Association between Epstein-Barr virus and classic Hodgkin lymphoma in Jordan: a comparative study with Epstein-Barr virus-associated Hodgkin lymphoma in North America

An association between Epstein-Barr virus and Hodgkin lymphoma has been shown in several parts of the world. The reported incidence of Epstein-Barr virus in Hodgkin lymphoma varies significantly from one country to another and ranges from <30% in Swedish patients to 100% in patients from Kenya. Using in situ hybridization for detection of Epstein-Barr virus-encoded RNA and immunohistochemistry for detection of Epstein-Barr virus latent membrane protein, we analyzed 28 cases of Hodgkin lymphoma from Jordan and 30 cases from the United States. Eight of 28 Jordanian cases and 9 of 30 North American cases were Epstein-Barr virus positive. Our studies show that the incidence of Epstein-Barr virus among Jordanian patients with Hodgkin lymphoma is similar to the rate in patients from the United States. This rate appears to be low to intermediate compared with rates in other parts of the world.     

Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain

The opioid peptide beta-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.     

Acute lower extremity ischemia in a 7-year-old boy: an unusual case of popliteal entrapment syndrome

Popliteal artery entrapment syndrome is a rare cause of acute limb ischemia that most commonly is seen in young adults. The most significant complications associated with popliteal entrapment include aneurysm formation and acute thrombosis. This case presents the youngest patient ever reported with this syndrome and highlights the advantages of multimodal treatment including thrombolysis, popliteal aneurysm resection, and revascularization. Although a significant body of literature exists on popliteal entrapment syndrome in teenagers and young adults, it has not been reported previously in a patient younger than 11 years. Limb salvage was achieved in this patient with a combination of endovascular and surgical techniques.     

Increased numbers of opioid expressing inflammatory cells do not affect intra-articular morphine analgesia

Background. Both locally expressed ß-endorphin (END)and low doses of morphine relieve pain within inflamed kneejoints. Here we examined whether enhanced inflammation and ENDexpression within the synovial tissue of patients undergoingarthroscopic knee surgery might shift the analgesic dose–responsecurve of intra-articular (i.a.) morphine. Methods. Following IRB approval and informed consent, patientswere randomly assigned to the following i.a. treatments at theend of surgery: group I (n=39), isotonic saline; group II (n=40),1 mg morphine hydrochloride; group III (n=48), 2 mg morphinehydrochloride; group IV (n=39), 4 mg morphine hydrochloride.Postoperative pain intensity was assessed by the visual analoguescale (VAS), by the time to first analgesic request and by thesupplemental piritramide consumption. Synovial specimens fromeach patient were stained for the presence of inflammatory cellsand END and were discriminated into groups with low versus highnumbers of these cells. Differences between groups were statisticallyanalyzed by     

Reliable visceromotor responses are evoked by noxious bladder distention in mice

PURPOSE: A mouse model of bladder distension (UBD) induced acute visceral nociception was characterized. Murine models of nociception may allow for the investigation of mechanisms of pain and analgesia through the use of genetic models. MATERIALS AND METHODS: Isoflurane anesthetized, spontaneously breathing female C3H/J mice had 24 gauge intravesical catheters transurethrally placed and electrodes implanted in the abdominal musculature and in upper limbs for electromyograms and electrocardiograms. RESULTS: UBD (10 to 80 mm Hg for 20 seconds, phasic air distention) produced reliable, reproducible visceromotor responses (VMRs), that is increased abdominal muscle activity, which were graded with graded UBD. Heart rate and respiratory responses were reliable but not reproducible. Subcutaneous morphine (1 to 4 mg/kg) and intravesical lidocaine (500 microg) produced reversible VMR inhibition. Inflammation produced by intravesical mustard oil (2.5% for 15 minutes with an olive oil control) produced a marked increase in sensitivity to UBD with more robust responses evoked by lower UBD intensities. VMRs were present in decerebrate but not in spinal cord transected mice. Unanesthetized mice had similar responses to UBD but with lower pressure thresholds for VMRs. CONCLUSIONS: These findings suggest the usefulness of the current model system for the study of bladder nociception. In mice UBD evoked VMRs are spinobulbospinal reflexes that are reliable and reproducible, graded in relation to the stimulus, inhibited by analgesics and augmented by the presence of inflammation. Together these data strongly support the use of this model because it may allow the assessment of pharmacogenetic differences among murine strains and the use of transgenic technologies.     

Clinical and inheritance profiles of Kallmann syndrome in Jordan

Background  

Proper management of patients with Kallmann syndrome (KS) allows them to attain a normal reproductive health. The purpose of this study is to demonstrate the presentation modalities, phenotypes and the modes of inheritance among 32 patients with Kallmann syndrome in Jordan. Recognition of the syndrome allows for prompt proper management and provision of genetic counselling.     

Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53

Alliin, a compound derived from garlic, demonstrated dose-dependent inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model. Additionally, alliin demonstrated potent inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis in the CAM model. The antioxidant vitamins C and E significantly (P < 0.001) enhanced the inhibitory efficacy of alliin on FGF2-induced EC tube formation and angiogenesis. Alliin significantly increased (P < 0.01) nitric oxide (NO) release into the CAM fluid, which was further enhanced by vitamins C and E. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) reversed the anti-angiogenesis efficacy of alliin in the CAM model. Vitamins C and E significantly enhanced the anticancer efficacy of alliin in inhibiting colon and fibrosarcoma tumor growth. Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner. Additionally, alliin up-regulated the p53 production in FGF2-stimulated EC. These data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin.     

Alpha v integrin affinity/specificity and antiangiogenesis effect of a novel tetraaza cyclic peptide derivative, SU015, in various species

The present study was undertaken to define the alpha v beta3 and alpha v beta5 binding potency and specificity of SU015, an integrin antagonist. SU015 inhibited alpha v beta3-mediated human umbilical vein endothelial cell or 293/beta3-transfected CHO cell adhesion to fibrinogen, with IC50 values of 0.21 +/- 0.11 muM and 0.32 +/- 0.02 microM. SU015 demonstrated comparable affinity to alpha v beta5 as compared with alpha v beta3 affinity, as well as a relatively high degree of specificity for human alpha v beta3- and alpha v beta5-mediated functions, as compared with other human integrins, including alphaIIbbeta3 (IC50 >100 microM), alpha5/beta1 (IC50 >100 microM), and alpha4/beta1 (IC50 >100 microM). SU015 demonstrated different degrees of species specificity in blocking alpha v beta3-mediated cellular adhesion, with relatively higher affinity to monkey (IC50 = 0.10 microM) and dog (IC50 = 1.30 microM) endothelial or smooth muscle cell alpha v beta3-mediated adhesion. Additionally, SU015 demonstrated a high degree of alpha v beta3 and alpha v beta5 specificity as compared with alpha4beta1-, alpha5beta1-, or alpha IIb beta3-mediated binding in the above species. In conclusion, SU015 is an alpha v beta3 and alpha v beta5 antagonist with relatively higher potency and specificity as compared with alpha IIb beta3, alpha5beta1, or alpha4beta1 integrins. Additionally, comparable alpha v beta3 and alpha v beta5 affinity for SU015 was demonstrated with human and monkey endothelial cells. These data also suggest that this bicyclic RGD analogue linked to a linker at the bottom leaves the RGD at the top available for binding and allows for conjugation with radioisotope for imaging and radiotherapy.     

Automated RIBA HCV strip immunoblot assay: a novel tool for the diagnosis of hepatitis C virus infection in hemodialysis patients

Hemodialysis (HD) patients remain a high-risk group for hepatitis C virus (HCV) infection. Serological assays (enzyme-linked immunosorbent assays, ELISAs) are the only tests currently approved by the Food and Drug Administration in the United States for the diagnosis of HCV. The RIBA HCV Strip Immunoblot Assay (SIA) is an established method for supplemental testing of repeat reactive hepatitis C ELISA patients on HD. However, the current manual procedure is labor intensive, requiring subjective band scoring and result interpretation. Recently, the automated CHIRON RIBA HCV Processor System has been designed to perform RIBA supplemental testing. The CHIRON RIBA HCV Processor System consists of a bench-top instrument that provides objective evaluation of the RIBA immunoblot strips, by measuring the light differentially reflected from the developed bands and white background, creating a density of reflectance. The CHIRON RIBA HCV Processor System assesses the intensity of each of the reactive bands in relation to the intensity of the internal control bands on each RIBA HCV strip. Comparison between processor and manual protocols was performed using a large (n = 200) cohort of ELISA 3.0 HCV negative and positive patients on maintenance HD. The test characteristics of RIBA HCV 3.0 SIA were identical with manual and automated runs. The relative intensity values of antigenic bands by the CHIRON RIBA HCV 3.0 Processor System between anti-HCV positive and negative patients were significantly different; only 15 of 784 (1.9%) antigenic bands had borderline reactivities. The correlation of test results between manual and automated runs was very high (kappa value 0.989). Among positive results by RIBA HCV 3.0 SIA, there was a strong concordance between manual and automated runs with regard to the pattern of reactivity (kappa value 0.943). The discordant results between manual and automated protocols were attributable to increased variability of antigen scores close to the cutoff value for both tests. In conclusion, the CHIRON RIBA HCV 3.0 Processor System is capable of performing RIBA HCV 3.0 SIA in the HD population accurately with minimal operator involvement. The test characteristics of RIBA HCV 3.0 SIA were identical by manual and automated runs. There was a strong correlation between the results of the manual and automated runs; the few discordant results between the two procedures were mostly due to increased variability of antigen scores close to the cutoff value for both tests. The Centers for Disease Control and Prevention in the USA have recently included chronic HD patients among those persons for whom routine HCV testing is recommended; HCV-infected patients on HD often have a high rate of indeterminate results by manual RIBA technology which is operator dependent for band scoring and result interpretation. The CHIRON RIBA HCV 3.0 Processor System may be very useful for supplemental anti-HCV testing of ELISA repeat reactive specimens in clinical practice within dialysis units.