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Biomedical subjects

J F Jones

Publications and source records attributed to J F Jones.

At least 19 recordsLinked to original sources

Information processing in chronic fatigue syndrome: a preliminary investigation of suggestibility.

This study examines the effects of certain types of information processing on the subjective experience of cognitive deficits in persons with chronic fatigue syndrome (CFS). Two groups of participants, persons with CFS and a group of healthy controls, were administered a symptom inventory and measures of intellectual functioning, memory, automatic processing, and suggestibility. The groups differed significantly on number and severity of reported symptoms and on measures of global suggestibility and automatic processing, but not on measures of intellectual functioning and memory. Suggestibility was related to number and severity of reported symptoms, as well as the inability to inhibit the automatic processing of information. Implications of these findings are discussed, as well as directions for future research and treatment of symptoms associated with CFS.

Adult↗

Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome.

The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms. In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight-matched and were known to have normal basal metabolic rates and thyroid function. CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. CBT time series were analysed by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and sigma2. Average parameters for each group were compared by Student's t-test. By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0.02). The optimal harmonic-regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant. We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.

Adult↗

Evidence of a functional role in lung inflation for the buccal pump in the agamid lizard, Uromastyx aegyptius microlepis.

This study has demonstrated that the agamid desert lizard Uromastyx aegyptius microlepis ventilates its lungs both with a triphasic, thoracic aspiratory pump and by gulping air, using a buccal pump. These two mechanisms never occur simultaneously because bouts of buccal pumping are always initiated after the passive expiration that terminates a thoracic breath. Lung inflation arising from thoracic and buccal ventilation was confirmed by direct recording of volume changes using a whole-body plethysmograph. This observation was further confirmed by mechanical separation of the inflationary pressures associated with these two breathing mechanisms, enabling the effects of lung inflation on buccal breathing to be observed. This revealed that the buccal pump is influenced by a powerful Hering-Breuer-type reflex, further confirming its role in lung inflation. Bilateral thoracic vagotomy tended to increase the variance of the amplitude and duration of the breaths associated with the aspiration pump and abolished the effects of lung inflation on the buccal pump. Uromastyx has vagal afferents from pulmonary receptors that respond to changes in lung volume and appear not to be sensitive to CO2. This study describes two lung-inflation mechanisms (an amphibian-like buccal pump and a mammalian-like aspiration pump) in a single extant amniote, both of which are subject to vagal feedback control.

Animals↗

Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats.

It has been demonstrated previously that the vagal bradycardia evoked by activation of pulmonary C-fibres is not respiratory modulated. Experiments were carried out in alpha-chloralose anaesthetized cats to determine if these cardiac vagal preganglionic neurones (CVPNs) in the nucleus ambiguus (NA), which have respiratory modulated activity, can be activated when pulmonary C-fibre afferents are stimulated by right atrial injections of phenylbiguanide (PBG). Eleven CVPNs with B-fibre axons in the right cardiac vagal branches were identified and found to be localized within or ventrolateral to the nucleus ambiguus. Ionophoretic application of a high current of dl-homocysteic acid (DLH) induced a vagally mediated bradycardia and hypotension in six of eight sites from which CVPNs were recorded. The activity of B-fibre CVPNs, whether spontaneous (n = 4) or induced by ionophoresis of DLH (n = 7) was respiratory modulated, firing perferentially during post-inspiration and stage 2 expiration. This activity also correlated with the rising phase of the arterial blood pressure wave consistent with these CVPNs receiving an arterial baroreceptor input. Right atrial injections of PBG excited nine of eleven CVPNs tested. In eight of these activated neurones the onset latency of the excitation was within the pulmonary circulation time, consistent with being activated only by pulmonary C-fibre afferents. In two neurones the PBG-evoked excitation still occurred when central inspiratory drive was inhibited, as indicated by the disappearance of phrenic nerve activity. In conclusion, B-fibre respiratory modulated CVPNs can be activated following stimulation of pulmonary C-fibre afferents.

Action Potentials↗

Analysis and significance of anti-latent membrane protein-1 antibodies in the sera of patients with EBV-associated diseases.

Anti-latent membrane protein-1 (LMP-1) is an EBV-encoded type III integral membrane protein with oncogenic potential that is expressed most consistently in various EBV-associated malignancies. Unlike many other EBV proteins, LMP-1 Abs have rarely been demonstrated in EBV-associated disease conditions. We established a high level LMP-1-expressing cell clone and used it for the detection, quantitation, and characterization of these Abs in various human sera in immunoblots and ELISA. Our results demonstrate that, in contrast to the commonly held notion, LMP-1 induces significant humoral immune responses in EBV-associated malignant conditions especially in nasopharyngeal carcinoma (NPC) patients in whom >70% sera are positive for these Abs, and their titers correlate with the clinical condition of the tumors. Interestingly, anti-LMP-1 Abs of IgA isotype were found only in NPC patients. These Abs were absent from the sera of infectious mononucleosis and chronic EBV infection patients, whereas a small fraction ( approximately 5%) of the healthy, EBV-seropositive individuals were positive for them; however, their OD values were much lower than those of NPC patients. These studies demonstrate, for the first time, the potential significance of LMP-1-specific Abs for the diagnosis and prognosis of EBV-associated malignancies, especially of NPC.

Antibodies, Viral↗

Elevated serum transforming growth factor beta1 levels in Epstein-Barr virus-associated diseases and their correlation with virus-specific immunoglobulin A (IgA) and IgM.

Transforming growth factor beta (TGF-beta) is an immunosuppressive cytokine which can induce immunoglobulin A (IgA) switch and Epstein-Barr virus (EBV) replication in latently infected cells. Here we report elevated serum levels of TGF-beta in various EBV-associated diseases correlating positively with EBV-specific IgA titers and negatively with IgM titers, suggesting a role for this cytokine in the pathogenesis of these diseases.

Antibodies, Viral↗

Activity of aortic chemoreceptors in the anaesthetized rat.

1. It has been widely accepted that the rat aortic depressor nerve contains only baroreceptors. However, the experiments which have provided these negative data have employed whole aortic nerve recording. In the present study, the technical difficulties associated with recording single fibres in vivo, from the rat aortic nerve (diameter 25-50 microm), have been surmounted using a small tip, glass suction electrode technique. 2. Upon switching from normocapnic hyperoxia to hypercapnic hypoxia, irregularly firing units (n = 13) appeared and these were significantly excited by intravenous injections of sodium cyanide (20 microg) but not by rises in arterial blood pressure induced by methoxamine (an alpha1-adrenoreceptor agonist; 10 microg). Inhalation of 100 % oxygen rapidly and reversibly silenced, or profoundly reduced, ongoing activity. 3. Intravenous injection of phenylbiguanide (PBG; a 5-HT3 receptor agonist; 8 microg) strongly stimulated the chemoreceptors and was followed by a period of chemodepression (3-21 s). In contrast none of the single fibre baroreceptors recorded (n = 15) were excited by PBG but all significantly increased their discharge in response to the increases in arterial blood pressure associated with methoxamine and cyanide. Both the excitatory and inhibitory effects of PBG on the chemoreceptor fibres were abolished by ondansetron (a 5-HT3 receptor antagonist: 1 mg kg-1 i.v.; n = 5 animals) whilst the chemoexcitatory action of cyanide was preserved. 4. It is concluded that there are chemoreceptor afferents contained in the aortic nerve of the Sprague-Dawley rat. The 5-HT3 receptor appears not to be a pre-requisite for aortic body chemoexcitation.

Anesthesia↗

Asymmetric DDE (D35E)-like sequences in the RAG proteins: implications for V(D)J recombination and retroviral pathogenesis.

Experimental evidence suggests that the mechanism of vertebrate V(D)J recombination catalyzed by the vertebrate RAG proteins is similar to both retroviral integration and the transposition of IS630/Tc1-family transposons. The mechanism of both retroviral integration and IS630/Tc1 element transposition is well characterized and utilizes a functional metal ion binding site termed the DDE (or D35E) motif. We have previously identified a DDE-like region in the RAG-2 protein and a similar region within the RAG-1 protein. In this work, we propose that interference between DDE-like regions in the RAG proteins and the DDE-site of the HIV integrase may be a mechanism of retroviral pathogenesis in cells in which both the RAG proteins and retroviral integrase are co-expressed.

Amino Acid Sequence↗

The Epstein-Barr virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases.

gp350 of Epstein-Barr virus (EBV) induces a strong immune response in EBV-infected individuals, but relatively little is known about the clinical relevance of this response in patients with different EBV-associated malignancies and other diseases. Using our gp350-expressing cell clones, we studied gp350-specific humoral immune responses in the sera of individuals with nasopharyngeal carcinoma (NPC), chronic symptomatic EBV infection (CEI), Hodgkin's disease (HD), acute infectious mononucleosis (IM) and healthy EBV-seropositive individuals (HI). The titres of antibody-dependent cellular cytotoxicity (ADCC) antibodies were highest in HI followed by CEI, HD and NPC. EBV-neutralizing (NA) and gp350-specific IgG antibody profiles in these conditions were: CEI > HI > NPC > HD, whereas IgA titres were the highest in NPC sera followed by CEI and HD. The sera from IM patients were found to be negative for gp350-specific ADCC and IgA activities. Sera from HI were also negative for gp350-specific IgA. A significant positive correlation was found between serum gp350 IgA and viral capsid antigen IgA and a significant negative one between IgM and ADCC titres. High IgA titres were also found in CEI and EBV-genome positive HD in addition to NPC. Importantly, gp350-specific IgA titres were of prognostic value in NPC patients. Our data provide new insights about the clinical relevance of gp350-specific immune responses in these diseases.

Antibodies, Viral↗

Respiratory modulation of carotid and aortic body reflex left ventricular inotropic responses in the cat.

1. The reflex changes in the inotropic state of the left ventricle, measured as the dP/dt max (maximum rate of change of pressure), occurring in response to selective stimulation of the carotid and aortic body chemoreceptors by sodium cyanide, were studied in the cat anaesthetized with a mixture of chloralose and urethane. 2. The animals were artificially ventilated with an open pneumothorax. The heart rate and mean arterial blood pressure were maintained constant. 3. With on-going central respiratory activity, stimulation of the carotid bodies caused an increase in respiratory movements. Variable changes in left ventricular dP/dt max occurred, the predominant response being an increase. The mean change was 8.3 +/- 2.9 % from a control value of 6850 +/- 450 mmHg s-1. Stimulation of the aortic bodies resulted in a smaller increase in respiration or no effect, but a significant increase occurred in left ventricular dP/dt max of 19.6 +/- 2.9 % from a control value of 6136 +/- 228 mmHg s-1. No significant changes in left ventricular end-diastolic pressure occurred in response to stimulation of either group of chemoreceptors. 4. Tests of chemoreceptor stimulations were repeated during temporary suppression of the secondary respiratory mechanisms: the central respiratory drive was suppressed reflexly by electrical stimulation of the central cut ends of both superior laryngeal nerves and lung stretch afferent activity was minimized by stopping artificial respiration. Carotid body stimulation again evoked variable responses, the predominant now being a reduction in left ventricular dP/dt max of 3.1 % from a control value of 5720 +/- 320 mmHg s-1, which was significantly different to that occurring during on-going spontaneous respiration. Aortic body stimulation caused an increase in left ventricular dP/dt max similar to the response during on-going spontaneous respiration. 5. The positive inotropic responses were mediated via the sympathetic nervous system, as indicated by their abolition as a result of intravenous injections of the beta-adrenoceptor blocking agent, propranolol. 6. It is concluded that the carotid bodies exert a small variable effect on left ventricular dP/dt max, the predominant positive inotropic response being due to the concomitant neurogenic effects of the increase in respiration. In contrast, the positive inotropic response to excitation of the aortic chemoreceptors is not respiratory modulated.

Adrenergic beta-Agonists↗

Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats.

1. Bradycardia can be evoked by stimulation of both myelinated and non-myelinated vagal efferent fibres. The on-going activity and synaptic inputs to cardiac vagal preganglionic neurones with myelinated axons have been studied in detail, but there is little information regarding cardiac preganglionic neurones with non-myelinated axons. In the present study, the on-going discharge and afferent inputs to cardiac vagal efferents with non-myelinated axons were studied in anaesthetized rats and cats. 2. Extracellular recordings were made from vagal preganglionic neurones in the dorsal vagal motor nucleus (DVMN) of anaesthetized rats following electrical stimulation of the cervical vagus nerve. Based on calculated axonal conduction velocities, fifty-six neurones had non-myelinated axons. Sixteen of these C fibre neurones had on-going activity but this showed no relationship to central respiratory drive, lung inflation or the cardiac cycle. Activity of twenty-one of these fifty-six neurones was increased at short latency following right atrial injections of phenylbiguanide (PBG). 3. Eight presumed cardiac vagal preganglionic neurones were also recorded in the DVMN. Five of these were activated by PBG administration, and the one neurone with resting activity showed no indication of respiratory-related activity. 4. Finally, twenty-one single C fibres were recorded in peripheral branches of the cardiac vagus. They had a low rate of on-going activity, and in twelve fibres this on-going discharge was analysed in detail. On-going activity in seven of these fibres showed no relationship to central respiratory drive, lung inflation or the cardiac cycle, whereas the other five had prominent relationships with both central respiratory drive and lung inflation, and two of these also showed a relationship to heart period. PBG administration evoked an increased activity in fourteen of the fifteen fibres tested, and the latencies of nine of these responses (1.3 +/- 0.5 s) were within the pulmonary circulation time. 5. In anaesthetized cats, extracellular recordings were made in the DVMN from thirty-three cardiac vagal preganglionic neurones with C fibre axons. The on-going activity of these neurones, when present, never exhibited an on-going- or reflexly induced respiratory rhythm, nor any indication of an input from the arterial baroreceptors. Right atrial injection of PBG evoked a short-latency response in four of the five spontaneously active neurones but was without effect on the eight neurones tested which did not exhibit on-going activity. 6. In conclusion, the majority of cardiac vagal preganglionic neurones located in the DVMN have C fibre axons, show no obvious input from central or peripheral respiratory- or cardiac-related inputs, but are activated by stimulation of pulmonary C fibre afferent fibres.

Anesthesia, General↗

Core body temperature is normal in chronic fatigue syndrome.

BACKGROUND: Subjects with chronic fatigue syndrome (CFS) frequently report symptoms of subnormal body temperature and low-grade fever. We conducted a study to determine whether CFS subjects manifest any abnormality of core body temperature (CBT) that might help explain their fatigue. METHODS: Continuous 24-hour recordings of CBT measured every 5 min were performed in 7 subjects meeting the Centers for Disease Control definition of CFS. Three additional groups were studied: normal controls, subjects with seasonal allergy, and subjects with major depression. Subjects (n = 7) in each group were age-, sex-, and weight-matched to the CFS group and had normal basal metabolic rates, thyroid function, and 24-hour urinary free cortisol excretions. CBT was measured with an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. Each pill was factory-calibrated to +/- 0.1 degree C and field-calibrated with a water bath calibration prior to use. RESULTS: The 24-hour mean calibration-adjusted CBTs of each group were not significantly different (control: 37.00 +/- 0.17 degrees C; CFS: 37.04 +/- 0.31 degrees C; allergy: 37.15 +/- 0.18 degrees C; depression: 37.16 +/- 0.18 degrees C). Similarly, the mean peak and trough circadian temperatures were not statistically different. The mean 24-hour profile of CBT for each group showed a similar circadian rhythm. In simultaneously collected blood samples, each group showed a similar circadian profile of serum cortisol with a peak occurring at 08:00. CONCLUSIONS: Subjects with CFS have normal CBT despite frequent self-reports of subnormal body temperature and low-grade fever.

Adult↗

Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables.

BACKGROUND: We investigated a role for allergic inflammation and psychologic parameters in the development of chronic fatigue syndrome (CFS). METHODS: The design was a comparison between subjects with CFS and age- and sex-matched control cohorts. Studies were performed on CFS subjects (n = 18) and control cohorts consisting of normal subjects (n = 11), allergic subjects (n = 14), and individuals with primary depression (n = 12). We quantified cytokines at baseline as cell-associated immunoreactive peptides and as transcripts evaluated by means of semiquantitative RNA-based polymerase chain reactions. Psychologic evaluations included administration of the Diagnostic Interview Schedule, the Structured Clinical Interview, and the Symptom Checklist 90-Revised. RESULTS: Increases in tumor necrosis factor (TNF)-alpha were identified in individual subjects with CFS (50.1 +/- 14.4 pg TNF-alpha per 10(7) peripheral blood mononuclear cells [PBMCs]; mean +/- SEM) and allergic subjects (41.6 +/- 7.6) in comparison with normal subjects (13.1 +/- 8.8) (P < .01 and P < .05, respectively). Similar trends were observed for interferon (IFN)-alpha in allergic subjects (3.0 +/- 1.7 pg/10(7) PBMCs) and subjects with CFS (6.4 +/- 3.4) compared with normal subjects (1.9 +/- 1.4). A significant increase (P < .05) in TNF-alpha transcripts was demonstrated between subjects with CFS and depressed subjects. In contrast to these proinflammatory cytokines, both subjects with CFS (2.6 +/- 1.8 pg/10(7) PBMCs) and allergic subjects (3.4 +/- 2.8) were associated with a statistically significant (P < .01) decrease in IL-10 concentrations compared with normal subjects (60.2 +/- 18.2). As shown in other studies, most of our subjects with CFS were allergic (15 of 18) and therefore presumably demonstrated cytokine gene activation on that basis. The seasonal exacerbation of allergy was associated with a further increase in cellular IFN-alpha (from 2.1 +/- 1.2 to 14.2 +/- 4.5 pg/107 PBMCs; P < .05) but no further modulation of TNF-alpha or IL-10. Similarly, self-reported exacerbations of CFS were associated with a further increase in IFN-alpha (from 2.5 +/- 1.0 to 21.9 +/- 7.8; P < .05) and occurred at times of seasonal exposures to allergens. This linkage does not permit making any definitive conclusions regarding a causative influence of either seasonal allergies or the increase in cellular IFN-alpha with the increase in CFS symptoms. The close association between atopy and CFS led us to speculate that CFS may arise from an abnormal psychologic response to the disordered expression of these proinflammatory and antiinflammatory cytokines. Psychologic variables were predictive of immune status within the CFS sample (65.9% of the variance in immune status; F (3,10) = 6.44, P < .05). Specifically, the absence of a personality disorder but greater endorsement of global psychiatric symptoms was predictive of immune activation. CONCLUSIONS: Most of our subjects with CFS were allergic, and the CFS and allergy cohorts were similar in terms of their immune status. However, the CFS subjects could be discriminated by the distinct psychologic profiles among subjects with and without immune activation. We propose that in at least a large subgroup of subjects with CFS who had allergies, the concomitant influences of immune activation brought on by allergic inflammation in an individual with the appropriate psychologic profile may interact to produce the symptoms of CFS. In a psychologically predisposed individual, symptoms associated with allergic inflammation are recognized as illness.

Adult↗

Levels of microbial contamination on surgical instruments.

OBJECTIVE: To ascertain the microbial load and type of organisms on used surgical instruments following standard cleaning, which consisted of the use of a washer sterilizer followed by sonic cleaning. DESIGN: In this prospective experimental study, used surgical instruments were immersed in Peptamin Tween broth, the broth agitated, and then filtered through a 0.45 microm filter. Quantitative cultures were performed, and all microbes were identified by using standard techniques. SETTING: This study was conducted at a 660-bed university hospital. RESULTS: The microbial load remaining on used surgical instruments after cleaning was as follows: 36 (72%) instruments 0 to 10 colony-forming units (CFU), 7 (14%) instruments 11 to 100 CFU, and 7 (14%) instruments > 100 CFU. Organisms contaminating the instruments included coagulase-negative staphylococcus (56%) followed by Bacillus (22%) and diphtheroids (14%). No other microbes were isolated from more than 4% of the instruments. CONCLUSION: Most used nonlumen surgical instruments contain less than 100 CFU of relatively nonpathogenic microorganisms after cleaning. This suggests that new low-temperature sterilization technologies are likely to be highly effective in preventing cross-transmission of infection via nonlumen medical instruments.

Bacteria↗

Reflex cardiac dromotropic responses to stimulation of the carotid and aortic chemoreceptors in the anaesthetized cat.

1. The reflex changes in the dromotropic state of the heart (P-R interval or atrioventricular conduction time) in response to selective stimulation of the carotid and aortic bodies by sodium cyanide were studied in the anaesthetized cat. The heart was paced and the arterial blood pressure was kept constant to minimize secondary effects of changes in arterial baroreceptor activity. 2. Stimulation of the carotid and aortic bodies caused an increase in the atrioventricular conduction time. 3. Evidence is presented to suggest that this negative dromotropic response was due predominantly to a vagal cholinergic mechanism. There is a small sympathetic component but only in so far as the carotid body reflex is concerned. 4. The negative dromotropic responses were enhanced during reflex suppression of the central inspiratory neuronal drive combined with minimal activity of the slowly adapting pulmonary stretch afferents indicating that they are respiratory modulated. 5. The clinical implications of these results are discussed.

Analysis of Variance↗

Dissociation of EBV genome replication and host cell proliferation in anti-IgG-stimulated Akata cells.

The Epstein-Barr virus (EBV)-positive Burkitt's lymphoma cell line, Akata, was treated with dimethyl sulfoxide (DMSO) for 96 hr in order to reversibly arrest cell cycle progression in G1 phase. Stimulation of the cells with anti-IgG antibody induced a marked and synchronous replication of EBV DNA within 12 hr, before the cells entered into S-phase after release from DMSO-induced arrest. Furthermore, a reduced efficiency of productive replication was demonstrated if anti-IgG stimulation was delayed after release. The results indicate that entry into S-phase of host cells is not only unnecessary for, but also may have negative consequences for the productive phase of EBV infection. Also, it was shown that addition of acyclovir, an inhibitor of the EBV-encoded DNA polymerase, to anti-IgG-stimulated Akata cells inhibited the productive replication of EBV DNA, but had no effect on the expression of early genes of the virus, including BZLF1, BRLF1, BMRF1, and BHRF1.

Antibodies, Anti-Idiotypic↗