A brief study of the selectivity of norbinaltorphimine, (-)-cyclofoxy, and (+)-cyclofoxy among opioid receptor subtypes in vitro

Norbinaltorphimine (nor-BNI) is a bifunctional reagent developed as a selective antagonist of the kappa opioid receptor. In this paper we examined the in vitro selectivity of nor-BNI, 6-desoxy-6 beta-fluoronaltrexone (cycloFOXY), and the enantiomer of cycloFOXY, among opioid receptor subtypes. Nor BNI exhibited the highest affinity for kappa binding sites labeled by 3H-U69593 (Ki = 1.8nM), and was 27- to 29-fold less potent at mu and delta binding sites. In contrast, cycloFOXY had the highest affinity for mu binding sites (Ki = 2.62 nM), and bound to kappa and delta binding sites with Ki's of 9.3 nM and 89 nM, respectively. The enantiomer of cycloFOXY, did not inhibit binding even at concentrations greater than 10 microM, validating in part the use of 18F-labeled (+)-cycloFOXY to estimate "non-specific binding" in positron emission tomography. Additionally, we report that (S,S)-U50 488 and (R.R)-U50 488 bind to kappa binding sites labeled by 3H-U69 593 with Ki's of 0.89 nM and 299 nM, respectively.     

Disturbances of bone growth and development

"What is growth anyway? Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age?" Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but the early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability.     

The blast path: theoretical basis, experimental data and clinical application

Use of the "blast path" may be helpful in patients where positioning for ESWL treatments is difficult. Good pressures are maintained along the blast path and an alternate fracture mechanism may be in effect. The rate of fragmentation, assessed using model material, decreases with distance beyond F2.     

The apical border plaque in chronic adult periodontitis. An ultrastructural study. I. Morphology, structure, and cell content.

THIS STUDY CONCERNS THE APICAL BORDER (AB) plaque in relation to chronic adult periodontitis (AP). Fifty-six teeth from 24 patients with AP were examined by transmission electron microscopy (TEM). The AB was not discrete with islands of bacteria in the so-called plaque-free zone (PFZ). Coronal to the AB, the established plaque commonly consisted of three to four layers of Gram-positive and Gram-negative cocci, rods, filaments, and spirochetes and a superficial layer, mainly of spirochetes, but including filaments, "test tube brush," and "corn-cob" formations. The most apical apparently intact organisms in the PFZ were in bacterial islands or in isolation and were predominantly Gram-negative cocci and rods, with occasional other morphotypes. The most apical microorganisms were invariably ghost cells. A cuticle of varying thickness and structure was present at the plaque/tooth interface. It was concluded that there was a limited range of intact bacterial morphotypes in the apical border plaque in chronic periodontitis.     

Probe tine diameter and probing depth

The aim of this study was to assess the effect of difference in tine diameter on probing pocket depth measurement. 2 sets of tines with Williams markings at 1, 2, 3, 5, 7, 8, 9 and 10 mm, and with a "round" tip, diameter 0.5 mm, were compared. One set was described as parallel-sided, the other as tapered. The parallel-sided tine was almost parallel from the 10 mm marking to the tip (tip diameter mean = 0.46 mm, 95% C.I. 0.456-0.464), while the corresponding diameter for the tapered tine varied (tip diameter mean = 0.48 mm, 95% C.I. 0.473-0.489). Calibration markings appeared highly consistent with the expected value to within 0.01 mm. The tines were mounted in Brodontic handles at 0.25 N. Examiner probing repeatability yielded kappa 0.86 for "parallel-sided" and 0.81 for "tapered" tines in vivo. 412 approximal pockets were assessed in 53 patients with routine chronic adult periodontitis, mean age 42.1 years. Each site had a probing depth of greater than or equal to 5 mm, PlI less than or equal to 1, GI less than or equal to 1, PBI less than or equal to 1. Each site was probed 2x with a 15-min interval. At the first 251 sites, the parallel-sided tine was used initially, and the tapered at the remaining 161 sites. Results indicated a highly significant tendency for the parallel-sided tine to yield a deeper reading when a difference occurred. These findings indicate that with adequate training providing high examiner repeatability, one source of error in probing data can be minimised.     

Pulmonary angiography in pulmonary embolic disease

Pulmonary thromboembolic disease is a serious and common complication in patients with various medical and surgical diseases. Pulmonary angiography is currently accepted as the "gold standard" for the diagnosis of pulmonary embolism, but its role is still somewhat controversial. This review article attempts to answer some of these controversies by exploring the how, when, what, and where of contemporary pulmonary angiography.     

Size-dependence of mercury (II) accumulation kinetics in the mosquitofish,Gambusia affinis (Baird and Girard)

Size-dependence of mercury (II) accumulation from water by the mosquitofish,Gambusia affinis was assessed under controlled laboratory conditions. Uptake rates were higher for smaller fish than for larger fish. Mean (±S.D.) uptake rate for mosquitofish exposed to 0.24 g/L of Hg was 0.32 ± 0.15 g/g dry wt/day. Uptake rate constants were similar for the Hg (II) and Hg° as reported elsewhere. Both inorganic species (Hg (II) and Hg°) were accumulated faster than methylmercury. Elimination rate constants averaged 0.530.14 per day (mean ± 1 S.D.). No significant size effects on elimination rate constants were detected. Elimination constants were similar to those reported elsewhere for Hg° elimination but larger than those for methylmercury elimination.     

Identical expression of ELAM-1, VCAM-1, and ICAM-1 in sarcoidosis and usual interstitial pneumonitis

Extravasation of leucocytes in tissues is mediated by leucocyte—endothelial cell interactions in which adhesion molecules play an important role. Until now, two pathways have been unravelled, i.e., the LFA-1/ICAM-1 and the VLA-4/VCAM-1 pathways. ELAM-1 has been shown to be involved in granulocyte accumulation and recently also in lymphocyte migration. The role of HECA-452 is under investigation. In this study we have investigated the expression of the above-mentioned adhesion molecules in lung tissue of patients with pulmonary sarcoidosis and usual interstitial pneumonitis (UIP), and in mediastinal lymph nodes of patients with sarcoidosis. ICAM-1 (CD54) was broadly distributed on the endothelium of all the vessels found in sarcoidosis and UIP. VCAM-1 was present on the endothelium of the venules, capillaries, and arterioles in both sarcoidosis and UIP. ELAM-1 reacted with endothelial cells lining venules and capillaries in chronic progressive sarcoidosis and in the active phase of UIP but not in the stationary phases of both diseases. HECA-452 activity could be detected only on high endothelial venules within sarcoid lymph nodes. In lung tissues, macrophages bearing the ICAM-1 antigen were present in sarcoid tissue but not in the interstitium and alveolar space of UIP. LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) were present on all leucocytes found but seemed to be more highly expressed on lymphocytes in sarcoidosis. These findings suggest that the LFA-1/ICAM-1 and VLA-4/VCAM-1 pathways are involved in leucocyte migration in both types of lung disease, while in the active phases of sarcoidosis and UIP, ELAM-1 is also involved.     

Analysis of the binding of peanut agglutinin (PNA) to leukaemic cells and its relationship to T-cell differentiation.

Several leukaemias have been screened with a panel of monoclonal antibodies as well as fluoresceinated peanut lectin (FITC-PNA). Approximately 25% of T-acute lymphoblastic leukaemias (T-ALLs) were strongly positive with FITC-PNA. The staining distribution pattern did not correlate with any other monoclonal antibody used, although the phenotypes of the PNA+ T-ALLs were similar to those found on cortical thymocytes and probably reflect a more mature cellular phenotype within the T-ALL group. Some myeloid leukaemias were also PNA+ although the staining was generally weak. Several T-cell lines were examined and generally the TdT- lines showed strongest fluorescence after incubation with FITC-PNA. If these lines were induced to differentiate with 12-O-tetradecanoyl phorbol 13-acetate (TPA) they became PNA-. This was accompanied by an increase in cellular sialyl transferase activity, suggesting that one step in the differentiation process of "early' T cells is the terminal sialylation of existing oligosaccharide chains. Metabolic labelling of PNA+ T-cell lines with [35S]-methionine followed by detergent lysis and affinity chromatography on PNA-agarose showed that several bands of molecular weights 40-100,000 were bound to the column when examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis. If TPA-treated cells were examined these bands were absent.