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K Jones

Publications and source records attributed to K Jones.

At least 271 records · Page 15Linked to original sources
PubMed1993

In vivo animal models of body composition in aging.

We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous 40K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron Light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCa and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass.

Aging↗
PubMed1993

Quality assurance programs for immunosuppressive drugs: cyclosporine and beyond.

Monitoring blood cyclosporine concentrations as a guide to therapy has become established as a useful guide for optimal prescription of the drug. Quality assurance programs for external assessment of cyclosporine measurements have helped to clarify many of the methodological problems associated with measurement of the drug. A number of new immunosuppressive agents are in development and, although experience in their routine monitoring in clinical practice is still at an early stage, some observations regarding external assessment of their measurement can be made. This article summarizes the lessons to be drawn from the experience of cyclosporine quality assurance programmes and suggests some areas in which these lessons could be applied in the field of new immunosuppressive drugs.

Cyclosporine↗
PubMed1993

Inactivation of leukotriene C4 in the airways and subsequent urinary leukotriene E4 excretion in normal and asthmatic subjects.

Leukotrienes (LT) are synthesized in the lung during asthmatic reactions and mediate certain inflammatory symptoms. Pulmonary metabolism and clearance of exogenously added peptidoleukotrienes were studied in nonasthmatics, asthmatics, and asthmatics challenged with allergen. [3H]LTC4 and [14C]dextran were instilled into the airways, and bronchoalveolar lavage fluid (BALF) was obtained 15 min later. After comparing the [3H]/[14C] ratio of the instilled solution with that in BALF, 77% of LT were found to have been removed from the airways of nonasthmatics, and 72% of unchallenged asthmatics. Allergen administration to asthmatics 1 min before LT instillation inhibited LT transfer out of the airways by 26%, compared with asthmatics not challenged with allergen. This decrease in the removal of LT from the airways during allergic reactions could potentiate the physiologic effects of LT produced in the airways. The predominant LT in BALF was LTE4, constituting 56% of the LT in asthmatics and 61% in nonasthmatics. The percentage of LTE4 in BALF increased to 87% in allergen-stimulated asthmatics (p < 0.05 compared with the two other groups), this again reflecting decreased transfer of LT out of the lung rather than an increase in metabolism. Urinary excretion of LT metabolites occurred rapidly, the majority being excreted excreted within 6 h after instillation. LTE4, the major urinary LT metabolite identified by high-performance liquid chromatography, was a similar percentage concentration in the three groups and, thus, can be accurately used as an index of LT synthesis.

Adult↗
PubMed1993

Interleukin-6 production in posttransplant lymphoproliferative disease.

IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients with posttransplant lymphoproliferative disease (PTLD), with a mean maximal level of 196.7 U/ml. This represents a 16.4 increase above the normal mean (11.3 U/ml). In contrast, only 3 of 10 solid organ transplant recipients with uncomplicated courses posttransplant had abnormally elevated serum/plasma IL-6 bioactivity (mean maximal level 41.4 U/ml, P = 0.0007). When transferred to single cell culture, the 11 PTLD tissues produced 640 to 1.25 x 10(6) IL-6 U/ml in the culture supernatant, with a mean maximal level of 35,025 IL-6 U/ml. Cell separation experiments demonstrated that the adherent cells, identified as non-B cells, were the principal source of IL-6 production in vitro by PTLD tissue. Control cultures of inflammatory lymphoid tissue negative for lymphoproliferative disease as well as of PBL from patients with acute EBV-induced infectious mononucleosis consistently produced < 10 IL-6 U/ml. Thus, IL-6 is produced at high levels by PTLD tissues and may play a critical role in the pathogenesis of PTLD.

Adult↗
PubMed1993

Past maternal experience of asthma, childhood morbidity, and the psychosocial impact of the disorder.

Both previous experience of asthma, either in person or in a close family contact, by the mother of an asthmatic child and the child's current morbidity may influence the psychosocial impact of the disorder. A questionnaire concerning prior asthma experience, current psychosocial impact, and morbidity was returned by the mothers of 124 young asthmatic children. Family communication was significantly worse in the past maternal contact group. There were significant trends between morbidity and family communication, emotional distress, and manipulation. No beneficial effect of previous experience of asthma on measures of psychosocial disturbance experienced by the mothers of asthmatic children was detected. Increased psychosocial disturbance was associated with higher morbidity from asthma in the child.

Asthma↗
PubMed1993

Confrontation: methods and skills.

By identifying personal "hot buttons," nurse managers gain insight into the reasons they avoid problems or use inappropriate confrontation techniques. Through appropriate guidelines, successful confrontation can resolve conflicts and improve communication.

Conflict, Psychological↗
PubMed1992

Clinical and histopathologic changes in the host cornea after epikeratoplasty for keratoconus.

Five consecutive patients underwent epikeratoplasty for keratoconus. Postoperatively, four patients had poor visual acuity (average, 20/200) secondary to folds in Descemet's membrane and interface scarring. Two underwent penetrating keratoplasty eight months later. Histopathologic examination of the host corneas and the overlying lenticules disclosed epithelial irregularity and subepithelial fibrosis. The host corneas showed folds in Descemet's membrane and focal posterior stromal fibrosis. Electron microscopy disclosed breaks in Bowman's membrane with irregular collagen, posterior aggregates of amorphous material, and focal endothelial degeneration. The fifth patient had graft ulceration and vascularization that required removal of the lenticule. She underwent a penetrating keratoplasty five months later and histopathologic examination demonstrated persistent folds in Descemet's membrane. Immunostaining of specimens from three cases disclosed a reduced expression of sulfated epitopes of keratan sulfate and an increase in sulfated dermatan sulfate in the lenticule and host corneal tissues. These alterations in stromal proteoglycans are characteristic of stromal scars and keratoconus and provide evidence of pathologic processes in the graft tissue. Because of potential complications, epikeratoplasty should be considered only for those patients who are unsuitable candidates for contact lenses or penetrating keratoplasty.

Adult↗
PubMed1992

Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester.

Lithium carbonate is an effective drug for prophylaxis and treatment of major affective disorders. In-utero exposure to lithium during the first trimester of pregnancy might be associated with an increased risk of cardiac malformations, especially the rare Ebstein's anomaly. We prospectively recruited and followed 148 women (mean age 30 years, SD 5 range 15-40) using lithium during the first trimester of pregnancy, who consulted four teratogen information centres in the USA and Canada. Pregnancy outcome was compared with that of controls matched for maternal age. We had complete follow-up of pregnancy outcome in 138 of 148 patients recruited. In the other 10, fetal echocardiograms were available but postnatal follow-up was not done. Mean daily dose of lithium was 927 mg (SD 340). Rates of major congenital malformations did not differ between the lithium (2.8%) and control (2.4%) groups. 1 patient in the lithium group chose to terminate pregnancy after Ebstein's anomaly was detected by a prenatal echocardiogram. There was 1 ventricular septal defect in the controls. Birthweight was significantly higher in the lithium-exposed infants than in the controls despite identical gestational ages (3475 [660] g vs 3383 [566] g, p = 0.02). The true difference in birthweight might have been even larger, since significantly more women using lithium than controls were cigarette smokers (31.8% vs 15.5%, p = 0.002). These results indicate that lithium is not an important human teratogen. Women with major affective disorders who wish to have children may continue lithium therapy, provided that adequate screening tests, including level II ultrasound and fetal echocardiography, are done.

Abnormalities, Drug-Induced↗
PubMed1992

Inhibition of protein kinase C by ether-linked lipids is not correlated with their antineoplastic activity on WEHI-3B and R6X-B15 cells.

To test the hypothesis that the action of antineoplastic ether-linked lipids in leukemic cells is associated with their ability to inhibit protein kinase C (PKC), we have compared the effects of two ether-linked lipids, 1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET16-OCH3-GPC) and 1-O-hexadecyl-2-O-methyl-sn-glycero-3-(S-beta-D-1'- thioglucopyranosyl)-sn-glycerol (ET16-OCH3-beta-thio-Glc), on two different leukemic cell lines (WEHI-3B and R6X-B15). ET16-OCH3-GPC killed WEHI-3B cells with an EC50 value of 2.5 microM, whereas it was far less effective against R6X-B15 cells (EC50 = 40 microM). In contrast, the beta anomer of ET16-OCH3-beta-thio-Glc did not kill either cell line at concentrations up to 40 microM. Both ET16-OCH3-GPC and ET16-OCH3-thio-Glc inhibited 12-O-tetradecanoylphorbol 12,13-dibutyrate (TPA)-induced PKC translocation in both WEHI-3B and R6X-B15 cells. When WEHI-3B cells were first exposed to TPA, and then to ET16-OCH3-GPC, no significant decrease in PKC activity in the particulate fraction was noticed. When, however, the cells were first exposed to ET16-OCH3-GPC and then to TPA, the enzyme activity in the particulate fraction was decreased by 20-30%. A phorbol dibutyrate binding assay showed that the decrease in membrane-associated PKC activity and the increase in cytosolic PKC activity did not result from impeded enzyme translocation. These results suggest that the similar PKC inhibitory potency of ET16-OCH3-GPC and ET16-OCH3-beta-thio-Glc: (a) is not correlated with the widely different cytotoxicities of these agents and (b) is probably due to interference with the binding of diacylglycerol/phosphatidylserine or TPA to PKC. Taken together, these results suggest that the ether-linked lipids compete with diacylglycerol/phosphatidylserine or TPA for binding sites on PKC required for enzyme activation.

Antineoplastic Agents↗
PubMed1992

Comparative analysis of computed tomographic and magnetic resonance imaging scans in Alzheimer patients and controls.

Ten patients with Alzheimer's disease underwent computed tomography and magnetic resonance imaging at the same point in time. The mean Mini-Mental State examination score of the patients was 23, indicating that they were mildly impaired. Ten age-equivalent controls also obtained computed tomographic and magnetic resonance imaging scans. A semiautomated computer program analyzed nine comparable regions of interest on each set of scans. When regions of interest from both types of scans were combined in the same discriminant function analysis, the first two variables selected were from the magnetic resonance imaging data set, and they significantly differentiated 95% of the patients and controls.

Aged↗
PubMed1992

Ocular-chondrodysplasia in labrador retriever dogs: a morphometric and electron microscopical analysis.

Ocular-chondrodysplasia in Labrador Retriever dogs is characterized by short-limbed dwarfism and ocular abnormalities. The purposes of the present study were to develop morphological criteria to define the matrix and/or chondrocytic abnormalities associated with this chondrodysplasia, and to test the hypothesis that ineffective matrix-directed cellular swelling was associated with the decreased longitudinal bone growth in these animals. The proximal and distal radial growth plates were collected from four affected animals of the same litter. Stereological techniques were used to analyze both cellular shapes and cellular volume changes in the hypertrophic zone. The pathological changes seen in these growth plates varied between animals and included disorganization of cellular columns with abnormal extent of calcification. Chondrocytes of all zones contained two types of abnormal cellular inclusions classified as light and dark, based on the intensity of eosinophilic staining. Both types of inclusions contained material that resembled the surrounding extracellular matrix, varying only in the apparent hydration of the contents. It could be demonstrated that light inclusions were located in the peripheral cytoplasm and connected to the extracellular matrix through narrow channels. By contrast, dark inclusions were membrane bound and perinuclear. Chondrocytes with multiple, large inclusions appeared to be undergoing degenerative changes. Although the final volume achieved by hypertrophic chondrocytes was consistent with that of normal growth plates, there was a high level of variability of chondrocytic shape and evidence of premature cellular condensation in the maturation zone. The severity of the dwarfism correlated both with the extent of chondrocytic changes and the severity of the ocular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Unrestricted principal components analysis of brain electrical activity: issues of data dimensionality, artifact, and utility.

Principal components analysis (PCA) was performed on the 1536 spectral and 2944 evoked potential (EP) variables generated by neurophysiologic paradigms including flash VER, click AER, and eyes open and closed spectral EEG from 202 healthy subjects aged 30 to 80. In each case data dimensionality of 1500 to 3000 was substantially reduced using PCA by magnitudes of 20 to over 200. Just 20 PCA factors accounted for 70% to 85% of the variance. Visual inspection of the topographic distribution of factor loading scores revealed complex loadings across multiple data dimensions (time-space and frequency-space). Forty-two non-artifactual factors were successful in classifying age, gender, and a separate group of 60 demented patients by linear discriminant analysis. Discrimination of age and gender primarily involved EP derived factors, whereas dementia primarily involved EEG derived factors. Thirty-eight artifactual factors were identified which, alone, could not discriminate age but were relatively successful in discriminating gender and dementia. The need to parsimoniously develop real neurophysiologic measures and to objectively exclude artifact are discussed. Unrestricted PCA is suggested as a step in this direction.

Adult↗
PubMed1992

Triphenyl phosphite-induced ultrastructural changes in bovine adrenomedullary chromaffin cells.

Primary cultures of bovine adrenomedullary chromaffin cells were treated with the phosphorus acid ester triphenyl phosphite (TPP), a chemical capable of producing Type II organophosphorus compound-induced delayed neurotoxicity (OPIDN), and the morphological changes were assessed by transmission electron and scanning microscopy. Following a 24-hr incubation with 100 microM TPP nearly all mitochondria were either disrupted or swollen and glycogen buildup within the cytoplasm was evident. The viability of cells treated with TPP and cultured on coverslips for scanning electron microscopy was very low. By scanning electron microscopy, the filopodia of these cells appeared contracted. The surface texture was very irregular and giant globular bodies were evident. Parallel studies were carried out with the cholinergic compound O,O-diethyl 4-nitrophenyl phosphate (paraoxon) and the Type I delayed neurotoxicant O,O-diisopropylphosphorofluoridate (DFP). Transmission and scanning electron microscopy revealed that treatment with these organophosphorus compounds did not produce the ultrastructural effects that were seen with TPP. The morphological data were confirmed biochemically by assessing the viability of the mitochondria via measurement of [3H]adenosine incorporation into ATP. Treatment with 100 microM TPP for 4 or 24 hr caused a marked inhibition (90% relative to controls) of adenosine incorporation. Neither 100 microM paraoxon nor 100 microM DFP had an inhibitory effect on incorporation. The effect of TPP was time-dependent with significant biochemical effects as early as 60 min. In contrast, ultrastructural changes were not seen until 24 hr. Morphologically, the 60-min incubations showed no perturbation in mitochondrial integrity. Our results support a specific effect of the triphenylphosphite, TPP, a Type II OPIDN compound, not a general toxic effect of organophosphorus compounds since the cholinergic agent paraoxon and the Type I delayed neurotoxic compound DFP did nto alter the cells ultrastructurally or compromise the mitochondria biochemically. The apparent target for TPP toxicity is the mitochondria.

Adenosine↗