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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 631 records · Page 35Linked to original sources

Infrared thermographic imaging, magnetic resonance imaging, CT scan and myelography in low back pain.

Sixty-five cases of chronic low back pain were studied. Infrared thermography (IRT) was abnormal in 92%, magnetic resonance imaging (MRI) in 89%, computerized tomography (CT) in 87% and myelography in 80%. IRT correlated with MRI in 94% of cases, and with CT in 87% of cases. Of 22 MRI positive disc and root cases, 21 (95%) had significant leg abnormalities on IRT. All 19 cases with radicular involvement on CT and all 18 with radicular involvement on myelography demonstrated significant leg changes on IRT.

Adult↗

Altered responsiveness of proximal tubule fluid reabsorption of peritubular angiotensin II in spontaneously hypertensive rats.

Stimulation of proximal tubular fluid reabsorption by peritubular angiotensin II (Ang II) was examined by split-drop micropuncture in 5- and 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). In WKY, the maximum stimulation occurred at 10(-11) mol/l and the response did not vary with age. In 5-week-old SHR, the dose-response relationship was similar in shape and in the extent of the maximum response but was shifted one half-logarithmic step to the right, indicating decreased sensitivity to Ang II. In contrast, the dose-response relationship was shifted one half-logarithmic step to the left in 12-week-old SHR compared with WKY. Alterations in the responsiveness of the proximal tubule to Ang II in young SHR could contribute to sodium retention observed during development of hypertension in these rats.

Angiotensin II↗

Microtiter plate assay for selecting "macrophage virulent" strains of Mycobacterium avium intracellulare mycobacteria in mouse pulmonary alveolar macrophages.

Currently used macrophage-mycobacterial in vitro infection models require substantial numbers of macrophages. We developed a miniaturized version of such a model, using microtiter plates, which is comparable to standardly published methods, is reproducible, and requires fewer macrophages. In addition to its ease of handling and its economy in time, number of animals, and supplies, this method is preferable when limited numbers of macrophages are available. We have used this assay as a means of selecting human derived isolates from patients with M. avium intracellulare pulmonary disease for their ability to infect and multiply in cultured mouse pulmonary alveolar macrophages.

Animals↗

Proton motive force, energy recycling by end product excretion, and metabolic uncoupling during anaerobic growth of Pseudomonas mendocina.

Batch cultures of Pseudomonas mendocina, grown in rich medium with glucose excess, showed metabolic differences dependent upon whether the growth conditions were aerobic or anaerobic, with or without added electron acceptor. Under anaerobic conditions in the absence of nitrate, P. mendocina reached the stationary phase of growth after 2 or 3 days, followed by a stationary phase of 4 to 5 days. Under these conditions, a mixed-type fermentative metabolism (formic, lactic, and acetic acids) appeared. A fivefold-higher specific rate of glucose consumption and eightfold-higher production of organic acids, compared with aerobic cultures, were shown by this microorganism growing anaerobically in the absence of exogenous electron acceptors. The gradients of organic acid produced by P. mendocina under these conditions reached a maximum (lactate, 180 mV; formate, 150 mV; acetate, 215 mV) between days 2 and 3 of culture. The proton motive force (delta p) decreased during growth from -254 to -71 mV. The intracellular pH remained alkaline during the culture, reaching a steady-state value of 7.9. The gradients of organic acids apparently contributed to the generation of a delta p, which, according to the Energy Recycling Model (P. A. M. Michels, J. P. J. Michels, J. Boonstra, and W. N. Konings, FEMS Microbiol. Lett. 5:357-364, 1979), would produce an average energy gain of 1 or 1.5 mol of ATP equivalents per mol of glucose consumed with H+/ATP stoichiometry of 3 or 2, respectively. Low YATP and Yglucose values were observed, suggesting that an uncoupled metabolism exists; i.e., ATP produced by catabolic processes is not directly used for biomass synthesis. This metabolic uncoupling could be induced at least in part by organic acids and the ATP wastage could be induced by a membrane-bound ATPase involved in intracellular pH regulation.

Acids↗

Glutaraldehyde effect on hemoglobin: evidence for an ion environment modification based on electron paramagnetic resonance and Mossbauer spectroscopies.

Glutaraldehyde is a widely used reagent for hemoglobin cross-linking in blood substitutes research. However, hemoglobin polymerization by glutaraldehyde involves modifications of its functional properties, such as oxygen affinity, redox potentials, and autoxidation kinetics. The aim of this article is to investigate, by electron paramagnetic resonance and Mossbauer spectroscopies, the changes that occur in the iron environment after glutaraldehyde cross-linking. Spectrometric studies were performed with native hemoglobin and hemoglobin cross-linked as soluble and insoluble polymers. Spectrometry data comparison with glutaraldehyde-modified hemoglobin functional properties allows to interpret from a structural point of view that glutaraldehyde action occurs as a decrease of the O--N(F8His) distance, an increase of the Fe--N(F8His) bond length, and the decrease of the distal-side steric hindrance.

Cross-Linking Reagents↗

Cutaneous manifestations of Takayasu arteritis. A retrospective study of 80 cases.

The aim of this retrospective study is to delineate in Europe the frequency and type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty patients with TA were analyzed. Symptoms suggestive of Raynaud's syndrome were noted in 11 patients (14%) and could be directly related to large vessel involvement. Other skin lesions were observed in 10 patients (12.5%). Five had acute tender erythematous nodules on the legs with a clinical diagnosis of erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma-gangrenosum-like ulcerations of the four limbs which resulted from the breakdown of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had urticarial lesions with livedo reticularis. Skin samples were obtained from 4 patients. Three of them agreed that reiterated biopsies be done on recurrent lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal arterioles in one case and veins in the other. The other pathological findings were septal and lobular panniculitis which can be associated with granulomatous vasculitis. Different histological findings on reiterated biopsies were frequently found. The absence of any other etiology and chronological arguments suggested a relationship between these skin lesions and TA. Tuberculosis was probable in 1 case but apparently was not related to the skin lesions.

Adult↗

[Tolerance of treatment with nitrate derivatives].

Tolerance to treatment with nitrate derivatives, suspected for many years and often ignored in everyday clinical practice, has recently been the subject of much study. Although the phenomenon has been clearly demonstrated in patients on long-term therapy, it seems to vary from patient to patient, with the underlying pathology and the galenic form of nitrate used. The mechanism of tolerance to nitrates is multifactorial, related on the one hand to depletion of sulfhydryl groups in the body and on the other to activation of the sympathetic and renin-angiotensin systems. The administration of sulfhydryl groups in the form of N-acetylcysteine partially restores the effects of nitrates in some patients.

Administration, Cutaneous↗

Generation of radical oxygen species by neural crest cells treated in vitro with isotretinoin and 4-oxo-isotretinoin.

The effects of isotretinoin (IR) and its primary metabolite (in the human), 4-oxo-isotretinoin (4-OIR or OIR), on isolated chick neural crest cells (NCC's) in culture were studied. NCC's were found to be deficient in both superoxide dismutase (SOD) and catalase, two of the enzymes known to function in the "scavenging" (dismutation) of toxic radical oxygen species (ROS) such as the superoxide anion and hydrogen peroxide. The addition of IR or OIR to the culture medium significantly depressed the viability of the NCC's when compared to untreated cells. OIR was more potent in this regard than IR. In the presence of either IR or OIR, NCC's generated superoxide anions (O2.), hydrogen peroxide (H2O2), and hydroxyl anions (OH.). OIR was again more potent. The cytotoxicity of IR or OIR was demonstrated by the "leakage" of radioactive chromium from prelabeled cells. The latter is suggestive of a primary surface membrane defect, most logically via the induction of lipid peroxides by the retinoids. The latter is accompanied by an increase in membrane permeability and porosity as evidenced by the fact that various fluorescently labeled molecules, including BSA-FITC (MW 69,000), gain entrance into the cytoplasm of the retinoid treated cells. No label was seen in the cytoplasm of similarly treated control cells. When SOD (200 units/ml) or catalase (400 units/ml) was added to the culture media of IR- or OIR-treated NCCs, cell viability was increased and the concentration of the various ROS generated was decreased. Membrane leakiness to chromium and FITC-BSA was also decreased in the presence of these enzymes. Free radicals, when not inactivated (dismutated), are known to be pathobiotic to most cells. Cell membranes are at a particular high risk from ROS which induce structural, physiological, and biochemical alterations in the cell membrane. The latter can have a negative effect on cell permeability, maintenance of normal ionic gradients, membrane enzyme activity, cell-to-cell communication, etc. Such defects can ultimately culminate in hypoplasia, aplasia, and cell necrosis. This study has shown that NCC's may be overtly sensitive to ROS, especially since these undifferentiated cells apparently lack inherent SOD and/or catalase activity. From this study it appears as if both IR and OIR perturb the normal functional state of NCC's by "triggering" the generation of ROS. This may certainly explain the teratogenicity of these drugs as related to the viability of neural crest derived ectomesenchymal cells and normal craniofacial morphogenesis.

Animals↗

Cortisol release in infants in response to inoculation.

Using a cross-sectional design, salivary cortisol was obtained from infants aged 2, 4, and 6 months, prior to and 15 min following an inoculation. Cortisol rose significantly following inoculation. Behavioral responses to inoculation were consistent with the observed patterns of cortisol release. Cortisol base level was significantly and negatively related to the cortisol change score. At 6 months the basal levels also were influenced by an adult-like circadian rhythm; infants tested shortly after awakening had higher basal levels than those tested later in the day. These data provide strong evidence that studies of stress and cortisol release in infants must be sensitive to basal level, circadian rhythm, and behavioral effects, and that appropriate statistical procedures should be employed.

Age Factors↗