Hyper-reactivity to amphetamine in rats with dopaminergic grafts

Summary Rats with dopaminergic lesions were subsequently given grafts of dopaminergic (DA) neurons in various brain regions, and later tested for behavioral reactivity to amphetamine. Two experimental situations were used. 1) Amphetamine-induced circling behavior was measured in animals with unilateral lesion of the nigrostriatal pathway implanted with intrastriatal grafts, 2) locomotor activation by amphetamine was measured in animals with bilateral lesions and grafts in the nucleus accumbens. In both situations, behavioral overcompensation was observed after grafting. Ipsilateral circling, which is caracteristic of a unilateral lesion of the nigrostriatal pathway, gave way to contralateral circling, and locomotor activity was restored to levels above those observed for control animals. This behavioral overcompensation is a reflection of hyperreactivity of grafted animals to amphetamine: they were found to respond to much lower doses than controls and the effect of the drug lasted longer. This enhanced response does not seem to be due to post-synaptic hypersensitivity, but rather to hyper-reactivity of the grafted neurons themselves to amphetamine. The mechanism of this phenomenon, which seems to be a general property of grafted DA neurons is discussed.     

Immunohistochemistry of a spontaneous murine ovarian teratoma with neuroepithelial differentiation. Neuron-associated beta-tubulin as a marker for primitive neuroepithelium

Spontaneous ovarian teratomas develop in a large proportion of female LT strain mice. These tumors display a large neuroectodermal component with morphologic differentiation ranging from primitive neuroepithelium (medulloepithelial and ependymoblastic rosettes) to mature neurons, and provide a useful system for the study of various asynchronous stages of neuroepithelial differentiation. The aim of this study was to assess the expression of various cytoskeletal proteins in conjunction with other differentiation-related antigens in these tumors. We found that the medulloepithelial rosettes reacted with only two anti-beta-tubulin monoclonal antibodies. One of these (TU27) recognizes an epitope common to all of the mammalian beta-tubulin isotypes. The other monoclonal antibody (TUJ1) recognizes an epitope unique to class III beta-tubulin isotypes (neuronal-associated). Whereas immunoreactivity in the ependymoblastic rosettes was limited to TU27, differentiating polar neuroblasts reacted with both TU27 and TUJ1 and expressed neuron-specific enolase, synaptophysin, and the 68 kilodalton subunit of neurofilament protein. In well-differentiated foci, mature neurons were positive for all three neurofilament protein subunits (68, 168 and 200 kilodaltons), microtubule-associated-protein 2, synaptophysin, and neuron-specific-enolase, and reacted with both TU27 and TUJ1. By contrast, glial elements expressed glial fibrillary acidic and S-100 proteins, Leu-7 and TU27 but not TUJ1. Myelin basic protein and myelin-associated glycoprotein reactivity was found in the neuropile of these mature areas. The neuroepithelial components were negative for retinal S-antigen and cytokeratin. The expression of the class III beta-tubulin isotype by medulloepithelial rosettes suggests that this isotype may be one of the earliest markers to signal neuronal commitment in primitive neuroepithelium.     

Treatment of malignant gliomas in adults with BCNU plus metronidazole

Summary Twenty-six adult patients with astrocytomas were treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) 180–240 mg/m² 1.V. every 6–9 weeks, with metronidazole 1.5 g/m² p. o. 12 h and 1 h before BCNU and again 6 h and 24 h after BCNU. Of twenty-two evaluable patients, 9 (41%) responded with evidence of reduced tumor size on CT scan, 3 (14%) stabilized and 10 (45%) failed. Patients with no prior chemotherapy or radiotherapy, good performance. status, low grade tumors, and age 50 years had the highest response rates, although differences were not statistically significant. Median survival and duration of response have not been reached with a median follow-up time of ten months. Hematological toxicity was dose-limiting and was probably not augmented by the metronidazole. There was one death from infection that was possibly drug-related. Gastrointestinal toxicity was substantial, and was probably increased by the metronidazole.While the combination of BCNU and metronidazole were tolerable, the response rate seen was no higher than that noted for BCNU alone, and further studies using this dose-schedule are not recommended in astrocytomas.Presented at the 13th International Congress of Chemotherapy, Vienna Austria, August 1983.     

Penetration of teniposide (VM-26) into human intracerebral tumors

Thirty-four consenting patients received VM-26 50–100 mg/m² I.V. before surgical resection of intracerebral tumor, and drug was measured using a high pressure liquid chromatographic technique. Sufficient tumor for analysis was obtained from 29 patients. Brain metastases (13 patients) had higher concentrations of V M-26 than did gliomas (13 patients). Concentrations were comparable in brain metastases and meningiomas (3 patients). Prolonged (24 h) infusion of V M-26 did not appear to result in higher tumor drug concentrations in 5 patients than did rapid (1 h) infusion in 24 patients. Pretreatment with Amphotericin-B 10 mg/m² 12 h and 1 h before VM-26 did not appear to have any effect on VM-26 uptake into 4 intracerebral tumors, although data were limited, and VM-26 concentrations were very high in 1 metastasis. Pretreatment with oral glycerol 500 mg/kg 18 h, 12 h, 6 h, and immediately before I.V. VM-26 may have resulted in increased penetration of VM-26 into 9 tumors, although confirmation is required. Amphotericin-B, glycerol, and operative conditions did not appear to alter VM-26 plasma pharmacokinetics.VM-26 4-demethylepipodophyllotoxin 9-(4-6-O-thenylidene-B-D-glucopyranoside) - VP-16 4-demethylepipodophyllotoxin 9-(4-6-O-ethylidene-B-D-glucopyranoside) Presented in Part at the 74th Annual Meeting of the American Association for Cancer Research, San Diego, California, May 25–28, 183(1).     

Iterative reconstruction algorithms

In this paper a survey of recent results on iterative reconstruction algorithms is given. These results, many of which have not yet appeared elsewhere, are applicable to a very general formulation of the reconstruction problem based on the series expansion approach. A set of optimization criteria and a number of iterative reconstruction algorithms are stated, together with theorems on the convergence of the algorithms to optimum images. The efficacy of the algorithms is compared to that of the convolution method. In particular, the falseness of the claim that ART and the backprojection method are the same is demonstrated.