Gallo retires from NIH to launch new research facility.
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Laboratories↗
Biomedical subjects
P Newman
Publications and source records attributed to P Newman.
Long-term chemotaxis studies on adherent cells: effect of platelet-derived growth factor-BB on human vascular smooth muscle cell migration.
Several chemotaxis methods have been developed which allow the study of different aspects of cell migration. The major limitation of such methods is the lack of a sustained chemotactic signal. Long-term chemotaxis phenomena which are known to take place in vivo have remained largely uninvestigated. Ways to maintain sustained chemotactic signals were sought and the used to investigate the long-term chemotactic effect of platelet-derived growth factor BB (PDGF-BB) on human vascular smooth muscle cells (HVSMC). PDGF-BB was adsorbed onto microcarrier beads and then embedded in agar. PDGF-BB diffusion was slow and a high and sustained local concentration was maintained in the agar. When PDGF-BB-loaded beads embedded in agar were placed at the edge of a tissue culture dish with HVSMC plated in the center, preferential movement was observed in the direction of the PDGF-BB source. This method was subsequently used to study directional movement of HVSMC arising from explants. This report demonstrates that PDGF-BB if present in an anisotropic concentration induces directional cell movement from such explants. By allowing the study of the effect of sustained chemotactic signals upon cultured cells or cells arising from explants, this method may provide a suitable model for investigating in vivo chemotaxis phenomena.
Cell Movement↗
Modulation of endothelin receptor expression in human vascular smooth muscle cells by interleukin-1 beta.
Endothelin may play a role in atherosclerosis as it causes smooth muscle cell proliferation and its levels are elevated in patients with atherosclerosis. We report that interleukin-1 beta is a potent inducer of endothelin receptor expression in cultured human vascular smooth muscle cells. The effect is dose- and time-dependent and is due to an increase in receptor number. Endothelin receptor mRNA levels are also elevated. Interleukin-1 beta is a major regulator of endothelin release so, together with its effects on endothelin receptors, it may be responsible for a generalized activation of the endothelin system in diseased vessels.
Aorta↗
Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient.
Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron disease (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/beta protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.
Aged↗
Screening for gestational diabetes in a multi-ethnic population.
A multi-ethnic population was screened for gestational diabetes mellitus (GDM) using a venous plasma glucose estimation, 1 h following a standard 50 g glucose load. A significant difference in the ethnic distribution of screen-positivity was found. Amongst the screen-positive group the odds ratio (OR) for special care baby facility (SCBU) admission and birthweight > 3999 g were both increased (OR = 1.87 and 1.99). Only limited diagnostic testing by a glucose tolerance test (GTT) could be achieved for the screen-positive population. For patients with confirmed GDM (two or more abnormal values on a GTT) the OR for SCBU admission was further increased to 5.1, while the OR for increased birthweight was only 1.34. Clinical attention should be directed towards outcome assessment in order to properly evaluate the nature of and place for screening for GDM in multi-ethnic populations.
Africa, Northern↗
An evaluation of fructosamine estimation in screening for gestational diabetes mellitus.
Although persuasive arguments against routine screening for gestational diabetes mellitus (GDM) have been made, it is widely but not universally performed as a part of antenatal care. There is no international agreement on methods or criteria used for screening (or for diagnosis), and administered glucose-load methods have significant practical difficulties in a busy antenatal clinic setting. However, recent evidence supports the concept of an increased level of importance being given to a diagnosis of GDM, with interest in the fetal and neonatal origins of adult disease being added to the short-term obstetric and fetal concern during pregnancy. A second generation fructosamine test, corrected for total protein, has been evaluated as a practical alternative to glucose screening for GDM in a busy, multi-ethnic antenatal clinic. This achieved a 79.4% sensitivity and a 77.3% specificity for a diagnosis of GDM confirmed by a glucose tolerance test using Carpenter's modified criteria. In view of the organizational simplicity of this sample/test requirement, a wider evaluation is suggested together with a re-evaluation of clinical outcome criteria rather than blood glucose levels alone.
Adult↗
The proliferative responsiveness of human vascular smooth muscle cells to endothelin correlates with endothelin receptor density.
BACKGROUND: Endothelin (ET), a potent vasoconstrictor peptide, is implicated in disorders of intimal hyperplasia such as atherosclerosis and restenosis. Data from animal models and in vitro studies indicate that ET may act at the level of vascular smooth muscle cell proliferation. In this study the effect of ET on human vascular smooth muscle cells (HVSMC) was investigated. EXPERIMENTAL DESIGN: The mitogenic effect of ET on 30, early passage, HVSMC lines derived from normal donors and those undergoing aorto-coronary vein bypass grafting (ACVB) operation was examined and characterized. This was correlated with the density of endothelin receptors on these cells as well as with the rate of endothelin secretion. RESULTS: There were no clear differences in the mitogenic responsiveness of cells from normal donors and those undergoing ACVB. In 10 HVSMC lines, DNA synthesis was significantly stimulated (30 to 120% stimulation above control, defined as responders), and an insignificant stimulation (< 30% above control) was observed in 20 cell lines (called non-responders); a similar pattern was observed in the cell multiplication assay. In the responder HVSMC lines, the rank order of ET isopeptides in stimulating mitogenesis was ET-1 = ET-2 > ET-3, and the effect was inhibited by the ET antagonist (BQ-123) suggesting that the ET-receptor-A (ETA) subtype was involved in mediating the actions of ET. Measurement of 125I-ET-1 binding to cells indicated there to be a strong correlation between the extent of ET mitogenic effect and receptor binding (N = 30, p = 0.034) but none with the rate of ET secretion. CONCLUSIONS: These results suggest that increased levels of ET receptors on HVSMC, as observed in atherosclerotic plaques, may predispose them to ET-stimulated proliferation.
Adolescent↗
Implant supported fixed distal extension prostheses.
The distal extension fixed implant supported prosthesis is now available as an alternative to a partial denture. However, not all patients will be suitable for such treatment. Limitations imposed on fixture length, the effect of gape upon instrumentation, the size of abutment components and the design of the superstructure are discussed in this article, to assist the general practitioner in case referral.
Contraindications↗
Effects of insertion depth and use of the sidearm of the introducer sheath of pulmonary artery catheters in cardiac output measurement.
OBJECTIVE: To investigate the effects of various insertion depths and sidearm functions of the introducer sheath of pulmonary artery flotation catheters on cardiac output measurement. DESIGN: Prospective, randomized, crossover study. SETTING: A general intensive care unit. PATIENTS: Ten patients who had a pulmonary artery flotation catheter placed in the right internal jugular vein as part of their clinical management. INTERVENTIONS: Cardiac output was measured at three insertion depths of the pulmonary artery catheter, each with a different rate of flow into the introducer sheath. MEASUREMENTS AND MAIN RESULTS: Significant differences of up to 23% occurred in the measurement of cardiac output under the various conditions. Cardiac output measurement is greater, the closer the injection port lies to the introducer sheath and the more open the introducer sheath sidearm. CONCLUSIONS: All users of pulmonary artery catheters should be alert to this problem. For reliable measurements of cardiac output by thermodilution, the cold saline injection port of the pulmonary artery catheter must be downstream of the introducer sheath, and the introducer sidearm must be closed.
Adult↗
Look After Your Heart programme: impact on health status, exercise knowledge, attitudes, and behaviour of retired women in England.
OBJECTIVES: To evaluate the impact of the Health Education Authority's 20 hour Look After Your Heart health promotion course on a large group of retired women. DESIGN: Three groups of retired women were compared: group 1 women, drawn from 12 retirement groups, participated in the programme; group 2, drawn randomly from the same groups, declined; group 3, selected randomly from 12 different retirement groups matched for geographical area, were not offered the course. SETTING: Twenty four retirement groups established by a major national retail company in England. SUBJECTS: A total of 739 women with a mean age of 66 years participated. Altogether 200 women were in group 1, 192 in group 2, and 347 in group 3. MAIN OUTCOME MEASURE: The Nottingham Health Profile was administered and exercise knowledge, attitudes, and behaviour of the three groups were assessed using a validated, reliable questionnaire. RESULTS: Group 1 had significantly better self-perceived health, indicated by lower Nottingham Health Profile scores, more exercise knowledge, and positive exercise attitudes and they did more exercise than the other two groups. The responses of groups 2 and 3 were similar. Time since completion of the programme did not have any effect on Nottingham Health Profile scores, exercise knowledge, and behaviour. CONCLUSION: The Look After Your Heart programme is associated with beneficial and persistent effects in retired women. Detailed studies are needed to confirm whether these associations are due to the programme or reflect the selection of fitter, healthier subjects.
Aged↗
Pre-emptive analgesia.
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Amputation, Surgical↗
Characterization of Alzheimer amyloid precursor protein transcripts in platelets and megakarocytes.
Immunoblot analyses indicate that the platelet is a reservoir of several Alzheimer amyloid precursor protein (APP) isoforms, including C-terminal reactive species which could potentially serve as the precursor of the amyloid beta protein (AB*) in Alzheimer's disease (AD). Since platelets are known to sequester several plasma proteins from the blood, we employed the polymerase chain reaction (PCR) to amplify reverse transcribed mRNA and detect the 3 major APP transcripts (APP695,751,770) in platelets and the Dami megakaryocyte cell line. PCR amplification of glycoprotein IIb and HLA-DR mRNA was used to demonstrate that APP transcripts were derived from cells of megakaryocytic lineage, and the results were compared with those obtained from peripheral blood mononuclear cells, human umbilical vein endothelial cells, B lymphocyte and astrocytoma cell lines. The identity of PCR products was confirmed by hybridization with APP specific oligonucleotide probes, and sequencing of amplified segments.
Amyloid beta-Protein Precursor↗
Supplementary oxygen causing surgical emphysema.
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Child↗
Polyisoprenylation of the CAAX motif--an in vitro protein synthesis study.
A number of proteins, including most nuclear lamins, certain fungal mating pheromones, G-protein gamma-subunits and ras proteins, contain a C-terminal cysteine-aliphatic-aliphatic-undefined amino acid (CAAX) motif which is thought to be a roughly defined consensus sequence capable of directing a series of posttranslational events, beginning with the addition of a polyisoprene moiety to the cysteine. So far such a motif has been found in every protein known to have this type of modification. We have utilized the rabbit reticulocyte lysate translation system, which is capable of carrying out the polyisoprene modification in vitro, to investigate features of the C-terminal motif which affect its suitability as a substrate. We demonstrate that a cysteine is only isoprenylated when situated at position -4 from the C-terminus. We further show that the presence of a glycine at position -3 or a terminal aromatic residue, features typical of some G-protein alpha subunits, cause a reduction and abolition respectively of isoprenylation.
Amino Acid Sequence↗
Carcinoma of the urachus associated with urachal adenoma.
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Adenocarcinoma↗
Squamous carcinoma in the liver.
Squamous carcinoma of the liver has only rarely been reported. We present a case which highlights not only the difficulties in diagnosis but also how it can closely mimic sclerosing cholangitis.
Aged↗
The Rosai Dorfman syndrome in a 50-year-old male.
A case is presented of a 50-year-old man with Rosai Dorfman Syndrome (Sinus histiocytosis with massive lymphadenopathy) who had facial, cervical and cutaneous involvement.
Histiocytes↗
Influence of cytochalasin D-induced changes in cell shape on proteoglycan synthesis by cultured articular chondrocytes.
There is growing evidence that cell shape regulates both proliferation and differentiated gene expression in a variety of cell types. We have explored the relationship between the morphology of articular chondrocytes in culture and the amount and type of proteoglycan they synthesize, using cytochalasin D to induce reversible cell rounding. When chondrocytes were prevented from spreading or when spread cells were induced to round up, 35SO4 incorporation into proteoglycan was stimulated. Incorporation into the cell layer was stimulated more than into the medium. When the cells were allowed to respread by removing cytochalasin D, proteoglycan synthesis returned to control levels. Cytochalasin D-induced stimulation of 35SO4 incorporation reflected an increase in core protein synthesis rather than lengthening of glycosaminoglycan chains, because [3H]serine incorporation into core protein was also stimulated. The observed stimulation of proteoglycan synthesis was not due to an overall stimulation of protein synthesis, to inhibition of DNA synthesis, or to accumulation of cells in one phase of the cell cycle. Cytochalasin D-treatment of cells in suspension caused no further stimulation of 35SO4 incorporation, suggesting that the observed effects were due to cell rounding rather than exposure to cytochalasin D per se; nevertheless, we cannot completely rule out other, nonspecific, effects of the drug. Fibroblasts and chondrocytes that had been passaged to stimulate dedifferentiation did not incorporate more 35SO4 when treated with cytochalasin D, suggesting that increased proteoglycan synthesis in response to rounding may itself be a differentiated property of chondrocytes.
Animals↗