and monkeys. Changes in high affinity nicotine and alpha BTX receptors in the thalamus may contribute to symptoms observed in neuropathological conditions associated with disorders of perception and movement such as Dementia with Lewy Bodies, Alzheimer's Disease and Schizophrenia.
Adult↗
CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens.
We have previously demonstrated that CD34+ cells, selected from peripheral blood progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in tandem with unmanipulated PBPC with little or no toxicity. In this study, four patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells alone. The two patients with NHL received cyclophosphamide and total body irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in one case the expanded cells were contaminated. No definitive conclusions may therefore be drawn concerning engraftment in these two cases. However, the other two cases received high doses of committed progenitors. Following infusion of the expanded material, all four patients failed to show sustained neutrophil engraftment and none showed evidence of platelet engraftment. Back-up, unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and subsequently all four cases achieved satisfactory engraftment of both neutrophils and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using the conditions described in this report, may not provide durable engraftment following fully myeloablative conditioning.
Adult↗
CD34+ cells can be selected efficiently from cryopreserved peripheral blood progenitor cells and can retain their proliferative potential.
Hematopoietic stem and progenitor cells express the CD34 antigen. Techniques have been developed that enable purified populations of CD34+ cells to be selected from hematopoietic tissues. These selected CD34+ cells have several potential applications, including CD34 selection to obtain a tumor purging effect in autologous transplantation studies and using CD34+ cells as the starting cells for ex vivo expansion studies and as a vehicle for gene transduction protocols. We have investigated the feasibility of using cryopreserved peripheral blood progenitor cells (PBPC) for CD34 selection. Cells could be recovered from cryopreservation with good yields and high viability. After CD34 selection, the final product was, on average, 84% pure, with a recovery of 54%. These cells retained extensive proliferative potential, as demonstrated by ex vivo expansion culture. We believe that cryopreserved PBPC could be thawed, and CD34+ cells could be selected and used for transplantation following high-dose chemotherapy.
Blood Cell Count↗
Very late antigen (VLA) expression by normal and neoplastic human plasma cells; including an assessment of antibodies submitted to the Vth International Workshop on Leucocyte Differentiation Antigens using human myeloma cell lines.
The biology of normal plasma cells and the pathophysiology of human multiple myeloma remain poorly understood. Functional assays are scarce and at present cell phenotyping is providing the most information about how human plasma cells may behave. Three different types of human plasma cells: normal, fresh neoplastic myeloma cells and plasma cell lines, have been studied for their reactivity with antibodies to the beta-1 integrins (Very Late Antigens; VLAs), including a panel obtained from the Vth International Workshop on Leucocyte Differentiation Antigens. Most plasma cell targets express VLA-4 (CD49d positive) and the common beta chain recognized by CD29. CD49e (VLA-5) was occasionally positive. Other VLAs were not usually expressed. These data suggest the wide use by plasma cells of VLA-4, possibly as a ligand with fibronectin and high endothelial venules (HEV). Of other adhesion structures expressed by plasma cells, only CD44 is seen as frequently, and this is also a HEV ligand.
Antibodies↗
Effects of lesions of different parts of the septo-hippocampal system in primates on learning and retention of information acquired before or after surgery.
Data from a large series of experiments on marmosets with lesions of the septal/diagonal band area (DB), fornix or CA1 area of the hippocampus are analysed in terms of retention of information learned before surgery, acquisition of new information and retention of information acquired after surgery. It is shown that although all three lesions impair acquisition of a specific type of new information, lesions of CA1 result in a severe retrograde amnesia but no forgetting of that type of information adequately acquired after surgery, whereas lesions of the DB do not cause retrograde amnesia but do result in significant forgetting. Monkeys with fornix transection occupied an intermediate position in their pattern of learning impairments; some animals showed evidence of forgetting, whereas the great majority showed retrograde amnesia. These data may be relevant to an understanding of the different extent of amnesia in patients with different pathology within the medial temporal lobe and associated subcortical structures.
Animals↗
Morphological organization of oligodendrocyte processes during development in culture and in vivo.
In order to meet the requirements for myelin biogenesis, the processes of oligodendrocytes must differentiate into specialized cellular compartments. For translation of myelin basic protein mRNA to occur in the oligodendrocyte processes or the myelin membrane, these structures must contain ribosomes and other components of the protein translation machinery. Light microscopy and electron microscopy (EM) were used to explore this possibility by analyzing the cytoskeletal organization and the organelle population of the processes of oligodendrocytes during development in vivo and in culture. Microtubules (MTs) were few and bundled in the younger processes of oligodendrocytes in culture. Some of these processes were characterized by the additional presence of serpentine MTs. EM revealed the presence of clusters of ribosomes in both immature and mature oligodendrocyte processes. In the former these clusters were frequently found at regular intervals along the processes. A similar interval characterized the distribution of myelin-like figures along the processes of mature cells in culture. Both in vivo and in culture, the processes became enriched in endoplasmic reticulum cisternae and mitochondria as the cells matured. The spatial arrangement of cellular organelles is compatible with protein and lipid synthesis occurring in the processes, at or near the site of myelin assembly.
Aging↗
CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.
PURPOSE: The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy. PATIENTS AND METHODS: For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin. RESULTS: The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (> or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls. CONCLUSION: These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.
Adolescent↗
Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies.
The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5+/20+ positive cells (0.8 +/- 0.3 vs 0.5 +/- 0.1 vs 1.1 +/- 0.3 x 10(8)/l; p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage.
Abortion, Habitual↗
Parents and procedures: a randomized controlled trial.
INTRODUCTION: Previous work has shown that parents prefer to be present when their children undergo common invasive procedures, although physicians are ambivalent about parental presence. PURPOSE: To determine the effect of a parent-focused intervention on the pain and performance of the procedure, anxiety of parents and clinicians, and parental satisfaction with care. POPULATION: Children younger than 3 years old undergoing venipuncture, intravenous cannulation, or uretheral catheterization. SETTING: Pediatric emergency department of Boston City Hospital. DESIGN: Randomized controlled trial with three groups; parents present and given instructions on how to help their children; parents present, but no instructions given; and parents not present. INTERVENTION: The parents were instructed to touch, talk to, and maintain eye contact during the procedure. RESULTS: A total of 431 parents was randomized to the intervention (N = 153), present (N = 147), and not present (N = 131) groups. The groups were equivalent with respect to measured sociodemographic variables and parents' previous experience in the pediatric emergency department. No differences emerged with respect to pain (3-point scale measured by parent and clinician, and analysis of cry); performance of the procedure (number of attempts, completion of procedure by first clinician, time); clinician anxiety; or parental satisfaction with care. Parents who were present were more likely to rate the pain of the children as extreme/severe (52%) in comparison to clinicians (15%, kappa .07, poor agreement) and were significantly less anxious than parents who were not present. CONCLUSION: Overall, the intervention was not effective in reducing the pain of routine procedures. Parental presence did not negatively affect performance of the procedure or increase clinician anxiety. Parents who were present were less anxious than those who were not present. CLINICAL IMPLICATION: In general, parents have indicated that they want to be present when their children undergo procedures. The results of this study challenge the traditional belief that parental presence negatively affects our ability to successfully complete procedures. We should encourage parents who want to be present to stay during procedures.
Adult↗
Binding of an invariant-chain peptide, CLIP, to I-A major histocompatibility complex class II molecules.
Invariant chain (Ii) associates with major histocompatibility complex (MHC) class II molecules and is crucial for antigen presentation by class II molecules. The exact nature of Ii interaction with MHC class II molecules remains undefined. A nested set of Ii peptides, CLIPs (class II-associated Ii peptides), have been eluted from various MHC class II molecules, suggesting that CLIPs correspond, at least in part, to the Ii motif which blocks the conventional peptide binding site in MHC class II molecules. Here we report how CLIPs interact with class II MHC molecules, I-A. We have identified regions critical for binding of CLIPs and I-A class II molecules. In most cases, the binding of CLIPs to a number of I-A molecules is modulated by the steric bulk of methionine residues at positions 93 and 99. In addition, the binding of CLIPs to an I-A molecule, I-Au, is sensitive to substitutions at aspartic acid-59 in the alpha chain and threonine-86 in the beta chain, whereas the binding of an antigen-derived peptide is not. Taken together, these results provide an insight as to how CLIPs bind to MHC class II heterodimers.
Animals↗
Efficient isolation of human CD34 positive hemopoietic progenitor cells by immune panninga.
In this study we have assessed the use of soybean agglutinin (SBA) and CD34 microcellector devices for the selection of CD34 positive hemopoietic progenitor cells. Burst forming unit-erythroid (BFU-E), colony forming unit-granulocyte/macrophage (CFU-GM) and the recently developed multipotential human colony forming unit-type A (CFU-A) clonogenic assays were used to measure progenitor numbers in the starting mononuclear cell (MNC), the SBA negative, the nonadherent CD34 negative and the adherent CD34 positive fractions during panning. CFU-A progenitors were present at a relatively high incidence in the MNC fraction (220 per 10(5) MNC) and were enriched 15-fold in the adherent CD34 positive fraction. This progenitor incidence and enrichment were similar to those of CFU-GM and BFU-E. The mean recovery for CD34 positive cells was 2.3 x 10(6) cells per marrow aspirate. Analyses by flow cytometry demonstrated that 1-5% of input MNC were CD34 positive, that the purity of the CD34 fraction was approximately 80% and that the calculated recovery for CD34 positive cells was 61%. Recoveries for CFU-GM, BFU-E and CFU-A were between 18 and 40%. CFU-A progenitors were found exclusively in the adherent CD34 positive fraction, whereas a significant proportion of both CFU-GM and BFU-E were present in the nonadherent CD34 negative fraction. We propose that the Applied Immune Sciences (AIS) flasks preferentially bind the cells which express CD34 most strongly and that this is reflected in the finding of primitive CFU-A only in the CD34 positive fraction, with lineage-restricted progenitors found in both CD34 positive and negative fractions. This hypothesis is strengthened by data on long-term bone marrow cultures in which the CD34 positive fraction is better able to maintain output of CFU-GM compared with the CD34 negative fraction. In conclusion, relatively pure populations of CD34 positive cells may be rapidly and efficiently isolated from bone marrow samples with good recovery. The isolated cells show enhanced colony forming capacity in standard clonogenic assays and in the multipotential CFU-A assay.
Antigens, CD↗
B cell number and function in Graves' disease.
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Antigens, CD↗
Facing ethical dilemmas in the neonatal intensive care unit.
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Ethicists↗
Dinucleotide repeat polymorphism at the PI locus.
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Base Sequence↗
Congenital heart malformation in Yunis-Varón syndrome.
We describe a male infant with Yunis-Varón syndrome who has tetralogy of Fallot. This appears to be the first case of Yunis-Varón syndrome associated with congenital heart malformation.
Abnormalities, Multiple↗
Increased risk of coronary artery dissection during coronary angiography with 6F catheters.
The use of smaller sized catheters for coronary angiography (CA) is increasing, but little is known about the safety of CA with 6F catheters. The authors reviewed all cases of CA in which 6F and 8F catheters were used in adult patients between 1988 and June, 1990. There were 597 patients in the 6F group and 2,409 patients in the 8F group. Cases of CA with 6F catheters were more likely to be elective (95% vs 87%), to have no coronary disease (35% vs 24%), and to be performed by nonfirst-year fellows (70% vs 54%) when compared with CA with 8F catheters. There were 5 cases of coronary artery dissection. The incidence of dissections was significantly higher (p = .007) in the 6F group (0.67%) than in the 8F group (0.04%). The incidence of dissections was highest for first-year fellows using 6F catheters (1.7%), which was significantly higher (p = .008) than for first-year fellows using 8F catheters. The incidence of major vascular complications tended to be lower (p = .068) in the 6F group (0.17%) than in the 8F group (0.95%). In summary, CA with 6F catheters is associated with an increased risk of coronary artery dissection, particularly with less experienced operators, but tends to be associated with a lower risk of major vascular complications.
Adult↗