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Biomedical subjects

C A Jones

Publications and source records attributed to C A Jones.

At least 127 records · Page 7Linked to original sources
PubMed1995

Monocytes cultured in cytokine-defined environments differ from freshly isolated monocytes in their responses to IL-4 and IL-10.

To investigate the regulatory effects of the prototypic Th2 lymphocyte products and potential immunotherapeutic agents interleukin-4 (IL-4) and IL-10 on macrophages differentiated in vitro under different cytokine-defined environments, blood monocytes were incubated for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor or IL-4. The effect of monocyte culture in the presence or absence of serum was also investigated. Functional responses by 7-day-cultured cells to IL-4, quantified as decreased CD14 expression and suppression of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta production, and as a positive response, increased CD23 expression, were compared directly with the responses by monocytes from which they were derived. In response to IL-10, decreases in LPS-induced TNF-alpha and IL-1 beta production and reduction in the expression of major histocompatibility complex (MHC) class II antigens were examined. Seven-day cultured monocytes/macrophages showed (1) diminished TNF-alpha production in response to IL-10 but not IL-4 (2), diminished IL-1 beta production in response to both IL-4 and IL-10, and compared with fresh monocytes (3), diminished CD14 expression in response to IL-4, and (4) a lesser increase in CD23 expression in response to IL-4. This was the case regardless of the cytokine in the presence of which the cells had been cultured for 7 days. Monocytes cultured for 7 days in GM-CSF expressed increased levels of MHC class II and LPS-induced TNF-alpha and responded inefficiently to IL-10 for decreased MHC class II. The responses by monocytes cultured for 7 days with GM-CSF resemble the published properties of synovial fluid macrophages from patients with chronic inflammatory arthritis. The study highlights the complexity of monocyte/macrophage responses to the immunoregulatory cytokines IL-4 and IL-10 and concludes that responses to IL-4 and IL-10 by blood monocytes may not be representative of responses by their differentiated or activated counterparts.

Antigens, CD↗
PubMed1995

Use of granulocyte colony stimulating factor to reduce the toxicity of super-VAC chemotherapy in advanced solid tumours in childhood.

Children with advanced solid tumours at the Royal Alexandra Hospital for Children (RAHC) receive an intensive four drug chemotherapy combination, Super-VAC (cyclophosphamide, 500 mg/m2, adriamycin, 30 mg/m2, actinomycin-D, 0.5 mg/m2, all daily for 3 days, and vincristine, 1.5 mg/m2 weekly). The majority of patients respond well to three courses of such therapy, but with considerable morbidity, including fever, neutropenia, and mucositis. In an attempt to reduce the morbidity of Super-VAC, G-CSF was added. We documented various parameters in 12 patients who received 28 cycles with G-CSF and compared them to an historical control group of 37 cycles in the preceding 14 patients who received Super-VAC. The median duration of each cycle was 23 days with G-CSF and 28 days without G-CSF (P = 0.004). However, differences in requirements for inpatient care (median 16 v. 20 days), intravenous antibiotics (median 9 v. 10 days), amphotericin (median 5 v. 3 days), morphine (median 8.5 v. 7 days), or TPN (median 6.5 v. 8 days) did not reach statistical significance. As expected, a significant difference in neutrophil recovery was demonstrated between the two groups (median 11 v. 16 days, P < 0.0001) but not in platelet recovery (median 13 v. 13 days). The use of G-CSF with Super-VAC resulted in a shorter cycle length, so increasing the dose intensity. A reduction in morbidity could not be demonstrated. No toxic side effects from G-CSF were noted.

Adolescent↗
PubMed1995

Effects of cocaine in pigeons responding under a progressive-ratio schedule of food delivery.

Although the progressive-ratio schedule has been used frequently to quantify the reinforcing effectiveness of self-administered drugs, it has seldom been used to examine the effects of drugs on food-maintained behavior and has never been used to evaluate the effects of cocaine on such behavior. In the present study, the effects of acute administrations of cocaine were evaluated in pigeons responding under a progressive-ratio 5 schedule of food delivery that continued for 1 h or until responding ceased for 5 consecutive min, whichever occurred first. The largest ratio completed each session (breaking point) was the primary dependent variable. In general, acute administrations of cocaine at 0.56 to 3.2 mg/kg increased breaking points, whereas doses above 5.6 mg/kg decreased breaking points. Although cocaine reduces food intake and subjective hunger for food, the present data indicate that the drug reduces the reinforcing effectiveness of food only at high doses.

Animals↗
PubMed1995

Serum creatinine levels in older adults: relationship with health status and medications.

We aimed to examine the association of serum creatinine with health status and current medications in the population of older adults. We employed a cross-sectional study within an ongoing cohort of 3999 residents of three communities of the Established Populations for Epidemiologic Studies of the Elderly who had venepuncture at the 6-year follow-up when they were aged 71 years and older. Serum creatinine levels, history of diabetes and heart attack, current medications, and blood pressure were measured. Creatinine levels were higher in men than in women, and in blacks than in whites. Higher creatinine levels were observed in persons with a history of diabetes or heart attack, and in those reporting use of cimetidine and diuretic medications. Persons taking frusemide and the potassium-sparing diuretics had higher creatinine levels than those taking thiazides. This study confirms associations of higher creatinine with male sex, older age, black race, history of diabetes and cimetidine use reported from cross-sectional research in younger populations and in smaller, more selected groups of older adults. Longitudinal studies will be necessary to strengthen our understanding of the causes of changes in kidney function in the older population.

Activities of Daily Living↗
PubMed1995

Interleukin 4 production by human amnion epithelial cells and regulation of its activity by glycosaminoglycan binding.

The pro-inflammatory molecules, tumor necrosis factor alpha (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and prostaglandin E2 (PGE2), are postulated to have a role in human pregnancy and parturition. The ability of interleukin 4 (IL-4) to suppress the production of TNF alpha, IL-1, IL-6, and PGE2 by activated monocytes prompted us to investigate a possible regulatory role for IL-4 in human gestation. Immunohistochemical techniques were used to show that human amnion epithelium stained positively for IL-4. Tissue from both the first (n = 5) and third (n = 46) trimester expressed immunoreactive IL-4, which was detected by the use of four antihuman IL-4 monoclonal antibodies. Analysis of mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA extracts of amnion epithelial cells indicated that they were the source of IL-4. One of the anti-IL-4 antibodies used stained IL-4 protein associated with the basement membrane of the amnion epithelium. The mechanism of this association was investigated. IL-4 was shown to be a heparin-binding cytokine, which would enable it to bind to components of the extracellular matrix. Thus, this study identified a previously undescribed cellular source of IL-4, implicating a role for IL-4 in human gestation. Additionally, glycosaminoglycan binding may regulate IL-4 activity in vivo.

Amnion↗
PubMed1995

Predicting the outcome of symptomatic congenital cytomegalovirus infection.

The prognosis of babies with symptomatic congenital cytomegalovirus (CMV) infection is worse than for those with asymptomatic CMV, but is difficult to quantify. Babies affected as a result of primary maternal CMV are at greater risk than after reactivation CMV. Chorioretinitis occurs in 10-15% of symptomatic babies and almost always indicates significant mental impairment. Microcephaly occurs in around 50% at birth, but does not always persist, and does not necessarily imply later neurological handicap. Investigative findings that increase the likelihood of handicap include radiographic or computerized tomography scan finding of intracranial calcification and raised cerebrospinal fluid protein. Late deafness is always unpredictable and all babies with congenital CMV infection should have an audiological follow up. The mortality of symptomatic congenital CMV infection is about 30%.

Brain↗
PubMed1995

Tryptase, the dominant secretory granular protein in human mast cells, is a potent mitogen for cultured dog tracheal smooth muscle cells.

Hyperplasia of airway smooth muscle cells is present in the airways of asthmatic patients and may contribute to the development of the bronchial hyperresponsiveness that occurs in these patients. Because tryptase is an abundant component of mast cell granules and has demonstrated growth-stimulatory effects in other mesenchymal cells (J. Clin. Invest. 1991; 88:493-499), the goal of our study was to determine whether tryptase is a mitogen for airway smooth muscle cells. The mitogenic effects of tryptase were tested in passages 1 through 5 of dog tracheal smooth muscle cells, either by counting smooth muscle cells or by monitoring uptake of bromodeoxyuridine (BrdU) into cellular DNA during S-phase. With respect to its efficacy, at a near maximal concentration (4 nM), tryptase increased cell numbers 2.1 +/- 0.2- or 2.8 +/- 0.6-fold above controls after 2 or 4 days, respectively, and these increases were approximately the same as those induced by platelet-derived growth factor (50 ng/ml) or 10% calf serum. With respect to potency, tryptase caused concentration-dependent increases in BrdU uptake, as detected in an enzyme-linked immunosorbent assay or by counting BrdU-labeled nuclei, with an EC50 of 2 nM. Pretreatment of tryptase with diisopropylfluorophosphate, to reduce markedly its catalytic as a activity as a proteinase, attenuated its growth-stimulated effects by 58 +/- 16%. Tryptase-induced mitogenesis was not a nonspecific effect of all serine proteinases, because thrombin, another proteinase with mitogenicity for fibroblasts, stimulated neither increases in cell counts nor BrdU uptake in our cells. We conclude that tryptase is a potent mitogen for airway smooth muscle cells in culture.

Animals↗
PubMed1994

Reflex behavior during walking in incomplete spinal-cord-injured subjects.

Reflexes evoked by stimulation of the posterior tibial nerve at the ankle during walking were investigated in 10 subjects with incomplete injury of the spinal cord. Low-intensity stimuli (1.5 to 1.7 times the motor threshold) were delivered during treadmill walking. Reflexes were recorded by surface electromyography from the tibialis anterior (TA) and soleus (SOL) muscles. Responses were evoked at early, medium, and late latencies in all subjects. The reflex activity at a medium latency (50 to 80 ms) was cyclically modulated in all of the subjects during walking in both muscles, but the pattern of modulation was different from that seen in normal subjects (Yang and Stein, J. Neurophysiol., 63, 1109-1117). Most spinal-cord-injured subjects did not show inhibitory responses in the TA; excitatory responses were seen in the swing phase and occasionally in the stance phase. Inhibitory responses were typically evoked in the SOL muscle during the stance phase, but abnormal excitatory responses were also seen during the swing phase in the majority of subjects. Excitatory responses were seen in some subjects during the stance phase as well. Functional walking ability and clinical measures of muscle tone were not correlated with the degree of reflex modulation in walking. The lack of correlation between these measures could be related to many factors including the small number of subjects, the subjectivity of clinical measures, and the different movement conditions under which these measures were taken. The results demonstrated that most spinal-cord-injured subjects retained the ability to modulate this reflex during walking, but the pattern of modulation was abnormal. Moreover, excitatory responses were more frequently evoked than inhibitory responses.

Adult↗
PubMed1994

Glucosyltransferase mediates adhesion of Streptococcus gordonii to human endothelial cells in vitro.

Human umbilical vein endothelial cells (HUVEC) were used as an experimental host model to investigate the mechanism(s) of streptococcal adhesion in infective endocarditis. Adhesion activity of Streptococcus gordonii was maximal during the logarithmic phase of growth and was greatly reduced or eliminated by pretreatment of bacteria with heat, formaldehyde, or trypsin. At saturating numbers of streptococci, an average of 81 bacteria were bound per HUVEC. Streptococcal adhesion was inhibited by low-molecular-weight dextran and heparin but not by sucrose, fibronectin, or laminin. Adhesion was also prevented by pretreatment of HUVEC with proteins dissociated from the surface of S. gordonii with 10 mM EDTA or isolated from spent culture medium. Western blot (immunoblot) assays detected a single adhesion protein of 153 kDa (AP153) on HUVEC after incubation with unfractionated extracts of streptococci. The adhesin exhibited glucosyltransferase (GTF) activity when incubated with sucrose and Triton X-100 after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The AP153 was purified by affinity chromatography on dextran beads and show to have binding activity for HUVEC, GTF activity, an amino acid composition similar to that reported for GTF of S. gordonii, and the ability to inhibit S. gordonii adhesion. Incubation of the streptococci with antibodies to the adhesin inhibited bacterial attachment to HUVEC monolayers. These results indicate that surface-localized GTF mediates adhesion of S. gordonii to HUVEC in vitro and may serve as a mechanism for colonization of the endocardium in infective endocarditis.

Adhesins, Bacterial↗
PubMed1993

Glutamate stimulates dopamine release from cortical and limbic rat brain in vitro.

In vitro superfusion studies were performed to compare the glutamatergic control of dopamine release from minislices of rat striatum, olfactory tubercle and frontal cortex. In the absence of Mg2+, release of endogenous dopamine from olfactory tubercle and striatum, and [3H]dopamine from frontal cortex, was stimulated by glutamate (at concentrations of 0.3, 3 and 1 mM respectively). In all three areas the response to N-methyl-D-aspartate (NMDA) was greater than that to kainate, implying mediation largely by NMDA receptors, with non-NMDA receptors contributing to a smaller extent. This was confirmed by antagonist studies in the frontal cortex, where the response to glutamate was largely (70%) blocked by 2-amino-5-phosphonopentanoic acid (AP5), and further blocked by AP5 + 6,7-dinitroquinoxaline-2,3-dione (DNQX). In the olfactory tubercle and striatum, glutamate was as effective as NMDA, but in the frontal cortex the response to NMDA was significantly larger than that to glutamate.

Animals↗
PubMed1993

Synovial fluid macrophages and blood monocytes differ in their response to IL-4.

IL-4 has been described as a potential anti-inflammatory molecule because of its ability in vitro to down-regulate human monocyte production of proinflammatory mediators. In this study, the activity of IL-4 on mononuclear cells and CD14+ macrophages from a site of chronic inflammation, namely, the joints of patients with rheumatoid and psoriatic arthritis, was investigated and compared directly with its activity on PBMC and monocytes from the same patients. In contrast to the response by blood monocytes, the response to IL-4 by synovial fluid cells was selective; IL-4 did not significantly suppress LPS-induced TNF-alpha production, but decreased CD14 expression to a similar extent in the two cell populations. IL-4 induction of monocyte/macrophage CD23 expression was investigated as a stimulatory response to IL-4, and although significantly increased on synovial fluid CD14+ cells by IL-4, the induction was considerably reduced compared with that measured for blood cells. Activation and differentiation in vitro of blood monocytes reduced their response to IL-4 for decreased TNF-alpha production and induction of CD23 and suggested that these biologic phenomena may contribute to the decreased responsiveness to IL-4 by synovial fluid monocytes/macrophages. Thus, IL-4 does not have the same anti-inflammatory properties in vitro on synovial fluid cells as on blood monocytes.

Antigens, CD↗
PubMed1993

Cis-urocanic acid stimulates human peripheral blood monocyte prostaglandin E2 production and suppresses indirectly tumor necrosis factor-alpha levels.

Photoisomerization of trans-urocanic acid (UCA) in the stratum corneum has been implicated in the immunosuppression detected after irradiation with UVB (UV wavelength of 280-320 nm). In this study, cis-urocanic acid suppressed human monocyte production of TNF-alpha by a PGE2-dependent mechanism. This contrasted with the mechanism involving histamine type 2 receptors by which the UCA structural analogue, histamine, suppressed monocyte TNF-alpha production. Histamine type 1 receptor antagonists were without effect on both the cis-UCA- and histamine-induced suppression of monocyte TNF-alpha levels. As indomethacin can reverse UVB-immunosuppression in murine models, we may have identified one of the cellular mechanisms responsible for reduced delayed-type hypersensitivity responses. Decreased TNF-alpha levels, by restricting further cytokine recruitment, may also limit the development of the inflammatory components of hypersensitivity responses.

Brompheniramine↗
PubMed1993

The impact of comorbid and sociodemographic factors on access to renal transplantation.

OBJECTIVE: To assess the impact of sociodemographic factors and comorbid conditions on access to renal transplantation for adult US dialysis patients with end-stage renal disease (ESRD). DESIGN: Cohort analytic study. Data on comorbid conditions at onset of ESRD were abstracted from patients' medical records and matched to sociodemographic and ESRD data from the United States Renal Data System database. SETTING: United States Medicare dialysis population. PATIENTS: Random, national sample of ESRD patients starting dialysis in 1986 and 1987 (n = 4118). MAIN OUTCOME MEASURE: Time to first renal transplant (living or cadaver donor) since onset of ESRD regressed with two nested Cox proportional hazards models, first against sociodemographic factors alone, and then against sociodemographic factors and comorbid conditions. RESULTS: Cardiovascular diseases are most predictive of who received a transplant; patients with coronary heart disease, congestive heart failure, or left ventricular hypertrophy showed lower transplantation rates relative to patients without the disease (relative rate [RR] = 0.65 to 0.80, P < .05 each). Obese patients and patients with peripheral vascular disease also showed lower transplantation rates (RR = 0.65 to 0.75, P < .05 each). Previously reported sociodemographic effects of lower transplantation rates for older patients, women, nonwhite patients, and lower income patients were confirmed (P < .01). Sociodemographic effects remained essentially unchanged when adjusted for comorbid conditions. CONCLUSIONS: These findings indicate that sociodemographics have strong independent effects on access to transplantation that cannot be explained away as "surrogate" effects related to comorbid factors. Furthermore, the results suggest that lower mortality rates for transplant recipients relative to dialysis patients are due, in part, to a healthier case mix among patients receiving transplants.

Adult↗
PubMed1993

Inflammatory fluids regulate TNF-alpha, but not IL-1 beta, production by human peritoneal macrophages. A study of patients on continuous ambulatory peritoneal dialysis with peritonitis.

To gain insight into the factors regulating an inflammatory response in vivo, the activities of peritoneal macrophages and the influence of the inflammatory fluids from which they were harvested were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis. Specifically, the production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and prostaglandin E2 (PGE2) by lipopolysaccharide-stimulated human peritoneal macrophages from CAPD patients with peritonitis was examined in the presence of the inflammatory dialysates from which they were isolated. When tested at a dilution of 20%, the dialysates inhibited production of TNF-alpha, a key monokine in the orchestration of the inflammatory response. In contrast to the effect on TNF-alpha, the dialysates did not affect IL-1 beta production by stimulated macrophages. The activity inhibitory for TNF-alpha synthesis was not fully characterized, but a number of known inhibitors were shown not to be responsible for the suppressive activity. The inhibitory activity was detected in cases of noninfective peritonitis and excluded the possibility that a bacterial product was responsible. Hyperosmolality, pH, protein levels, glucose, uremic molecules, cortisol, heparin, and antibiotics were not responsible for the inhibitory activity. The activity had some similarity to the reported actions of alpha-globulins (which are acute phase proteins), PGE2, TNF-alpha soluble receptors, and IL-6, but there was no evidence for their involvement. Whether the selective suppression of TNF-alpha production is a general finding in inflammatory responses will require additional studies. This study nevertheless illustrates the potential for the host to regulate tightly the development of an excessive inflammatory response and thus to limit tissue pathology. However, it is unknown whether an appropriate host defense is compromised.

Acute-Phase Proteins↗