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Biomedical subjects

J G Jones

Publications and source records attributed to J G Jones.

At least 109 records · Page 6Linked to original sources

The PIO2 vs. SpO2 diagram: a non-invasive measure of pulmonary oxygen exchange.

A non-invasive method for measuring pulmonary oxygen exchange is described using a plot of inspired oxygen partial pressure (PIO2) vs. oxygen saturation (SpO2). This method was assessed using nine normal subjects and 35 patients undergoing major surgery, including five thoracotomies. In each patient PIO2 was varied to produce a range of values of SpO2 between 85% and 99%. A model based on the inspired to arterial oxygen difference involving the shunt equation, solved by simultaneous numerical methods, was used to show how the PIO2 vs. SaO2 relationship could be used to derive two parameters of oxygen exchange, the PIO2-Pco2 difference and the Virtual Shunt. The model allows the inspired to arterial difference in PO2 to be divided into (a) an inspired to 'ideal' alveolar difference attributable to the balance between alveolar ventilation and oxygen uptake; (b) an 'ideal' alveolar to end-capillary difference attributable to inhomogeneity in ventilation/perfusion ratios; and (c) end-capillary to arterial difference attributable to true shunt, which was termed 'virtual shunt' because of the uncertainties of assuming fixed values for haemoglobin concentration and arteriovenous oxygen content difference. The coefficient of determination showed that there was a good fit of the model to the data. Because the method is model-based it enables extrapolation to different PIO2 values as well as the study of the evolution of changes in gas exchange under varying conditions.

Adult↗

Cutaneous metastases from squamous cell carcinoma of the vulva. A case report and review of the literature.

Cancer of the vulva, the fourth most common malignancy of the female genital tract, accounts for approximately 4% of all gynecologic malignancies. Only one prior case of a cutaneous metastasis from a vulvar cancer has been previously reported and involved a FIGO Stage III (T2N1M0) lesion. We report a patient with Stage II (T2N0M0) vulvar carcinoma who developed cutaneous metastases. This case demonstrates the ability of vulvar carcinoma to disseminate hematogenously, despite complete surgical resection with negative skin margins, and negative lymph nodes. In addition, this case emphasizes the importance of careful and close follow-up of all patients with vulvar carcinoma.

Carcinoma, Squamous Cell↗

The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma.

Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.

Adenocarcinoma↗

Orientation-conserved transfer of symmetric Krebs cycle intermediates in mammalian tissue.

Metabolism of [2-13C]-, [3-13C]-, and [1,2,3-13C]propionate in perfused rat livers and [2-13C]-acetate in perfused rat hearts has been examined in tissue extracts by 13C NMR. Label from [2-13C]-propionate was preferentially incorporated into the C2 carbon of lactate, alanine, and aspartate in liver tissue while label from [3-13C]propionate appeared preferentially in the C3 carbon of those same molecules. These data suggest that 13C may not be completely randomized in the symmetric citric acid cycle intermediates succinate and fumarate as is normally assumed but that some fraction of those intermediates may be transferred between enzymes in this span of the cycle with conservation of spatial orientation, consistent with recent results obtained in yeast [Sumegi et al. (1990) Biochemistry 29, 9106-9110]. This was confirmed by performing similar experiments with [1,2,3-13C]propionate. Time-dependent asymmetry was also observed between the intensities of the glutamate C2 and C3 resonances and between the aspartate C2 and C3 resonances in 13C NMR spectra of intact hearts and heart extracts during early perfusion with [2-13C]-acetate. A model is presented which predicts that isotopic asymmetry is observed only during the first 2-3 turns of the cycle pools when isotope enters the cycle via acetyl-CoA even if all symmetric cycle intermediates retain a unique molecular orientation on each pass through the citric acid cycle.

Acetates↗

A method for obtaining 13C isotopomer populations in 13C-enriched glucose.

13C NMR analysis of 13C-enriched glucose containing multiple isotopomers is hampered by chemical shift similarities of several carbon resonances and by the presence of two anomeric forms. A convenient and quantitative method of enzymatically oxidizing glucose to gluconate in tissue and perfusate extracts is presented. The six carbon resonances of the resulting 13C-enriched gluconate are fully resolved at high pH, thereby allowing a determination of the fractional population of each 13C isotopomer by 13C NMR. The utility of this method is demonstrated using the effluent from an isolated perfused liver containing 13C-enriched glucose produced by hepatic metabolism of sodium [1,2,3-13C3]propionate via the citric acid cycle and gluconeogenesis. An analysis of the gluconate C2 and C5 resonances in this sample showed that pentose phosphate activity was insignificant during this perfusion protocol. As demonstrated, this method provides a means of fully describing 13C isotopomer populations in enriched glucose samples where isotope may be derived from multiple metabolic pathways, thus expanding the scope of experimental design and enrichment strategies.

Animals↗

A first look at biosensors.

This is a very elementary guide to biosensors, outlining the principles of operation of some optoelectronic and current measuring biosensors. Factors which can influence successful translation to the marketplace are addressed.

Journal Article↗

Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts.

The effects of a xanthine oxidase-mediated free radical-generating system containing purine and iron-loaded transferrin or solutions containing hydrogen peroxide and iron-loaded transferrin on substrate utilization and high-energy phosphates were evaluated by nuclear magnetic resonance (NMR) spectroscopy in isolated perfused rat hearts. Hearts were supplied with lactate, acetate, and glucose, and the contribution of each substrate to acetyl coenzyme A was measured in control hearts and in the presence of a free radical-generating system. Perfused hearts were monitored by 31P NMR, and tissue extracts were analyzed by 13C NMR. Free radicals decreased the phosphocreatine and beta-ATP peak areas and reduced contractile function. Under control conditions, lactate, acetate, and endogenous sources were the major contributors of acetyl coenzyme A units, with only 5% originating from glucose. In the presence of a xanthine oxidase-mediated free radical-generating system, the glucose contribution increased to 54%, while contributions from acetate and endogenous sources were significantly reduced. Both 13C and 31P NMR analyses showed no significant accumulation of glycolytic sugar phosphates, suggesting little inhibition of glyceraldehyde-3-phosphate dehydrogenase. The increased contribution of glucose to the tricarboxylic acid cycle relative to acetate and endogenous sources is consistent with activation of pyruvate dehydrogenase. In contrast, hearts exposed to a hydrogen peroxide-based free radical-generating system showed an increase in lactate utilization, a decrease in acetate utilization, and no change in glucose utilization compared with control hearts. Glycolytic sugar phosphates were found to accumulate, suggesting possible inhibition of glyceraldehyde-3-phosphate. Thus, different radicals or their metabolites may have varying effects on myocardial metabolism.

Acetates↗

Unique dermatological complication of rhM-CSF treatment.

A patient is presented who developed cutaneous papular histiocytic infiltrates after treatment with monocyte colony stimulating factor (rhM-CSF). This is the first reported complication of this type after treatment with this new cytokine.

Humans↗

Free radicals in anaesthesia and intensive care.

This review aims to outline the nature and origin of free radicals, or oxidants, in biological systems and to summarise their involvement in diseases of interest to anaesthetists, with particular reference to reperfusion injury (of the gut, brain, myocardium and transplanted organs), shock/trauma, inflammation/sepsis and halothane hepatitis. In-vitro and animal studies examining the role of free radicals and antioxidants in the pathophysiology and treatment of these conditions are presented. Some of the evidence from clinical studies supporting the use of antioxidant therapy in patients is also presented.

Anesthesia↗

Management of recurrent penile cancer following partial or total penectomy.

The initial management of localized penile carcinoma determines the probability of recurrence. Although potentially disfiguring, the management of recurrent carcinoma of the penis requires aggressive surgical resection of both the primary lesion and nodal sites to effect the best chance for long-term survival.

Adult↗

Effect of hypoxaemia on the resting electrocardiogram (ECG) in patients with cardiac ischaemia.

The effect of hypoxaemia on the heart at rest was studied using the electrocardiogram (ECG) in 38 patients. The majority had symptoms of cardiac disease and all were scheduled to have an exercise ECG test under standard conditions. Two ECG variables were examined; (i) depression of the ST segment at the point 60 ms after the QRS-ST junction as well as (ii) the slope of the J-60 ms segment. During exercise breathing air, 11 patients showed positive changes of cardiac ischaemia, 5 were equivocal and 22 showed little or no change. When the patients had recovered from the exercise study they breathed a hypoxic mixture to lower their arterial oxygen saturation to 85% for 3 minutes. No changes were seen in the ST segment in any subject. We conclude that a 3-minute period of hypoxaemia at an oxygen saturation of 85% with subjects at rest did not cause ST segment depression in patients with either positive or negative exercise tests.

Adult↗

Sources of acetyl-CoA entering the tricarboxylic acid cycle as determined by analysis of succinate 13C isotopomers.

A new 13C NMR technique for measuring substrate utilization by the citric acid cycle based on an analysis of succinate 13C isotopomers is presented. The relative contribution of up to three different labeling patterns in acetyl-CoA entering the citric acid cycle may be determined under non-steady-state conditions. We present experimental data from perfused rat hearts subjected to a brief period of ischemia, where both succinate and glutamate resonances were observed in the 13C spectrum. The contributions of labeled exogenous acetate and lactate and unlabeled sources to the acetyl-CoA pool were compared using this succinate analysis and a previously published glutamate analysis [Malloy et al. (1990) Biochemistry 29, 6756-6761], and the two methods give identical results. This indicates that the succinate and glutamate isotopomers originated from a common alpha-ketoglutarate pool, verifying that glutamate is in isotopomeric equilibrium with alpha-ketoglutarate under these conditions.

Acetyl Coenzyme A↗