Serum interleukin 4 and interleukin 10 levels in patients with chronic hepatitis C virus infection

The antiproliferative effect of 5-fluorouracil (5-FU) in colon cancer can be enhanced by interferons (IFN-alpha and IFN-gamma). The mechanisms by which IFNs modulate 5-FU activity are not completely elucidated. IFN-alpha may elevate the levels of the active 5-FU metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) in the cell, possibly leading to increased inhibition of the target enzyme thymidylate synthase (TS), which might enhance DNA damage. It has been shown that IFN-gamma can prevent 5-FU induced overexpression of TS. We studied IFN modulation in three colon cancer cell lines (SW948, WiDr, human; C26-10, murine) and the sublines WiDr/F and C26-10/F, which were adapted to low folate levels. A 1.5-fold increase in 5-FU sensitivity was observed in C26-10 and C26-10/F (by murine IFN-alpha, beta); in SW948, WiDr and WiDr/F (by human IFN-gamma) and in SW948 and WiDr/ F (by human IFN-alpha). In none of the cell lines did human IFN-alpha, IFN-gamma or murine IFN-alpha, beta increase FdUMP levels after exposure to 5-FU. TS activity, indirectly measured by incorporation of [6-3H]-deoxyuridine into DNA, was inhibited by 5-FU, but the IFNs did not enhance inhibition. DNA damage was measured as a drug-induced decrease of double-stranded (dss) DNA compared to control cells. After 5-FU exposure, dss DNA decreased to 60-75% in WiDr, WiDr/F and SW948 cells. Human IFN-alpha alone caused minimal DNA damage (95% dss DNA), but increased 5-FU-induced effects to 35-50% dss DNA. IFN-gamma did not cause DNA damage and did not enhance 5-FU-mediated DNA damage. Expression of TS protein, analysed by ELISA, was increased after 5-FU exposure of SW948 cells, but this increase was not affected by addition of either IFN-alpha or IFN-gamma. It is concluded that one of the mechanisms involved in modulation of 5-FU activity is the effect of IFN-alpha on 5-FU-mediated DNA damage, but for IFN-gamma no mechanism of action was found.     

Assessment of cerebral blood flow reserve using functional magnetic resonance imaging

Imaging of activated brain areas based on changes of blood deoxyhemoglobin levels is now possible with MRI. Acetazolamide (ACZ) increases cerebral blood flow (CBF) without changing cerebral oxygen consumption; this results in signal changes observed in gradient echo MR images from the areas with an increase in CBF. We assessed signal changes after ACZ application in seven healthy subjects with a conventional 1.5-T MRI scanner. The susceptibility-sensitized three-dimensional fast low-angle shot (FLASH) sequence was used to visualize signal changes induced by ACZ. We analyzed anatomic localization of different ranges of detected signal changes. ACZ caused significant signal changes in the gray matter and at the edge of the cerebral cortex, the latter corresponding to draining surface veins. No significant differences were seen among different brain areas within the same slice. Using the maximal intensity projection technique, we were able to partially separate signal changes originating in draining veins from signal originating in the gray matter microvasculature. Signal changes from the microvessels reflect cerebrovascular reserve. Blood-oxygen-level-dependent (BOLD) based MRI can evaluate CBF reserve with high spatial and temporal resolution. To assess cerebrovascular reserve, it is necessary to separate signal changes originating in large vessels from signal from brain microvasculature.     

Memory for novel and familiar spatial and linguistic temporal distance information in hypoxic subjects

Hypoxia is known to cause damage to the hippocampus as well as memory impairments in humans. Subjects who have experienced a hypoxic episode and age-, gender-, and education-matched control subjects were tested for memory for spatial and linguistic temporal distance information using sentences and spatial locations. Each test contained a familiar component based on information that is meaningful and is thought to be stored as part of the knowledge system (prior knowledge) as well as a novel component based on new information. Subjects were presented a list of eight-word sentences or eight spatial locations (Xs) on a grid on a Macintosh computer and tested for memory for temporal distances. Temporal distance is defined as the number of items that occur between the two test items, in the study phase. Compared to control subjects, hypoxic subjects were impaired across all temporal distances on the novel spatial and linguistic tasks. As the temporal distance increased, hypoxic subjects showed some improvement in memory performance. In addition, memory of familiar temporal distance information was also assessed. Hypoxic subjects were impaired, compared to control subjects, for familiar temporal distance information. For hypoxic subjects there was a proportionally greater impairment for novel compared to familiar spatial and linguistic temporal distance information. There was a significant difference in their performance on the familiar temporal distance tasks compared to their performance on the novel tasks. Prior knowledge appears to attenuate the deficits seen in the familiar temporal distance tasks. It appears that hypoxia may cause more selective damage to the hippocampus and this damage is sufficient to produce profound memory impairments for primarily novel and less severe memory impairments for familiar spatial and linguistic temporal distance information.     

Neutralizing antibodies to Escherichia coli Vero cytotoxin 1 and antibodies to O157 lipopolysaccharide in healthy farm family members and urban residents

An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Escherichia coli O157 lipopolysaccharide (LPS) was developed with sera from 63 children with confirmed recent E. coli O157 infection and from 256 age-stratified urban controls. The median ELISA values for control and case sera were 0.05 (interquartile range, 0 to 0.20; mean +/- standard deviation [SD], 0.15 +/- 0.22) and 1.41 (interquartile range, 1.11 to 1.59; mean +/- SD, 1.41 +/- 0.53), respectively (P < 0.001). With a breakpoint of 0.59 (mean ELISA value of the control sera + 2 SDs), the assay had a sensitivity, specificity, and positive and negative predictive values of 95, 94, 80, and 98%, respectively, for recent E. coli O157 infection. The O157 LPS assay and Vero cytotoxin (VT) 1-neutralizing-antibody (NAb) assay were used to compare the relative frequencies of O157 LPS antibodies and VT1-NAbs in an age-stratified urban population from Toronto, Ontario, Canada, and in 216 healthy family members from dairy farm in southern Ontario. The frequency of O157 LPS antibodies was about threefold higher in dairy farm residents (12.5%) than in urban residents (4.7%) (P < 0.01). Similarly, the frequency of VT1-NAbs was about sixfold higher in dairy farm residents (42.0%) than in urban residents (7.7%) (P < 0.001). These findings are consistent with a greater level of exposure of dairy farm residents to VT-producing E. coli (VTEC) strains. The high rate of seropositivity to VT1 in farm residents probably reflects the booster effect of repeated VTEC exposures and argues against a sustained generalized immunosuppressive effect of VT1. Seroepidemiological studies may help in assessing the level of exposure of different populations to VTEC strains.     

MR imaging of soft-tissue masses: role of gadopentetate dimeglumine

To assess the effectiveness of gadopentetate dimeglumine in the magnetic resonance (MR) imaging evaluation of soft-tissue masses without osseous involvement, 30 patients underwent MR imaging before and after administration of contrast material (0.1 mmol/kg). Of the 30 lesions, 22 were benign and eight were malignant; histologic confirmation was available in all lesions except one benign lesion. Overall, enhancement was detected in 26 (87%) of 30 lesions: 18 (82%) of the 22 benign lesions and eight (100%) of eight malignant lesions. Enhancement was characterized as homogeneous (two [11%] benign lesions, two [25%] malignant lesions), inhomogeneous (11 [61%] benign lesions, six [75%] malignant lesions), or peripheral (five [28%] benign lesions, no malignant lesions). Of the 19 lesions assessed for a change in enhancement over time, seven (37%) showed an increase and two (11%) showed a decrease in signal intensity. The authors conclude that benign and malignant soft-tissue lesions could not be differentiated solely on the basis of enhancement (pattern, degree, or time course).     

Flavone acetic acid enhances accumulation of IL-2 activated NK cells within established metastases

OBJECTIVE: In 1995, we presented our experience in hysteroscopic resection of hemorrhagic submucous fibroids in 196 patients. The objective of the present work was to analyze functional outcome three years later. PATIENTS: One hundred ninety-six patients with abnormal uterine bleeding were treated between 1987 and 1993. Equipment, techniques, characteristics of the procedures and early results were detailed in the previous article. RESULTS: With a mean follow-up of 73 months (range 50,104), results were: 13.8% of the patients were lost to follow-up; 68.4% had symptomatic improvement and failure was observed in 17.8% (subsequent hysterectomy in 12.7%). Forty-nine patients had repeat resection in this series; 61 became menopausal after surgery, and 21 were taking hormone replacement therapy with good results. CONCLUSION: Developed as an alternative to hysterectomy, operative hysteroscopy has proven to be a safe and effective procedure. This treatment modality appears to give satisfactory long-term results, with a low rate of complications.