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Biomedical subjects

N L Jones

Publications and source records attributed to N L Jones.

At least 55 records · Page 3Linked to original sources
PubMed1997

Enhanced pulmonary and active skeletal muscle gas exchange during intense exercise after sprint training in men.

1. This study investigated the effects of 7 weeks of sprint training on gas exchange across the lungs and active skeletal muscle during and following maximal cycling exercise in eight healthy males. 2. Pulmonary oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured before and after training during incremental exercise (n = 8) and during and in recovery from a maximal 30 s sprint exercise bout by breath-by-breath analysis (n = 6). To determine gas exchange by the exercising leg muscles, brachial arterial and femoral venous blood O2 and CO2 contents and lactate concentration were measured at rest, during the final 10 s of exercise and during 10 min of recovery. 3. Training increased (P < 0.05) the maximal incremental exercise values of ventilation (VE, by 15.7 +/- 7.1%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 15.0 +/- 4.2%). Sprint exercise peak power (3.9 +/- 1.0% increase) and cumulative 30 s work (11.7 +/- 2.8% increase) were increased and fatigue index was reduced (by -9.2 +/- 1.5%) after training (P < 0.05). The highest VE, VCO2 and VO2 values attained during sprint exercise were not significantly changed after training, but a significant (P < 0.05) training effect indicated increased VE (by 19.2 +/- 7.9%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 12.7 +/- 6.5%), primarily reflecting elevated post-exercise values after training. 4. Arterial O2 and CO2 contents were lower after training, by respective mean differences of 3.4 and 21.9 ml l-1 (P < 0.05), whereas the arteriovenous O2 and CO2 content differences and the respiratory exchange ratio across the leg were unchanged by training. 5. Arterial whole blood lactate concentration and the net lactate release by exercising muscle were unchanged by training. 6. The greater peak pulmonary VO2 and VCO2 with sprint exercise, the increased maximal incremental values, unchanged arterial blood lactate concentration and greater sprint performance all point strongly towards enhanced gas exchange across the lungs and in active muscles after sprint training. Enhanced aerobic metabolism after sprint training may contribute to reduced fatigability during maximal exercise, whilst greater pulmonary CO2 output may improve acid-base control after training.

Adult↗
PubMed1997

Capsaicin as an inhibitor of the growth of the gastric pathogen Helicobacter pylori.

Capsaicin, the active ingredient in chili, has been implicated as both a cytoprotective and a detrimental agent to the gastric mucosa. The effect of capsaicin on Helicobacter pylori has not been investigated previously. Therefore, we performed in vitro time- and concentration-dependent studies to examine the growth of H. pylori in the presence of capsaicin. Capsaicin specifically inhibited growth of H. pylori dose-dependently at concentrations greater than 10 micrograms ml-1 (P < 0.05) but did not inhibit the growth of a human fecal commensal Escherichia coli strain. Bactericidal activity was observed within 4 h. Capsaicin continued to exhibit bactericidal activity when incubated at pH values as low as 5.4. Ingestion of chili, therefore, could have a protective effect against H. pylori-associated gastroduodenal disease. This effect deserves further study in animal models.

Capsaicin↗
PubMed1997

Effect of progressive incremental exercise and beta-adrenergic blockade on erythrocyte ion concentrations.

Ion concentrations in whole blood, plasma, and erythrocytes from arterialized venous blood were examined in eight healthy males performing incremental exercise tests to fatigue on an electrically braked cycle ergometer. Exercise was performed during control and low dose (LD) and high dose (HD) of propranolol (beta-blockade). The LD and HD resulted in a significant decrease in peak heart rate compared with control, while peak oxygen uptake during HD was significantly less than either control or LD. Plasma potassium concentration ([K+]) increased significantly during exercise for control, LD, and HD, while LD and HD plasma [K+] were both significantly greater than control. Erythrocyte [K+] increased significantly for control to 119.2 +/- 1.3 mmol/L, for LD to 116.9 +/- 2.0 mmol/L, and for HD to 117.7 +/- 1.2 mmol/L. Plasma lactate concentration ([Lac-]) increased significantly during exercise for control, LD, and HD. Erythrocyte [Lac-] increased significantly for control to 6.4 +/- 0.8 mmol/L, for LD to 6.4 +/- 0.6 mmol/L, and for HD to 5.0 +/- 0.5 mmol/L, with HD [Lac-] less than either control or LD. beta-Blockade did not significantly alter the percent change in mean corpuscular volume (% delta MCV) during exercise. The results indicate that incremental exercise produces an increase in erythrocyte [Lac-] and [K+]. Although beta-blockade increased plasma [K+] at peak exercise, there was no alteration in erythrocyte [K+] response. The treatment did not impair the ability of the erythrocyte to maintain MCV.

Adrenergic beta-Antagonists↗
PubMed1997

Evidence for prolonged cell-surface contact of acetyl-LDL before entry into macrophages.

Acetyl-LDL stimulates acyl-CoA:cholesterol acyltransferase (ACAT) much more effectively than LDL in mouse peritoneal macrophages. Previous work with another potent ACAT stimulator, beta-VLDL, suggested that atherogenic lipoproteins may use internalization pathways distinct from that of LDL. Brief incubation of fluorescently labeled acetyl-LDL and LDL followed by a short chase period without lipoproteins was used to compare endocytic pathways. LDL was delivered rapidly to perinuclear vesicles, corresponding to late endosomes and lysosomes. A substantial fraction (> 40%) of acetyl-LDL was initially retained in the cell periphery, while the rest was rapidly delivered to late endosomes that also contained LDL. Fluorescence of peripheral 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI)-acetyl-LDL could be quenched by TNBS, indicating accessibility of the peripheral acetyl-LDL to the extracellular space. Quantification of fluorescence intensities demonstrated that > 40% of the cell-associated DiI-acetyl-LDL but only about 10% of DiI-LDL fluorescence was quenchable by TNBS after a 3-minute chase. Fucoidin can efficiently displace DiI-acetyl-LDL bound to cells at 0 degree C. DiI-acetyl-LDL in the TNBS-quenchable peripheral compartments, however, was resistant to fucoidin. Electron microscopy of colloidal gold-acetyl-LDL showed that acetyl-LDL on the cell surface was often associated with microvilli or ruffles. After clearance from the surface, the peripheral acetyl-LDL was also delivered to the late endosomes and lysosomes. These results indicate that a substantial portion of acetyl-LDL enters macrophages through a pathway that initially differs from that of LDL. This pathway involves a prolonged retention of acetyl-LDL on the plasma membrane. This surface retention may affect ACAT activation in macrophages.

Animals↗
PubMed1997

Simultaneous labeling of lipoprotein intracellular trafficking in pigeon monocyte-derived macrophages.

Macrophage foam cell formation resulting from the accumulation of cholesterol and cholesterol esters derived from plasma lipoproteins is important for progression of atherosclerosis. Hypothetically, intracellular processing of lipoproteins that stimulate foam cell formation differs from processing of lipoproteins that do not. To test this, we examined simultaneous subcellular trafficking of lipoproteins in pigeon monocyte-derived macrophages. Pigeon beta-very-low-density lipoprotein (beta-VLDL), low-density lipoprotein (LDL), and acetylated low-density lipoprotein (Ac-LDL), differentially labeled with colloidal gold, were added in pairs to cells at 4 degrees C for 2 hours before uptake at 18 degrees C, 22 degrees C, or 37 degrees C for either 30 minutes or 2 hours. The colloidal gold distribution and percent co-labeling as observed by transmission electron microscopy were determined for organelles of the endocytic pathway. Incubations at 18 degrees C and 22 degrees C blocked lipoprotein trafficking to lysosomes. Incubation at 18 degrees C increased the percent distribution of lipoproteins in the endocytic pathway up to the early cisternal endosomes. Incubations at 22 degrees C resulted in a greater distribution of lipoproteins in the spherical late endosomes and late endosomal-prelysosomal tubular reticular compartment. The distribution in the endocytic pathway was a factor of time and temperature rather than lipoprotein type. The percentage of co-labeling of organelles for the three pairs of lipoproteins examined, Ac-LDL plus beta-VLDL, LDL plus beta-VLDL, and LDL plus Ac-LDL, was similar. Fewer noncoated and clathrin-coated pits and vesicles were co-labeled (average of 6%, maximum of 17%) than the rest of the endocytic pathway, early cisternal endosomes, spherical late endosomes, late endosomal-prelysosomal tubuloreticular compartment, and spherical lysosomes (average of 36%, maximum of 47%). The 36% of co-labeled later endocytic organelles contained an average of 58% of the labeled lipoproteins. This study suggests differential sorting does not occur for high-affinity uptake of lipoproteins.

Animals↗
PubMed1997

Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection.

Childhood acquisition of Helicobacter pylori is a critical risk factor for gastric cancer. Since tumorigenesis involves deregulation of proliferation and apoptosis, we examined gastric epithelial cell proliferation and apoptosis in H. pylori-infected children. Apoptosis and proliferation of gastric antral epithelial cells in biopsy specimens from patients with H. pylori-induced gastritis, secondary gastritis, and noninflamed controls were compared. p53 protein expression was examined immunohistochemically. Apoptotic cells were identified in the surface epithelium in each group. The apoptotic index was higher in specimens from patients with H. pylori gastritis (120 +/- 10) than secondary gastritis (50 +/- 10) and noninflamed controls (40 +/- 10, analysis of variance P < 0.005). Apoptosis decreased following H. pylori eradication and resolution of gastritis (P < 0.02). An expanded proliferative compartment was identified in H. pylori-induced gastritis (32.4 +/- 3.5; proliferative labeling index +/- SE) compared with secondary gastritis (18.9 +/- 2.8) and noninflamed controls (13.7 +/- 3.1, analysis of variance P < 0.01). The accelerated cell turnover was associated with p53 overexpression (analysis of variance P < 0.005). Accumulation of p53 was not associated with expression of the cyclin-dependent kinase inhibitor p21. The occurrence of altered cell turnover early in the natural history of chronic infection provides an explanation for the increased risk of gastric cancer development associated with childhood acquisition of infection.

Adolescent↗
PubMed1996

A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

Alleles↗
PubMed1996

The nursing triage process: a video review and a proposed audit tool.

OBJECTIVE: To review the activity of the nurse triage process. SETTING: The triage room for adults attending the accident and emergency department of the Cardiff Royal Infirmary. METHODS: 226 triage processes were videotaped over 31 h during July 1994. Activities were subsequently analysed using a specially designed chart. RESULTS: Areas for improvement in staff communication skills and patient privacy were identified. CONCLUSIONS: The use of video in the triage room allows assessment of the triage process and is a valuable aid to training. Additionally, a potential visual audit tool has been identified.

Adult↗
PubMed1996

Quantification of intensity of sensations during muscular work by normal subjects.

Eleven subjects performed a series of 30-s work bouts on a cycle ergometer at power outputs ranging from 20-120% of the work capacity (Wcap) achieved during an incremental cycle to exhaustion and estimated the intensity of several sensations (leg effort, muscle tension, muscle discomfort, muscle pain, and breathing discomfort) by using Borg's category-ratio scale (range 0-10 units). Leg effort was perceived as "just noticeable" at 31 +/- 15% Wcap, muscle tension was just noticeable at 31 +/- 16% Wcap, muscle discomfort was just noticeable at 47 +/- 21% Wcap, breathing discomfort was just noticeable at 52 +/- 19% Wcap, and muscle pain was just noticeable at 58 +/- 33% Wcap. The intensity of all sensations increased in a positively accelerating manner with increases in power output (P < 0.001). Above 60% Wcap, the intensity of leg effort and muscle tension exceeded the intensity of muscle pain (P < 0.01), and above 100% Wcap the intensity of muscle discomfort also exceeded the intensity of muscle pain (P < 0.01). At 120% Wcap, leg effort, muscle tension, and muscle discomfort were rated between "severe" and "very severe" (6.1 +/- 2.2, 6.4 +/- 2.0, and 5.6 +/- 2.1 Borg units, respectively), whereas muscle pain and breathing discomfort were rated between "moderate" and "somewhat severe" (3.6 +/- 2.1 and 3.3 +/- 1.9 Borg units, respectively). These results suggest that subjects have a perception of muscle pain during muscular work that is distinct from perceptions of leg effort, muscle tension, and muscle discomfort.

Adult↗
PubMed1996

Symptom intensity and subjective limitation to exercise in patients with cardiorespiratory disorders.

The aim of the study was to compare (1) the intensity of leg effort and dyspnea during exercise and (2) subjective limitations to performance in normal subjects, patients receiving medication for cardiac disorders, patients with pulmonary impairment, patients with pulmonary impairment who were also receiving cardiac medications, patients experiencing chest pain during exercise, and patients who had a reduced exercise capacity but did not have pulmonary impairment and were not receiving cardiac medication. Five hundred seventy-eight subjects rated the intensity of leg effort, discomfort with breathing (dyspnea), and chest pain every minute (Borg scale) during an incremental exercise task (100 kpm/min each minute) to maximum work capacity on a cycle ergometer and following exercise indicated their subjective limitation by completing a simple questionnaire. Leg effort and dyspnea increased systematically with power output in a positively accelerating manner in all groups; both symptoms were significantly more intense in the impaired groups compared with the normal group at submaximal power outputs. In all groups, there was a significant relationship between symptom intensity at submaximal power outputs and the maximal power output achieved. Leg discomfort in combination with breathing discomfort was the predominant subjective limitation in all groups; chest pain in combination with leg and breathing discomfort was the major subjective limitation in individuals with angina. Activation of the sensory systems during exercise is accompanied by a perception of discomfort associated with the peripheral exercising muscles and discomfort with breathing; both discomfort associated with the exercising muscles and discomfort associated with breathing contribute to exercise limitation to a large degree in normal subjects and patients with cardiorespiratory diseases.

Angina Pectoris↗
PubMed1995

Tissue factor expression during coculture of endothelial cells and monocytes.

The role of monocytes as initiators of coagulation through the expression of tissue factor has been well documented in vitro, and the relationship of monocyte tissue factor to the thrombotic complications of atherosclerosis has been suggested. Tissue factor antigen has been identified in the plasma membranes of monocytes adherent to the vascular endothelium overlying atherosclerotic plaques and the presence of tissue factor in adherent mononuclear cells correlates with the polymerization of fibrin at these same sites. To further understand the relationship of cellular adhesion to tissue factor expression, human monocytes were cocultured for periods ranging from 30 min to 24 hr with endothelial cells isolated from human umbilical veins (HUVEC). Tissue factor antigen, as assayed by both ELISA and immunogold electron microscopy, was minimal on either monocytes or HUVEC maintained in homogeneous cultures or on the cells when cocultured for 1 hr or less. This was true whether the HUVEC were in a native state or if they had been stimulated with interleukin-1 (IL-1 beta) or lipopolysaccharide (LPS) prior to monocyte adhesion. Typically, less than 13% of the cells in short-term cocultures were positively labeled through anti-tissue factor immunogold microscopy. The level of tissue factor, however, was increased 3-fold above baseline when monocytes were cocultured with unstimulated HUVEC for 4 hr, and it was more than double this if the HUVEC had been exposed to IL-1 beta or LPS (7-fold increase). By 24 hr, the expression of tissue factor antigen was nearly 50-fold higher in cocultures involving stimulated HUVEC, and at later times greater than 70% of the cells were labeled with immunogold. Through the use of quantitative immunogold electron microscopy, the increase in tissue factor was most pronounced on monocytes which had three times greater increase in tissue factor than HUVEC in the same cultures. These studies document the stimulation of tissue factor expression by monocytes upon coculture with endothelial cells, and the data document an enhancement of this coculture effect upon HUVEC stimulation with cytokines. These observations have relevance to atherosclerotic disease by suggesting that interaction of monocytes with dysfunctional endothelial cells overlying atherosclerotic plaques would be sufficient to induce tissue factor and by so doing predispose to localized thrombotic events.

Cell Adhesion↗
PubMed1995

The LDL receptor and LRP are receptors for beta VLDL on pigeon monocyte-derived macrophages.

Receptors for the lipoprotein, beta very low density lipoprotein (beta VLDL), have been identified through the binding of beta VLDL-gold conjugates on two ligand-induced regions of pigeon monocyte-derived macrophages. These regions were microvilli/retraction fibers and membrane ruffles. The present study investigated the location and identity of beta VLDL receptors using an antiserum directed against the epidermal growth factor (EGF) precursor region of the human low density lipoprotein (LDL) receptor. The anti-receptor serum recognized two membrane proteins from pigeon monocyte-derived macrophages, a 116 kDa (LDL receptor) protein and a 600 kDa (low density lipoprotein receptor-related protein; LRP) protein. Ligand blot analysis demonstrated that pigeon beta VLDL bound to both the LDL receptor and LRP. Immuno-gold electron microscopy using the anti-receptor serum resulted in immunoglobulin localization on the same two ligand-induced regions, microvilli/retraction fibers and membrane ruffles, to which the ligand had bound. Furthermore, simultaneous immunogold localization of the lipoprotein receptor antigens and beta VLDL-gold (ligand) binding substantiated co-localization of the receptor antigens and beta VLDL on the ligand-induced regions. Cross-competition studies with the anti-receptor serum and beta VLDL-gold conjugate documented that increasing concentration of the anti-receptor serum resulted in 70% inhibition of beta VLDL-gold conjugate binding. These data suggest that pigeon monocyte-derived macrophages utilize both the LDL receptor and LRP as receptors for pigeon beta VLDL.

Amino Acid Sequence↗
PubMed1995

Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment.

Cross-linking of surface receptors results in altered receptor trafficking in the endocytic system. To better understand the cellular and molecular mechanisms by which receptor cross-linking affects the intracellular trafficking of both ligand and receptor, we studied the intracellular trafficking of the transferrin receptor (TfR) bound to multivalent-transferrin (Tf10) which was prepared by chemical cross-linking of transferrin (Tf). Tf10 was internalized about two times slower than Tf and was retained four times longer than Tf, without being degraded in CHO cells. The intracellular localization of Tf10 was investigated using fluorescence and electron microscopy. Tf10 was not delivered to the lysosomal pathway followed by low density lipoprotein but remained accessible to Tf in the pericentriolar endocytic recycling compartment for at least 60 min. The retained Tf10 was TfR-associated as demonstrated by a reduction in surface TfR number when cells were incubated with Tf10. The presence of Tf10 within the recycling compartment did not affect trafficking of subsequently endocytosed Tf. Retention of Tf10 within the recycling compartment did not require the cytoplasmic domain of the TfR since Tf10 exited cells with the same rate when bound to the wild-type TfR or a mutated receptor with only four amino acids in the cytoplasmic tail. Thus, cross-linking of surface receptors by a multivalent ligand acts as a lumenal retention signal within the recycling compartment. The data presented here show that the recycling compartment labeled by Tf10 is a long-lived organelle along the early endosome recycling pathway that remains fusion accessible to subsequently endocytosed Tf.

Animals↗