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T Jones

Publications and source records attributed to T Jones.

At least 199 records · Page 11Linked to original sources
PubMed1996

Noninvasive quantification of regional myocardial metabolic rate for oxygen by use of 15O2 inhalation and positron emission tomography. Theory, error analysis, and application in humans.

BACKGROUND: A method has been developed to measure the regional myocardial metabolic rate of oxygen consumption (rMMRO2) and oxygen extraction fraction (rOEF) quantitatively and noninvasively in humans by use of 15O2 inhalation and positron emission tomography. This article describes the theory, an error analysis of the technique, and procedures of the method used in a human feasibility study. METHODS AND RESULTS: Inhaled 15O2 is transported to peripheral tissues, where it is converted to 15O-labeled water of metabolism, which exchanges with the relatively large extravascular tissue space. Quantification of this buildup of radioactivity allows the calculation of rMMRO2 and rOEF. However, a correction for the spillover of the pulmonary gas radioactivity signal into myocardial regions is required and has been made by use of a gas volume distribution estimated from the transmission scan. This was validated by comparative measurements using the inert gas [11C]CH4 in four greyhounds. Spillover of the cardiac chamber radioactivity has been corrected for with an inhaled [13O]CO (blood volume) scan. The underestimation of myocardial radioactivity due to wall motion and thickness has been corrected for by use of values of tissue fraction obtained from the flow measurement [15OKCO2 scan). Values of rOEF were similar (within 4%) whether obtained from gas volume measurements determined from the transmission or [11C]CH4 scan data. 15O2 scan information from six healthy volunteers showed a clear distribution of myocardial radioactivity after the vascular and pulmonary gas 15O background was subtracted. Subsequent compartmental analysis resulted in values for rOEF and rMMRO2 of 0.60 +/- 0.11 and 0.10 +/- 0.03 mL.min-1.g-1 in the human myocardium at rest. CONCLUSIONS: The results of this study are in good agreement with established values. This is the first known approach to allow the direct quantitative determination of rOEF and oxygen metabolism to be made noninvasively on a regional basis.

Adult↗
PubMed1996

Noninvasive quantification of regional myocardial metabolic rate of oxygen by 15O2 inhalation and positron emission tomography. Experimental validation.

BACKGROUND: The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMRO2, mL.min-1 x 100 g-1) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of 15O-labeled molecular oxygen gas (15O2). METHODS AND RESULTS: Twenty-four measurements were performed in eight closed-chest anesthetized greyhounds at baseline and during infusions of adenosine (100 to 200 micrograms.kg-1.min-1), isoproterenol (1 to 10 microgram/min), and propranolol (5 mg botus +0.2 to 1 mg/min) with morphine (5 mg slow infusion +0.2 to 0.5 mg/ min) to obtain a wide range of oxidative metabolism. The PET imaging protocol consisted of 15O2 emission (OEF and MMRO2), transmission, [15O]CO emission (blood pool), and [15O]CO2 emission (myocardial blood flow: MBF(pets) mL.min-1.g-1) scans. OEF was calculated from the PET data (OEFpet) by three different analytical techniques: steady-state, 5-minute, and 8-minute autoradiographic analyses. Reference measurements of MBF (MBFref) and OEF (OEFref) were obtained during 15O2 inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMRO2 was calculated from the PET (MMRO2pet) and the reference (MMRO2ref) data as follows: MMRO2 = OEF x MBF x (O2 content of arterial blood). OEF measured by the steady-state PET method was well correlated with the reference data over the range 0.16 to 0.73 (OEFpet = 1.03 OEFref -0.01, r = .97), as was MMRO2 over the range 2.4 to 27.5 mL.min-1 x 100 g-1 (MMRO2pet = 0.98 MMRO2ref +0.91, r = .94). OEFpet calculated by use of the 5-minute and 8-minute autoradiographic analyses were equally well correlated with the reference measurements (r = .95 and r = .97, respectively). There were no significant differences between values of MMRO2pet calculated by use of the steady-state, 5-minute, and 8-minute autoradiographic analyses (P = NS by ANOVA). Regional values of MBFpet, OEFpet, and MMRO2pet were homogeneously distributed and similar to the whole-heart values both at baseline and during the various pharmacological interventions. CONCLUSIONS: Accurate quantification of OEF and MMRO2 is feasible with 15O2 inhalation and PET imaging using both the steady-state and autoradiographic analytical approaches. These studies suggest the applicability of this method for quantitative assessments of regional cardiac oxidative metabolism in clinical studies.

Adenosine↗
PubMed1996

Silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia.

OBJECTIVE: To test whether the silence of painless myocardial ischemia is caused by abnormal handling by the central nervous system of afferent messages from the heart. DESIGN: Nonrandomized study. SETTING: A tertiary referral center (postgraduate medical school). PATIENTS: 2 matched groups of nondiabetic patients with coronary artery disease. Group A consisted of nine patients with reproducible stress-induced angina; group B consisted of nine patients with reproducible stress-induced myocardial ischemia but no angina. INTERVENTIONS: Intravenous placebo infusion and low-dose (5 and 10 micrograms/ kg per minute) and high-dose (20 to 35 micrograms/kg per minute) dobutamine infusions. MEASUREMENTS: Positron emission tomography was used to measure regional cerebral blood flow changes as an index of neuronal activation during painful and silent myocardial ischemia induced by intravenous dobutamine. RESULTS: Regional cerebral blood flow changes during myocardial ischemia were compared with those during baseline conditions and during placebo infusion. During myocardial ischemia, regional cerebral blood flow increased bilaterally in the thalami and prefrontal, basal frontal, and ventral cingulate corticles in patients in group A. Both thalami were activated in group B, but cortical activation was limited to the right frontal region. A formal comparison of groups A and B showed significant differences (P < 0.01) in activation of the basal frontal cortex, ventral cingulate cortex, and left temporal pole. In both groups, thalamic regional cerebral blood flow remained increased after the symptoms and signs of ischemia had ceased. CONCLUSIONS: Bilateral activation of the thalamus can be shown in both angina and silent ischemia; thus, peripheral nerve dysfunction cannot completely explain silent ischemia. Frontal cortical activation appears to be necessary for the sensation of pain. Abnormal central processing of afferent pain messages from the heart may play a determining role in silent myocardial ischemia.

Afferent Pathways↗
PubMed1996

Imaging allergen-invoked airway inflammation in atopic asthma with [18F]-fluorodeoxyglucose and positron emission tomography.

BACKGROUND: Airway inflammation is a feature of asthma and can be quantified invasively with bronchial lavage and endobronchial histology. Inflammatory foci can be imaged non-invasively with positron emission tomography (PET) and [18F]-fluorodeoxyglucose (18FDG) to quantify glucose uptake in activated granulocytes. We used this technique to study airway inflammation in asthma. METHODS: Nine men with mild atopic asthma were studied. In five, we studied the effect of bronchoscopic segmental allergen challenge on 18FDG uptake. Allergen was instilled into the posterior segment of the right upper lobe; a similar volume (20 mL) of isotonic saline was instilled into the posterior segment of the left upper lobe. At 1-32 h after instillation, PET with 18FDG was done. In the other four patients, we administered aerosolised allergen. FINDINGS: 18FDG uptake was increased four-fold in the right compared with the left upper lobe (geometric mean of ratios 4.30, 95% Cl 2.39-7.72, p=0.002). Aerosolised administration of allergen did not significantly increase 18FDG uptake. INTERPRETATION: These data show that local allergen-invoked airway inflammation can be visualised with 18FDG and PET in asthma. The cellular localisation of the 18FDG signal remains to be determined.

Adult↗
PubMed1996

Azotobacter vinelandii NIFL is a flavoprotein that modulates transcriptional activation of nitrogen-fixation genes via a redox-sensitive switch.

The NIFL regulatory protein controls transcriptional activation of nitrogen fixation (nif) genes in Azotobacter vinelandii by direct interaction with the enhancer binding protein NIFA. Modulation of NIFA activity by NIFL, in vivo occurs in response to external oxygen concentration or the level of fixed nitrogen. Spectral features of purified NIFL and chromatographic analysis indicate that it is a flavoprotein with FAD as the prosthetic group, which undergoes reduction in the presence of sodium dithionite. Under anaerobic conditions, the oxidized form of NIFL inhibits transcriptional activation by NIFA in vitro, and this inhibition is reversed when NIFL is in the reduced form. Hence NIFL is a redox-sensitive regulatory protein and may represent a type of flavoprotein in which electron transfer is not coupled to an obvious catalytic activity. In addition to its ability to act as a redox sensor, the activity of NIFL is also responsive to adenosine nucleotides, particularly ADP. This response overrides the influence of redox status on NIFL and is also observed with refolded NIFL apoprotein, which lacks the flavin moiety. These observations suggest that both energy and redox status are important determinants of nif gene regulation in vivo.

Adenosine Diphosphate↗
PubMed1996

The development of in vivo tracer methods to obtain new information about human disease: a study of the hallucinating brain.

An outline is provided of the development of methodological strategies to address the question of focal cerebral activation during hallucinations in schizophrenic patients. In so doing, the innovation and diligence required to tailor in vivo tracer procedures to specific clinical research issues are highlighted. Attention is drawn to the complexity of methodological advances and the way in which they are based upon close scientific and technical collaboration between clinical scientists, and non-clinical scientists and research support staff.

Hallucinations↗
PubMed1996

The imaging science of positron emission tomography.

To meet the goals of converging molecular imaging with molecular biology and molecular medicine, there is a need to define the strategy and structure for perfecting the accuracy of functional images derived using PET. This also relates directly to how clinical research, diagnostic questions and challenges from the pharmaceutical industry are addressed. In order to exploit the sensitivity and specificity of PET, an integrated, multidisciplinary approach is imperative. The structure to provide this needs to been seen in the context of an institutional approach, collaborations within the academic and industrial sectors and the funding needed to meet the challenges of addressing difficult questions.

Humans↗
PubMed1996

The role of positron emission tomography within the spectrum of medical imaging.

The aim of the survey is to help to define the role of positron emission tomography (PET) as an investigative procedure, and to identify strategies to perfect PET and in vivo tracer studies in general so that their full potential is realised. Within this context, the sensitivity and specificity of PET are reviewed. The impact of PET through studies of regional cerebral activation based on blood flow measurements is discussed. Emphasis is placed on the role of PET in clinical research and as a means of assessing new therapeutic agents. This latter ability renders PET of much interest to pharmaceutical companies.

Animals↗
PubMed1996

Transcriptional competition and homeosis in Drosophila.

Interference between different classes of RNA polymerase II alleles causes a mutant phenotype called the "Ubx effect" that resembles one seen in flies haploinsufficient for the transcription factor, Ultrabithorax (Ubx). Flies carrying the mutation in the largest subunit of Drosophila RNA polymerase II, RpII215(4), display the Ubx effect when heterozygous as in RpII215(4)/+ but not when homozygous mutant or wild type. In this report we demonstrate that the interaction between alleles in different classes of polymerase occurs even in the absence of transcription by the wild-type polymerase. We utilized the resistance to the transcriptional inhibitor alpha-amanitin conferred by RpII215(4) to show that RpII215(4)/+ flies raised on alpha-amanitin-containing food still show the Ubx effect and are indistinguishable from flies raised on normal food. We demonstrate using HPLC that the intracellular concentration of alpha-amanitin in the developing larvae is sufficient to inhibit transcription by alpha-amanitin-sensitive polymerase. Furthermore, fluorescein-labeled alpha-amanitin accumulates in imaginal discs, which are the precursor cells for the tissue showing the homeotic transformation in adults. We conclude that the interaction between different classes of RNA polymerase II alleles resulting in the Ubx effect occurs prior to the block in transcription caused by alpha-amanitin.

Alleles↗
PubMed1996

Genomic structure, chromosome location, and alternative splicing of the human NKG2A gene.

A cosmid containing the human NKG2A gene was isolated. The gene was partially sequenced, revealing 7 exons, including one 5' untranslated exon. The 54 base pair exon 5 was missing in the published cDNA clone NKG2B, consistent with the existence of differential splicing. This was confirmed by reverse transcription-polymerase chain reaction of total RNA from normal lymphocytes. The NKG2A gene was mapped by FISH to chromosome 12p12. 3-p13.1 in proximity to the CD69 and Prp genes. These data support the presence of a human lectin-like NK gene complex, analogous to the NK complex on mouse chromosome 6.

Alternative Splicing↗
PubMed1996

Impact of complementary parathyroid scintigraphy and ultrasonography on the surgical management of hyperparathyroidism.

BACKGROUND: An ongoing debate exists regarding the relative merits of full versus limited neck exploration in the surgical management of parathyroid adenomata. The aim of this study was to assess the impact of localization studies on the subsequent surgical management of hyperparathyroidism. METHODS: The accuracy of complementary ultrasonography and 201TI/99mTc parathyroid subtraction scintigraphy in hyperparathyroidism was evaluated retrospectively during a 10-year period in patients referred for localization studies. Surgical and pathologic confirmation of the diagnosis was possible in 121 patients, and these data formed the basis of this study. Operative procedure, times, outcome, and complications were recorded. RESULTS: The sensitivity, specificity, and accuracy for combined scintigraphy and ultrasonography were 86%, 98%, and 96%, respectively. Limited neck exploration was performed in 61 of 121 patients, and 60 patients underwent full neck exploration. In primary hyperparathyroidism 59 of 105 patients underwent limited and 46 underwent full neck exploration with average operative times of 70 and 109 minutes, respectively. (p < 0.0001). Complications developed in five patients who underwent full neck exploration. CONCLUSIONS: Confident localization of parathyroid adenomata facilitated successful limited neck exploration in most of the patients, questioning the need for full neck exploration in all patients with primary hyperparathyroidism.

Adenoma↗
PubMed1996

Factors affecting size and configuration of electrovaporization lesions in the prostate.

OBJECTIVES: Transurethral electrovaporization of the prostate is a new, minimally invasive technique being used by urologists for surgical ablation of prostatic tissue. There are insufficient data concerning factors affecting the vaporization and coagulation lesions produced by this technique. The aim of this study was to determine the role of various parameters for adequate tissue evaporation. METHODS: This study compared bovine liver and human prostatic lesions made by the Vaportrode instrument with those produced by standard electrocautery loops, roller balls, and laser fibers. Additionally, two electrosurgical instruments with differing technical capabilities were compared for their ability to cause vaporization of tissue. RESULTS: Results revealed that the Vaportrode lesions were maximal with a new electrode when used with a Force 40S electrosurgical generator set at 300 W and a drag speed of 25 to 30 seconds per 10 mm of tissue. The lesions produced by this technique had a 74% greater coagulation volume compared to a standard cautery loop. The evaporation defect was comparable to a laser lesion produced in contact at 60 W. CONCLUSIONS: We conclude that electrovaporization under optimal conditions causes a vaporization lesion comparable to that produced by high power density laser prostatectomy. Additionally, the coagulation volume of a vaportrode lesion is considerably greater than that produced by standard electrocautery resection.

Animals↗
PubMed1996

Transurethral vaportrode electrovaporization of the prostate: physical principles, technique, and results.

OBJECTIVES: This is a study to evaluate technique, efficacy, and safety of a new electrosurgical instrument (Vaportrode) in management of benign prostatic hyperplasia (BPH). METHODS: Forty-two symptomatic BPH patients form the subject of this study. Preoperative and postoperative International Prostate Symptom Score (IPSS), peak flow rates (PFR), postvoid residual urine (PVR), operative details, and complications were recorded in each patient. Baseline, 1, 3, and 6 months follow-up data were used for analyses. RESULTS: Results reveal that transurethral electrovaporization of the prostate (TUEVP) is a reasonable procedure to treat symptomatic BPH, and at 6 months, this procedure results in 68% reduction in IPSS, 128% improvement in PFR, and 58% reduction in PVR. Even in patients who are in retention prior to TUEVP, at 6 months the IPSS is 7.7, PFR is 20.4 cc/s, and PVR reduces to 130 cc. The procedure is well tolerated without any significant short-term complications. CONCLUSIONS: The results of this modality in improving the symptoms and PFR in symptomatic BPH patients in the short term appear promising. Advantages over transurethral resection (TUR) of the prostate and laser prostatectomy include familiarity of the transurethral route, lack of need for high-cost laser equipment and fibers, excellent intraoperative hemostasis, lack of bleeding or fluid absorption, and ability to cause a predictable TUR-like prostate defect at the end of the procedure. Further studies involving larger numbers of patients and longer follow-up are warranted to assess further the utility of this procedure.

Aged↗