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L S Wilkinson

Publications and source records attributed to L S Wilkinson.

At least 73 records · Page 4Linked to original sources
PubMed1991

Detection of human and murine common idiotypes of DNA antibodies in tissues and sera of patients with autoimmune diseases.

The expression in tissue and serum of a panel of murine and human common DNA antibody idiotypes (Ids) (BEG 2, PR 4, F-423, I-402, II-28, IV-228, V-88) has been investigated. The murine V-88 Id was detected in eight out of 10 and the human BEG 2 Id in five out of 10 labial biopsies from patients with Sjögren's syndrome. The murine F-423, I-402 and IV-228 Ids were identified in one out of 10 biopsies. In each case the pattern of staining was similar with staining of the acinar basement membrane and a cell population. Using double-labelling immunohistochemistry this cell population were identified as plasma cells. No staining was seen in four normal labial biopsies. The V-88 Id was detected on the epithelial aspect of the thickened basement membrane in three out of nine renal biopsies from patients with systemic lupus erythematosus (SLE). None of the other Ids (BEG 2, PR4, IV-228, F-423 or I-402) could be detected in renal tissue. None of the Ids were found in skin biopsies from SLE patients. Id V-88 may, like the 16/6 Id to which it is phenotypically related, play a role in the pathogenesis of renal lesions in SLE. The BEG 2 Id could be detected in the serum of patients with rheumatoid arthritis (RA) and active untreated tuberculosis. Ids II-28, V-88 and I-402 were elevated in serum from patients with Sjögren's syndrome and II-28 Id in serum from patients with myositis and RA. None of the Ids were elevated in serum from patients with SLE. Apart from the BEG 2 Id, none of the Ids were elevated in serum from patients with tuberculosis or Gram-negative infections. The presence of murine Ids in human tissue and serum suggests that they are cross-species idiotypes and have been conserved through evolution.

Animals↗
PubMed1991

Conflicting views on the measurement of blood pressure in pregnancy.

Current practice with regard to the technique of blood pressure measurement in pregnancy was assessed by means of a self-completed questionnaire sent to all midwives (116) and obstetricians (11) working in a UK District General Hospital obstetric unit. The response rate was 72% (91 respondents). Over half of the respondents (53%) use the fifth phase diastolic end point (contrary to current recommendations). Of the 75 respondents who had access to a large adult cuff 54 (72%) had used it on 'less than two occasions' over the preceding four weeks. Only 10% (9) of respondents reported that they record blood pressure to the nearest 2 mmHg and 23% (22) reported that they round blood pressure readings to the nearest 10 mmHg. There were diverse views on the interpretation of multiple blood pressure recordings. The conclusion is that compliance with current recommendations on blood pressure measurement technique in pregnancy is poor. There is poor agreement among midwives and obstetricians as to how blood pressure should be recorded in pregnancy.

Blood Pressure Determination↗
PubMed1991

An emerging consensus among clinicians on treating mild hypertension but persistent uncertainty as to how blood pressure should be measured.

In 1986 and 1989 the British Hypertension Society published its recommendations on the techniques for the measurement of blood pressure and the level of pressure requiring drug therapy. In order to assess the impact of these recommendations on clinical practice among non-members of the society, we have conducted a survey using a self-reported questionnaire among 196 hospital-based clinicians, and compared our findings with a similar survey conducted in 1979. The response rate to the 1990 survey was 64% (126 respondents). Over one-third (37%) of respondents reported that they usually record the diastolic blood pressure at the fourth Korotkoff phase (muffling of sounds), 52% reported that they use the fifth phase (disappearance of sounds), and 10% reported that they record both the fourth and fifth phase. They also disagreed considerably on a number of other basic issues, including whether blood pressure should be routinely measured in the sitting or lying position, and whether readings should be taken to the nearest 2, 5 or 10 mmHg. A clear majority of clinicians indicated that they would prescribe antihypertensive drugs if the diastolic blood pressure was consistently over 100 mmHg. This represents a marked shift from the opinions expressed in 1979 and is in line with the British Hypertension Society's recommendations. However, many clinicians still measure blood pressure in a manner contrary to the society's guidelines.

Blood Pressure Determination↗
PubMed1990

Terminal N-acetylglucosamine in chronic synovitis.

The distribution of terminal GlcNAc residues in normal and diseased synovial tissue has been studied using a mouse monoclonal antibody (mAb) which binds to terminal N-acetylglucosamine (GlcNAc). Normal human connective tissue, including synovium, showed no staining for terminal GlcNAc. Normal epithelial tissues, including tonsillar epithelium, skin, small intestinal epithelium and salivary epithelium showed cellular staining. Synovium from patients with definite rheumatoid arthritis showed dense granular staining of macrophages. In addition, synovium from 9 of 12 patients with definite rheumatoid arthritis showed reticular extracellular staining indicating deposition of material bearing terminal GlcNAc in the connective tissue stroma. The extracellular staining was not seen in synovium from patients with osteoarthritis. Extracellular material bearing terminal GlcNAc may act as an inflammatory stimulus in rheumatoid arthritis, either by acting as antigen or by interaction with receptors on macrophage membranes which also recognize GlcNAc on bacterial material, thus triggering biochemical pathways normally occurring in response to the presence of micro-organisms.

Acetylglucosamine↗
PubMed1990

Immunohistological reassessment of accessory cell populations in normal and diseased human synovium.

Accessory cell populations in normal and diseased synovial tissue have been reanalyzed following the development of the monoclonal antibody, EBM11, directed against the CD68 epitope which is expressed by macrophages in all locations so far examined. Previous studies used as a macrophage marker the monoclonal antibody RFD7 which binds only a proportion of (mature) macrophages. Using double indirect immunofluorescence, normal and rheumatoid synovial samples were examined for the presence of cells which bind the putative dendritic cell marker, RFD1, in conjunction with either RFD7 or EBM11. RFD1 positive cells were found in five of 40 normal synovia. Of these cells, 30-35% were negative for RFD7 or EBM11 and, when closely apposed to T-lymphocytes, showed a typical interdigitating morphology. In contrast, all of ten rheumatoid synovia contained RFD1 positive cells; the extent of double labelling with macrophage markers varied with the position of the cells in the tissue. As expected, EBM11 stained a larger number of cells with macrophage morphology than RFD7. The combination of RFD1 and EBM11 appears to be a useful method for identifying interdigitating dendritic cells in connective tissue, these cells being characterized by positive RFD1 and negative EBM11 binding. On this criterion, interdigitating dendritic cells were plentiful in rheumatoid synovium and present, albeit infrequently, in normal synovium.

Antibodies, Monoclonal↗
PubMed1990

Synaptosomal tryptophan uptake and efflux following lesion of central 5-hydroxytryptaminergic neurones.

1. This study attempted to determine whether the activation of the tryptophan carrier in rat forebrain synaptosomes caused by depolarization or by extracellular sodium depletion occurred exclusively in 5-hydroxytryptaminergic nerve endings. 2. Ascending 5-hydroxytryptaminergic neurones were lesioned either electrolytically or by intraventricular administration of 5,7-dihydroxytryptamine. The extent of the lesion was assessed by comparing the uptake of [3H]-5-hydroxytryptamine (5-HT) in lesioned animals and in sham-operated controls. [3H]-5-HT uptake was reduced by 85.9 +/- 1.63% (mean +/- s.e. mean) in animals receiving electrolytic lesions, and by 87.4 +/- 4.51% in those receiving 5,7-dihydroxytryptamine. 3. The uptake of [3H]-tryptophan by synaptosomes from lesioned animals incubated in standard Na(+)-rich media was slightly lower (278.8 +/- 27.3 pmol mg-1 protein min-1) than that observed in sham-operated controls (360.6 +/- 30.3 pmol mg-1 protein min-1). However, uptake in the absence of extracellular Na+ was increased to a similar extent in both the sham-operated (539 +/- 54.5 pmol mg-1 protein min-1) and lesioned animals (507.2 +/- 42.4 pmol mg-1 protein min-1). 4. The efflux of [3H]-tryptophan in response to extracellular Na+ depletion was similar in sham-operated and lesioned animals. Release expressed as a percentage of tissue [3H]-tryptophan released in response to the pulse of Na(+)-free medium was 6.691 +/- 0.585 (n = 4) in sham-operated controls and 8.195 +/- 0.906 in lesioned animals. 5. The efflux of [3H]-tryptophan in response to K+ depolarization was also unchanged in lesioned animals when compared with sham-operated controls. Release, expressed as described above was, in sham-operated controls 3.76 +/- 0.41 (n = 4) and 4.09 +/- 0.30 in lesioned animals. 6. The results of this study show that the tryptophan carrier which is activated by depolarization or by extracellular Na+ depletion is not located exclusively on 5-hydroxytryptaminergic nerve endings. Moreover the contribution made by 5-hydroxytryptaminergic neurones appears to be only minor.

5,7-Dihydroxytryptamine↗
PubMed1989

Structural and functional analysis of raphe neurone implants into denervated rat spinal cord.

The ability of grafts of embryonic raphe cells to the adult rat spinal cord to reverse the morphological, neurochemical and functional deficits caused by ablation of the serotoninergic afferents has been studied. After grafting, extensive reinnervation was observed by 5HT-immunoreactive fibres, many of which appeared to make contacts with host motoneurones. The neurotransmitter complement was apparently normal. There was also a reinstatement of 5HT levels in the denervated cord after transplantation, amounting to some 40% of normal at the level of the graft. Similarly, Na+-dependent uptake of [3H]-5HT into P3 fractions was over 40% of that recorded in unlesioned animals. Antidromic stimulation of the ventral roots of the spinal cord was used to assess the degree of motoneurone excitability. The field potential in the ventral horn of grafted animals was increased by electrical stimulation of discrete regions along the cord, probably corresponding to the graft loci. It is concluded that serotoninergic neurones transplanted to the denervated spinal cord survive and develop normally, reinnervating the host tissue extensively. Furthermore, the graft/host connections appear to be functionally viable.

Action Potentials↗
PubMed1989

Microvascular distribution in normal human synovium.

The distribution of vessels in normal human synovium has been investigated using frozen sections and staining with Ulex Europaeus lectin by an indirect immunoperoxidase technique. The presence of a vascular net close to the tissue surface was confirmed. Quantitative analysis showed the majority of vessel profiles to be small venules with a peak density 25-100 microns beneath the tissue surface. A smaller number of capillaries was present with a peak density within 25 microns of the tissue surface. It is suggested that important functions of the numerous venules seen in synovium may include the provision of a source of fresh monocytes to replace surface macrophages and provision of nutrients for the surface layer of cells as a whole, and that the density of the vascular net may reflect angiogenic signals from this cell layer.

Anthropometry↗
PubMed1989

Membrane N-acetylglucosamine: expression by cells in rheumatoid synovial fluid, and by pre-cultured monocytes.

After 21-48 h in culture, 2-8% of human peripheral blood monocytes strongly express terminal N-acetylglucosamine (GlcNAc) on their membranes. This can be detected with a monoclonal antibody selected for binding to asialo-agalacto-fetuin, and is eliminated by incubating the cells in pure N-acetylglucosaminidase. Expression of GlcNAc is transient, and can no longer be detected by day 4. These cells are a subset of macrophages since they are positive for non-specific esterase and stained by the monoclonal antibody EBM 11. GlcNAc-positive cells showing double staining with monoclonal antibodies UCHM1 and RFD7 were detected. Their numbers were not influenced by the addition of GM-CSF, IFN-gamma, 1,25-(OH)2 cholecalciferol or indomethacin. Macrophages which give membrane staining for terminal GlcNAc were also found in rheumatoid synovial fluid, and in synovial tissue, though in the peripheral blood their frequency was the same in samples from normal donors and from patients with rheumatoid arthritis. Immunoblots of 24-48-h monocyte cultures or of fresh synovial fluid cells using the anti-GlcNAc monoclonal, show the anticipated agalactosyl IgG heavy chains, and an additional band of 70-80kDa.

Acetylglucosamine↗
PubMed1988

Studies on the mechanism by which tryptophan efflux from isolated synaptosomes is stimulated by depolarization.

1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused synaptosomes was found to be enhanced by K+ depolarization in a Ca2+ and dose-dependent manner. In contrast, [3H]-phenylalanine efflux was only poorly stimulated by depolarization and only by very high concentrations of K+. 3. Tryptophan efflux was also enhanced by decreasing the extracellular Na+ concentration, but this effect was not dependent on extracellular Ca2+. 4. Influx of [3H]-tryptophan into synaptosomes was stimulated by extracellular Na+ removal, but the uptake of [3H]-phenylalanine was unaffected by this procedure. 5. Both the induced influx and efflux of tryptophan observed under these experimental conditions was inhibited by immobilizing the plasma membrane carrier with parachlorophenylalanine. This implied that both the enhanced influx and efflux arose as a consequence of the activation of the membrane tryptophan carrier, the direction of the observed effect being dependent upon the manner in which the experiments were conducted. 6. The relationship between depolarization, the activation of the membrane tryptophan carrier and the significance of this to the in vivo situation is discussed.

Animals↗
PubMed1988

Evidence for excitatory 5-HT2-receptors on rat brainstem neurones.

1. The technique of microiontophoresis was used to investigate the identity of the receptor mediating the excitatory effects of 5-hydroxytryptamine (5-HT) upon neurones in the midline of the medullary brainstem of the rat in vivo. 2. The 5-HT1-like receptor agonists 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) failed to excite the majority of neurones excited by 5-HT. The mobilities of 5-CT and 8-OH-DPAT when tested in vitro were found not to differ significantly from that of 5-HT, suggesting that the lack of effect of these agonists was not due to a lower rate of release from the microelectrodes. 3. The excitatory responses to 5-HT were attenuated by the 5-HT 2-receptor antagonists ketanserin and methysergide when applied microiontophoretically or administered intravenously (0.3 and 1 mg kg-1 respectively). Excitatory responses to glutamate and noradrenaline were not reduced. 4. The 5-HT3-receptor antagonist MDL 72222 failed to attenuate selectively the excitatory response to 5-HT when applied either by microiontophoresis or administered intravenously (1 mg kg-1). 5. Microiontophoretic application of the alpha 1-adrenoceptor antagonist prazosin did not attenuate excitatory responses to either 5-HT or noradrenaline. Intravenously administered prazosin (0.8 mg kg-1) also failed to attenuate excitatory responses to 5-HT, but did block excitatory responses to noradrenaline. 6. These results suggest that 5-HT2-receptors, but not 5-HT1-like receptors, 5-HT3-receptors or alpha 1-adrenoceptors, are involved in the excitatory response of midline medullary neurones to 5-HT.

Action Potentials↗
PubMed1988

Evidence for depressant 5-HT1-like receptors on rat brainstem neurones.

1. The technique of microiontophoresis was used to evaluate the contribution of 5-HT1-like, 5-HT2- and 5-HT3-receptors to the depressant effects of 5-hydroxytryptamine (5-HT) on neurones in the midline of the medullary brainstem of the rat in vivo. 2. Depressant responses to 5-HT were resistant to antagonism by the 5-HT2-receptor antagonist ketanserin and the 5-HT3-receptor antagonist MDL 72222 applied either microiontophoretically or administered systemically. 3. Microiontophoretic or systemic administration of the 5-HT antagonist metergoline, which shows nanomolar affinity for the 5-HT1-binding site, also failed to attenuate the depressant responses to 5-HT. 4. Systemic administration of high doses of methysergide (30-40 mg kg-1) attenuated the depressant responses to 5-HT but did not block depressant responses to GABA or excitatory responses to glutamate. 5. The depressant effects of 5-HT were potently mimicked by the 5-HT1-like receptor agonists 5-carboxamidotryptamine and 8-OH-DPAT. 6. These results indicate that neither 5-HT2-receptors nor 5-HT3-receptors are involved in the depressant effects of 5-HT on midline brainstem neurones. The depressant effects of 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and blockade of the response to 5-HT by high doses of methysergide suggests the involvement of 5-HT1-like receptors. The lack of effect of metergoline, however, indicates that this receptor may be different from any of the 5-HT1 binding sites yet described.

Animals↗
PubMed1986

Acquired immune deficiency syndrome in homosexual men with Hodgkin's disease. Three case reports.

Fatal opportunistic infections developed in three homosexual men with Hodgkin's disease. Widely disseminated Kaposi's sarcoma developed in one, and another had persistent lymphadenopathy with a biopsy specimen showing benign follicular hyperplasia two years before the diagnosis of Hodgkin's disease. Physicians are alerted to the possible association of Hodgkin's disease and the acquired immune deficiency syndrome (AIDS). They are cautioned to consider the diagnosis of Hodgkin's disease in homosexual men with lymphadenopathy and warned of the risk of serious infections in homosexual men receiving therapy for Hodgkin's disease.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Opposite effects of extracellular sodium removal on the uptake of tryptophan into rat cortical slices and synaptosomes.

The removal of extracellular sodium decreased L-tryptophan (L-TRP) uptake into brain slices but increased uptake into synaptosomes. The uptake of 5-hydroxytryptamine (5-HT) was inhibited in both preparations under these conditions. It is suggested that the different effects on L-TRP uptake may be due to differences in cellular composition between the two preparations rather than to any differences in sample handling.

Animals↗
PubMed1984

Mild bleeding disorders: review of 120 patients.

Of 120 patients presenting with mild bleeding disorders, 63 were found to have a definite coagulopathy. The commonest disorders were haemophilia, Christmas disease and von Willebrand's disease (vWd), the latter being predominant. Diagnosis led to prophylactic treatment prior to surgery in 18 patients with prevention of excessive haemorrhage. Three patients who had received blood products developed hepatitis. DDAVP (desamino-cys-1-8-D-arginine vasopressin) is the treatment of choice in suitable mildly affected patients with haemophilia A and vWd. Examination of blood group distribution suggests an excess of group O among patients with bleeding disorders, especially those with vWd.

Adult↗
PubMed1983

Marked lymphocytosis suggesting chronic lymphocytic leukemia in three patients with hyposplenism.

Three patients with hyposplenism of diverse cause are described, in whom marked persistent lymphocytosis suggested the diagnosis of an early phase of chronic lymphocytic leukemia. Absolute lymphocyte counts ranged from 4,900/mm3 to 10,500/mm3. Patient follow-up ranged from 120 months to 294 months. The clinical course and additional test results, including results of lymphocyte surface marker analysis in all three patients and bone marrow biopsy in two, excluded the diagnosis of chronic lymphocytic leukemia. The finding of marked lymphocytosis in the hyposplenic state is emphasized, extending the degree of absolute lymphocytosis previously reported and thereby expanding the differential diagnosis of sustained lymphocytosis. In addition, the normal findings on both bone marrow and surface marker studies, along with the prolonged clinical course, support the contention that this is a benign entity.

Adult↗
PubMed1982

The stimulus-induced release of 5-hydroxytryptamine and tryptophan from superfused rat brain synaptosomes.

The synthesis of 5-hydroxytryptamine (5-HT) from 3H-tryptophan in rat forebrain synaptosomes was studied. Synaptosomes which had been preincubated with 3H-tryptophan were perfused with Krebs solution and the release of tryptophan, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) was determined. K+ depolarization induced a Ca2+ -dependent release of 5-HT and tryptophan but had no effect on 5-HIAA efflux. This finding suggests that the release of tryptophan is unlikely to be a non-specific effect of depolarization.

Animals↗