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Characterization of monoclonal antibodies recognizing a Mr 180,000 P-glycoprotein: differential expression of the Mr 180,000 and Mr 170,000 P-glycoproteins in multidrug-resistant human tumor cells.

P-glycoprotein is a plasma membrane protein believed to mediate resistance to natural product drugs such as vincristine, Adriamycin, and actinomycin D. To facilitate the study of human P-glycoprotein, monoclonal antibodies (designated HYB-612, HYB-241, and HYB-195) were raised against vincristine-resistant human neuroblastoma (SH-SY5Y/VCR) cells. The antibodies recognize a Mr 180,000 plasma membrane phosphoglycoprotein produced in increased amounts in SH-SY5Y/VCR as well as in vincristine-resistant human neuroepithelioma (MC-IXC/VCR), vinblastine-resistant human leukemia (CEM/VLB100), and actinomycin D- or vincristine-resistant Chinese hamster (DC-3F/AD X and DC-3F/VCRd-5L) cells, as compared to control cells. Radioimmunoprecipitation of proteins in cells metabolically labeled with [35S]methionine, 32Pi, or [3H]glucosamine and Western transfer procedures were used for these studies. Characterization of the HYB-612 or HYB-241 antigen by destructive degradation produced a pattern of results typical of a conformation-dependent protein epitope. HYB-612 recognizes complexes of the Mr 180,000 antigen with an iodinated photoaffinity analogue of vinblastine or with tritiated azidopine. Furthermore, pretreatment of MC-IXC and MC-IXC/VCR cells with HYB-612 or HYB-241 before measurement of tritium-labeled actinomycin D or vincristine uptake increases the amount of drug accumulation in resistant, but not in sensitive, cells. Of importance is the fact that the Mr 180,000 protein is expressed in cells which also contain a Mr 170,000 P-glycoprotein. The relative amounts of the Mr 180,000 and 170,000 species vary from one drug-resistant cell line to another. Evidence that the Mr 180,000 protein is a P-glycoprotein and that there is a conserved complex pattern of resistance-related surface proteins in multidrug-resistant cells is presented in this report.

ATP Binding Cassette Transporter, Subfamily B, Mem

Purification of the Mr 80,000 and Mr 210,000 proteins of the sea urchin sperm plasma membrane. Evidence that the Mr 210,000 protein interacts with egg jelly.

Two immunologically cross-reactive plasma membrane proteins, of Mr 80,000 and Mr 210,000, have been purified to apparent homogeneity from sperm of the sea urchin Strongylocentrotus purpuratus. Purification includes a combination of antibody and wheat germ agglutinin affinity chromatography. The two proteins have similar but not identical amino acid compositions; however, their carbohydrate composition differs substantially. After purification, the Mr 210,000 protein binds to both living eggs and isolated egg jelly in a species-specific manner, but the Mr 80,000 protein does not. The inactivity of the Mr 80,000 protein could be due to denaturation during purification. The data are consistent with a model in which the Mr 210,000 protein acts as a jelly receptor in the sperm membrane, promoting the ion movements necessary to initiate the sperm acrosome reaction.

Amino Acids

Phosphorylase phosphatase catalytic subunit. Evidence that the Mr = 33,000 enzyme fragment is derived from a native protein of Mr = 70,000.

An active form of phosphorylase phosphatase of Mr = 33,000, referred to as the catalytic subunit for over a decade, was purified to near-homogeneity from rabbit skeletal muscle. Repeated immunization of a sheep produced immunoglobulins that blocked the activity of the phosphatase. These immunoglobulins were affinity-purified on columns of immobilized phosphorylase phosphatase and used as macromolecular probes in a "Western" immunoblotting procedure with peroxidase-conjugated rabbit anti-sheep immunoglobulins. Only one protein, of Mr = 33,000, was stained in samples of the immunogen, attesting to the specificity of the probes. However, the Mr = 33,000 phosphatase protein was not detected in muscle extracts or in partially purified preparations. Instead, a single protein of Mr = 70,000 was detected. Limited proteolysis, in particular by Staphylococcus aureus V8 protease and thermolysin, converted the immunoreactive protein from Mr = 70,000 to Mr = 33,000. Coagulation of the phosphatase preparation with 80% ethanol at room temperature rendered the Mr = 70,000 protein insoluble, but allowed extraction of the Mr = 33,000 protein from the precipitate. Thus, we conclude that the immunoreactive protein of Mr = 70,000 is the "catalytic subunit" of phosphorylase phosphatase with a catalytic domain of Mr = 33,000. Previous purification schemes have yielded only the fragment of Mr = 33,000 due to its relative resistance to proteolysis and coagulation. Gel filtration chromatography of the "native" form of phosphorylase phosphatase showed Mr approximately 230,000. Both the Mr = 70,000 catalytic subunit and a Mr = 60,000 protein related to inhibitor-2 were detected by immunoblotting in the same fractions that exhibited activity after treatment with Co2+ and trypsin. Only the Mr = 60,000 protein was degraded during this activation process. We propose that the native phosphorylase phosphatase is an elongated structure with two-fold symmetry, containing one catalytic subunit of Mr = 70,000 and one regulatory subunit of Mr = 60,000.

Animals

Association of the Mr 58,000 postsynaptic protein of electric tissue with Torpedo dystrophin and the Mr 87,000 postsynaptic protein.

Dystrophin was purified by immunoaffinity chromatography from detergent-solubilized Torpedo electric organ postsynaptic membranes using monoclonal antibodies. A major doublet of proteins at Mr 58,000 and minor proteins at Mr 87,000, Mr 45,000, and Mr 30,000 reproducibly copurified with dystrophin. The Mr 58,000 and Mr 87,000 proteins were identical to previously described peripheral membrane proteins (Mr 58,000 protein and 87,000 protein) whose muscle homologs are associated with the sarcolemma (Froehner, S. C., Murnane, A. A., Tobler, M., Peng, H. B., and Sealock, R. (1987) J. Cell Biol. 104, 1633-1646; Carr, C., Fischbach, G. D., and Cohen, J. B. (1989) J. Cell Biol. 109, 1753-1764). The copurification of dystrophin and Mr 58,000 protein was shown to be specific, since dystrophin was also captured with a monoclonal antibody against the Mr 58,000 protein but not by several control antibodies. The Mr 87,000 protein was a major component (along with the Mr 58,000 protein) in material purified on anti-58,000 columns, suggesting that the Mr 58,000 protein forms a distinct complex with the Mr 87,000 protein, as well as with dystrophin. Immunofluorescence staining of skeletal and cardiac muscle from the dystrophin-minus mdx mouse with the anti-58,000 antibody was confined to the sarcolemma as in normal muscle but was much reduced in intensity, even though immunoblotting demonstrated that the contents of Mr 58,000 protein in normal and mdx muscle were comparable. Thus, the Mr 58,000 protein appears to associate inefficiently with the sarcolemmal membrane in the absence of dystrophin. This deficiency may contribute to the membrane abnormalities that lead to muscle necrosis in dystrophic muscle.

Animals

Immunocytochemical determination of the estrogen-regulated proteins Mr 24,000, Mr 52,000 and DF3 breast cancer associated antigen: clinical value in advanced breast cancer and correlation with estrogen receptor.

The Mr 24,000 and Mr 52,000 estrogen-regulated cytosol proteins, and the breast cancer-associated antigen DF3 have been studied in an immunocytochemical assay. Primary tumor specimens from 119 patients with advanced breast cancer who received endocrine therapy have been studied. Monoclonal antibodies were used for the detection of the proteins in formalin-fixed paraffin-embedded blocks. No correlation between Mr 52,000-positive specimens and the presence of estrogen receptor (ER) could be established (p = 0.87, chi-square test) whereas a statistically significant association between Mr 24,000 (p = 0.0002), DF3 antigen (p = 0.044) and ER was demonstrated. No intercorrelation was found between Mr 24,000 and Mr 52,000 or DF3 (p = 0.63, 0.98 and 0.12 respectively). Clinical response was evaluated for immunocytochemical findings, Mr 24,000 (p = 0.37), Mr 52,000 (p = 0.61) and DF3 (p = 0.68) showed no association whereas ER was statistically correlated (p = 0.00005). Neither overall survival nor disease-free survival correlated to Mr 24,000 (p = 0.18 and 0.75 respectively, logrank test), Mr 52,000 (p = 0.095 and 0.38), or DF3 (p = 0.22 and 0.13) staining, whereas ER-positive tumors did (p = 0.00005). Discrimination between ER-positive responders and ER-positive non-responders was not possible using either Mr 52,000, Mr 24,000 or DF3 staining. Based on our findings we conclude that immunocytochemical staining for Mr 52,000, Mr 24,000 or DF3 cannot be used as a marker to predict response to endocrine therapy in patients with advanced or recurrent breast cancer.

Adult

Receptor-binding and down-regulatory properties of 22000-Mr human growth hormone and its natural 20000-Mr variant on IM-9 human lymphocytes.

Our earlier binding studies of the 22000- and 20000-Mr variants of human growth hormone (somatotropin) to pregnant-rabbit liver and mammary receptors [Closset, Smal, Gomez & Hennen (1983) Biochem. J. 214, 885-892] suggested that the 20000-Mr variant was a lower-affinity analogue of the 22000-Mr molecule. Since the receptor population in these tissues is not fully characterized, we have now investigated the binding of both variants to the well-characterized and highly specific human-growth-hormone receptor of the human lymphocyte IM-9 cell line. The maximum bindability of radioiodinated 22000- and 22000-Mr to IM-9 cells was 60 and 45% respectively. Both hormone variants have essentially the same binding characteristics: slow association (equilibrium reached in 8-10h at 30 degrees C), poor reversibility ('tight binding'), linear Scatchard plot, same specificity as shown by lack of competition by bovine, porcine or equine growth hormones or human growth hormone-(32-46)-(missing in the 20000-Mr variant),-(1-134)- and -(141-191)-peptides. Both unlabelled hormones inhibit binding of both tracers completely, with the 20000-Mr variant being only half as potent as the 22000-Mr one. The apparent affinity is 2.8 X 10(9)M-1 for the 22000-Mr variant and 1.6 X 10(9)M-1 for the 20000-Mr variant. This decreased affinity of the 20000-Mr variant appears to be due to a lower association rate constant. Concentrations (5 ng/ml) of the two variants that occupy about 15% of the total sites induce a marked down-regulation of the receptors after 18h incubation, but the 20000-Mr variant (50% decrease) has a smaller effect than the 22000-Mr variant (75% decrease). Thus the only consequence of the residues-32-46 deletion in the 20000-Mr variant is a lower association rate and affinity for the IM-9 lymphocyte human-growth-hormone receptor. The close binding characteristics of the two forms suggest that the known differences in their insulin-like effects cannot be explained by differences in the nature of their interaction with the human-growth-hormone receptor.

Binding Sites

Binding of the bovine basic pancreatic trypsin inhibitor (Kunitz) to the 33,000 Mr and 54,000 Mr species of human urokinase: thermodynamic study.

The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the bovine basic pancreatic trypsin inhibitor (BPTI, Kunitz inhibitor) to the 33,000 Mr and 54,000 Mr species of human urokinase (EC 3.4.21.31) has been investigated. Under all the experimental conditions, values of Ka for BPTI binding to the 33,000 Mr and 54,000 Mr species of human urokinase are identical. On lowering the pH from 9.5 to 4.5, values of Ka (at 21.0 degrees C) for BPTI binding to human urokinase (33,000 Mr and 54,000 Mr species) decrease thus reflecting the acidic pK-shift of the His-57 catalytic residue from 6.9, in the free enzyme, to 5.1, in the proteinase:inhibitor complex. At pH 8.0, values of the apparent thermodynamic parameters for BPTI binding to human urokinase (33,000 Mr and 54,000 Mr species) are: Ka = 4.9 x 10(4) M-1, delta G degree = -6.3 kcal/mol, and delta S degree = -37 entropy units (all at 21.0 degrees C); and delta H degree = +4.6 kcal/mol (temperature independent over the explored range, from 5.0 degrees C to 45.0 degrees C). Thermodynamics of BPTI binding to human urokinase (33,000 Mr and 54,000 Mr species) have been analyzed in parallel with those of related serine (pro)enzyme Kazal- and /Kunitz-type inhibitor systems. Considering the known molecular models, the observed binding behaviour of BPTI to human urokinase (33,000 Mr and 54,000 Mr species) was related to the inferred stereochemistry of the proteinase/inhibitor contact region.

Animals

Effects of the benzomorphan kappa-opiate, MR 2266 and its (+) enantiomer MR 2267, on thermonociceptive reactions in different strains of mice.

The effects of the benzomorphan kappa opiate MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in Swiss Webster, C57BL/6, BALB/c and DBA/2 strains of mice. In the hot plate (60 +/- 0.5 degrees C, cut-off time 120 s and tail immersion tests, MR 2266 (10 mg/kg, s.c., 15 min before) decreased, while MR 2267 (10 mg/kg s.c., 15 min before) increased the reaction latencies. In the hot plate test, the sensitivities for the effects of MR 2266 and MR 2267 on jump latency in different strains of mice were as follows: MR 2266; BALB greater than Swiss greater than C57BL greater than DBA and MR 2267; DBA greater than BALB = Swiss greater than C57BL. In the immersion test, for the hyperalgesic response of MR 2266, the rank order of strains was; BALB greater than C57BL and DBA greater than or equal to Swiss while the rank order for the analgesic effect of MR 2267 was; Swiss greater than DBA and BALB. The results indicate the presence of tonic kappa-receptor-mediated regulation of the spinal and supra-spinal thermonociceptive reactions which is stereospecific and strain dependent.

Animals

Determination of left ventricular volume and mass with use of biphasic spin-echo MR imaging: comparison with cine MR.

In this study, the authors compared a new rapid spin-echo magnetic resonance (MR) imaging method, biphasic MR, with cine MR in the determination of left ventricular volume and mass in healthy volunteers. Biphasic spin-echo MR images covering the entire heart were obtained with use of the electrocardiogram R wave and the downslope of the T wave at both end diastole and end systole, respectively. Biphasic MR-determined values correlated well with small standard errors of the estimate (end-diastolic volume = 7.82 cm3, end-diastolic mass = 10.20 g, end-systolic mass = 10.08 g, ejection fraction = 2.62%) and were more reproducible. Cine MR-defined end-systolic volume was significantly larger (P less than .01) and ejection fraction was significantly smaller (P less than .005) than biphasic MR-determined values probably because of the uncertainty in isolating end systole with cine MR. Left ventricular volumes, mass, and ejection fraction are more accurately and reproducibly quantified in a more time-efficient manner with use of biphasic MR than with cine MR because of its significantly shorter image acquisition and reconstruction times.

Adult

Dopamine D2 receptor binding subunits of Mr congruent to 140,000 and 94,000 in brain: deglycosylation yields a common unit of Mr congruent to 44,000.

The ligand-binding subunit of the porcine striatal dopamine D2 receptor was identified by photoaffinity labeling with [125I]N-azidophenethylspiperone ([125I]NAPS). Upon photolysis, [125I]NAPS covalently incorporated into a broad band of apparent Mr congruent 140,000 with an appropriate pharmacological profile for D2 receptors as assessed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Smaller subunits of apparent Mr congruent 94,000 and 34,000 were specifically labeled by [125I]NAPS with an appropriate D2 receptor profile and were similar to the major ligand-binding subunits of photoaffinity-labeled canine striatal D2 receptors. Photoaffinity labeling in the absence or presence of multiple protease inhibitors did not alter the migration pattern of the Mr congruent to 140,000/94,000 subunits upon denaturing electrophoresis in either the absence or presence of thiol-reducing/alkylating reagents. In order to investigate the possible basis for the existence of these high molecular weight forms of the D2 receptor, we assessed the carbohydrate nature of photolabeled D2 ligand-binding subunits by the use of lectin affinity chromatography and specific exo- and endoglycosidase treatments. Both photoaffinity-labeled D2 receptor proteins from porcine striatum (Mr congruent to 140,000 and 94,000) were glycoproteins as indexed by their absorption and specific elution from wheat germ agglutinin lectin resins. The exoglycosidase neuraminidase altered the electrophoretic mobility of both the Mr congruent to 140,000 and 94,000 labeled subunits to a single band of apparent Mr congruent to 51,000. Prior removal of sialic acid residues did not alter the reversible binding characteristics of [3H]spiperone to D2 receptors. Complete removal of receptor-associated N-linked carbohydrate by the endoglycosidase glycopeptidase F (peptide-N4[N-acetyl-beta-glucosaminyl]asparagine amidase) produced a further increase in the mobility of the Mr congruent to 51,000 subunit to apparent Mr congruent to 44,000. The porcine Mr congruent to 34,000 photolabeled peptide is an N-linked glycoprotein as assessed by lectin affinity chromatography and susceptibility to digestion by glycopeptidase F to a peptide of apparent Mr congruent to 23,000.(ABSTRACT TRUNCATED AT 400 WORDS)

Affinity Labels

Comparison of CT, low-field-strength MR imaging, and high-field-strength MR imaging. Work in progress.

To assess objectively the sensitivity and specificity of low-field-strength (0.064 T) magnetic resonance (MR) imaging, a prospective blind study of 280 examinations was performed to compare low-field-strength MR imaging with computed tomography (CT) and with high-field-strength (1.5-T) MR imaging of the cranium. The sensitivity (defined as the true-positive rate) with high-field MR imaging was superior to that with low-field MR imaging and CT in helping detect overall abnormalities. Sensitivities were generally similar over a broad range of specific cranial central nervous system diseases. Low-field and high-field MR imaging were equivalent in the blind diagnoses of neoplasms and white matter disease, whereas low-field MR and CT were equivalent in the blind diagnoses of contusion, subdural and epidural hematoma, sinus disease, normality, and abnormality. The specificities with low-field MR imaging and CT were substantially better than those with high-field MR imaging.

Brain

Comparative distribution of messenger RNAs encoding glutamic acid decarboxylases (Mr 65,000 and Mr 67,000) in the basal ganglia of the rat.

Glutamic acid decarboxylase, the enzyme required for GABA synthesis, exists as distinct isoforms, which have recently been found to be encoded by different genes. The relative expression of messenger RNAs encoding two isoforms of glutamic acid decarboxylase (Mr 67,000 and Mr 65,000) was measured at the single-cell level in neurons of the rat basal ganglia with in situ hybridization histochemistry. Both messenger RNAs were expressed in neurons of the striatum, pallidum, and substantia nigra pars reticulata, but marked differences in the relative level of labelling were observed with the two probes. In striatum, efferent neurons were more densely labelled for the messenger RNA encoding glutamic acid decarboxylase (Mr 65,000) than for the messenger RNA encoding glutamic acid decarboxylase (Mr 67,000), whereas the reverse was observed for GABA-ergic interneurons. Neurons of the entopeduncular nucleus were much more densely labelled for messenger RNA encoding glutamic acid decarboxylase (Mr 65,000) than for messenger RNA encoding glutamic acid decarboxylase (Mr 67,000). In addition, labelling for messenger RNA encoding glutamic acid decarboxylase (Mr 65,000) was higher in the entopeduncular nucleus (internal pallidum) than in the globus pallidus (external pallidum), a structure which expressed similar levels of both mRNAs. In contrast to neurons of the internal pallidum, efferent neurons of the substantia nigra pars reticulata expressed slightly more messenger RNA encoding glutamic acid decarboxylase (Mr 67,000) than that encoding the other isoform of the enzyme. The results suggest a differential expression of the messenger RNAs encoding the two isoforms of glutamic acid decarboxylase in subpopulations of basal ganglia neurons in rats.

Animals

Conversion of human placental alkaline phosphatase from a high Mr form to a low Mr form during butanol extraction. An investigation of the role of endogenous phosphoinositide-specific phospholipases.

Alkaline phosphatase in a wide range of tissues has been shown to be anchored in the membrane by a specific interaction with the polar head group of phosphatidylinositol. It has previously been suggested that the production of low Mr alkaline phosphatase during the commonly used butanol extraction procedure may result from the activation of an endogenous phosphoinositide-specific phospholipase C which removes the 1,2-diacylglycerol responsible for membrane anchoring. This conversion process was investigated in greater detail with human placenta used as the source of alkaline phosphatase. Mr and hydrophobicity of the alkaline phosphatase were determined by gel filtration on TSK-250 and partitioning in Triton X-114, respectively. Alkaline phosphatase extracted from human placental particulate fraction with butanol at pH 5.4 or released by incubation with Staphylococcus aureus phosphatidylinositol-specific phospholipase C produced a form of alkaline phosphatase of Mr approx. 170,000 and relatively low hydrophobicity. By contrast, the butanol extract prepared at pH 8.3 was an aggregated form of Mr approx. 600,000 and was relatively hydrophobic. The effect of a variety of inhibitors and activators on the amount of low Mr alkaline phosphatase produced during butanol extraction revealed that it was a Ca2+- and thiol-dependent process. Proteinase inhibitors had no effect. [3H]Phosphatidylinositol hydrolysis by the particulate fraction, unlike low Mr alkaline phosphatase production, was relatively sensitive to heat inactivation, indicating that the phosphoinositide-specific phospholipases C from cytosol and lysosomes were unlikely to be responsible for conversion. A butanol-stimulated activity which removed the [3H]myristic acid from the variant surface glycoprotein ( [3H]mfVSG) of Trypanosoma brucei was detectable in the human placental particulate fraction. Since this activity was acid active, Ca2+- and thiol-dependent and relatively heat stable, it may be the same as that responsible for production of low Mr alkaline phosphatase. The only 3H-labelled product identified was phosphatidic acid, suggesting that the [3H]mfVSG-cleaving activity is a phospholipase D. These data strongly support the proposal that production of low Mr alkaline phosphatase during butanol extraction is an autolytic process occurring as the result of an endogenous phospholipase. However, they also suggest that the lysosomal and cytosolic phosphoinositide-specific phospholipases C that have previously been described in many mammalian tissues are not responsible for this process.

1-Butanol

MR arthrography of the shoulder: comparison with conventional MR imaging.

Twenty-three patients underwent both conventional MR imaging of the shoulder and MR shoulder arthrography for clinically suspected labral or rotator cuff abnormalities. Images obtained before and after contrast administration were studied independently, and without knowledge of clinical findings, by two radiologists for the presence of abnormalities of the glenoid labrum or rotator cuff. Results were correlated with surgical findings in all patients. Nine patients had surgically proved labral tears. MR arthrography detected all nine labral abnormalities, while six of the nine were missed on conventional MR imaging. Fourteen patients had surgically proved rotator cuff tears. MR arthrography detected 11 of the 14 tears and missed three partial tears on the bursal surface. Conventional MR imaging detected nine cuff tears and missed five tears; two of these were complete rotator cuff tears and three were partial tears of the undersurface of the rotator cuff. Our results suggest that MR arthrography enhances the accuracy of MR in the evaluation of the glenoid labrum and rotator cuff tendon.

Adolescent

Lipomatous tumors and tumors with fatty component: MR imaging potential and comparison of MR and CT results.

This retrospective study was performed to assess the potential of magnetic resonance (MR) imaging for demonstrating various types of lipomatous tumors and tumors with fatty component and to compare the results of MR with those of computed tomography (CT). MR examinations of 17 patients with 18 lipomatous tumors (16, benign; two, liposarcoma) and two patients with fibrosarcomas were reviewed; CT scans were available for comparison in all patients. In the 16 benign lesions (12 benign lipomas, two ovarian dermoid cysts, and two renal angiomyolipomas), the fatty component of the tumors was readily demonstrated by both MR and CT. The T1 and T2 relaxation times and spin density of benign lipomatous tumors were in a range similar to those of normal subcutaneous fat. Differentiation between lipomas and liposarcomas was achieved with both MR and CT. On MR images using a short repetition time (TR = .5 sec), liposarcomas (long T1) were imaged with a lower MR intensity than lipomas (short T1).

Adolescent

Rotator cuff disease: assessment with MR arthrography versus standard MR imaging in 36 patients with arthroscopic confirmation.

Standard proton-density- and T2-weighted magnetic resonance (MR) imaging and MR arthrography were used to depict rotator cuff disease in 36 shoulders in 36 patients; the findings were compared with arthroscopic findings in every patient. In 19 rotator cuffs normal at arthroscopy, MR arthrography revealed no tear in 16 patients, a partial tear in one patient, and a full-thickness tear in two patients. Standard proton-density- and T2-weighted images were normal in 15 of these patients and revealed a partial tear in two patients and a full-thickness tear in two patients. In 13 partial tears found at arthroscopy, MR arthrography showed a partial tear in six patients, no tear in five patients, and a full-thickness tear in two patients; standard MR imaging revealed a partial tear in one patient, no tear in 10 patients, and a full-thickness tear in two patients. All four full-thickness tears proved with arthroscopy were correctly diagnosed with both MR imaging methods. The main advantage of MR arthrography was better depiction of partial tears in the articular surface.

Adolescent

Detection of hepatic metastases: comparison of contrast-enhanced CT, unenhanced MR imaging, and iron oxide-enhanced MR imaging.

Diagnostic accuracy of contrast-enhanced CT, unenhanced MR imaging, and MR images enhanced with superparamagnetic iron oxide was evaluated in 10 patients with histologically proved hepatic metastases. First, diagnostic performance of the imaging technique with respect to the ability of radiologists to recognize the presence or absence of a metastasis was measured by using receiver-operating-characteristic (ROC) analysis of single images. Second, the total number of lesions (N = 108) detected by "complete" CT and MR examinations was counted. Finally, lesion-liver contrast-to-noise ratios (CNR) were measured in all MR sequences. The area under the ROC curve was .67 +/- .03 for contrast-enhanced CT, .81 +/- .07 for the unenhanced SE 260/14 sequence, and .92 +/- .01 for the iron oxide-enhanced SE 1500/40 sequence. The enhanced SE 1500/40 sequence yielded significantly (p less than .005) greater accuracy than did contrast-enhanced CT. The same sequence detected significantly (p less than .05) more lesions than all other imaging techniques (19% more than the best unenhanced MR sequence and 36% more than contrast-enhanced CT). The enhanced SE 1500/40 sequence also yielded the highest CNR value (19.5 +/- 10.2) of all MR sequences. These results indicate that iron oxide-enhanced MR imaging is a superior imaging technique for the detection of hepatic lesions.

Adult

MR imaging of the pituitary gland in infants and children: changes in size, shape, and MR signal with growth and development.

It has been reported that on MR images of the brain in neonates the entire pituitary gland is hyperintense. This is quite different from the well-established observation that portion is isointense. To better understand the development of the neonatal pituitary gland, we studied the timing and magnitude of changes in the size, shape, and MR signal of the pituitary gland in early childhood and infancy. The study included 76 infants and children ages 3 days to 4 years old. In each MR study, the signal intensity of the pituitary gland on T1-weighted coronal (n = 24) and sagittal (n = 76) images was compared with the signal intensity of the pons by using region-of-interest methods. The size and shape of the pituitary glands were recorded. Statistical comparisons were made for signal intensity and size of the pituitary gland between boys and girls and among age groups. The results showed that the MR signal of the posterior lobe remained hyperintense relative to the pons for all age groups represented in our study (through 4 years). However, the signal intensity of the anterior lobe gradually diminished and by approximately age 2 months was isointense with the pons. Thus, by approximately age 2 months the MR signal intensity of the infant's pituitary gland has changed from being entirely hyperintense (as seen in neonates) to isointense in the anterior lobe and hyperintense in the posterior lobe (as seen in adults). In the first 2 months of life the pituitary gland is bulbous in shape; later it has a flatter upper surface. We found no significant changes in the length or signal intensity of the pituitary gland; no differences among sexes in size, shape, or signal intensity were demonstrated. Findings of a bulbous pituitary gland and high MR signal of the entire pituitary are normal in neonates up to 2 months of age. After that, the gland gradually flattens and the MR signal of the anterior lobe decreases until it has characteristics similar to the adult pituitary. Lack of high signal or discovery of a small pituitary gland in a neonate should alert the radiologist to the possibility of pituitary malformation or dysfunction.

Child, Preschool