Incorporation of fowl plague virus hemagglutinin into murine leukemia virus particles and analysis of the infectivity of the pseudotyped retroviruses

We describe retrovirus particles carrying the fowl plague virus (FPV) hemagglutinin (HA). When expressed in cells providing Moloney murine leukemia virus (MoMLV) Gag and Pol proteins and a lacZ retroviral vector, FPV HA was found to be efficiently expressed, correctly processed, and stably incorporated into retroviral particles. HA-bearing retroviruses were infectious with a wide host range and were only 10-fold less infectious than retroviruses carrying wild-type MLV retroviral envelopes. We also coexpressed HA proteins in retroviral particles with chimeric MoMLV-derived envelope glycoproteins that efficiently retarget virus attachment but are only weakly fusogenic. Our results suggest that HA can in some cases enhance the fusion ability of these retroviral particles, depending on the cell surface molecule that is used as a receptor.     

Rapid, corticosterone-induced disruption of medullary sensorimotor integration related to suppression of amplectic clasping in behaving roughskin newts (Taricha granulosa)

Endogenously secreted or injected corticosterone (CORT) rapidly suppresses courtship clasping in male roughskin newts (Taricha granulosa) by an action on a specific neuronal membrane receptor. Previous studies, using immobilized newts, showed that CORT administration rapidly depresses excitability of reticulospinal neurons and attenuates medullary neuronal responsiveness to clasp-triggering sensory stimuli. The present study used freely moving newts to examine clasping responses and concurrently record sensorimotor properties of 67 antidromically identified reticulospinal and other medullary reticular neurons before and after CORT injection. Before CORT, reticulospinal neurons fired in close association with onset and offset of clasps elicited by cloacal pressure. Reticulospinal neurons also showed firing correlates of nonclasping motor events, especially locomotion. Neuronal activity was typically reduced during clasping and elevated during locomotion. Medullary neurons that were not antidromically invaded (unidentified neurons) usually showed sensorimotor properties that resembled those of reticulospinal neurons. Intraperitoneal CORT (but not vehicle) reduced the probability and quality of hindlimb clasping in response to cloacal pressure, especially within 5-25 min of injection. Simultaneously, responses of reticulospinal and unidentified neurons to cloacal pressure and occurrence of clasping-related activity were attenuated or eliminated. CORT effects were relatively selective, altering clasping-related neuronal activity more strongly than activity associated with nonclasping motor events. The properties of CORT effects indicate that the hormone impairs clasping by depressing processing of clasp-triggering afferent activity and by disrupting the medullary control of clasping normally mediated by reticulospinal neurons. The rapid onset of these CORT effects implicates a neuronal membrane receptor rather than genomic action of the steroid.     

1,N2-propanodeoxyguanosine adducts: potential new biomarkers of smoking-induced DNA damage in human oral tissue

Diarrhea is a non-specific symptom which may be associated with Addison's disease and several causes had been demonstrated in the aetiology. We describe a patient with Addison's disease who was suffering from chronic diarrhea for three months. She was diagnosed as having collagenous colitis and successfully treated with Sulphasalazine, 2 g/day. Collagenous colitis is an uncommon cause of chronic diarrhea and the association of collagenous colitis with Addison's disease has not previously been described. We think that collagenous colitis may play a role in the aetiology of diarrhea in patients with Addison's disease and therefore we suggest a full colonoscopic examination in other patients with Addison's disease and diarrhea to determine the incidence of collagenous colitis in the aetiology of diarrhea.     

Adrenomedullin and CGRP receptors mediate different effects in the rat adrenal cortex

Adrenomedullin (AM) exerts its effects through two distinct receptor subtypes: the AM receptor, and the CGRPI receptor. In most tissues activation of these subtypes brings about similar effects, with only the magnitude of the effect varying. In the rat adrenal cortex, however, this does not appear to be the case. Both CGRPI and AM receptors are present in the rat adrenal cortex. Incubation of zona glomerulosa cells with AM caused an increase in aldosterone secretion, but AM had no effect on angiotensin II-stimulated aldosterone secretion. The action of AM was not affected by CGRP8-37, the CGRP receptor antagonist, suggesting that its effect was mediated by the adrenomedullin receptor. CGRP on the other hand, did not significantly affect basal aldosterone although it attenuated the response to angiotensin II. These data suggest that the CGRP receptor and the AM receptor mediate different effects in the rat adrenal zona glomerulosa.     

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.