Biomedical subjects
Publications and source records attributed to R S Taylor.
The psychological well being of the patient and the patient's entire family is critically important to successful rehabilitation of individuals with multiple sclerosis (MS). This article deals with the psychotherapeutic management and problems faced by the person with MS, including fatigue, chronic pain, stressful life events, and cognitive defects.
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Telomeres shorten with successive cell divisions in normal somatic cells, while telomerase plays an important role in maintaining their lengths. Although telomerase activity was originally described as being expressed exclusively by immortal cells and germline cells, a recently developed PCR-based technique (telomeric repeat amplification protocol (TRAP)) has revealed that normal peripheral blood leukocytes also exhibit this activity following mitogenic stimulation. In this study, we examined mechanisms by which mitogenic stimuli up-regulated telomerase activity in T cells. Splenic T cells freshly isolated from BALB/c mice exhibited only negligible telomerase activity. When stimulated with Con A or immobilized anti-CD3 mAb at 10 microg/ml, they acquired an increased telomerase activity and maximal proliferation. By contrast, T cells treated with a much lower concentration (0.03 microg/ml) of anti-CD3 mAb required exogenous IL-2 for telomerase activation and proliferation. Likewise, adult thymocytes treated with anti-CD3 mAb exhibited telomerase activation and proliferation only in the presence of exogenous IL-2, IL-4, IL-7, or IL-15. Furthermore, IL-2 alone was sufficient for telomerase activation in Con A blasts. These results illustrate a pathway through which cytokine receptors transduce telomerase activation signals in T cells. Although telomerase activation was concomitant with cell growth in normal T cells, we have identified T cell lines that showed discrepancies; the CTLL-2 line showed constitutive telomerase activity regardless of cell proliferative state, whereas the 7-17 line proliferated vigorously in response to IL-2, IL-7, or IL-15, without detectable telomerase activity. Thus, telomerase activity, which is ordinarily associated with proliferation in normal T cells, is not necessarily required or sufficient for cell growth.
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The discovery of additional endogenous Golgi proteins will lead to significant new insights into Golgi function. To this end, stacked Golgi fractions (SGFs) were isolated from rat liver before (CTL SGF) and after molecules in transit through the Golgi were cleared by pre-treatment with cycloheximide (CHX SGF). Electron microscopic (EM) morphometric and biochemical analyses showed that the in vivo stacked morphology is retained, that > 90% of the elements can be positively identified as Golgi stacks and cisternae, and that transmembrane protein markers of the Golgi complex are enriched 300- to 800-fold over starting postnuclear supernatant (PNS). High-resolution two-dimensional (2-D) gel mapping has been carried out on the CTL PNS, CTL SII (an intermediate fraction), CTL SGF, CHX SGF, CHX SGF - high pH supernatant, and CHX SGF - high pH pellet. This analysis, coupled with immunoblotting and alignment of the 2-D gels with master gels, has allowed the identification of a number of known proteins and the preliminary characterization of the most abundant 173 Golgi-specific proteins. These 173 proteins have been placed into three categories: cargo, cytosolic Golgi-associated, and resident Golgi proteins. These categories are tentative and will be modified as more data are acquired from immunoblotting and protein sequencing.
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OBJECTIVES: To investigate the predictive value of laser Doppler fluxmetry and transcutaneous oximetry in 41 patients undergoing technically successful revascularisation for severe leg ischaemia. DESIGN: Toe and ankle systolic arterial pressures, transcutaneous oxygen tension (tcpO2), and stressed laser Doppler fluxmetry at the foot (time to peak laser Doppler flux following 2 min arterial occlusion, tp LDF, and the response of LDF to raising the leg 40 cm, the elevated:supine LDF ratio) were measured before revascularisation. Six months later these measurements were compared in those patients who were clinically improved, and those who still had symptoms of severe ischaemia or had lost their limb. SETTING: Vascular Laboratory, St. George's Hospital, London SW17, U.K. RESULTS: Six months following revascularisation 30 (73%) of the 41 patients had partial or complete symptomatic relief. Six (15%) had undergone major amputation and five (12%) still had symptoms of severe ischaemia. Before intervention toe and ankle systolic pressures were similar in the 30 who were improved and the 11 who had lost, or were still at risk of losing, their leg. Pre-revascularisation tcpO2 was significantly lower (18.3 mm Hg vs 33.5 mm Hg; p < 0.05) and tp LDF significantly longer (140 s vs 92 s; P < 0.05) in the 11 patients who were not clinically improved at 6 months. Whilst pre-revascularisation toe and ankle pressures below 30 mm Hg and 50 mm Hg respectively identified only 55% of those patients who were not improved 6 months later, a tp LDF in excess of 100 s identified 82% (p < 0.05) and was noted in five of the six amputees. CONCLUSION: Microcirculatory assessments performed in patients with limb-threatening ischaemia are likely to be more deranged in those patients who suffer clinical failure or amputation despite an apparently successful revascularisation procedure.
OBJECTIVES: To determine whether preoperative hypercoagulable abnormalities are independent risk-factors for the failure of arterial reconstruction in leg ischaemia. METHODS: Sixty consecutive patients were studied before, and for 1 year following, elective peripheral revascularisation. Antithrombin III, protein C and protein S levels, and tests for lupus anticoagulant were performed preoperatively, and then repeated on the first and third postoperative days and after 1 and 6 months. Heparin-associated thrombocytopenia was also investigated if there was a postoperative fall in platelet count greater than 100 x 10(9)/l. RESULTS: Forty-six (77%) procedures were performed for critical ischaemia and 15 (25%) involved infrapopliteal reconstruction. The nature of surgery or accepted risk factors for occlusion were comparable between the 40 (67%) patients with patent reconstructions at 1 year and the 20 (33%) who had suffered failure. Preoperative hypercoagulable abnormalities were detected in 21 (35%) patients, with a three times greater incidence in those whose reconstructions failed (65% vs. 20%, p < 0.01), and in 11 of 12 patients suffering early (within 1 month) occlusion. The lupus anticoagulant was more frequently detected when prosthetic grafts were already present (p < 0.05) and carried a positive predictive value for reocclusion of 67% (p < 0.01). All three postoperative deaths occurred in patients with low protein S levels before surgery. CONCLUSIONS: Hypercoagulable abnormalities are common prior to arterial revascularisation and are independently associated with subsequent failure.
OBJECTIVES: To investigate the association between changes in the ankle-brachial pressure index (ABPI) and simultaneous changes in calf volume following percutaneous transluminal angioplasty (PTA) for chronic leg ischaemia. MATERIALS: A total of 37 consecutive patients undergoing PTA for chronic leg ischaemia. METHODS: Bilateral calf volume, as calculated from girth measurements, and ABPI were determined before PTA, and repeated 24 h and 1 week following the procedure. Changes in the calf volume of the treated leg, both absolute and relative to changes of the non-treated leg, were then related to simultaneous changes in ABPI. RESULTS: Twenty-four hours following PTA, the calf volumes of both legs were decreased, although the ratio of the treated: untreated leg had increased by 2.4% (CI + 1.1-3.7, p < 0.01). After 1 week there was no difference in calf volume. These patterns were observed both in the 21 patients who had ABPI improvement of 0.15 or more 1 week following PTA, and in the 16 whose ABPI was unchanged. In the former group ABPI improved by a further 0.13 between 24 h and 1 week following PTA (p < 0.05), but there was no relationship between this delayed ABPI increase and simultaneous changes in calf volume. CONCLUSIONS: We did not detect any significant calf swelling following PTA. Furthermore, changes in ABPI were not related to changes in calf volume.
OBJECTIVES: To document changes in toe-brachial pressure indices (TBPI) during the 6 months following percutaneous transluminal angioplasty (PTA) and relate these changes to restenosis. Furthermore, to ascertain the effect of administering a vasodilator, glyceryl trinitrate (GTN), immediately following PTA. DESIGN: Eighty-three technically successful PTA procedures were studied. Fifty-six were for intermittent claudication, 14 for ischaemic rest pain, and 13 for non-healing ulcers. Immediately following balloon dilatation an intra-arterial bolus of either 150 micrograms GTN, with or without a 10 mg GTN patch for 24 h, or a saline placebo was administered. TBPI were measured before and for 6 h after PTA and then at 24 h, 1 week, 1 month and 6 months. At this time, patency at the PTA site was determined by arteriography. RESULTS: There was continuing TBPI improvement over 1 month in patients given saline following PTA. In patients given GTN, peak TBPI was achieved by 1 week, and corresponded with the TBPI observed immediately following GTN administration. Restenosis occurred in 27 (33%) patients, and was significantly more frequent following the procedures for rest pain or ulceration, or where a TBPI increase of more than 0.15 by 1 week was observed. CONCLUSIONS: Haemodynamic changes following PTA continue for at least 1 month, can be modified by GTN administration, and are predictive of subsequent restenosis. Measuring the TBPI increase during the first week following PTA underestimates total improvement, and may give false reassurance with respect to recurrent disease.
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To characterize endogenous molecules and activities of the Golgi complex, proteins in transit were > 99% cleared from rat hepatocytes by using cycloheximide (CHX) treatment. The loss of proteins in transit resulted in condensation of the Golgi cisternae and stacks. Isolation of a stacked Golgi fraction is equally efficient with or without proteins in transit [control (CTL SGF1) and cycloheximide (CHX SGF1)]. Electron microscopy and morphometric analysis showed that > 90% of the elements could be positively identified as Golgi stacks or cisternae. Biochemical analysis showed that the cis-, medial-, trans-, and TGN Golgi markers were enriched over the postnuclear supernatant 200- to 400-fold with and 400- to 700-fold without proteins in transit. To provide information on a mechanism for import of calcium required at the later stages of the secretory pathway, calcium uptake into CTL SGF1 and CHX SGF1 was examined. All calcium uptake into CTL SGF1 was dependent on a thapsigargin-resistant pump not resident to the Golgi complex and a thapsigargin-sensitive pump resident to the Golgi. Experiments using CHX SGF1 showed that the thapsigargin-resistant activity was a plasma membrane calcium ATPase isoform in transit to the plasma membrane and the thapsigargin-sensitive pump was a sarcoplasmic/endoplasmic reticulum calcium ATPase isoform. In vivo both of these calcium ATPases function to maintain millimolar levels of calcium within the Golgi lumen.
Telomerase is a ribonucleoprotein enzyme capable of adding hexanucleotide repeats onto the ends of linear chromosomal DNA. Whereas normal somatic cells with a limited replicative capacity fail to express telomerase activity, most immortal eukaryotic cells do. Cells of renewal tissues (e.g., skin, intestine, blood) require an extensive proliferative capacity. Some cells in such renewal tissues also express telomerase activity, most likely to prevent rapid erosion of their telomeres during cell proliferation. In this study, we measured the levels of telomerase activity in dissected compartments of the human hair follicle: hair shaft, gland-containing fragment, upper intermediate fragment (where it is thought undifferentiated stem cells reside), lower intermediate fragment, and in the bulb-containing fragment (an area with high mitotic activity containing a more differentiated pool of keratinocytes). In anagen follicles, high levels of telomerase activity were found almost exclusively in the bulb-containing fragment of the follicles, with low levels of telomerase in the bulge area (intermediate fragments) and gland-containing fragment. In comparison, catagen follicles had low levels of telomerase activity in the bulb-containing fragments as well as in other compartments. Such observations indicate that, in anagen hair follicles, the fragments containing cells actively dividing (e.g., transient amplifying cells) express telomerase activity, whereas fragments containing cells with low mitotic activity, for example, quiescent stem cells, express low levels of telomerase activity.
BACKGROUND AND PURPOSE: There has been concern about carotid percutaneous transluminal angioplasty (PTA) carrying a greater risk of cerebral ischemia than carotid endarterectomy. We set out to compare cerebral hemodynamics and microembolization during carotid PTA and CEA. METHODS: We used transcranial Doppler to monitor the middle cerebral artery of 28 patients undergoing carotid PTA (n = 14) or carotid endarterectomy (CEA) with a shunt (n = 14). Each period during which the internal carotid artery was occluded by PTA balloon or by clamp when the shunt was not in place was timed. Individual periods were summated to give a total occlusion time. Ischemic time was defined as the period for which mean middle cerebral artery velocity fell to a third or less of baseline. Microembolic signals were counted during each procedure. RESULTS: CEA resulted in significantly longer individual and total occlusion time than PTA (mean individual occlusion time, seconds), CEA, 168 +/- 51; PTA, 20 +/- 7; P < .001; mean total occlusion time; CEA, 337 +/- 70; PTA, 26 +/- 10; P < .001. Ischemic time was also significantly longer during CEA than during PTA (CEA, 165 +/- 40; PTA, 17 +/- 5; P = .001). There were significantly more microembolic signals during PTA than during CEA (mean number of microembolic signals during CEA, 52 +/- 64; during PTA, 202 +/- 119; P = .001). There was no correlation between any of the parameters measured and periprocedural stroke, which occurred in one patient in each group. CONCLUSION: PTA results in less hemodynamic ischemia but more cerebral microembolism than CEA. In this small series, however, it is not possible to comment on the relations between ischemic time, microembolism, and stroke.
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In a screening of plants used traditionally in Nepal to treat diseases that could be caused by viruses, methanol extracts from 21 species were assayed for activity against three mammalian viruses: herpes simplex virus, Sindbis virus and poliovirus. Assays were performed in UV-A or visible light, as well as dark. Individual species of Hypericum, Lygodium, and Maesa exhibited impressive antiviral activities, although their selective effects on the three viruses suggested that the antiviral ingredients were different in each extract. In addition, many of the other extracts showed partial inactivation of one or more test viruses.
Overexpression of dominant negative subunits previously has been shown to affect the whole cell delayed-rectifier potassium current (Ikv) in Xenopus spinal neurons. Here, we show that effects of overexpression of wild-type and dominant negative Kv1 channels are evident at the single channel level. The goal of these studies was to match molecular species of Kv subunits to specific, functionally identified single voltage-dependent potassium channels. In a heterologous system (the Xenopus oocyte), co-expression of wild-type and dominant negative mutant Kv1.1 subunits results in loss of active channels rather than channels of altered conductance. However, in situ overexpression studies are difficult to interpret due to the diversity in the control population of channels. Therefore, identification of endogenous channel populations containing Kv1 subunits is limited. Future work will reduce the endogenous diversity of potassium channels by study of single channels in identified subtypes of neurons.
In an ethnopharmacological screening of selected medicinal plants used in Nepal, methanol extracts from 20 plant species were assayed for activity against eleven strains of bacteria and four strains of fungi. Duplicate assays were conducted with and without exposure to ultraviolet (UV)-A radiation to test for light-activated or light-enhanced activity. Fifteen of the extracts showed activity against bacteria and fourteen showed activity against fungi. Five extracts were active only when exposed to UV-A light, and the antibiotic or antifungal effect of five extracts was enhanced upon exposure to light. Two of the most active extracts were from plants used to treat diarrhoea and dysentery. Bark from both Terminalia alata (Combretaceae) and Mallotus phillppensis (Euphorbiaceae) was active against Gram-positive and Gram-negative bacteria.