Ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome.

A 15-year-old girl developed a juvenile granulosa cell tumor associated with Maffucci's syndrome (enchondromatosis + hemangiomas). Clinical manifestations of the disease included an abdominal mass and progressive anemia. She underwent the removal of a Stage Ic juvenile granulosa cell tumor and subsequent adjuvant chemotherapy. On follow-up examination 4 years later, no recurrence of the ovarian tumor was noted. A review of the literature showed 10 previous cases of juvenile granulosa cell tumor associated with enchondromatosis, two associated with Maffucci's syndrome, and the rest with Ollier's disease (enchondromatosis). Ovarian juvenile granulosa cell tumor may occur not infrequently in female patients with enchondromatosis in the first or second decades, in contrast to the widely recognized sarcomatous changes of enchondromas that usually occur after the second decade. Data provided from these cases also emphasize the concept of a generalized mesodermal dysplasia.     

Beta-adrenergic receptor adaptation after an acute exercise in rat myocardium

An acute dynamic exercise provokes the translocation of beta-adrenergic receptors (beta-AR) from light vesicle fractions to sarcolemmal membranes in rat myocardium. However, 15 min after an acute exercise the density of beta-AR in both fractions returned to the pre-exercise level. The mean maximal activity of adenylate cyclase in response to isoproterenol roughly paralleled the redistribution of beta-AR. The dose-response curves, however, were substantially shifted to the right with increase in EC50 for isoproterenol stimulation of adenylate cyclase. Thus, the sensitivity of sarcolemmal beta-AR was found to be blunted 15 min afterwards.     

The combination of IFN-alpha2 and IFN-alpha8 exhibits synergistic antiproliferative activity on renal cell carcinoma (RCC) cell lines through increased binding affinity for IFNAR-2.

Although there are at least 13 interferon-alpha (IFN-alpha) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-alpha interactions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-alpha2 and IFN-alpha8 using six renal cell carcinoma (RCC) cell lines. Although IFN-alpha8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-alpha2 and IFN-alpha8. To analyze the interactions between IFN-alpha2 and IFN-alpha8, the receptor-binding kinetics of different combinations of IFN-alpha2 and IFN- alpha8 to the IFN-alpha receptors, IFNAR-1 or IFNAR-2, were measured using a surface plasmon resonance-based biosensor. Unexpectedly, the receptor binding kinetics to IFNAR-2 but not to IFNAR-1 were mutually related to antiproliferative activity and increase in the binding speed (K(a)) for IFNAR-2. Moreover, we observed the increased fluorescence intensity (FI) of biotin-labeled IFN-alpha8 to IFNAR-2 by receptor binding inhibition assay with unlabeled IFN-alpha2 but not the other combinations. These findings indicate that the binding manner of IFN-alpha8 for IFNAR-2 is different from that of IFN-alpha2, suggesting that binding of IFN-alpha8 rather than binding of IFN-alpha2 to IFNAR-2 leads to activation and subsequent antiproliferative activity despite the same antiviral activity in RCC.     

Induction of lymphosarcoma in sheep inoculated with bovine leukaemia virus

Five sheep were experimentally inoculated with BLV in order to study the humoral immune response in animals infected with bovine leukaemia virus (BLV). During experimental periods of 46 months, 2 sheep died with leukaemia and one sheep showed splenomegaly and proliferation of tumour cells. The other 2 sheep were clinically normal. All of the inoculated sheep developed antiviral antibodies 1 month after inoculation and BLV could be re-isolated in lymphocytes 2 to 3 months after inoculation. Antibody against glycoprotein antigen (gp51) of BLV appeared earlier than the antibody against protein antigen (p24) and antibody titres of the former were higher than those of the latter during the course of the experiment. The complement dependent antibody cytotoxicity test was performed for the detection of antibody against BLV-related cell membrane antigen with 2 different kinds of target cells; FLK cells which are foetal lamb kidney cells chronically infected with BLV and SF-28 cells which are sheep fibroblasts transformed with BLV in vitro. All 5 sheep developed cytotoxic antibodies against both types of cells. In sera from two leukaemic sheep, cytotoxic antibody titres against SF-28 cells gradually decreased 30 months after inoculation and finally became negative one to 3 months before they died of leukaemia. However, these leukaemic sheep persistently produced antibodies against gp51 and p24.     

Can the Scapular Dyskinesis Test be Associated with Throwing Related Injuries During the Course of Collegiate Baseball Seasons?

BackgroundA pattern of scapular dyskinesis on the dominant side has been demonstrated to be associated with a decrease in throwing arm conditions identified by a self-report outcome assessment in collegiate baseball pitchers during the course of a single season. However, it is unclear if symptomatic shoulders in baseball pitchers may be associated with the presence of scapular dyskinesis.PurposeTo study the relationship between the presence of scapular dyskinesis and throwing-related injury in collegiate baseball pitchers during each respective course of up to four subsequent seasons.MethodsA single Division 1 National Collegiate Athletic Association team participated in this study over a four-year-period. The scapular dyskinesis test was implemented during the preseason for baseball pitchers. Players were followed throughout each respective season to track the incidence of throwing-related upper extremity injuries.ResultsA total of 36 collegiate baseball pitchers (height: 185.3 ± 5.6 cm, weight: 88.8 ± 7.8 kg, age: 20.0 ± 1.5 years) consisting of 57 pitcher seasons were followed in this study, in which 18 pitchers remained with the team for more than one year. Twenty-seven of the 57 pitchers were classified as having scapular dyskinesis demonstrated at around 90° of shoulder flexion on the throwing side. Five injuries (13.2% of a total of 38 injuries) were diagnosed as throwing-related shoulder injuries during the course of the intercollegiate baseball seasons. Four of the five throwing-related shoulder injuries occurred in pitchers who had scapular dyskinesis on their dominant side. Consequently, the odds ratio was 5.04 for the collegiate pitchers with scapular dyskinesis on the throwing arm side associated with a throwing-related shoulder injury compared to those with no scapular dyskinesis (p = 0.16). No relationship was identified between scapular dyskinesis on the throwing arm side and throwing-related elbow injury. Eighty-one percent of the scapular dyskinesis test results were not changed on the throwing side from the previous to the following year for those 18 pitchers who were followed for more than one season, whereas 42.9% of the results remained unchanged on the non-throwing side.ConclusionThe results suggest that collegiate baseball pitchers with dominant arm scapular dyskinesis likely are at increased risk of throwing-related shoulder injury.Level of evidenceLevel 2, Prospective Cohort Study     

Brianodins A-D, briarane-type diterpenoids from soft coral Pachyclavularia sp

Four new briarane-type diterpenoids, brianodins A-D ( 1- 4), were isolated from a soft coral, Pachyclavularia sp., and the structures and relative stereochemistry of 1- 4 were elucidated on the basis of spectroscopic data. The absolute configurations of 3 and 4 were assigned by the MTPA method. Brianodin A ( 1) showed a modest cytotoxicity.     

Molecular diversity of TEX101, a marker glycoprotein for germ cells monitored with monoclonal antibodies: variety of the molecular characteristics according to subcellular localization within the mouse testis

TEX101 was characterized as a unique germ cell marker molecule using the specific monoclonal antibody (mAb), TES101. Although this mAb has strong affinity/specificity for TEX101, TES101 mAb loses its reactivity under reducing conditions. In this study, we have generated new mAbs against TEX101 to compensate for the shortcomings of the TES101 mAb using different approaches. First, we immunized mice with the antigen on a baculovirus expression system and isolated new anti-TEX101 mAbs, 6002 and 6035. Second, we raised the mAb Ts4 from spleen cells of an immunologically naive old mouse. Western blot analysis revealed that the new mAbs possess immunoreactivity under reducing/non-reducing conditions. Immunopositive staining of the mAbs against Bouin-fixed sections was observed in spermatocytes, spermatids and testicular spermatozoa, but not in other cells, similar to paraformaldehyde (PFA)-fixed frozen sections stained with TES101 as previously reported. However, whereas the mAbs 6002/6035 mainly showed immunoreactivity only in spermatocytes in PFA-fixed frozen sections, the reactivity of the mAbs to spermatids and testicular spermatozoa was clearly recovered when the PFA-fixed sections were autoclaved or treated with SDS. Peptide mapping and deglycosylation analysis indicated that the epitopes for TES101, 6002 and 6035 are located within TEX101(25-94), whereas Ts4 recognized N-linked carbohydrate moieties on TEX101 in Triton X-100-soluble mouse testicular extracts but not in the extracellular or water-soluble fractions. These results suggest strongly that the molecular association or structure of N-linked carbohydrate moieties of TEX101 varies according to its subcellular localization within the seminiferous tubules. These new mAbs will be valuable tools for further analysis of TEX101, including its function(s).     

Phospholamban p.Arg14del Cardiomyopathy: A Japanese Case Series

Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients.