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Interobserver variability in determining enhancement of renal masses on helical CT.

OBJECTIVE: Because enhancing renal masses are often surgically excised, we assessed interobserver variability in determining enhancement of renal masses. SUBJECTS AND METHODS: Forty-nine complicated cysts or solid lesions were imaged with helical CT. Simple cysts (n = 20) were included, for a total of 69 lesions. Three radiologists obtained three region-of-interest measurements for each lesion in the unenhanced and nephrographic phases. Enhancement was defined as an attenuation increase of 15 H or more, provided that partial volume effects were not the cause. Observer concordance was defined as agreement among all three observers on whether a lesion was enhancing or nonenhancing. Measurement-interpretation agreement was defined as an observer's measuring an attenuation increase of less than 15 H and interpreting the lesion as nonenhancing or measuring an increase of 15 H or greater and interpreting the lesion as enhancing. RESULTS: For the 20 simple cysts, observer concordance was 100% and measurement-interpretation agreement was 100%. For the 49 complicated lesions, observer concordance was 90% and measurement-interpretation agreement was 84% (41/49). Of the five discordant lesions, three were 1.1 or 1.0 cm in size and were interpreted as being of high attenuation on the unenhanced scans, with enhancement, versus a high-attenuation mass with increasing attenuation attributed to volume averaging. The remaining two discordant observations were due to differing interpretations of normally enhancing renal parenchyma versus cyst wall or tumor nodularity. CONCLUSION: For most renal lesions, the observers agreed on whether enhancement was present or absent. Observers were prone to disagree about enhancement for small lesions (1.0-1.5 cm). Occasional disagreements on classification of larger lesions were due to differing interpretations of enhancing normal parenchyma versus abnormal tissue. Discrepancies between an observer's opinion on enhancement and the results of region-of-interest measurements suggest the possibility of disagreement among multiple observers.

Aged↗

Dynamic contrast-enhanced MR imaging of bacterial abscess and VX2 carcinoma in rabbits: comparison of gadopentetate dimeglumine and a macromolecular contrast agent.

OBJECTIVE: The objective of this study was to compare enhancement patterns of a blood-pool contrast agent, Gadomer-17, with those of gadopentetate dimeglumine in bacterial abscesses and VX2 carcinoma in rabbits. MATERIALS AND METHODS: Fourteen rabbits with experimentally induced bacterial abscesses and VX2 carcinoma in both thighs underwent dynamic contrast-enhanced MR imaging with Gadomer-17 and gadopentetate dimeglumine at a 24-hr interval. The enhancement ratios (postcontrast to precontrast signal intensities) of lesions in the same animal were assessed and correlated with microvessel density. RESULTS: For Gadomer-17, the enhancement ratio of the abscesses (1.66 +/- 0.39) peaked 15 min after the injection, while that of the carcinoma (2.05 +/- 0.16) peaked at 10 min. The enhancement ratios of the carcinoma were consistently higher than those of the abscesses up to 30 min. For gadopentetate dimeglumine, peak enhancement ratio of the abscesses (2.30 +/- 0.75) was seen 5 min after the injection, while that of the carcinoma (2.32 +/- 0.51) was seen at 3 min. The enhancement ratios of the carcinomas were significantly higher at 1 min, but significantly lower at 20-30 min, compared with those of the abscesses, as a result of rapid decrease of enhancement ratios in the carcinomas. The microvessel density was 9.8 +/- 5.2 vessels per field of view for the abscesses and 36.3 +/- 9.5 vessels per field of view for the carcinoma (p < 0.001). CONCLUSION: Delayed peak enhancement and slow decay were found in both bacterial abscess and VX2 carcinoma with Gadomer-17, whereas early peak enhancement and rapid decay were found especially in VX2 carcinoma with gadopentetate dimeglumine. Enhancement ratios on MR imaging with a blood-pool contrast agent correlated well with the microvessel density in bacterial abscess and VX2 carcinoma.

Abscess↗

Enhancement characteristics of papillary renal neoplasms revealed on triphasic helical CT of the kidneys.

OBJECTIVE: The purpose of this study was to determine whether renal tumor enhancement or heterogeneity on triphasic helical CT scans is predictive of the papillary cell subtype or nuclear grade of renal cell carcinoma. MATERIALS AND METHODS: We reviewed the CT scans of 90 consecutive patients with renal masses who had undergone triphasic renal helical CT before a complete or partial nephrectomy (12 with papillary renal cell carcinomas, 66 with nonpapillary renal cell carcinomas, and 12 with benign lesions). Three radiologists who were unaware of the patients' diagnoses retrospectively and independently measured the attenuation of each patient's tumor, abdominal aorta, and normal renal parenchyma on the scans obtained during all three phases. Ratios of tumor-to-aorta enhancement and tumor-to-normal renal parenchyma enhancement were calculated for both of the phases performed after contrast material had been administered. Tumor heterogeneity was calculated as the difference between the highest and lowest attenuation values divided by the value of the enhancement of the aorta. Values were correlated with cell type and nuclear grade found at surgical pathology. RESULTS: Low tumor-to-aorta enhancement and low tumor-to-normal renal parenchyma enhancement ratios on the vascular phase scans significantly correlated (p < 0.001) with papillary renal cell type carcinoma. Homogeneity and tumor-to-parenchyma enhancement ratios on the parenchymal phase scans also significantly correlated (p < 0.001) with papillary renal cell type carcinoma. Heterogeneity and tumor enhancement ratios did not correlate with the nuclear grade of the carcinoma. CONCLUSION: Papillary renal cell carcinomas are typically hypovascular and homogeneous. A high tumor-to-parenchyma enhancement ratio (> or = 25%) essentially excludes the possibility of a tumor being papillary renal cell carcinoma. A low tumor-to-aorta enhancement ratio or tumor-to-normal renal parenchyma enhancement ratio is more likely to indicate papillary renal cell carcinoma.

Adult↗

Dynamic contrast-enhanced MRI analysis of perfusion changes in advanced hepatocellular carcinoma treated with an antiangiogenic agent: a preliminary study.

OBJECTIVE: To evaluate the perfusion changes in advanced hepatocellular carcinoma (HCC) treated with the antiangiogenic agent thalidomide, we used dynamic contrast-enhanced MRI. SUBJECTS AND METHODS: Dynamic contrast-enhanced MRI was performed before and during thalidomide treatment in seven patients with advanced unresectable HCC that had failed to respond to prior local therapy. A turbo fast low-angle shot sequence was performed in a 1.5-T MR scanner. An operator-defined region of interest was placed in the maximal enhancement region of the tumor site and adjacent tumor-free parenchyma of all patients. A time-intensity curve was plotted and analyzed. The peak enhancement in the first-pass study, the maximal enhancement, and the initial enhancement slope percentage in the first-pass study of the tumor and parenchyma were measured. The changes in these three perfusion parameters were estimated and correlated with clinical outcomes. The seven patients were categorized into two groups on the basis of their clinical outcomes: group A patients were those who had progressive disease, whereas group B patients were those who had stable disease or partial response. RESULTS: Four of the seven patients were classified as group A, and the other three were classified as group B patients. When comparing the MRI parameters for the tumors before and during treatment in group A and group B patients, we found a statistically significant difference for the peak enhancement in the first-pass study, the maximal enhancement, and the enhancement slope percentage in the first-pass study. When comparing the parenchymal parameters, we found a statistically significant difference in the maximal enhancement and borderline significance in the peak enhancement in the first-pass study (p = 0.057) between group A and group B patients. CONCLUSION: The dynamic MRI parameters showed significant differences between two groups of patients with different clinical outcomes.

Adult↗

Use of computed tomographic densitometry to quantify contrast enhancement of compressive soft tissues in the canine lumbosacral vertebral canal.

OBJECTIVES: To evaluate computed tomography (CT) densitometry as a technique for quantifying contrast enhancement of compressive soft tissues in the canine lumbosacral vertebral canal and to determine whether the degree of contrast enhancement can be used to help predict tissue type or histopathologic characteristics. ANIMALS: 29 large breed dogs with lumbosacral stenosis. PROCEDURE: Contrast-enhanced CT of L5-S3 was performed by use of a previously described protocol. At each disk level, CT densities of a water-filled syringe, epaxial muscles, and 4 vertebral canal locations were measured. Mean tissue enhancement was calculated by vertebral canal location, using water-filled syringe enhancement as a correction factor. Corrected CT enhancement was compared with tissue type, degree of tissue inflammation, and degree of tissue activity. RESULTS: Intravenous contrast administration of contrast medium significantly increased CT densities of water-filled syringes and epaxial muscles. Corrected CT enhancement of vertebral canal soft tissues at stenotic sites was greater than at nonstenotic sites. There was no association between enhancement and tissue type for any vertebral canal location. There was no correlation between enhancement and degree of tissue inflammation. There was a correlation between enhancement and tissue activity in the dorsal vertebral canal only. CONCLUSIONS AND CLINICAL RELEVANCE: A water-filled syringe is a useful calibration tool for CT density measurements. The degree of tissue contrast enhancement, measured by CT densitometry, can be helpful for predicting the location of compressive soft tissues in dogs with lumbosacral stenosis. However, it is of limited value for predicting compressive soft-tissue types or histopathologic characteristics.

Animals↗

Radial keratotomy enhancements for residual myopia.

BACKGROUND: A systematic method of performing radial keratotomy enhancements in undercorrected eyes may increase accuracy and predictability and decrease the number of procedures required. A consecutive series of 372 radial keratotomy procedures, including 110 eyes that received enhancements under a systematic protocol, was evaluated. METHODS: Radial keratotomy was performed using the Reliable Keratotomy software, which uses the Thornton nomogram for primary radial keratotomy and provides a systematic method of performing enhancements. RESULTS: Ninety eyes (24%) received one enhancement, 16 eyes (4%) received two enhancements, and four eyes (1%) received three enhancements. Mean final spherical equivalent refraction was -0.44 D (-4.00 to +1.875 D, SD 0.86) for eyes that did not receive enhancements and -0.44 D (-2.50 to +1.00 D, SD 0.61) for eyes that had enhancements. Mean final residual myopia for the entire cohort was -0.44 D (-4.00 to +1.875 D, SD 0.79). At final examination, 242 (65%) eyes had a refraction within +/- 0.5 D and 298 (80%) within +/- 1.00. Among eyes that received enhancements, 75 (68%) had a refraction within +/- 0.50 D, and 89 (81%) within +/- 1.00 D; 40 eyes (36%) had uncorrected visual acuity of 20/20 or better, 99 eyes (90%) 20/40 or better, and all but one eye (99%) 20/80 or better at the final postoperative examination. Among the entire cohort, 130 eyes (35%) had uncorrected visual acuity of 20/20 or better, 312 (84%) had 20/40 or better, and 350 (94%) had 20/80 or better. No eye lost more than one line of spectacle-corrected visual acuity. CONCLUSION: A systematic approach to enhancement of undercorrected eyes after radial keratotomy, combined with accurate surgery, may reduce the need for multiple enhancements as well as the overcorrection rate, and provide improved uncorrected visual acuity.

Adolescent↗

Tentorial enhancement on MR images is a sign of cavernous sinus involvement in patients with sellar tumors.

BACKGROUND AND PURPOSE: This study was undertaken to analyze enhancement patterns of the dura around sellar tumors and to compare the results with tumor invasion or compression of the cavernous sinuses. Postoperative enhancement patterns on MR images were compared with preoperative findings. METHODS: Contrast-enhanced coronal and sagittal MR images were examined prospectively in 96 patients with sellar tumors (65 macroadenomas, 15 microadenomas, 14 Rathke cleft cysts, and two chordomas at the sella). All patients underwent surgical treatment, and pre- and postsurgical features on MR images were compared. RESULTS: Presurgical MR images showed dural enhancement in 36.5% of the patients: asymmetric tentorial enhancement in 24 patients, symmetric tentorial enhancement in seven, and sphenoidal ridge or clivus enhancement in four. Asymmetric tentorial enhancement disappeared after surgical decompression in seven patients. For evaluation of cavernous sinus invasion ipsilateral to the enhancement, sensitivity and specificity of the asymmetric tentorial enhancement sign were 81.3% and 86.3%, respectively. Sensitivity and specificity of the sign were 42.9% and 93.6% for cavernous sinus involvement, including compression and invasion. CONCLUSION: Asymmetric tentorial enhancement is a useful sign in the diagnosis of invasion or severe compression of the cavernous sinus by sellar tumor. The sign may represent venous congestion or collateral flow in the tentorium due to obstructed flow in the medial portion of the cavernous sinus.

Adenoma↗

[Non-tumor enhancement at the surgical margin on CT after the removal of brain tumors].

Marginal enhancement is occasionally seen at the surgical margin on CT after the total removal of brain tumors. This enhancement disappears in due time, and therefore we call it non-tumor enhancement. It is often difficult, however, to differentiate non-tumor enhancement from tumor recurrence. In this study, we attempted to determine the characteristics of non-tumor enhancement. The subjects of the study consisted of 15 patients with astrocytoma and one with metastatic tumor in whom sequential CT scans had been performed after total removal of the tumor. Based on the observation of these sequential CT scans, the characteristics of non-tumor enhancement were presumed to be as follows: 1) In four cases, enhancement at the surgical margin persisted more than four months after surgery and then disappeared. Therefore, these cases were considered non-tumor enhancement. Prolonged duration of enhancement such as that in these cases is not necessarily due to recurrence. 2) Marginal enhancement within 3 mm in thickness and with a well-demarcated border like that of a falx is likely to be non-tumor enhancement.

Adolescent↗

Contrast enhancement of the labyrinth on MR scans in patients with sudden hearing loss and vertigo: evidence of labyrinthine disease.

The sudden onset of hearing loss and vertigo presents a difficult diagnostic problem. We describe the finding of labyrinthine enhancement on MR images in five patients with sudden unilateral hearing loss or vertigo or both and correlate the MR findings with audiologic and electronystagmographic studies. All patients were studied with T2-weighted axial images through the whole brain, contrast-enhanced 3-mm axial T1-weighted images through the temporal bone, and enhanced T1-weighted sagittal images through the whole brain. Cochlear enhancement, on the side of hearing loss only, was found in all five patients. The presence of associated vestibular enhancement correlates with objective measures of vestibular function on the electronystagmogram. In two patients, the resolution of symptoms 4-6 months later correlated with resolution of the enhancement on gadopentetate dimeglumine-enhanced MR images. Two patients had luetic labyrinthitis. No labyrinthine enhancement was seen in a series of 30 control subjects studied with gadopentetate dimeglumine-enhanced MR using the same protocol. Labyrinthine enhancement in patients with auditory and vestibular symptoms is a new finding and is indicative of labyrinthine disease. While abnormalities on electronystagmograms and audiograms are nonspecific and indicate only a sensorineural problem, gadopentetate dimeglumine-enhanced MR may separate patients with retrocochlear lesions, such as acoustic neuromas, from those in whom the abnormal process is in the labyrinth or is intraaxial. This group of patients underscores the importance of identifying and commenting on the structures of the membranous labyrinth when evaluating MR studies of the internal auditory canal and the cerebellopontine angle in individuals with hearing loss.

Adult↗

Enhancement of the activity of immunotoxins by analogues of verapamil.

Verapamil has been shown to enhance immunotoxin activity but only at concentrations that are too high for in vivo use. Therefore, four structural analogues of verapamil (D792, D595, D528, and Sz45) were evaluated for their ability to enhance the in vitro activity of immunotoxins made with either ricin A chain or Pseudomonas exotoxin. The following immunotoxins were used: HB21-PE and 454A12-rRTA which recognize the human transferrin receptor; and 260F9-rRTA which reacts with human ovarian carcinoma and breast carcinoma cells. The activities of the immunotoxins were determined in ovarian carcinoma cells and in KB cells using inhibition of either protein synthesis or colony formation as a measure for the cytotoxicity of the immunotoxins. Each of the four analogues enhanced the activity of ricin A-immunotoxins in a dose-dependent manner. D792 and D595 also increased the activity of IIB21-PE. Low concentrations of either Sz45 or D528 enhanced the activity of HB21-PE, but high concentrations of these two analogues either had less enhancing potency than low concentrations or even decreased the activity of HB21-PE. Specificity of enhancement by the analogues was shown by competition of the activity of the immunotoxins by the corresponding antibody and by inactivity of an irrelevant immunotoxin. The amount of enhancement ranged from 2-fold to greater than 60-fold and was dependent on the cell line and on the experimental conditions. The enhancing ability of the drugs did not correlate with their calcium-antagonistic activity. When compared with verapamil, D792 and D595 had greater enhancing potency with regard to both ricin A-immunotoxins and Pseudomonas exotoxin-immunotoxins. Greater enhancing potency and less in vivo toxicity makes D792 a candidate for use in the enhancement of immunotoxins in vivo.

ADP Ribose Transferases↗

Platelet enhancement of O2-. responses in stimulated human neutrophils. Identification of platelet factor as adenine nucleotide.

Human neutrophils stimulated with immune complexes in the presence of platelets show enhanced superoxide anion (O2-.) responses that are proportional to the amount of agonist present and the number of platelets added. Platelet related enhancement of O2-. responses also occurs with the neutrophil agonists phorbol ester, formyl chemotactic peptide and zymosan particles. Pretreatment of platelets with cycloheximide does not alter their ability to enhance O2-. responses of neutrophils. In parallel with platelet-related enhancement of O2-. responses of immune complex-stimulated neutrophils, secretory release of myeloperoxidase is also increased. The platelet effects on O2-. responses can be reproduced with platelet lysates or with supernatant fluids which have been obtained from thrombin or immune complex-stimulated platelets and are rich in ATP and ADP content. Solutions containing ATP and ADP in amounts similar to those found in supernatant fluids of activated platelets reproduce the enhancement of O2-. responses in N-formyl methionyl leucyl phenylalanine (FMLP) or immune complex-activated neutrophils. The platelet factor responsible for the effects of neutrophils is heat-stable, elutes in gel sieving chromatography near the position of phenol red and does not, in the absence of a neutrophil agonist, trigger an O2-. response. With formyl peptide-stimulated neutrophils, ATP and ADP enhance O2-. responses while the responses are depressed by addition of AMP or adenosine. In immune complex-stimulated neutrophils, adenosine and all adenine nucleotides enhance the O2-. responses. Taking advantage of this information, treatment of ATP or of supernatant fluids from thrombin-stimulated platelets with alkaline phosphatase (resulting in formation of adenosine) converts the O2-. enhancing activity for formyl peptide-activated neutrophils into an inhibitory activity. In contrast, using immune complex-activated neutrophils, similar manipulations of ATP or supernatant fluids from stimulated platelets result only in enhanced O2-. responses. These data support the conclusion that the platelet-derived factor responsible for enhanced O2-. responses in neutrophils is ATP/ADP. In FMLP stimulated neutrophils, the presence of ATP or ADP leads to enhanced increases in intracellular levels of Ca++ as determined by the fura-2 probe, while the presence of AMP or adenosine results in inhibition of the increases in FMLP induced elevations in cytosolic Ca++. These data demonstrate a direct relationship between effects of adenine compounds on FMLP induced changes in cytosolic Ca++ and the associated O2-. responses.

Adenine Nucleotides↗

Enhancement by monokines of leukotriene generation by human eosinophils and neutrophils stimulated with calcium ionophore A23187.

Human blood eosinophils and neutrophils that had been incubated with the supernatants of cultures of lipopolysaccharide (LPS)-stimulated blood mononuclear cells demonstrated respective enhanced abilities to produce immunoreactive leukotriene C4 (LTC4) and immunoreactive leukotriene B4 (LTB4) after activation by the calcium ionophore A23187. Under optimal conditions, the enhancing effect was observed with the eosinophils (n = 21) and the neutrophils (n = 14) from all but one donor of each type of granulocyte. Enhancement was maximum when granulocytes were preincubated with a 1/3 dilution of LPS-stimulated mononuclear cell culture supernatants for 1 to 2.5 min and were then stimulated with 2.5 microM ionophore for 1 to 2 min (neutrophils) or 15 min (eosinophils). Maximal enhancement ranged from 20 to 4500% for LTC4 generation by eosinophils (geometric mean, 87%) and from 30 to 1600% for LTB4 generation by neutrophils (geometric mean, 105%). There was no enhancement of leukotriene biosynthesis when the LPS-stimulated mononuclear cell culture supernatants and ionophore were added simultaneously to the granulocytes. The enhancing activity for LTC4 generation by eosinophils was removed by washing the cells after the addition of the LPS-stimulated mononuclear cell culture supernatants and before the introduction of ionophore. This enhancing activity was produced by Ig-, Leu-1- adherent blood mononuclear cells, which are presumed to be monocytes; supernatants of adherent cells augmented A23187-induced LTC4 generation by eosinophils from 21 to 2300% (geometric mean, 402%) in 11 experiments and LTB4 generation by neutrophils from 7 to 200% (geometric mean, 60%) in 10 experiments. There was an inverse correlation between the percent enhancement and the LTC4 levels produced by stimulated eosinophils in the absence of the monokine(s) (r = -0.79, p less than 0.01), but not between percent enhancement and the LTB4 levels generated by ionophore-activated neutrophils in the control buffer. The activity of the monocyte-derived enhancing material on each type of granulocyte was relatively heat stable. Enhancement of eosinophil production of LTC4 was associated with an acidic group of monocyte-derived molecules having isoelectric points of 4.2 to 4.3, 4.5 to 4.6, and 4.9, and exhibiting marked heterogeneity in size.(ABSTRACT TRUNCATED AT 400 WORDS)

Arachidonic Acid↗

Antibody-mediated enhancement of Wesselsbron virus in P388D1 cells.

Antibody-mediated enhancement of Wesselsbron virus was investigated in P388D1 cell cultures. Virus infection was enhanced in culture by various dilutions of homologous and heterologous flavivirus antibody. Highest enhancement ratios and enhancing antibody titres were obtained with the homologous antibody. Enhancement of Wesselsbron virus infection in P388D1 cultures was also dependent on the multiplicity of infection (MOI) used; cultures infected at the lowest MOI produced the highest enhancement ratios. Of the four heterologous flavivirus IMAF tested for ability to enhance Wesselsbron virus infection, Potiskum virus antibody produced highest fold enhancement and possessed the highest enhancing antibody titre. Zika, Uganda S and Dakar bat IMAF produced lower fold enhancement and had lower enhancing antibody titres.

Animals↗

Biological characterization of a granulomonopoietic enhancing activity derived from cultured human lipid-containing macrophages.

We describe the biologic characteristics of an activity produced by human monocyte-derived lipid-containing cells (MDLCCs) that enhances the colony-forming capacity of granulocyte-macrophage progenitors (CFU-GM). Medium conditioned by well-developed MDLCCs (at day 21 to day 28 of cultivation) was added to bone marrow cultures containing GCT cell line-conditioned medium (GCT-CM) or other material as a source of granulocyte-macrophage colony-stimulating factors (GM-CSFs). MDLCC-conditioned medium (CM) had no detectable granulocyte-macrophage colony-stimulating activity (GM-CSA), but it contained an activity that enhanced the colony number in both day 7 and day 14 CFU-GM cultures. Dose-response curves for GCT-CM in the presence of MDLCC-CM demonstrated that this enhancing effect occurred at concentrations of GM-CSFs that stimulate maximal CFU-GM growth. This enhancing effect was seen with both granulocytic and monocytic progenitor cells. It was titratible and required the continuous presence of MDLCC-CM from initiation of culture. No enhancement was noted when MDLCC-CM was added 48 hours after plating. The enhancement still occurred when marrow cells were first incubated with MDLCC-CM and GCT-CM was added at later times. Neither the enhancing activity nor its production was dependent on horse serum contained in MDLCC culture medium. The enhancing effect was also seen when other sources of GM-CSA were used: medium conditioned by 5637 cell line, phytohemagglutinin-stimulated lymphocytes (PHAL), or placenta tissue. Furthermore, this enhancing activity appeared to be specific for CFU-GM. Addition of MDLCC-CM to mixed and erythroid cultures, stimulated by suboptimal and optimal concentrations of PHAL-CM did not modify the number of mixed colonies or erythroid bursts. This granulomonopoietic enhancing activity contained in MDLCC-CM was heat stable (56 degrees C and 75 degrees C for 30 minutes) and nondialyzable (3,500 and 14,000 molecular weight cut off tubing). Its production was increased by treating MDLCC with lipopolysaccharide (5 micrograms/mL) or zymosan (60 micrograms/mL) and inhibited by lactoferrin (10(-7) mol/L). The production of a granulomonopoietic enhancing activity by MDLCCs represents the demonstration of another positive feedback regulator of myelopoiesis involving the monocyte-macrophage system.

Cells, Cultured↗

Enhancement of carrageenan and dextran-induced edemas by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

Paw edema formation after the subplantar injection of carrageenan was enhanced in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The enhanced carrageenan response could be detected as early as 4.5 hr after TCDD; however, the magnitude of enhancement was greatest when rats were challenged with carrageenan 5 days after TCDD. In the latter case, the ED50 of TCDD in enhancing the carrageenan response was 6 micrograms/kg. TCDD also enhanced dextran-induced paw edema, which follows a time course different from that of carrageenan-induced edema and is produced by a different mechanism. The enhancement of carrageenan and dextran paw edemas was due to an increase in the edema-producing potency of the irritants and not to a change in their maximum effect. The ability of other 3-methylcholanthene-type inducers to enhance carrageenan-induced paw edema and the inability of phenobarbital-type inducers to cause the response suggest that the TCDD binding protein might be involved in edema enhancement. TCDD also enhanced carrageenan-induced pleural edema; however, the number and type of leukocytes recovered in the pleural exudate was not affected. TCDD did not alter granuloma formation produced by the subcutaneous implantation of cotton pellets, indicating that enhancement by TCDD was peculiar to edema formation and not to inflammation in general. It is suggested that TCDD may enhance carrageenan and dextran edemas by increasing the availability of mediators involved in each type of edema formation and/or by increasing the responsiveness of the vasculature to mediators.

Animals↗

Enhanced binding and uptake of remnant lipoproteins by hepatic lipase-secreting hepatoma cells in culture.

Rat hepatoma McA-RH7777 cells transfected with a human hepatic lipase (HL) cDNA synthesized and secreted 50-80 ng of human HL/mg of cell protein at 4 h, approximately 50% of which was bound to cell-surface heparan sulfate proteoglycans (HSPG). The newly synthesized HL possessed enzymatic activity. When rabbit beta-very low density lipoproteins (beta-VLDL) and canine chylomicrons or chylomicron remnants were incubated with HL-secreting cells, remnant binding and uptake were enhanced 3-fold compared with nontransfected cells. Furthermore, fluorescence microscopy showed enhanced uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled beta-VLDL by the HL-transfected cells. When 125I-beta-VLDL were added to conditioned medium from HL-secreting cells, the HL in the media enhanced the binding and uptake of the remnant lipoproteins by nontransfected cells about 3-fold. Likewise, surface-bound HL (without HL in the medium) also was able to mediate the enhanced binding of the remnants. This HL-enhanced binding was shown to be mediated by an interaction with cell-surface HSPG. Heparinase treatment to remove cell-surface HSPG or chlorate treatment to prevent HSPG sulfation of the HL-secreting cells abolished all the HL-mediated enhanced binding and uptake. Furthermore, heparinase pretreatment of nontransfected cells prevented the enhanced binding and uptake of beta-VLDL incubated with conditioned medium from HL-secreting cells. As binding was not enhanced in the absence of HSPG, an HL-HSPG initial interaction appears essential. Addition of apolipoprotein (apo) E to the beta-VLDL did not facilitate HL-mediated binding and uptake; in fact, beta-VLDL from apoE-null mice demonstrated a similar degree of enhanced binding as did rabbit beta-VLDL with or without added apoE. On the other hand, beta-VLDL from transgenic mice overexpressing binding-defective apoE(Arg142-->Cys) did not display any enhanced binding and uptake by the HL-secreting cells, and it appears that the apoE(Arg142-->Cys) actually inhibited the HL-mediated interaction. This mutant form of apoE is associated with a dominant mode of expression of type III hyperlipoproteinemia in contrast to the more commonly occurring recessive disorder. Impaired HL interaction with the apoE(Arg142-->Cys) beta-VLDL may contribute to remnant lipoprotein accumulation in the plasma of patients with this mutant form of apoE. Thus, HL contributes to the enhanced cell association of specific types of remnant lipoproteins by initiating their binding to cell-surface HSPG.

Animals↗

Gadolinium-enhanced nerve roots in lumbar disk herniation.

PURPOSE: To analyze contrast-enhanced features of intrathecal nerve roots in lumbar disk herniation in patients who have not had surgery and to evaluate the possible correlation with herniated disk, peridiscal enhancement, and symptomatology. METHODS: Twenty patients with a syndrome of lumbar herniated disk without surgery were studied with pre- and postcontrast MR imaging. RESULTS: In six patients (30%), ipsilateral intradural roots affected with large disk herniations showed consistent enhancement along their whole length, from the site of compression to the root-medullary junction. This enhancement persisted on delayed scanning. "Selective" enhancement differed from the minimal enhancement seen in normal intrathecal roots in 11 (55%) patients. Enhancement around herniated disks was a common finding (92% of patients) and did not correlate with selective or normal root enhancement (P > .05). No symptom differences were found among patients with and without selective enhancement. CONCLUSION: Selective intrathecal root enhancement seems to be the direct visualization of the radiculopathy resulting from disk herniation. It is probably a transient event more likely to be noted in the acute phase. Although there is no evidence of immediate clinical utility of this finding, gadolinium-enhanced MR gives insights into the basic pathophysiologic alterations involved in degenerative disk disease.

Adult↗

The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse.

The mossy fiber synapse between dentate granule cells and CA3 pyramidal cells in the guinea pig hippocampus shows a robust short-term synaptic enhancement. We have simultaneously measured presynaptic residual free calcium ([Ca2+]i) and postsynaptic field potentials at this synapse to examine the role of [Ca2+]i in this enhancement. Single action potentials produced an increase in [Ca2+]i of 10-50 nM that decayed to resting levels with a time constant of about 1 sec. Trains of action potentials produced larger [Ca2+]i increases that returned more slowly to resting levels. Following the onset of moderate frequency stimulus trains (0.1-5 Hz), synaptic transmission and [Ca2+]i both increased and eventually plateaued. During the steady-state phase a linear relationship between [Ca2+]i and synaptic enhancement was observed. During the initial buildup, however, [Ca2+]i rose more rapidly than synaptic enhancement. Similarly, during the decay phase immediately following termination of a stimulus train, [Ca2+]i returned to prestimulus levels faster than synaptic enhancement. High concentrations of the calcium buffer EGTA in the presynaptic terminal slowed the buildup and decay of both [Ca2+]i and synaptic enhancement produced by stimulus trains. Under these conditions, the time course of [Ca2+]i and synaptic enhancement were well matched. This suggests that, despite the differences in kinetic rates observed for normal buffering conditions, increases in [Ca2+]i play a causal role in short-term enhancement. An increase in [Ca2+]i of 10-30 nM produced a twofold enhancement. We propose a simple kinetic model to explain these results. The model assumes that synaptic enhancement is controlled by a Ca-dependent first-order reaction. According to this scheme, a change in [Ca2+]i alters neurotransmitter release, but the slow kinetics of the underlying reaction introduces a temporal filter, producing a delay in the change in synaptic enhancement.

Animals↗