MRI analysis of extra-capsular ganglia at the gastrocnemius origin and their association with osteoarthritis.

AIM: To evaluate the prevalence, clinical relevance, and magnetic resonance imaging (MRI) features of extra-capsular ganglia at the gastrocnemius origin and to assess their association with internal derangement and osteoarthritis of the knee. MATERIALS AND METHODS: One hundred consecutive knee MRI examinations, obtained within a 6-month period from patients with no history of recent knee trauma, recent injections, inflammatory arthritis, infection, or tumours, were evaluated retrospectively for the presence of ganglia at the gastrocnemius origin. The lesions were divided into two groups: an intra-capsular and an extra-capsular group. Cyst morphology (size, shape, and internal septa), internal derangement of the knee (cartilage lesion, cruciate ligament injury, meniscal tear, and corner injury on MRI, and osteoarthritis of the knee on radiographs) were evaluated. The chi-square, Fisher's exact, and t-tests were used to compare the two groups, in addition to multivariate stepwise logistic regression analysis. RESULTS: Thirty-nine ganglia with an extra-capsular location were identified on 100 knee MRI (39 %). Rounded shape and internal septa were more common in the extra-capsular than in the intra-capsular group (p<0.001). Frequencies of high-grade cartilage, meniscal tear, and high-grade osteoarthritis significantly differed between the groups (p≤0.038). In multivariate analysis, the only significant association was between high-grade osteoarthritis and the extra-capsular group. CONCLUSION: Extra-capsular ganglia at the gastrocnemius origin were not uncommon on knee MRI and had features typical of ganglia found at other sites. High-grade osteoarthritis was significantly associated with extra-capsular ganglia.

Facet joint injection versus epidural steroid injection for lumbar spinal stenosis: intra-individual study.

AIM: To evaluate the efficacy of facet joint injection (FJI) for patients with lumbar central canal stenosis (LCS) in comparison with epidural steroid injection (ESI) in the same individuals. MATERIAL AND METHODS: Two hundred and fifty-two patients who underwent both FJI and ESI for LCS between January 2014 and December 2014 were considered for enrolment in the study. A radiologist retrospectively conducted a chart review and recorded which injection was chosen as the third injection after sequential injections of FJI and ESI, and why clinicians chose the particular injection method. The response was measured via the use of a five-point satisfaction scale. RESULTS: Among 252 patients, only 73 patients were included in the study (the remaining patients did not fulfil the inclusion criteria). Out of 73 patients (mean age, 69.7 years; range, 49∼87 years), 50 patients had received a third injection, 33 patients (66%) underwent FJIs as a third injection. Out of 19 patients who had experienced an ineffective first ESI, 13 (68.4%) patients reported the second FJI as effective. Out of six patients for whom the first FJI had been ineffective, three (50%) patients reported the second ESI as effective. CONCLUSION: FJIs can be administered as an alternative to ESIs in cases of LCS.

MRI findings of spinal arteriovenous fistulas: focusing on localisation of fistulas and differentiation between spinal dural and perimedullary arteriovenous fistulas.

AIM: To investigate the magnetic resonance imaging (MRI) findings of spinal arteriovenous fistulas (AVFs) to predict their locations and types. MATERIALS AND METHODS: Patients who underwent spinal angiography for suspected spinal AVF between April 2003 and April 2013 were enrolled. Spine MRI images were analysed by two radiologists in consensus focusing on the distribution patterns of flow void pial vessels (FVPVs): longitudinal distribution pattern along the spinal level (even or uneven, with description of the most crowded level in uneven cases) and axial distribution pattern in relation to the cord (ventral, dorsal, or co-dominance). Spinal angiography served as the reference standard for the locations and types of fistulas. RESULTS: Thirty-two patients (M:F=24:8, mean age, 53 years; range, 2-74 years) were included. There were 18 patients with spinal dural AVFs (SDAVFs), seven with perimedullary AVFs, four with epidural AVFs, and three diagnosed as normal. In 12 of 15 longitudinally uneven AVFs, the most crowded levels of FVPVs corresponded to the true fistulous levels within two-level differences. While dorsal dominance was predominant in SDAVFs (13/18), ventral dominance was predominant in perimedullary AVFs (5/7; p<0.01). CONCLUSION: Fistulous levels may be predicted to be within two levels of the most crowded levels of FVPVs. The dorsal dominance pattern of FVPVs favours SDAVFs, whereas ventral dominance suggests perimedullary AVFs.

Comparison of three-dimensional isotropic and conventional MR arthrography with respect to the diagnosis of rotator cuff and labral lesions: focus on isotropic fat-suppressed proton density and VIBE sequences.

AIM: To compare the diagnostic accuracies of three-dimensional (3D) isotropic magnetic resonance arthrography (MRA) using fat-suppressed proton density (PD) or volume interpolated breath-hold examination (VIBE) sequences with that of conventional MRA for the diagnosis of rotator cuff and labral lesions. MATERIALS AND METHODS: Eighty-six patients who underwent arthroscopic surgery were included. 3D isotropic sequences were performed in the axial plane using fat-suppressed PD (group A) in 53 patients and using VIBE (group B) in 33 patients. Reformatted images were obtained corresponding to conventional images, and evaluated for the presence of labral and rotator cuff lesions using conventional and 3D isotropic sequences. The diagnostic performances of each sequence were determined using arthroscopic findings as the standard. RESULTS: Good to excellent interobserver agreements were obtained for both 3D isotropic sequences for the evaluation of rotator cuff and labral lesions. Excellent agreement was found between two-dimensional (2D) and 3D isotropic MRA, except for supraspinatus tendon (SST) tears by both readers and for subscapularis tendon (SCT) tears by reader 2 in group B. 2D MRA and 3D isotropic sequences had high diagnostic performances for rotator and labral tears, and the difference between the two imaging methods was insignificant. CONCLUSIONS: The diagnostic performances of 3D isotropic VIBE and PD sequences were similar to those of 2D MRA.

Ulnar nerve morphology on magnetic resonance imaging predicts nerve recovery after surgery for cubital tunnel syndrome.

Magnetic resonance imaging (MRI) can evaluate nerve morphology in cubital tunnel syndrome (CuTS), but its value in predicting surgical outcome is unclear. The purpose of this study was to determine whether ulnar nerve morphology on MRI correlated with outcome after CuTS surgery. We reviewed 40 patients who had preoperative MRI and electrodiagnostic (EDX) examinations for CuTS and outcome evaluation 6 months and 2 years postoperatively. Using MRI, ulnar nerve cross-sectional area (UNCSA), changes in signal intensity, and any space-occupying lesion were evaluated. Other factors assessed were age, symptom duration and severity, type-2 diabetes and EDX parameters. Factors associated with unfavorable surgical outcome were identified. At 6 months postoperatively, 12 patients (30%) had excellent, 19 (47.5%) good, 8 (20%) fair and 1 (2.5%) poor results on modified Wilson-Krout criteria. On univariate analysis, unfavorable outcomes were associated with increased UNCSA, space-occupying lesion, and decreased motor nerve conduction velocity (mNCV), and on multivariate analysis with increased UNCSA 1 cm distal from the epicondyle only (model 1) or increased UNCSA 1 cm proximal from the epicondyle and decreased mNCV (model 2). At 2 years, 15 patients (37.5%) had excellent, 21 (52.5%) good, 3 (7.5%) fair and 1 (2.5%) poor results, and no factors correlated with unfavorable outcome. Increased UNCSA on MRI was associated with unfavorable outcome at 6 months but not at 2 years. This study suggests that morphologic ulnar nerve changes can predict delayed nerve recovery after surgery for CuTS.

Using multivariate statistical methods to model the electrospray ionization response of GXG tripeptides based on multiple physicochemical parameters.

Response factors were determined for twelve GXG peptides (where G stands for glycine and X is any of alanine [A], arginine [R], asparagine [N], aspartic acid [D], glycine [G], histidine [H], leucine [L], lysine [K], phenylalanine [F], serine [S], tyrosine [Y], valine [V]) by electrospray ionization mass spectrometry (ESI-MS). The response factors were measured using a novel flow injection method. This new method is based on the Gaussian distribution of analyte concentration resulting from band-broadening dispersion experienced by the analyte upon passage through an extended volume of PEEK tubing. This method removes the need for preparing a discrete series of standard solutions to assess concentration-dependent response. Relative response factors were calculated for each peptide with reference to GGG. The observed trends in the relative response factors were correlated with several analyte physicochemical parameters, chosen based on current understanding of ion release from charged droplets during the ESI process. These include analyte properties: nonpolar surface area; polar surface area; gas-phase basicity; proton affinity; and Log D. Multivariate statistical analysis using multiple linear regression, decision tree, and support vector regression models were investigated to assess their potential for predicting ESI response based on the analyte properties. The support vector regression model was more versatile and produced the least predictive error following 12-fold cross-validation. The effect of variation in solution pH on the relative response factors is highlighted, as evidenced by the different predictive models obtained for peptide response at two pH values (pH = 6.0 and 9.0). The relationship between physicochemical parameters and associated ionization efficiencies for GXG tripeptides is discussed based on the equilibrium partitioning model.

Synthesis of oligopeptide and peptidomimetic libraries.

The elaboration of peptide libraries prepared by either chemical or biological methods in a format useful for discovery of peptides with specific biological activities was first introduced in the 1980s. A virtual explosion of activity in this area has occurred recently, and the basic approaches have been applied to a wide variety of chemistries and for all manner of biological, chemical and physical targets. Recent advances include new synthetic methodologies, new analytical methods, new design methods and new assay procedures.

Overcoming aggregation in indium salen catalysts for isoselective lactide polymerization.

A methodology for controlling aggregation in highly active and isoselective indium catalysts for the ring opening polymerization of racemic lactide is reported. A series of racemic and enantiopure dinuclear indium ethoxide complexes bearing salen ligands [(ONNOR)InOEt]2 (R = Br, Me, admantyl, cumyl, t-Bu) were synthesized and fully characterized. Mononuclear analogues (ONNOR)InOCH2Pyr (R = Br, t-Bu, SiPh3) were synthesized by controlling aggregation with the use of chelating 2-pyridinemethoxide functionality. The nuclearity of metal complexes was confirmed using PGSE NMR spectroscopy. Detailed kinetic studies show a clear initiation period for these dinuclear catalysts, which is lacking in their mononuclear analogues. The polymerization behavior of analogous dinuclear and mononuclear compounds is identical and consistent with a mononuclear propagating species. The isotacticity of the resulting polymers was investigated using direct integration and peak deconvolution methodologies and the two were compared.

Development of potent truncated glucagon antagonists.

In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally constrained analogues containing the sequence of the middle region of glucagon (5-15), and truncated analogues containing the sequence of the C-terminal region (16-23). Biological assays of these analogues showed that the truncated glucagon analogues with the sequence of the C-terminal region possess significantly better binding affinity compared to the truncated analogues with the sequence of the middle region, and these analogues (17-23) demonstrated potent antagonistic activity (pA(2) values between 6.5 and 7.5). On the basis of these results, it can be suggested that glucagon interacts with its receptor with two hydrophobic patches located in the middle and the C-terminal regions of glucagon, and both hydrophobic patches are necessary for significant receptor recognition. These two hydrophobic binding motifs, located in two different regions of glucagon, appear to be the reason why the earlier attempts to obtain truncated analogues with good binding affinity did not result in any success. Long peptide hormones such as glucagon seem to require more than one binding pocket on the receptors for maximal interaction.

A new approach to search for the bioactive conformation of glucagon: positional cyclization scanning.

In search for the bioactive conformation of glucagon, "positional cyclization scanning" was used to determine secondary structures of glucagon required for maximal interaction with the glucagon receptor. Because glucagon is flexible in nature, its bioactive conformation is not known except for an amphiphilic helical conformation at the C-terminal region. To understand the conformational requirement for the N-terminal region that appears to be essential for signal transduction, a series of glucagon analogues conformationally constrained by disulfide or lactam bridges have been designed and synthesized. The conformational restrictions via disulfide bridges between cysteine i and cysteine i + 5, or lactam bridges between lysine i and glutamic acid i + 4, were applied to induce and stabilize certain corresponding secondary structures. The results from the binding assays showed that all the cyclic analogues with disulfide bridges bound to the receptor with significantly reduced binding affinities compared to their linear counterparts. On the contrary, glucagon analogues containing lactam bridges, in particular, c[Lys(5), Glu(9)]glucagon amide (10) and c[Lys(17), Glu(21)]glucagon amide (14), demonstrated more than 7-fold increased receptor binding affinities than native glucagon. These results suggest that the bioactive conformation of glucagon may adopt a helical conformation at the N-terminal region as well as the C-terminal region, which was not evident from earlier biophysical studies of glucagon.

The role of phenylalanine at position 6 in glucagon's mechanism of biological action: multiple replacement analogues of glucagon.

Extensive evidence gathered from structure-activity relationship analysis has identified and confirmed specific positions in the glucagon sequence that are important either for binding to its receptor or for signal transduction. Fifteen glucagon analogues have been designed and synthesized by incorporating structural changes in the N-terminal region of glucagon, in particular histidine-1, phenylalanine-6, and aspartic acid-9. This investigation was conducted to study the role of phenylalanine at position 6 on the glucagon mechanism of action. These glucagon analogues have been made by either deleting or substituting hydrophobic groups, hydrophilic groups, aromatic amino acids, or a D-phenylalanine residue at this position. The structures of the new analogues are as follows: [des-His1, des-Phe6, Glu9]glucagon-NH2 (1); [des-His1,Ala6,Glu9]glucagon-NH2 (2); [des-His1,Tyr6,Glu9]glucagon-NH2 (3); [des-His1,Trp6,Glu9]-glucagon-NH2 (4); [des-His1,D-Phe6,Glu9]glucagon-NH2 (5); [des-His1,Nle6,Glu9]glucagon-NH2 (6); [des-His1,Asp6,Glu9]glucagon-NH2 (7); [des-His1,des-Gly4,Glu9]glucagon-NH2 (8); [desPhe6,-Glu9]glucagon-NH2 (9); [des-Phe6]glucagon-NH2 (10); [des-His1, des-Phe6]glucagon-NH2 (11); [des-His1, des-Phe6,Glu9]glucagon (12); [des-Phe6,Glu9]glucagon (13); [des-Phe6]glucagon (14); and [des-His1, des-Phe6]glucagon (15). The receptor binding potencies IC50 values are 48 (1), 126 (2), 40 (3), 19 (4), 100 (5), 48 (6), 2000 (7), 52 (8), 113 (9), 512 (10), 128 (11), 1000 (12), 2000 (13), 500 (14), and 200 nM (15). All analogues were found to be antagonists unable to activate the adenylate cyclase system even at concentrations as high as 10(-5) M except for analogues 6 and 8, which were found to be weak partial agonists/partial antagonists with maximum stimulation between 6-12%. In competitive inhibition experiments, all the analogues caused a right shift of the glucagon-stimulated adenylate cyclase dose-response curve. The pA2 values were 8.20 (1), 6.40 (2), 6.20 (3), 6.25 (4), 6.30 (5), 6.30 (7), 6.05 (8), 6.20 (9), 6.30 (10), 6.25 (11), 6.10 (12), 6.20 (13), 6.20 (14), and 6.35 (15).

Design and synthesis of conformationally constrained glucagon analogues.

Glucagon was systematically modified by forming lactam bridges within the central region of the molecule to give conformationally constrained cyclic analogues. Six cyclic glucagon analogues have been designed and synthesized. They are c[Asp(9),Lys(12)][Lys(17,18), Glu(21)]glucagon-NH(2) (1), c[Asp(9),Lys(12)]glucagon-NH(2) (2), c[Lys(12),Asp(15)]glucagon-NH(2) (3), c[Asp(15), Lys(18)]glucagon-NH(2) (4), [Lys(17)-c[Lys(18), Glu(21)]glucagon-NH(2) (5), and c[Lys(12),Asp(21)]glucagon-NH(2) (6). The receptor binding potencies and receptor second messenger activities were determined by radio-receptor binding assays and adenylate cyclase assays, respectively, using rat liver plasma membranes. Most interestingly, analogues 1, 2, 3, and 4 were antagonists of glucagon stimulated adenylate cyclase activity, whereas analogues 5 and 6 were partial agonists in the functional assay. All of the cyclic analogues were found to have reduced binding potencies relative to glucagon. The structural features that might be responsible for these effects were studied using circular dichroism spectroscopy and molecular modeling. These results demonstrated the significant modulations of both receptor binding affinity and transduction (adenylate cyclase activity) that can accompany regional conformational constraints even in larger polypeptide ligands. These studies suggest that the entire molecular conformation, including the flexible middle portion, is important for molecular recognition and transduction at the hepatic glucagon receptor.

Structure-function studies on positions 17, 18, and 21 replacement analogues of glucagon: the importance of charged residues and salt bridges in glucagon biological activity.

We have designed and synthesized eight compounds 2-9 which incorporate various amino acid residues in positions 17, 18, and 21 of the glucagon molecule: 2, [Lys17]glucagon amide; 3, [Lys18]glucagon amide; 4, [Nle17,Lys18,Glu21]glucagon amide; 5, [Orn17,18, Glu21]glucagon amide; 6, [d-Arg17]glucagon; 7, [d-Arg18]glucagon; 8, [d-Phe17]glucagon; and 9, [d-Phe18]glucagon. Compared to glucagon (IC50 = 1.5 nM), analogues 2-9 were found to have binding affinity IC50 values (in nM) of 0.7, 4.1, 1.0, 2.0, 5.0, 25.0, 43.0, and 32.0, respectively. When these compounds were tested for their ability to stimulate adenylate cyclase (AC) activity, they were found to be full or partial agonists having maximum stimulation values of 100, 100, 100, 100, 87, 78, 94, and 100%, respectively. On the basis of the X-ray crystal structure of [Lys17,18,Glu21]glucagon amide reported here, the ability to form a salt bridge between Lys18 and Glu21 is probably key to their increased binding and second messenger activities. Among the eight analogues synthesized here, only analogue 4 preserves the ability to form a salt bridge between Lys18 and Glu21. However, since these modifications are minor they do not seem to change the amphiphilic character of the C-terminus, allowing these analogues to reach 78-100% stimulation in the adenylate cyclase assay. Biological data from analogues 6-9 supports the idea that position 18 of glucagon may influence binding only, while position 17 may influence both receptor recognition and transduction.

Transverse ligament and its effect on meniscal motion. Correlation of kinematic MR imaging and anatomic sections.

RATIONALE AND OBJECTIVES: To evaluate the effect of the transverse ligament on translation of the menisci. METHODS: Six cadaveric knees were examined by MR imaging inside a positioning device before and after transecting the transverse ligament. The knees were examined at various positions: extension, 30 degrees of flexion, 60 degrees of flexion, and full flexion. Sagittal T1-weighted spin-echo images were generated at each knee position and evaluated for statistical differences with regard to anterior-posterior meniscal excursion. RESULTS: Statistically significant differences in meniscal excursion were found before and after transsecting the transverse ligament for anterior-posterior meniscal motion of the anterior horn of the medial meniscus at 30 degrees of knee flexion. No such significant differences were found, however, at 60 degrees of flexion and full flexion in anterior-posterior meniscal excursion of the anterior or posterior horn of either meniscus before and after transsecting the transverse ligament. CONCLUSIONS: The transverse ligament has a restricting effect on anterior-posterior excursion of the anterior horn of the medial meniscus at lower degrees of knee flexion.

Exacerbated pain in cervical radiculopathy at axial rotation, flexion, extension, and coupled motions of the cervical spine: evaluation by kinematic magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors evaluate the functional changes in patients with cervical radiculopathy and increasing symptoms after provocative maneuvers at flexion, extension, axial rotation, and coupled motions of the cervical spine. METHODS: Twenty-one patients with cervical disc herniation (n = 17) or cervical spondylosis (n = 4) in whom symptoms were elicited at flexion, extension, axial rotation, and coupled motions of the cervical spine were studied. The patients were examined inside a positioning device by using a circular surface coil for signal reception. At neutral position (0 degrees) and at provocative positions sagittal T2-weighted turbo spin-echo, axial T2-weighted two-dimensional flash sequence, sagittal three-dimensional (3D) fast imaging with steady state precision sequence and coronal 3D double-echo-in-the-steady-state sequences were obtained. The 3D sequences were reformatted in the axial and oblique coronal planes perpendicular to the exiting nerve roots. The images were evaluated for the size of disc herniations, the foraminal size and cervical cord rotation or displacement at provocative position compared with neutral position (0 degrees). RESULTS: Compared with neutral position (0 degrees), change in size of disc herniation was not found in any (0%) of the provocative positions. In five (24%) patients cervical cord rotation or displacement was noted at axial rotation. The foraminal size increased at flexion, axial rotation to the opposite side of pain and flexion combined with axial rotation to the opposite side of the pain. The foraminal size decreased at extension combined with axial rotation to the side of the pain. A decrease or no change in foraminal size was observed at either extension or axial rotation to the side of the pain. CONCLUSIONS: In patients with cervical disc herniation or cervical spondylosis, exacerbated pain at defined provocative maneuvers is related more to changes in the foraminal size and to nerve root motion with, in some cases, cervical cord rotation or displacement than to changes in the size of herniated discs.

Evaluation of the triangular fibrocartilage and the scapholunate and lunotriquetral ligaments in cadavers with low-field-strength extremity-only magnet. Comparison of available imaging sequences and macroscopic findings.

RATIONALE AND OBJECTIVES: The authors assessed the ability of a low-field-strength extremity-only magnet to provide visualization of the triangular fibrocartilage and the scapholunate and lunotriquetral ligaments. METHODS: Twelve human wrists were examined with a 0.2 T extremity-only magnet. T1-weighted spin echo, proton density-weighted, and T2-weighted turbo spin echo, short-tau inversion recovery, and three-dimensional gradient recalled echo images were acquired, and sections of the specimens were then made that corresponded to the magnetic resonance images. Masked imaging analyses were correlated with macroscopic and limited histopathologic findings. RESULTS: Low-field-strength extremity-only magnet allowed consistent visualization of the triangular fibrocartilage and accurate assessment of a small number of complete tears of the triangular fibrocartilage. The scapholunate ligaments in all cases were identified using a combination of imaging sequences. Consistent visualization of the lunotriquetral ligament with a low-field-strength extremity magnet was difficult. CONCLUSIONS: Magnetic resonance imaging with a low-field-strength extremity-only magnet can be used to visualize the triangular fibrocartilage and the scapholunate ligament, but not the lunotriquetral ligament.

Relationship between global cytosolic Ca2+ concentration and Ca2+-activated K+ current in rabbit cerebral arterial myocyte.

In smooth muscle cells, the sarcoplasmic reticulum (SR) has been identified as the primary storage site for intracellular Ca2+. The peripheral SR is in close proximity with plasma membrane to make a narrow subsarcolemmal space. In this study, we investigated the regulation of subsarcolemmal [Ca2+] ([Ca2+]sl) and global cytosolic [Ca2+] ([Ca2+]c) of rabbit arterial smooth muscle using whole cell patch clamp technique and microspectrofluorimetry. The Ca2+-activated K+ current (IK(Ca)) and the ratio of fura-2 fluorescence (R340/380) were considered to reflect the [Ca2+]sl and [Ca2+]c, respectively. At a holding potential of 0 mV, extracellular application of 10 mM caffeine, a well known Ca2+-releasing agent, induced transient increase of IK(Ca) and R340/380 (IK(Ca)-transient and R340/380-transient, respectively). The increase and decay of IK(Ca) transient was faster than R340/380-transient. By repetitive application of caffeine, when the refilling state of SR was supposed to be lower than the control condition, IK(Ca)-transient and R340/380 transient were suppressed to different levels; e.g. the second application 20 sec after the first could induce smaller IK(Ca) transient than R340/380-transient. Dissociation of IK(Ca)-transient and R340/380-transient was removed by sufficient (>3 min) washout of caffeine. Recovery from the dissociation was also dependent upon the membrane potential; faster recovery was observed at negative (-40 mV) holding potential than at depolarized (0 mV) condition. Dissociation of IK(Ca) from [Ca2+]c was also partially prevented by perfusion with Na+-free (replaced by NMDG+) extracellular solution. These results suggest that, 1) there is prominent spatial inhomogeneity of [Ca2+] in cerebral arterial myocyte, 2) [Ca2+]Sl is preferentially affected by the interference from nearby plasmalemmal Ca2+ regulation mechanism which is partly dependent upon extracellular Na+.

Localization of interleukin-1 in human squamous carcinomas of the head and neck.

Recent investigations revealed that interleukin-1 can promote bone resorption by activating osteoclasts. The authors' immunocytochemical studies with monoclonal antibody against human interleukin-1 localized interleukin-1 at the bone resorption site of the squamous carcinomas as well as within the squamous carcinomas. In addition, Western blotting and dot blotting methods were used to isolate interleukin-1 from the extracts of the squamous carcinomas in the head and neck. Finding interleukin-1, a potent bone resorption-stimulating factor, in squamous carcinomas suggests that interleukin-1 might play an important role in the extensive local bone destruction seen in the head and neck patients with squamous carcinomas.

Transforming growth factor-alpha and rhinitis.

OBJECTIVES: Transforming growth factor-alpha (TGF-alpha) has been implicated in diverse physiologic and pathophysiologic functions including immunological, inflammatory, and neoplastic processes. TGF-alpha has been localized in the hyperproliferative, inflammatory environment of chronic otitis media, cholesteatoma, and asthmatic airways. TGF-beta1, which must be present with TGF-alpha to transform fibroblasts, has been found in rhinitic mucosa and in asthma in prior studies. The authors sought to identify whether TGF-alpha also played a role in the inflammatory cascade and fibrosis of rhinitis. STUDY DESIGN: A nonrandomized, prospective study was carried out in which samples of inferior turbinate and nasal polyps from rhinitic and nonrhinitic patients were subjected to immunohistochemistry and Western blotting to determine the presence of TGF-alpha. METHODS: Twenty-seven subjects undergoing surgery for rhinitis, obstructive sleep apnea, nasal fracture, and rhinoplasty were recruited for this study, the latter three groups acting as controls. Immunohistochemical and Western blotting techniques were employed to identify the presence of TGF-alpha in inferior-turbinate and nasal-polyp samples of rhinitic subjects. RESULTS: Immunohistochemistry demonstrated the selective staining of TGF-alpha in the basement membrane and extracellular matrix, including lymphatic, vascular, and glandular structures, in most turbinate samples and the absence of staining in corresponding controls. Further, TGF-alpha was isolated to a discrete 30-kD band in both inferior turbinate and polyp tissues by Western blotting without staining in the corresponding controls. CONCLUSIONS: These results suggest that TGF-alpha may play a role in the inflammatory derangement of rhinitis.

Hydrostatic versus oleic acid-induced pulmonary edema: high-resolution computed tomography findings in the pig lung.

RATIONALE AND OBJECTIVES: We evaluated the differences between combined hydrostatic and hypervolemic edema and oleic acid-induced edema on high-resolution computed tomography (HRCT) scans. METHODS: Twelve anesthetized and ventilated pigs were studied. Hydrostatic edema was induced by ligation of the abdominal aorta and infusion of normal saline (n = 4); permeability edema was induced by intravenous injection of oleic acid (n = 4). Four pigs were studied as normal controls. Serial scans were obtained before and after induction of edema at a constant position in the caudal lobe of the lung. The distribution of edema was assessed visually. Cross-sectional areas (CSAs) of the pulmonary artery and vein were measured both at the lobar and segmental levels. RESULTS: Gravity-dependent opacity, peribronchovascular fluid collection, prominent centrilobular core, thickening of the interlobular septa, and air-space consolidation at the dependent site were the sequential HRCT findings of hydrostatic edema. Randomly distributed, diffuse patchy high attenuation areas with a tendency for predilection in the subpleural and peripheral areas of the secondary lobule were the findings of oleic acid-induced edema. Hydrostatic edema increased the mean CSAs of the lobular vein by 137.8% +/- 78.7, but oleic acid edema decreased the mean CSAs by 33.2% +/- 22.7. Changes in the mean CSAs of the pulmonary arteries were not significant. The mean vein-to-artery ratio increased significantly in hydrostatic edema but decreased in oleic acid edema. CONCLUSION: HRCT findings for hydrostatic and oleic acid-induced pulmonary edema differed both in distribution of edema and in pulmonary vascular response.