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Biomedical subjects

S C Jones

Publications and source records attributed to S C Jones.

At least 37 records · Page 2Linked to original sources
PubMed1998

Abnormal regulation of cell membrane fluidity in diabetic nephropathy.

An abnormality of the physical properties of the cell membrane may underlie the defect that unites the clinical and biochemical abnormalities found in subjects with diabetic nephropathy. The cell membrane is linked both structurally and functionally with the cytoskeleton. The fluorescence anisotropy, a measure of membrane fluidity, was studied at baseline and after modulation of cytoskeletal proteins by thiol group alkylation with N-ethylmaleimide (NEM). 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess anisotropy in the deep hydrophobic regions of the lipid bilayer and trimethylammonium-diphenylhexatriene (TMA-DPH) was used to assess the superficial, relatively hydrophilic regions. We compared 17 subjects with insulin-dependent diabetes mellitus (IDDM) and nephropathy with 17 control subjects with IDDM and 24 non-diabetic control subjects. Median TMA-DPH anisotropy (0.271 (0.239-0.332) vs 0.269 (0.258-0.281) vs 0.275 (0.246-0.287)) and DPH anisotropy (0.221 (0.193-0.261) vs 0.227 (0.197-0.253) vs 0.226 (0.193-0.245)) were similar in erythrocytes from the three groups. However after alkylation of protein thiol groups with NEM clear differences emerged. In the control subjects with and without IDDM there was a significant fall in TMA-DPH anisotropy compared to the subjects with diabetic nephropathy in whom the addition of NEM had no effect (deltaTMA-DPH anisotropy -0.005 (-0.020 - +0.006) vs -0.005 (-0.011 - +0.016) vs +0.002 (-0.010 - +0.008) p < 0.001). This finding was confirmed when the deep regions of the lipid bilayer were assessed using DPH (deltaDPH anisotropy -0.017 (-0.029 - -0.007.) vs -0.015 (-0.029 - +0.001) vs + 0.003 (-0.021 - +0.018) p < 0.001). We conclude that cytoskeletal modulation of the physical properties of the cell membrane lipids by proteins is abnormal in subjects with diabetic nephropathy. Such an abnormality could explain some of the clinical and metabolic abnormalities found in this condition.

Adult↗
PubMed1997

Perfusion to colorectal cancer liver metastases is not uniform and depends on tumor location and feeding vessel.

Future effective therapies for hepatic metastases may depend on a better understanding of perfusion to these tumors. The purpose of this project was to define blood flow to colorectal cancer liver metastases using quantitative autoradiography (QAR). Liver tumors were established in F1 hybrids of WF x BN rats by intrasplenic injection of a DMH-induced rat colon adenocarcinoma. Rats underwent laparotomy 4-5 weeks later and [14C]iodoantipyrine (a radiotracer) was infused via the hepatic artery (HA) or portal vein (PV). Livers were harvested, frozen in liquid nitrogen, and sectioned at 20 microns through all tumors. QAR compared optical density of cross sections of tumors to surrounding normal liver tissue. Tumor:liver perfusion ratios (T/L PR) and tumor center:tumor periphery perfusion ratios (C/P PR) were calculated. All groups were analyzed with regard to tumor location and size. Seventy-seven tumors in 6 rats in the HA infusion group were analyzed; 74 tumors in 8 rats in the PV group were analyzed. Statistical analysis was by repeated measures analysis of variance. Mean HA T/L PR = 0.97 +/- 0.13, mean PV T/L PR = 0.25 +/- 0.11. Mean HA T/L PR for deep tumors was 1.38 +/- 0.17 and for superficial tumors was 0.57 +/- 0.15 (P < 0.01). Mean HA T/L PR for small tumors was 1.09 +/- 0.12 and for large tumors was 0.86 +/- 0.21 (P = 0.27). Mean PV T/L PR for deep tumors was 0.27 +/- 0.14 and for superficial tumors was 0.24 +/- 0.15 (P = 0.71). Mean PV T/L PR for small tumors was 0.31 +/- 0.15 and for large tumors was 0.20 +/- 0.14 (P = 0.54). Mean HA C/P PR = 1.15 +/- 0.15, mean PV C/P PR = 0.81 +/- 0.14 (P = 0.06). Mean HA C/P PR for small tumors was 1.37 +/- 0.16 and for large tumors was 0.92 +/- 0.17 (P = 0.01). Mean PV C/P PR for small tumors was 0.78 +/- 0.18 and for large tumors was 0.72 +/- 0.13 (P = 0.71). HA perfusion of tumors is significantly higher than PV perfusion compared to surrounding normal liver tissue. HA perfusion varies significantly depending on tumor location. There was a trend toward HA perfusion to the tumor center being slightly greater than to the periphery whereas the reverse was seen for PV perfusion. Tumor size did not affect overall perfusion but it did affect regional HA tumor perfusion.

Adenocarcinoma↗
PubMed1997

Inhibition of transforming growth factor alpha stimulation of human squamous cell carcinoma of the head and neck with anti-TGF-alpha antibodies and tyrphostin.

BACKGROUND: Transforming growth factor alpha (TGF-alpha) and its receptor (EGF-R) may regulate normal and malignant epithelial cell growth by an autocrine mechanism. We investigated the role of TGF-alpha in regulating head and neck SCC tumor growth. METHODS: TGF-alpha and EGF-R levels were measured in 7 SCC cell lines and 14 SCC biopsies by RIA, Scatchard, and Western analysis. TGF-alpha autocrine stimulation of DNA synthesis in SCC cell lines was assessed by incubation with TGF-alpha neutralizing antibodies and tyrphostin AG 1478, a selective and potent inhibitor of EGF-R kinase. RESULTS: All SCC cell lines synthesized TGF-alpha and expressed elevated EGF-R levels compared to normal keratinocytes. Twelve of the 14 SCC biopsies contained TGF-alpha protein and 8 had specific EGF-R. Exogenous TGF-alpha or EGF significantly increased DNA synthesis in 4 of 5 SCC cell lines. TGF-alpha neutralizing antibodies or tyrphostin AG 1478 reduced DNA synthesis in the two SCC cell lines (FaDu and SCC9) tested. CONCLUSIONS: These results indicate that SCC cell lines and tumors usually synthesize TGF-alpha, have elevated levels of EGF-R, and are mitogenically stimulated by a TGF-alpha autocrine system. Selective inhibition of the TGF-alpha system by EGF-R kinase inhibitors or TGF-alpha neutralizing antibodies may be useful strategies for treating SCC that overexpress TGF-alpha and its receptor.

Autocrine Communication↗
PubMed1997

Thiol group modulation of sodium-lithium countertransport kinetics in diabetic nephropathy.

Abnormal erythrocyte sodium-lithium countertransport (Na-Li CT) activity, traditionally measured at a single sodium concentration of 140 mmol.l-1 (V140), may represent an inherited risk marker for diabetic nephropathy. The membrane defect underlying this association is poorly understood, though modulation by key protein thiol groups appears to be important in essential hypertension. To improve understanding of this abnormality, Na-Li CT kinetics in untreated erythrocytes and after thiol group alkylation with N-ethylmaleimide were investigated in 18 subjects with diabetic nephropathy, 20 normoalbuminuric insulin-dependent diabetic (IDDM) subjects and 18 non-diabetic individuals. Using the traditional assay, V140 was similar in subjects with diabetic nephropathy compared to IDDM control subjects vs 0.311 (0.152-0.475) (0.247 (0.111-0.498) mmol Li.h-1.l erythrocytes-1). Kinetic parameters were abnormal in subjects with diabetic nephropathy compared with diabetic and non-diabetic control subjects with both Vmax (maximal Na-Li CT activity) (0.454 (0.257-0.963) vs 0.338 (0.183-0.972) vs 0.332 (0.213-0.603) mmol Li.h-1.l erythrocytes-1, p < 0.05), and Vmax/Km(So) ratio, reflecting ion association (6.03 (2.3-9.6) vs 4.73 (2.0-10.4) vs 4.48 (1.5-7.1), p < 0.01), significantly higher. N-ethylmaleimide decreased K(m)(So) and Vmax abolishing differences in Vmax/Km(So) ratio between groups (2.45 (1.18-4.21) vs 2.23 (0.96-4.3) vs 2.44 (1.4-3.7), but enhancing the differences in Vmax (0.186 (0.090-0.315) vs 0.120 (0.051-0.256) vs 0.128 (0.080-0.206) mmol Li.h-1.l erythrocytes-1, p < 0.0001). Of subjects with diabetic nephropathy, 78% were outside the 75th percentile of the non-diabetic control subjects when Vmax and Vmax/Km(So) ratio were combined, compared to 20% of the normoalbuminuric control subjects. We conclude that the traditional assay, V140, is poor at detecting individuals with diabetic nephropathy. Study of the kinetic parameters of the transporter, including thiol group modulation, suggests that increased ion association, Vmax/Km(So) ratio may represent the inherited defect and improves identification of subjects with diabetic nephropathy.

Adult↗
PubMed1997

Prevention of chronic cerebral vasospasm in dogs with milrinone.

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms for the treated group, compared with the control group (98.28 +/- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively; P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

Animals↗
PubMed1997

Suitability of laser stimulated TLD arrays as patient dose monitors in high dose x-ray imaging.

Skin entrance doses of patients undergoing interventional x-ray procedures are capable of causing skin damage and should be monitored routinely. Single TLD chips are not suitable because the location of maximum skin exposure cannot be predicted. Most photographic films are too sensitive at diagnostic x-ray energies for dosimetry, exhibit temporal changes in response, and require special packaging by the user. We have investigated the suitability of laser heated MgB4O7 TLDs in a polyimide binder in the range of 0.2-20 Gy. These are available in radioluscent arrays up to 30 x 30 cm for direct measurement of patient skin dose. Dose response was compared with a calibrated ion chamber dosimeter. Exposures were made at 60, 90, and 120 kVp, at low (fluoroscopy) and high (DSA) dose rates, and at different beam incidence angles. Longitudinal reproducibility and response to temperature changes during exposure were also checked. The dose response is linear below approximately 6 Gy where the slope starts to increase 2% per Gy. Errors were less than +/- 2% over a 0-80 degrees range of beam incidence angles; less than +/- 3% for both dose rate variations and kVp differences between 70 and 120 kVp. The response was unaffected by temperature changes between 20 and 37 degrees C. Reproducibility is current +/- 7%. MgB4O7 TLD arrays are suitable for patient dosimetry in high dose fluoroscopy procedures if appropriate calibrations are used. Uncertainty in skin dose measurement is less than 10%, which is substantially better than film dosimetry.

Biophysical Phenomena↗
PubMed1996

Evaluation of a novel nimodipine delivery system in conscious rats that allows sustained release for 24 h.

Methodologies that allow prolonged drug administration in animal models, while minimizing surgery and anesthesia, are an important contribution towards studies in awake conditions. Commercially available drug delivery systems like pellets can be customized for the evaluation of experimental therapies with minimal or no discomfort to animals. Our objective was to evaluate pharmacokinetic and physiologic parameters after subcutaneous implantation of rapid 24 h release nimodipine pellets in rats for their potential use as a delivery system for stroke therapeutics. A day prior to the study Sprague-Dawley rats were anesthetized (halothane, N2O, O2) for femoral vessel cannulation and later returned to their cages. On the day of the study the rats were briefly anesthetized (identical regimen as before), and assigned to two groups: nimodipine (NP) and placebo (PL). NP rats received either 0.5 (n = 4), 1 (n = 3), 2 (n = 2), 4 (n = 2), or 15 (n = 5) mg pellets (Innovative Research of America Inc., Sarasota, FL, USA) and PL, rats (n = 5) received placebo pellets. Nimodipine plasma levels were measured at 1, 3, and 6 h. In addition, the 15 mg NP group was followed at 18 and 24 h. Immediately following decapitation the brain was removed for later determination of nimodipine tissue concentration. The NP 15 mg group showed a significant decline of 10% in MABP from base line to 24 h post implantation (p < 0.001). All NP animals achieved at least 83% of their highest plasma concentration at 1 h and 94% at 3 h. A high degree of correspondence (r2 = 0.95, y = 0.36 + 0.28x, n = 16) between the plasma and brain concentrations of nimodipine was present. Although a significant drop in MABP was observed the drop was no greater than 10% in 24 h. Plasma nimodipine levels for the 15 mg animals were within the cerebrovascular effective range. This is the first report to show that 24 h release nimodipine pellets subcutaneously implanted in rats are a reliable delivery system that allows rapid rise and constant nimodipine plasma levels. Therefore, 24 h release pellets are a suitable alternative to other delivery systems like osmotic pumps.

Animals↗
PubMed1995

Estimation of cerebral blood flow from thermal measurement.

A thermal method has been developed to quantify continuous perfusion changes with self-calibration. A dynamic, one-dimensional bio-heat transfer model of the thermal probe and tissue describes the system response to either continuous or transient heating. A nonlinear least-squares fit of the model to experimental data yields estimates of the baseline perfusion and other model parameters. With a partial analytical solution of the model, the optimal estimation procedure is two orders of magnitude more efficient than with a total numerical solution of the model system. Experimental data is used to estimate the operating relations between perfusion and the temperature measurement. A new procedure has also been presented to obtain the dynamic response of the system for continuous measurement of perfusion.

Animals↗
PubMed1995

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.

Acute Disease↗
PubMed1995

Cortical cerebral blood flow cycling: anesthesia and arterial blood pressure.

Cycling of various cerebral metabolic substances, arterial vascular diameter, and flow has been noted by many workers at a frequency near 0.1 Hz. Suspicion that this phenomenon is dependent on the type of anesthesia led us to investigate the occurrence of cerebral blood flow (CBF) cycling with different anesthetics. Fifteen Sprague-Dawley rats were anesthetized with either pentobarbital (n = 5, 40-50 mg/kg), alpha-chloralose (n = 5, 60 mg/kg), or halothane (n = 5, 1-0.5%). Body temperature was maintained at 37 degrees C. Femoral arterial and venous catheters were placed, and a tracheotomy was performed, permitting artificial ventilation with 30% O2-70% N2. A closed cranial window was formed over a 3-mm diameter craniotomy. Mean arterial pressure (MABP), arterial partial pressures of CO2 and O2 (PaCO2 and PaO2), and pH were controlled and stabilized at normal values. CBF was determined using laser Doppler flowmetry. To induce cycling, MABP was transiently and repeatedly lowered by exsanguination. Fast Fourier analysis of selected 64-s flow recordings (n = 38) was performed. CBF cycling was observed, independent of the type of anesthesia, in all animals. In 36 epochs, cycling was induced when MABP was reduced to a mean pressure of 65 +/- 1.5 mmHg. The mean frequency and amplitude were 0.094 +/- 0.003 Hz and 6.6 +/- 0.5%, respectively. Cycling occurred without blood withdrawal in two epochs. With the use of the blood-withdrawal epochs (n = 36), all three anesthetics shared a common linear slope between amplitude and blood pressure (P < 0.02) and blood pressure change (P < 0.01). Pentobarbital differed from alpha-chloralose and halothane in the relation between cycling frequency and blood pressure. Only pentobarbital exhibited correlation between frequency and blood pressure (P < 0.02) and blood pressure change (P < 0.001). The occurrence of these oscillations is not related to the type of anesthesia, and they usually occur at MABP values that are near or just above the lower limit of autoregulation. At this pressure level, CBF oscillations would suggest that vasoconstrictive and dilatory forces are no longer in balance, but alternatively vying for control.

Analysis of Variance↗
PubMed1995

Brain glucose metabolism in hypobaric hypoxia.

Hypobaric hypoxia at one-half atmospheric pressure for 3 wk was reported to increase the brain capillary density and glucose transport at the blood-brain barrier in the adult rat. We examined the metabolic concomitants of these alterations in rats subjected to the same hypoxic insult. Hypoxic rats increased brain glucose and lactate concentrations and decreased brain glycogen. However, hypoxia had no significant effects on regional brain levels of ATP and phosphocreatine or on intracellular pH, indicating successful adaptation to the hypoxic insult. 2-Deoxyglucose studies showed that hypoxia increased the regional metabolic rate for glucose by 10-40%. These results indicate increased glycolysis in the hypoxic rat brain, which probably underlies the increased density of glucose transporters in brain microvessels and the increased blood-to-brain glucose influx in hypoxia.

Adenosine Triphosphate↗
PubMed1995

Sensitivity of magnetic resonance diffusion-weighted imaging and regional relationship between the apparent diffusion coefficient and cerebral blood flow in rat focal cerebral ischemia.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) diffusion-weighted imaging (DWI), a noninvasive procedure, may play an important role in detecting and accurately localizing the extent of evolving infarction within the period immediately following stroke. We evaluated the sensitivity and specificity of DWI in detecting ischemia and compared a quantitative measure derived from the DWI, the apparent diffusion coefficient (ADC), with autoradiographic cerebral blood flow (CBF) in an experimental model of focal cerebral ischemia in rats. METHODS: MR imaging data were obtained with a General Electric 4.7-T horizontal bore magnet CSI II system with self-shielded gradients. DWI was acquired within 41 +/- 6 minutes (mean +/- SD) after onset of ischemia and repeated at 169 +/- 14 minutes, followed by CBF determination at 237 +/- 21 minutes. DWI, ADC, and CBF images from each animal were then compared. RESULTS: The sensitivities for detecting an abnormality at 1 and 3 hours for DWI were significantly different, and the sensitivity of 3-hour DWI did not differ from the CBF sensitivity of 99%. A mean +/- SD ADC threshold of 460 +/- 95 microns 2/s was defined as 45% higher than the low ADC in the ischemic core compared with the contralateral ADC. Subthreshold ADC area and ischemic area were significantly correlated (r2 = .69, P < .05). In 19 of 48 regions of interest classified as ischemic (< 35 mL.100 g-1.min-1) from both the 3-hour ADC and CBF images, 3-hour ADC correlated significantly with CBF (r2 = .27, n = 19, P < .05), whereas in the nonischemic regions ADC was inversely correlated with CBF. Several ischemic regions showed a sharp drop in ADC to 37% (P < .001, n = 5) compared with all other regions (n = 43) from 1 to 3 hours. CONCLUSIONS: Because of the change in the sensitivity of detecting ischemia with DWI, the difference in correlation of CBF with ADC between ischemic and nonischemic cortex, and the presence of several regions in which ADC dropped to 37% from 1 to 3 hours, our data suggest that ADC values potentially can be used to monitor evolving infarction.

Animals↗
PubMed1994

Magnetic resonance diffusion-weighted imaging: sensitivity and apparent diffusion constant in stroke.

Magnetic resonance diffusion-weighted imaging (MR-DWI) is sensitive to the diffusibility of water and may offer characterization and anatomical localization of stroke leading to early tailored therapeutic intervention. We compared DWI, the apparent diffusion constant (ADC), and autoradiographic cerebral blood flow (CBF) in a model of focal cerebral ischemia in the rat. Sprague-Dawley rats were embolized with a single silicone cylinder injected into the internal carotid artery. Both common carotids were permanently ligated. The animals were anesthetized (isoflurane in O2), and paralyzed (gallamine). MR-DWI were obtained with a GE 4.7 T magnet (TE = 3 s, TR = 80 msec, b = 2393.10(-3) mm2/s, slice thickness 3 mm). DWI and CBF autoradiograms were compared visually. ADC was assessed in various regions, including ischemic cortex and a region homologous to ischemic cortex. Imaging times from stroke onset were 50 +/- 6 min (mean +/- SEM) for DWI, 185 +/- 17 min for a second DWI. CBF was determined at 258 +/- 15 min. The specificity was 100% at both 50 min and 185 min, indicating that there were no false positives; in 3 animals ischemia was not present. However, the sensitivity analysis indicated that early DWI yields some false negatives; at 50 min the sensitivity was 60%. We attribute our result of low early sensitivity to small infarcts in relation to the slice thickness. Later, at 185 min, sensitivity was 100%. The first ADCs were higher than the second ADC values in ischemic cortex. For infarcts larger than the slice thickness, early MR-DWI is highly sensitive for imaging evolving ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Thermal method for continuous measurement of cerebral perfusion.

A new thermal system using constant heating power for continuous measurement of cerebral perfusion is presented. It is designed and implemented for optimal perfusion sensitivity and dynamic response based on heat-transfer analysis of perfused brain tissue with thermistors on the cortical surface. Two matched thermistors are used, one to serve as a perfusion sensor and the other to compensate for the base-line temperature changes. To improve the signal-to-noise ratio of the measurement system, lock-in amplifiers are used to minimise long-term drift and low-frequency noise. Errors in the measurement caused by electrical and thermal fluctuations are tested and analysed. In vitro tests show that the measurement accuracy of temperature change is better than 10(-3) degrees C, and the temperature resolution is even greater. In vivo evaluation confirms that the system is responsive to cerebral perfusion changes associated with sudden changes in mean arterial blood pressure caused by bolus injection of norepinephrine, blood withdrawal and blood infusion. The dynamic response of the system is sufficient to detect the autoregulatory perfusion changes in response to arterial blood pressure alteration and the oscillations of cerebral blood flow.

Animals↗
PubMed1994

Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs and T-cell stimulation.

BACKGROUND: We have studied modulation of mucosal interleukin-6 (IL-6) secretion by T-cell activation and by anti-inflammatory agents in inflammatory bowel disease. METHODS: In vitro secretion of IL-6 by biopsy specimens from patients with active ulcerative colitis was investigated in the presence of cyclosporin-A (CsA) and drugs that have other anti-inflammatory actions. Biopsy specimens from patients with quiescent ulcerative colitis or controls were stimulated with anti-CD3 antibody to activate mucosal T cells. RESULTS: Stimulation of control specimens increased IL-6 secretion (median increase, 147%; p < 0.003), which was prevented by CsA. In quiescent ulcerative colitis there was enhanced spontaneous secretion of IL-6 but a smaller, non-significant increase after T-cell activation (125%). Dexamethasone inhibited secretion in active ulcerative colitis (p < 0.006). 5-Aminosalicylic acid, 6-mercaptopurine, methotrexate, and indomethacin had no effect. There also tended to be a small reduction with CsA, but this just failed to reach statistical significance. CONCLUSIONS: In quiescent ulcerative colitis the enhanced spontaneous secretion of IL-6 may be a consequence of mucosal T-cell or macrophage activation: the smaller increase after T-cell stimulation suggests that one or both of these two cell types are already pre-activated.

Anti-Inflammatory Agents↗