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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 559 records · Page 31Linked to original sources
PubMed1997

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.

Adolescent↗
PubMed1997

Müller-cell-derived leukaemia inhibitory factor arrests rod photoreceptor differentiation at a postmitotic pre-rod stage of development.

In the present study, we examine rod photoreceptor development in dissociated-cell cultures of neonatal mouse retina. We show that, although very few rhodopsin+ rods develop in the presence of 10% foetal calf serum (FCS), large numbers develop in the absence of serum, but only if the cell density in the cultures is high. The rods all develop from nondividing rhodopsin- cells, and new rods continue to develop from rhodopsin- cells for at least 6-8 days, indicating that there can be a long delay between when a precursor cell withdraws from the cell cycle and when it becomes a rhodopsin+ rod. We show that FCS arrests rod development in these cultures at a postmitotic, rhodopsin-, pre-rod stage. We present evidence that FCS acts indirectly by stimulating the proliferation of Müller cells, which arrest rod differentiation by releasing leukaemia inhibitory factor (LIF). These findings identify an inhibitory cell-cell interaction, which may help to explain the long delay that can occur both in vitro and in vivo between cell-cycle withdrawal and rhodopsin expression during rod development.

Animals↗
PubMed1997

Adverse psychological impact of operative obstetric interventions: a prospective longitudinal study.

OBJECTIVE: This paper reports the findings of a prospective longitudinal study of 272 nulliparous pregnant women, which investigated as one of its objectives the psychological sequelae of obstetric procedures. METHOD: Participants completed structured interviews and standardised, published psychometric questionnaires, including the Rosenberg Self-Esteem Scale and the Profile of Mood States late in pregnancy and again early in the postpartum period. RESULTS: Little evidence was found to support the notion that the total number of obstetric interventions was linked to a deterioration in postpartum mood. Significant adverse psychological effects were associated with the mode of delivery. Those women who had spontaneous vaginal deliveries were most likely to experience a marked improvement in mood and an elevation in self-esteem across the late pregnancy to early postpartum interval. In contrast, women who had Caesarean deliveries were significantly more likely to experience a deterioration in mood and a diminution in self-esteem. The group who experienced instrumental intervention in vaginal deliveries fell midway between the other two groups, reporting neither an improvement nor a deterioration in mood and self-esteem. CONCLUSIONS: The findings of this study suggest that operative intervention in first childbirth carries significant psychological risks rendering those who experience these procedures vulnerable to a grief reaction or to posttraumatic distress and depression.

Adult↗
PubMed1997

From long range mapping to sequence-ready contigs on human chromosome 6.

Our aim is to construct physical clone maps covering those regions of chromosome 6 that are not currently extensively mapped, and use these to determine the DNA sequence of the whole chromosome. The strategy we are following involves establishing a high density framework map of the order of 15 markers per Megabase using radiation hybrid (RH) mapping. The markers are then used to identify large-insert genomic bacterial clones covering the chromosome, which are assembled into sequence-ready contigs by restriction enzyme fingerprinting and sequence tagged site (STS) content analysis. Contig gap closure is performed by walking experiments using STSs developed from the end sequences of the clone inserts.

Chromosomes, Human, Pair 6↗
PubMed1997

Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody biodistribution in patients with colorectal tumors.

UNLABELLED: Copper-67 has comparable beta-particle emissions to that of 131I, but it displays more favorable gamma emission characteristics for application in radioimmunotherapy (RIT). This study investigates the potential of 67Cu-labeled monoclonal antibody (MAb) 35 for RIT of colorectal carcinoma. METHODS: Biokinetics of simultaneously injected 67Cu- and 125I-labeled MAb35 were studied in six patients scheduled for surgery of primary colorectal cancer. RESULTS: Whole-body clearance (T 1/2) of 67Cu, estimated from sequential anterior and posterior whole-body scans and corrected for decay of 67Cu, was 41 hr. Serum clearance of 67Cu was faster (27.41 hr) than that of 125I (38.33 hr). Mean tumor uptake of the 67Cu-labeled compound (0.0133% ID/g) exceeded that of 125I (0.0095% ID/g), and tumor-to-blood ratios were higher for 67Cu than for 125I, with averages of 6.07 and 2.41, respectively. The average 67Cu/125I ratio was 1.9 for tumor uptake, 0.7 for blood and 2.6 for tumor-to-blood ratios. Nonspecific liver uptake of 67Cu as calculated from whole-body scans was high in four patients, up to 25% of residual whole-body activity at 48 hr, but did not increase with time. We also observed some nonspecific bowel activity, as well as moderate to high uptake in benign polyps. CONCLUSION: Copper-67-labeled MAb35 is more favorable than its radioiodine-labeled counterpart for RIT of colorectal carcinoma due to higher tumor-to-blood ratios, but the problem of nonspecific liver and bowel uptake must first be overcome. The absolute accumulation of activity in tumor remains low, however, so the probability of cure with this compound alone is questionable. The use of 67Cu as one component of a multimodality adjuvant treatment seems to remain the most appropriate application for RIT.

Aged↗
PubMed1997

DMPS-arsenic challenge test. I: Increased urinary excretion of monomethylarsonic acid in humans given dimercaptopropane sulfonate.

The purpose of the present study was to evaluate in a novel manner the arsenic exposure of humans living in two towns in Northeastern Chile. Residents of one town drink water containing 593 microg As/l. Those in the control town drink water containing 21 microg As/l. Our hypothesis was that the administration of the chelating agent, 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS, DIMAVAL) would increase the urinary excretion of arsenic, alter the urinary profile of arsenic species and thus result in a better indication of the body load of arsenic and a better biomarker for arsenic exposure. The method used to evaluate these subjects was to give them 300 mg DMPS by mouth, after an overnight fast, and collect urine at specified time periods. The urine samples were analyzed for inorganic arsenic, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic by hydride generation and atomic absorption spectrophotometry. The results indicated that: 1) During the 2-hr period after DMPS administration, MMA represented 42%, inorganic As, 20 to 22% and DMA, 37 to 38% of the total urinary arsenic. The usual range of the MMA percentage in human urine has been 10 to 20%. The % MMA increased almost equally for both the arsenic-exposed and control subjects. 2) The exposed subjects had a greater urinary excretion of total arsenic, before and after DMPS administration, than the control subjects. 3) Although buccal cells were obtained only from a few subjects, the prevalence of mononucleated buccal cells, an indication of genotoxicity, was 5-fold greater for those who consumed drinking water with the higher arsenic content than among control subjects. Our conclusions are that 1) DMPS has a highly specific effect in humans on MMA metabolism and/or urinary excretion; 2) the human body stores substantial amounts of arsenic; and 3) the urinary arsenic concentration after DMPS administration may be more indicative of the body burden of arsenic because it was greater than that found before DMPS was given.

Adult↗
PubMed1996

Parallel synthesis and screening of a solid phase carbohydrate library.

A solid phase carbohydrate library was synthesized and screened against Bauhinia purpurea lectin. The library, which contains approximately 1300 di- and trisaccharides, was synthesized with chemical encoding on TentaGel resin so that each bead contained a single carbohydrate. Two ligands that bind more tightly to the lectin than Gal-beta-1,3-GalNAc (the known ligand) have been identified. The strategy outlined can be used to identify carbohydrate-based ligands for any receptor; however, because the derivatized beads mimic the polyvalent presentation of cell surface carbohydrates, the screen may prove especially valuable for discovering new compounds that bind to proteins participating in cell adhesion.

Acylation↗
PubMed1996

The Wolf-Hirschhorn syndrome in adulthood: evaluation of a 24-year-old man with a rec(4) chromosome.

We described a profoundly intellectually disabled 24-year-old man with Wolf-Hirschhorn syndrome, left hemiplegia, epilepsy, atrophy of the right cerebral hemisphere, and dilatation of the right ventricle. The patient had a small ventricular septal defect, was wheelchair bound, and totally dependent. He had no speech, but vocalised to show his feelings. In this patient, the del(4)(p15) was subtle and arose due to the inheritance of a recombinant chromosome (4) from a maternal pericentric inversion-46,XX,inv(4) (p15.32q35). Fluorescence in situ hybridisation with probe D4S96 confirmed the deletion. This is the second case of Wolf-Hirschhorn syndrome resulting from a large pericentric inversion of chromosome 4.

Abnormalities, Multiple↗
PubMed1996

A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung.

Effective gene therapy for lung tissue requires the use of efficient vehicles to deliver the gene of interest into lung cells. When plasmid DNA encoding chloramphenicol acetyltransferase (CAT) was administered intranasally to BALB/c mice without carrier lipids, CAT activity was detected in mouse lung extracts. Plasmid DNA delivered with optimally formulated commercially available transfection reagents expressed up to 10-fold more CAT activity in lung than observed with naked DNA alone. Liposome formulations consisting of (+/-)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis (dodecyloxy)-1-propanaminium bromide (GAP-DLRIE) plus the neutral colipid dioleoylphosphatidylethanolamine (DOPE) enhanced CAT expression by more than 100-fold relative to plasmid DNA alone. A single administration of GAP-DLRIE liposome-CAT DNA complexes to mouse lung elicited peak expression at days 1-4 posttransfection, followed by a gradual return to baseline by day 21 postadministration. Readministration of GAP-DLRIE liposome CAT complexes at day 21 led to another transient peak of reporter gene expression. Histological examination of lungs treated with GAP-DLRIE complexed beta-galactosidase DNA revealed that alveolar epithelial cells were the primary locus of expression and that up to 1% of all alveoli contained epithelial cells expressing the transgene.

Administration, Intranasal↗
PubMed1996

Role of hemopexin in protection of low-density lipoprotein against hemoglobin-induced oxidation.

Globin-free hemin and certain hemoproteins, predominantly hemoglobin, are active triggers of low-density lipoprotein (LDL) peroxidation, a contributing cause of atherosclerosis. The role of the plasma heme-binding protein, hemopexin, in protecting apolipoprotein B and LDL lipids from oxidation triggered by either hemin or hemoglobin in the presence of low amounts of H2O2, was investigated at physiological pH and temperature. Significantly, hemopexin prevented not only hemin-mediated modification of LDL but also LDL peroxidation induced by hemoglobin, both by met and oxy forms. Analysis of the data revealed that the rate of heme transfer from methemoglobin to hemopexin was highly dependent upon temperature: only minimal heme transfer occurred at 20 degrees C, whereas at the physiological temperature of 37 degrees C, heme transfer was rapid, within the lag phase of LDL oxidation, regardless of the presence or absence of H2O2. Heme did transfer to hemopexin from oxyhemoglobin as well, but only in the presence of H2O2. The proposed mechanism of the inhibition of oxyhemoglobin oxidative reactivity by hemopexin involves peroxidation of oxyhemoglobin (Fe(II)) to ferrylhemoglobin (FeIV), followed by a comproportionation reaction (FeIV+FeII-->2FeIII), yielding methemoglobin (FeIII) from which heme is readily transferred to hemopexin. Taken together, the data demonstrate that hemopexin can act as an extracellular antioxidant against hemoglobin-mediated damage in inflammatory states, which is especially important when haptoglobin is depleted or absent.

Antioxidants↗
PubMed1996

Fibrous matrix of ventricular myocardium in tricuspid atresia compared with normal heart. A quantitative analysis.

BACKGROUND: The collagen matrix is a small component of the myocardium, but it provides a supportive framework. An increase in collagen in the pressure-overloaded ventricle is known to cause myocardial stiffness. However, little is known about the collagen matrix in the volume-overloaded ventricle, particularly in relation to congenital heart disease. METHODS AND RESULTS: We examined a total of 53 hearts with tricuspid atresia and 58 normal hearts matched for age. Using a microscopic-morphometric method, we analyzed the percentage per field area occupied by interstitial fibrous tissue in four sites in the ventricular mass for each specimen. A comparison of sampling sites showed no significant variations between normal and malformed hearts. Results from a homogeneity of regression co-efficients analysis suggested that the two groups shared the same basic relation of proportion of fibrosis with age. The use of ANCOVA, however, revealed a clear separation between the extents of fibrous tissue in the two groups of hearts. CONCLUSIONS: The myocardium of hearts with tricuspid atresia is consistently more fibrotic than normal heart and is probably an inherent part of the malformation. This difference could explain, at least in part, the clinical observation that the left ventricle is frequently abnormal, even at an early age.

Adolescent↗
PubMed1996

Monocyte chemoattractant protein-1 gene expression in injured pig artery coincides with early appearance of infiltrating monocyte/macrophages.

Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are potent chemokines which attract circulating monocytes and neutrophils respectively to inflamed tissues. JE/MCP-1 gene expression has been previously studied in rabbit aortae after endothelial denudation and the rapid appearance of this transcript was thought to precede emigration of phagocytes. We now report MCP-1 gene expression following de-endothelialization of iliac arteries in the pig, a species which can develop spontaneous atherosclerosis. Using Northern blot analysis, we demonstrated that MCP-1 mRNA was rapidly induced in pig arteries at 2 h and continued to increase to reach a maximum at 8 h before returning to low levels at 16-24 h after injury. The increase seen for MCP-1 mRNA at 8 h was also observed for IL-8 mRNA but was not apparent for growth-related gene expressions, urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAI-1). Since smooth muscle cells, endothelial cells, and phagocytes are all capable of expressing MCP-1, we examined pig arteries for immunostaining using a monoclonal antibody to human MCP-1 (5D3-F7). At 8 h after injury, the predominant cell type staining positive for MCP-1 was the monocyte/macrophage. Staining was also observed in occasional scattered neutrophils, but MCP-1 protein could not be detected in smooth muscle cells or on extracellular matrix within the sensitivity constraints posed by our methodology. Our results are consistent with invading monocyte/macrophages having a major input into the production of this chemokine in the arterial wall following injury. The fact that MCP-1 expression accompanied monocyte/macrophage presence in damaged artery, rather than preceding it, is suggestive that continued MCP-1 expression is required for functions other than chemoattraction.

Animals↗