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Biomedical subjects

M Richardson

Publications and source records attributed to M Richardson.

At least 343 records · Page 19Linked to original sources
PubMed1987

Evidence for an alternative mechanism of human platelet secretion involving peripheralization of secretory granules and formation of membrane-associated multivesicular structures.

Stimulated platelets release the content of their granules to the environment by a process known as platelet secretion. The precise mechanism of platelet secretion is poorly understood. The most widely-held theory suggests that, during platelet activation, secretory granules centralize and their content is released into the surface-connected canalicular system. Using fixation techniques directed at preserving membrane structures, morphological evidence is provided that human platelet activation is associated with secretory granules migrating to the periphery of platelets, where they undergo transition to participate in the formation of membrane-associated multivesicular structures. These multivesicular structures then undergo dissolution resulting in granule content secretion to the environment. The formation of the membrane-associated multivesicular structures occurs in platelets in which some of the secretory granules have also become centralized. This suggests that during the activation of human platelets, membrane-associated multivesicular structure release may occur concurrently with other mechanisms of secretory granule content release. The present observations are consistent, however, with the hypothesis that during human platelet activation the formation of membrane-associated multivesicular structures by platelet secretory granules contributes importantly to the mechanism of platelet secretion.

Blood Platelets↗
PubMed1987

The Newbury Maternity Care Study: a randomized controlled trial to assess a policy of women holding their own obstetric records.

To assess a policy of women holding and thus having constant access to their own obstetric records, 290 women attending a peripheral consultant clinic in Newbury, West Berkshire, were randomly allocated to hold either their full case notes, or the more usual co-operation card. Women holding their full records were significantly more likely to feel in control of their antenatal care (rate ratio 1.45; 95% confidence interval 1.08-1.95) and to feel it was easier to talk to doctors and midwives (rate ratio 1.73; 95% confidence interval 1.16-2.59). No other beneficial effects were detected. Asked about their preferences for any subsequent pregnancies, women holding their own records in the index pregnancy were more likely to say they would prefer to hold the same kind of record again in a subsequent pregnancy than were women holding a co-operation card (rate ratio 1.56; 95% confidence interval 1.34-1.81). There was no evidence of negative effects. In particular, women holding their case notes did not feel more anxious than co-operation card holders. The policy of women holding their notes resulted in savings in clerical time, without evidence of an increase in the rate of lost notes.

Clinical Trials as Topic↗
PubMed1987

Metachromatic cell progenitors and specific growth and differentiation factors in human nasal mucosa and polyps.

We previously demonstrated that fluctuations in circulating metachromatic cell progenitors were inversely related to nasal metachromatic cell (NMC) counts and nasal symptoms in allergic rhinitis. Now, we have quantitated NMC progenitors and lineage-specific growth factors using a hemopoietic colony assay. Cell suspensions from excised collagenase-treated nasal polyps (n = 7) contained 3.8 +/- 1.1 granulocyte colony-forming cells per 10(6) cells plated, compared to less than or equal to 0.5 in human tonsil suspensions, less than or equal to 0.5 in nasal mucosal epithelial scrapings, and 33 +/- 8 in peripheral blood of patients with ragweed allergic rhinitis (p less than 0.01). The percentage of metachromatic cells in nasal-polyp-derived colonies was 47 +/- 10 compared with 3.0 +/- 0.7 in peripheral blood colonies (p less than 0.005). Highly potent metachromatic cell colony-stimulating activity (CSA) was detected in supernatants from cultured human nasal epithelial scrapings from both polyps and atopic nasal mucosa, but not from nonatopic nasal mucosa. Supernatants from polyp mononuclear cells stimulated with phytohemagglutinin also contained metachromatic cell-CSA, which had an approximate molecular size of 25 to 70,000 daltons on column chromatography. An IL-3-like activity was also detected in these supernatants. These observations provide further evidence for in situ hemopoietic mechanisms in human nasal mucosa, involving epithelium-derived stimulation of local metachromatic cell progenitor growth and differentiation in allergic rhinitis.

Basophils↗
PubMed1987

Reciprocal regulation of human basophil and eosinophil differentiation by separate T-cell-derived factors.

Basophil and eosinophil progenitors are present in human hemopoietic tissues, including cord blood. In the present studies, cord blood cultures demonstrating differentiation of basophils or eosinophils have been maintained for prolonged periods in the presence of conditioned medium from a human T-cell leukemia line (Mo-CM). Peak basophil counts and histamine levels were followed almost invariably by a second peak of eosinophils in vitro. Morphologic examination revealed the consistent presence of cells with mixed basophil-eosinophil granulation. Both basophil and eosinophil growth-stimulating activities were found in Mo-CM, were heat stable and nondialyzable, and could be partially separated from each other by a multistep procedure that included ion-exchange chromatography on DEAE-cellulose. Mixing experiments using separated basophil- and eosinophil-stimulating activities revealed that suppression of basophil growth was accompanied by reciprocal enhancement of eosinophil growth, a finding that could be confirmed on analysis of morphology of single colonies from cord blood progenitors in methylcellulose. These studies point to the existence of regulatory growth factors in Mo-CM that stimulate and/or inhibit the growth and differentiation of human basophils and eosinophils from a common, committed progenitor cell.

Basophils↗
PubMed1987

Identification of non-denuding endothelial injury by scanning electron microscopy.

Endothelial injury is important in the development of arterial disease. To examine the response to endothelial injury it is necessary to recognise if endothelium has been altered and how this relates to normal function. Of the several methods available to evaluate endothelial integrity, ultrastructural examination has certain advantages. In particular, scanning electron microscopy of the endothelium will permit large areas to be examined, and changes can be related to the overall anatomy of the vessel. There is good evidence that endothelial injury does not inevitably result in endothelial cell loss and denudation of the subendothelium, but that endothelial cells can be desquamated in a process of non-denuding injury. The morphological changes described in endothelial cells stimulated by a variety of agents suggest that the response varies according to the method of investigation, that there are some common features, but that each stimulus induces certain specific changes. The endothelial response to a range of agents was therefore examined in the same animal model, using carefully controlled preparation parameters. The observations indicate that the response to stimuli which induce an inflammatory type of reaction is characterised by fibrin formation and white cell adhesion. In contrast stimuli which result in vessel collapse show protruding cells and damage at vessel orifices. Certain features are seen irrespective of the stimulus. The significance of many of the observed changes remains to be elucidated.

Animals↗
PubMed1986

On the interaction of rabbit antithrombin III with the luminal surface of the normal and deendothelialized rabbit thoracic aorta in vitro.

Pure rabbit antithrombin III was isotope labeled (with 125I or 3H) by two different methods; neither procedure caused a loss of antithrombin activity although both methods affected the affinity of the protein for Sepharose-heparin. From segments from freshly excised rabbit aorta, the uptake of isotope-labeled antithrombin III by the endothelium was rapid and saturable, although relatively small compared to the uptake of thrombin; binding of 3H-antithrombin III to the endothelium resembled that of 125I-antithrombin III. Transendothelial passage of antithrombin III into the subendothelial layers (intima-media) was slow and progressive. Endothelium binding was not affected by pretreating the vessel with either heparin, thrombin, or glycosaminoglycan-specific enzymes. Endothelium-bound antithrombin III was not selectively displaced by either heparin or thrombin. In contrast, endothelium-bound thrombin was rapidly dislodged by antithrombin III as a thrombin-antithrombin III complex. The surface of the deendothelialized aorta (ie, subjected to a balloon catheter) bound antithrombin III avidly. Pretreatment of the deendothelialized vessel with glycosaminoglycan-specific enzymes, particularly heparitinase, decreased intima-media binding by up to 80%. 125I-antithrombin III, when bound to the deendothelialized vessel surface, was actively displaced by either heparin, thrombin, or by unlabeled antithrombin III. The relatively poor binding of antithrombin III compared with that of thrombin by the endothelium in vitro supports an earlier proposal (Lollar P, Owen WG: J Clin Invest 66:1222-1230, 1980) that thrombin bound to high-affinity sites, possibly pericellular proteoglycan, of the endothelium is inactivated by plasma antithrombin III in vivo. Such a situation probably holds for large arteries at least.

Animals↗
PubMed1985

The amino acid sequence of the enterotoxin from Clostridium perfringens type A.

The amino acid sequence of the enterotoxin from Clostridium perfringens type A was determined by analysis of peptides derived from the protein by digestion with trypsin chymotrypsin, thermolysin, pepsin, a lysine-specific protease. S. aureus V8 protease and a proline-specific protease, and fragments generated by cleavage with cyanogen bromide or by dilute acetic acid in 7 M guanidine HCl. The sequence which is complete except for the definite order of 3 small peptides between residues 88 and 103 consists of 309 amino acids and contains a correction to our preliminary announcement [(1984) FEMS Symp. 24, 329-330].

Acetates↗
PubMed1985

Sequence of a cloned 523-bp cDNA for thymosin beta 4.

The sequence of a 523-bp cDNA, isolated from a clone bank prepared from partially purified rat spleen mRNA coding for thymosin beta 4, was described. The 3' sequence extended through the poly(A) segment and the 5' sequence included 36 bp preceding the translated sequence. The putative amino acid sequence coded by this segment possesses some of the features of a signal peptide.

Amino Acid Sequence↗
PubMed1985

Proteoglycan distribution in catheter-induced aortic lesions in normolipaemic rabbits. An ultrastructural study.

The aortic lesions induced in normal-fed rabbits by an indwelling catheter were examined for changes in lipid content shown by oil red O-stained sections and associated proteoglycan distribution and ultrastructural changes by transmission electron microscopy of ruthenium red-stained sections, during an 8-week period of regression. Compared to normal aorta there was a highly significant increase in proteoglycan in lipid-containing lesions, which was also associated with the presence of regenerated endothelium. In the lesions which had regressed in terms of size and lipid content, the proteoglycan concentration, especially in superficial regions, was significantly reduced compared to early lesions and was similar to that seen in the normal vessel. Proteoglycan concentration decreased before lipid content of lesions was reduced. Proteoglycan was not associated with lipid-containing macrophages. These observations support the hypothesis that an increased glycosaminoglycan concentration is associated with lipid deposition in the vessel wall in response to injury in the absence of hyperlipaemia.

Animals↗
PubMed1985

Scanning electron microscopy of normal rabbit aorta: injury or artifact?

The reported morphology of both normal and "injured" aortic endothelium differs significantly from one study to another. To better understand these disparities, we examined the effects of manipulating the preperfusion conditions on the subsequent morphology of normal aortic endothelium in the rabbit. Glutaraldehyde perfusion without any preperfusion with an electrolyte solution, induced vasoconstriction and the accumulation of cellular and plasma protein on the luminal surface of the aorta. Prolonged preperfusion by Ringer-Locke solution and to a lesser extent, by Krebs-Henzleit solution or modified Eagles medium, induced changes in the endothelium similar to those reported as the response to injury induced by other stimuli. Profound vessel wall alterations also occurred in animals which were shocked (through acute blood loss) or killed (by overdose of anesthetic) prior to fixation. These observations may explain, in part, the discrepancies in previous descriptions of the appearance of "normal" rabbit aortic endothelium in SEM, and suggest that the type and duration of the preperfusion must be considered to avoid morphological artifacts.

Animals↗
PubMed1985

Bone marrow imaging: magnetic resonance studies related to age and sex.

Measurements of T1 and T2 relaxation values and spin density of the lumbar vertebral bone marrow were performed in 212 patients, and the results were correlated with the patients' age and sex. T1 and T2 relaxation times for bone marrow in the lumbar vertebral bodies showed a progressive decrease with age for both sexes (except for the T2 relaxation values in female patients). The replacement of hematopoietic marrow by fatty marrow could explain the decrease in T1 and T2. The T1 and T2 values were in the same range for the first two age groups (age 1-10 years and age 21-40 years) and became slightly greater for the older female patients (age 51 years and older) than for the older males. This could be due to the loss of bone and mineral content, which is more rapid and significant for women. These normal T1 and T2 values may provide a baseline for future evaluation of diseases involving the lumbar spine.

Adolescent↗
PubMed1984

The complete amino acid sequence of the major alpha subunit of the lectin from the seeds of Dioclea grandiflora (Mart).

The complete amino acid sequence of the major alpha subunit of the lectin from seeds of Dioclea grandiflora was determined. The sequence was deduced from analysis of peptides derived from the native alpha subunit by digestion with trypsin, chymotrypsin, the Staphylococcus aureus V8 protease, and pepsin; and from larger peptides produced by digestion of the citraconylated protein with trypsin. The alpha subunit consists of a single polypeptide chain of 237 amino acids which differs from the sequence of concanavalin in 53 positions. Significant levels of heterogeneity were observed in five positions in the sequence.

Amino Acid Sequence↗
PubMed1984

The amino acid sequences of the alpha 1 and alpha 2 subunits of the isolectins from seeds of Lathyrus ochrus (L) DC.

The complete amino acid sequences of the alpha 1 and alpha 2 subunits of the isolectins (LoL I and LoL II) from seeds of Lathyrus ochrus were determined by analysis of peptides derived from the proteins by digestion with trypsin, chymotrypsin and the S. aureus V8 protease. Both subunits consisted of single polypeptide chains of 53 amino acids, which differed from one another in only 4 positions near their C-termini, and exhibited high homology to the light (alpha) chains of the lectins from Lathyrus sativus, L. odoratus and a number of other legume seeds.

Amino Acid Sequence↗
PubMed1984

Proteoglycan distribution in rat aortic wall following indwelling catheter injury.

The morphologic response of the aortic wall of the normal fed rat to intimal injury by an indwelling catheter in place for 3 weeks was examined at the time of removal of the catheter and 4, 8, and 26 weeks later. Changes in the concentration of glycosaminoglycan were assayed morphometrically in ruthenium red-stained sections examined by transmission electron microscopy. Two types of ruthenium red-positive granules were identified in the intercellular matrix; large (greater than 20 nm), containing chondroitin sulphate and small (less than 20 nm) containing heparan sulphate. Endothelial denudation and some thrombus seen at the time of removal of the catheter, was associated with a decrease in the concentrations of both types of granules in the subendothelial space compared to normal rats. At later time intervals there was neointimal thickening containing no lipid, and occasional small areas of lipid accumulation. Compared to normal rats there was no significant change in granule concentration in the subendothelial space at any time interval. There was a slight increase in the concentration of large granules of the deep neointima at the time of removal of the catheter and after 4 weeks. In lipid-containing areas there was a highly significant increase in large granule concentrations compared to normal or to intimal thickening without lipid. The observations support the possibility that lipid accumulation is related to an increase in glycosaminoglycan concentration.

Animals↗
PubMed1984

Cloning and sequence analysis of cDNA for rat spleen thymosin beta 4.

Molecular cloning of a cDNA has established the sequence of the translated portion of the mRNA for rat spleen thymosin beta 4. The presence of a methionyl initiator codon immediately preceding the codon for the first seryl residue of mature thymosin beta 4 is consistent with previous results indicating the absence of a signal peptide in the product translated in vitro from rat spleen mRNA. The cDNA sequence analysis also established the presence of two terminator codons immediately following the codon for the COOH-terminal seryl residue. Thymosin beta 4 is thus synthesized as a 5100-dalton peptide containing 44 amino acid residues. Removal of the initiator methionyl residue and acetylation of the NH2-terminal serine residue would yield mature thymosin beta 4 containing 43 amino acids. The absence of a signal peptide makes it unlikely that thymosin beta 4 is a secreted peptide.

Amino Acid Sequence↗