Pb2+ modulates the NMDA-receptor-channel complex

Summary The actions of Pb²⁺ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb²⁺ were found. Pb²⁺ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 M, the current was reduced > 90% at concentrations over 100 M, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb²⁺-action, as preincubation in 50 M Pb²⁺-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb²⁺. This effect was reversed within 2 to 5 s of wash. Presence of Pb²⁺ or asp/Pb²⁺ or glycine/Pb²⁺ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb²⁺-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb²⁺ response did not change over the duration of an experiment. We conclude that Pb²⁺ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.Abbreviations NMDA N-methyl-D-aspartate - LTP long-term potentiation - AP5 2-amino-5-phosphonovalerate - EGTA ethylene glycol bis(-aminoethylether)-N,N,N,N-tetraacetic acid - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid Correspondence to H. L. Haas at the above address     

Saturable rate of cefatrizine absorption after oral administration to humans

This study examined the absorption kinetics of cefatrizine, an amino--lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.     

Karyotypic abnormalities in adenocarcinomas of the lung

Cytogenetic analysis of 114 adenocarcinomas of the lung revealed clonal abnormalities in 67 tumors. The chromosome numbers ranged from near-diploid to hypertetraploid. Clonal abnormalities seen as the sole anomaly were loss of the Y chromosome (21 tumors), trisomy 7 (2 tumors), and trisomy 12 (1 tumor). A supernumerary ring chromosome was the only clonal change in 4 tumors. The bands most often affected were 17p11-13 (13 cases), 1q10-12 and 1p22 (10 cases each), 1p11-13 and 1q21 (9 cases each), and 11p11, 11p15 and 15p11-13 (6 cases each). The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (30 cases), 11 (20 cases), 3 (17 cases), 17 and 7 (16 cases each). Repeated loss of material from chromosome arms 1p, 3p, 6q, 11p, and 17p and gains of 1q were found. Recurrent structural changes were del(1)(p22) and i(5)(p10) (5 cases each) i(1)(q10), i(13)(q10), i(14)(q10) and del(17)(p11) (3 cases each). We found no abnormalities that seemed to be specifically associated with pulmonary adenocarcinomas, but isochromosomes i(1)(q10), i(5)(p10) and i(13)(q10) and changes of 6q were present in our series at frequencies higher than those generally seen in the other main types of lung cancer.     

Hirntumorresektionen in einem offenen 0,5 T-MRT Zweijährige Erfahrungen aus neuroradiologischer Sicht

After two years clinical experience using an open 0.5 T-MRI, which make it possible to control all steps of a brain tumor resection, the high expense in relation to the effect is proofed. In 80 MRI-guided brain tumor resections the indication, the degree of resection, the appearance of operative induced changes, complications and clinical state are analysed. The advantage of the method consists in safety of localisation and detection especially of intra-axial cerebral tumors, recording of intraoperative invisible tumor parts and saving eloquent areas during tumor resection. To have optimal results, all over the operation time, the participation of a special experienced radiologist is necessary. The best results are shown in treatment of low grade gliomas and tumors near eloquent areas.     

Preliminary experience with interactive guided brain biopsies using a vertically opened 0.5-T MR system

The purpose of our study was to evaluate the feasibility and accuracy of brain biopsies performed within a vertically opened MR system. We worked with the interventional 0.5-T MR “SIGNA SP” (General Electric Medical Systems, Milwaukee, Wis.) with an integrated tracking device “Flashpoint Position Encoder” (Image Guided Technologies, USA). As a holding device for this instrument we constructed a special frame. The whole system allows an exact adjustment of an optimum biopsy direction and guidance of the biopsy in a non-stereotactic, interactive mode in near real-time. As biopsy tools we used MR-compatible aspiration and specially made side-cut needles (Daum, Germany; E-Z-EM, USA). We performed a prospective diagnostic brain biopsy study in 18 patients. Guidance of the needle was carried out using gradient-echo single-slice technique. The sample was taken after controlling the exact position of the needle tip on spin-echo images. In 12 cases an exact neuropathological diagnosis was possible. In 6 cases of negative biopsy (4 aspiration biopsies) the samples were not representative. Our results demonstrate the feasibility of interactive MR-guided minimally invasive brain biopsies in an open MR system. The best results were achieved using cut needles for biopsies of contrast-enhancing lesions visible on T1-weighted gradient-echo guidance sequence. Received: 2 February 1998; Revision received: 13 July 1998; Accepted: 2 September 1998     

Growing blood clot mimicking an aneurysm on postoperative computerized tomography and magnetic resonance imaging studies. Case report and review of the literature.

The authors describe the case of a 15-year-old boy who underwent resection of a large left temporal tumor. During a normal postoperative course, computerized tomography (CT) scanning demonstrated a spherically hyperdense structure near the internal carotid artery, enlarging on a control CT scan. A suspected false aneurysm was confirmed on magnetic resonance imaging; angiographic studies were negative. The authors believed they were dealing with a thrombosed false aneurysm and they performed operative revision. Intraoperatively the "aneurysm" could be dissected off the internal carotid artery and no lesion of the arterial wall was obvious. Histological findings showed a fresh blood clot. This case demonstrates that a blood clot may mimic an aneurysm on CT and magnetic resonance studies, which has not been described earlier. The origin of the blood clot remains unclear.     

Expression of BCL-2 oncoprotein on tumor cells and tumor-infiltrating lymphocytes (TIL) in meningiomas

The Expression of the antiapoptotic oncoprotein BCL-2 and its correlation to tumor grade in 62 meningiomas (48 classic, 9 atypical, and 5 anaplastic) using single and double immunohistochemistry was investigated. BCL-2 expression was found in two different cell populations identified as lymphocytes (BCL-2+CD3+) and tumor cells (BCL+/CD3–). Tumor-infiltrating lymphocytes (TIL) (CD3+) were found within classic (9.5% of cells), atypical (2.4% of cells), and anaplastic (1.8% of cells) meningiomas. In classic meningiomas, 66.5% of TIL were BCL-2-positive, in atypical meningiomas 79.2%, and in anaplastic meningiomas 37.9%. In 33 (68.8%) of the classic meningiomas, medium to high counts of BCL-2+ tumor cells were detected. Atypical meningiomas showed nearly equal percentages of high (two patients), medium (five patients), and low (two patients) BCL-2+ tumor cell counts, whereas anaplastic meningiomas showed only medium (two patients) and low (three patients) BCL-2 tumor cell counts or were BCL-2-negative (one patient). In summary, a significant inverse correlation between the number of BCL-2-positive tumor cells and tumor grade in meningiomas was found. These findings support the hypothesis of cell survival prolongation by the antiapoptotic ability of BCL-2 proto- oncogenes and demonstrate the prognostic relevance of BCL-2 immunoreactivity in meningiomas. Received: 10 June 1998 / Accepted: 23 February 1999