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Biomedical subjects

A Graham

Publications and source records attributed to A Graham.

At least 127 records · Page 7Linked to original sources
PubMed1996

Human (THP-1) macrophages oxidize LDL by a thiol-dependent mechanism.

The oxidative modification of low-density lipoprotein by macrophages may be an important mechanism in the pathogenesis of atherosclerosis. The human monocytic leukaemic cell line THP-1, when stimulated with phorbol ester, shares many properties with human monocyte-derived macrophages. Oxidation of LDL by these cells was characterised by depletion of alpha-tocopherol, increases in thiobarbituric acid reactive substances and increases in electrophoretic mobility. The LDL particles were also converted to a form which increased accumulation of cholesteryl esters within macrophages. The oxidative mechanism appeared to be dependent upon the presence of thiols in the cellular medium. Oxidation of LDL by THP-1 macrophages, and production of thiols by these cells, were dependent upon the presence of L-cystine in the medium. Furthermore, cellular oxidation of LDL could be partially mimicked by the addition of cysteine to Hams F10 medium. Macrophage-independent oxidation of LDL, mediated by the addition of copper ions, was inhibited by cystine and cysteine in phosphate buffered saline, but not in Hams F10 medium. The glutathione content of THP-1 macrophages was also dependent upon the presence of cysteine or cystine in the medium, but inhibition of glutathione synthesis by buthionine sulfoximine did not prevent the production of thiols or the oxidation of LDL by THP-1 macrophages.

Buthionine Sulfoximine↗
PubMed1996

[Thoracoscopic sympathectomy in the surgical treatment of axillary and palmar hyperhidrosis].

47 patients with axillary palmar hyperhydrosis underwent this surgery. There were 36 women (76.6%) and 11 men (23.4%) among them. The sympathetic trunk has been coagulated on the level between 2d and 4th ribs on both sides. There were no surgical mortality in this group. Nine patients (9.1%) had a pneumothorax, one patient (2.1%) had a subcutaneous emphysema, the other one had pneumonia and one had wound pyosis. In 43 cases the result of the surgery was very good. In 2 cases bilateral relapse and in 2 cases marked compensatory hyperhydrosis were resistered.

Adult↗
PubMed1996

The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo.

The proto-oncogene c-kit encodes the transmembrane tyrosine kinase receptor that has a role in the growth regulation of various cell types including melanocytes. In the present study we have examined the expression of the c-kit protein in the skin of seven patients with vitiligo. Melanocytes positive for c-kit protein were observed in the basal layer in non-lesional skin and the mean number of 25.8 +/- 5.2 (per 200 basal cells) compared with that of 21.8 +/- 3.5 from six control subjects. In perilesional skin there was a reduction in the numbers of c-kit positive melanocytes (6.7 +/- 2.6) and this was especially noticeable in six of the seven patients. Such a reduction was less obvious following staining with MEL-5 and in only two subjects were the numbers of melanocytes below the normal range. This suggests that the reduction in c-kit staining was the result of decreased expression of the protein rather than a loss of melanocytes. No melanocytes, positive for c-kit protein, or after staining with MEL-5, were identified in lesional skin although isolated tyrosinase-positive melanocytes were seen in one subject. There was no apparent change in the numbers of mast cells expressing c-kit protein and the intensity of staining in the dermis even in lesional skin was similar to that in the controls. These results demonstrate that c-kit protein is present on melanocytes in adult human skin and that in perilesional skin of some vitiligo patients there is a reduction in the numbers of melanocytes expressing this receptor. Whether this may contribute to the defective melanocyte growth and/or survival that occurs in vitiligo or whether it is a consequence of melanocyte damage remains to be seen.

Adult↗
PubMed1996

Patterning the cranial neural crest.

The pattern of skeletal elements and musculature in the branchial region of the chick embryo is profoundly influenced by the neural crest which migrates in separate streams. Neural crest emigration from the hindbrain into the branchial arches is discontinuous, and regions of crest production are separated from each other by two regions of crest apoptosis, rhombomeres (r) 3 and 5. Both r3 and r5 produce large numbers of crest cells when they are cultured in isolation; but, when co-cultured with their neighbouring segment neural crest apoptosis is restored. The expression of the signalling molecule Bmp-4 and the gene msx-2 in apoptotic domains of r3 and r5 is also dependent upon neighbour interactions and the addition of recombinant Bmp-4 to explant cultures of r3/r5 upregulates both Bmp-4 and msx-2 expression and restores apoptosis. This interactive mechanism acts to ensure the sculpting of crest outflow into non-mixing streams and, consequently, the fidelity of pattern transfer into the branchial arches.

Animals↗
PubMed1995

Changes in free cholesterol content, measured by filipin fluorescence and flow cytometry, correlate with changes in cholesterol biosynthesis in THP-1 macrophages.

The free cholesterol content of cells can be monitored by the intensity of fluorescence emissions from the polyene antibiotic filipin. In a previous study (Hassall: Cytometry 13:381-388, 1992) using THP-1 macrophages, a decrease in filipin fluorescence in response to increasing concentrations of modified lipoprotein was observed, suggesting a reduction in the free cholesterol content of the cells. In this study, THP-1 macrophages were treated with a number of agents known to modulate cholesterol biosynthesis and cholesterol esterification. Changes in filipin fluorescence emissions were measured by flow cytometry, and correlated with changes in cholesterol biosynthesis measured by incorporation of [14C]acetate into cholesterol. A correlation between decreases in filipin fluorescence and reductions in cholesterol biosynthesis was apparent, even when cholesterol esterification was inhibited. These results suggest that the decreases in filipin fluorescence observed may be due, at least in part, to reduction in cholesterol biosynthesis.

Acetates↗
PubMed1995

Structural requirements for oxidation of low-density lipoprotein by thiols.

Oxidation of low-density lipoprotein (LDL) by macrophages, endothelial cells and smooth muscle cells, may be mediated by production of free thiols in the presence of transition metals. We examined the structural requirements, within a series of cysteinyl derivatives, for oxidation of thiols and of LDL in Hams F10 medium. The primary mechanism by which such thiols mediate oxidation of LDL is largely independent of superoxide production, but strongly correlated with the susceptibility of each thiol to iron-catalysed auto-oxidation. These effects are compared and contrasted with thiol-dependent oxidation of LDL by stimulated human monocytes and macrophages.

Animals↗
PubMed1995

Regulation of lysophosphatidic acid-stimulated tyrosine phosphorylation of mitogen-activated protein kinase by protein kinase C- and pertussis toxin-dependent pathways in the endothelial cell line EAhy 926.

In the endothelial cell line EAhy 926, 1-oleoyl-lysophosphatidic acid (LPA) stimulated the tyrosine phosphorylation of the pp42 isoform of mitogen-activated protein (MAP) kinase. Maximum phosphorylation was observed within 5 min of LPA addition, but the response was sustained for up to 120 min. Re-addition of LPA after 60 min stimulated a further sustained increase in the tyrosine phosphorylation of MAP kinase. In cells pretreated with phorbol 12-myristate 13-acetate (PMA; 24 h) or preincubated with the protein kinase C inhibitor Ro-318220, LPA-induced tyrosine phosphorylation of pp42 MAP kinase was substantially reduced at 2 min but potentiated at 60 min. Ro-318220 in combination with either PMA or pertussis toxin pretreatment abolished the LPA response at all time points, suggesting an involvement of protein kinase C in the pertussis toxin-sensitive part of the pathway. Agents which raised intracellular cyclic AMP levels did not affect the initial phase of LPA-stimulated MAP kinase activation, but abolished the late phase. However, this effect was prevented by Ro-318220, implicating a greater role for protein kinase C than protein kinase A in the regulation of sustained MAP kinase responses. LPA stimulated an increase in the tyrosine phosphorylation of focal adhesion kinase pp125 (pp125FAK) in EAhy 926 cells which was both protein kinase C- and pertussis toxin-independent. These results are discussed in terms of the pathways regulating both MAP kinase and pp125FAK in response to LPA in the EAhy 926 endothelial cells line.

Cell Adhesion Molecules↗
PubMed1995

An animal model for hemolytic disease of the fetus and newborn. I. Alloimmunization techniques.

OBJECTIVE: Our purpose was to establish an animal model for hemolytic disease of the fetus and newborn by developing red blood cell alloimmunization techniques in the rabbit. STUDY DESIGN: Twenty-six nonpregnant New Zealand White or Red does underwent blood typing to identify them as homozygous at the HgA or HgF red blood cell antigen locus. Alloimmunization to incompatible red blood cells was attempted through a series of subcutaneous injections using complete then incomplete Freund's adjuvant. RESULTS: Successful induction of an antibody response occurred in 96% of cases. The median response in FF rabbits was 2560 (range 40 to 10,240), whereas the response in AA does was 2560 (range 320 to 20,480). These responses were not statistically different (p = 0.77). Responses were categorized as poor, moderate, or good. No difference was noted between FF and AA does in distribution of the categories of response (p = 0.53). CONCLUSION: Red blood cell alloantibodies of high titer can be induced successfully in the rabbit.

Animals↗
PubMed1995

An animal model for hemolytic disease of the fetus and newborn. II. Fetal effects in New Zealand rabbits.

OBJECTIVE: The addition of ultrasonography and ultrasonographically directed fetal blood sampling was attempted in an effort to study the fetal effects of red blood cell alloimmunization in a rabbit model. STUDY DESIGN: Nineteen New Zealand does were alloimmunized to incompatible red blood cells. Sensitized does were bred twice, once with a homozygous buck of incompatible blood type and once with a homozygous buck of compatible blood type. Ultrasonographic examinations were performed on days 20 and 27 of gestation (term 28 to 31 days). Fetal blood sampling was undertaken on day 27 of gestation, and hematologic data were compared between compatible and incompatible litters. RESULTS: A total of 41 pregnancies occurred in 19 does. Fetal hemoglobin was higher in the compatible litters (9.7 gm/dl vs 5.8 gm/dl, p < 0.001), whereas no difference could be detected between the respective reticulocyte counts (31.9 vs 36.0/100 red blood cells, p = 0.2). Hydrops fetalis was noted in none of 18 compatible litters versus 12 of 19 incompatible litters (p < 0.01). CONCLUSION: A disease analogous to human hemolytic disease of the newborn can be induced in the rabbit fetus.

Animals↗
PubMed1995

Pharmacological characterization of a new class of nonpeptide neurokinin A antagonists that demonstrate species selectivity.

We examined the pharmacology of ZM253,270 and two representative examples of the pyrrolopyrimidines, a new class of nonpeptide, NK-2 receptor (NK-2R) antagonists. ZM253,270 competitively inhibited [3H]NKA binding to native or cloned NK-2R from hamster urinary bladder (Ki = 2 nM), but was a weaker (48-fold) inhibitor of [3H]NKA binding to cloned human NK-2R. A similar species selectivity was observed with less potent analogs of ZM253,270. The pyrrolopyrimidines demonstrated only marginal inhibition of [3H]SP binding to NK-1R in guinea pig lung membranes (Ki > 2 microM). In hamster trachea, ZM253,270 competitively antagonized the contractile response evoked by neurokinin A (NKA, -logKB = 7.5). In human bronchus, ZM253,270 was about 90-fold less potent as a competitive antagonist of NKA. The data from ligand binding assays in cloned receptors combined with functional receptor assays in airway smooth muscles, demonstrate that the nonpeptide antagonist ZM253,270 is selective for the NK2 receptor species that are prevalent in hamster, compared with those found in human tissues.

Animals↗
PubMed1995

Evolution of regional identity in the vertebrate nervous system.

When and how did the mechanisms controlling regional identity in the vertebrate neural tube arise during evolution? The anatomy and embryology of the major deuterostome phyla (echinoderms, hemichordates, chordates) suggest that a true neural tube with dorsoventral and mediolateral regionalization arose with the chordates. We suggest that this was intimately associated with the origin of the notochord; this leads us to propose a modification of Garstang's century-old scenario for origins of the chordate neural tube. Differences along the rostrocaudal axis are seen in all chordates, but became particularly pronounced with the origin of a brain in craniates. Recent molecular data are starting to give insights into these evolutionary transitions. Here we review how Hox gene expression patterns are giving clues to brain origins and we examine the role of molecular phylogenetics in these analyses. We also ask whether the molecular evolution of genes such as noggin, Brachyury, Sonic hedgehog, Wnt, and En may have played direct or permissive roles in the origins of the neural plate, notochord, floor plate, and brain.

Animals↗
PubMed1995

Subcutaneous jugulofemoral bypass: a simple surgical option for palliation of superior vena cava obstruction.

BACKGROUND: Percutaneous placement of an intraluminal stent is usually a successful intervention for the disabling symptoms of Superior Vena Cava (SVC) obstruction. However, on occasion this may not be feasible and, as malignant disease is responsible for 90% of cases, the morbidity associated with median sternotomy or thoracotomy usually precludes surgical bypass. OBJECTIVE: To achieve good palliation of the symptoms of SVC obstruction by surgical bypass without performing sternotomy or thoracotomy. PATIENTS: Two patients with SVC obstruction secondary to lung cancer and a third after radiochemotherapy for malignant mediastinal teratoma. In all patients intraluminal stenting was considered but was not possible. METHODS: Jugulofemoral bypass was performed using long saphenous vein which was tunnelled subcutaneously from the femoral to the jugular vein. RESULTS: One patient required wound exploration for haemorrhage. Good palliation was achieved in all patients. One patient died 3 months post-operatively from lung cancer and the remaining two are alive without symptoms at 13 months and 6 weeks postoperatively. CONCLUSIONS: Though the majority of patients with SVC obstruction can be treated with non-surgical methods, subcutaneous jugulofemoral bypass may provide good palliation if these are not feasible.

Adult↗