Axon tracts correlate with netrin-1a expression in the zebrafish embryo

Netrins are secreted molecules that can attract or repel growth cones from a variety of organisms. In order to clarify the extent and scope of the effects of netrins for guiding growth cones, we have analyzed netrin-1a within the relatively simple and well-characterized nervous system of zebrafish embryos. netrin-1a is expressed in dynamic patterns that suggest that it guides the growth cones of a wide variety of neurons. The spatiotemporal relationship of netrin-1a expression and extending growth cones further suggests that netrins may act to delineate specific pathways and stimulate axonal outgrowth in addition to attracting and repelling growth cones. Furthermore, aberrant outgrowth by commissural growth cones in the spinal cords of floating head mutants, in which netrin-1a expression is altered, is consistent with an in vivo, chemoattractive action of netrin-1a. These data suggest that netrins act on many growth cones and influence their behavior in a variety of ways.     

Construct validity of the computerized version of the Category Test

PURPOSE: This study compared the sedative effects of sublingual tablet midazolam (Roche Dormicum 7.5 mg) with the oral route as premedication. METHODS: One hundred ASA physical status I and II gynaecological patients were randomly selected to receive a 7.5 mg tablet of midazolam either sublingually or orally as premedication about one hour before elective surgery. There were 50 patients in each group. The degree of sedation was assessed according to the Ramsay scale initially and then at 20, 30, 45 and 60 min intervals by a second observer blinded to the route of administration. The time for complete drug dissolution was studied in the sublingual group by the inspection of tablet residue under the tongue every five minutes for 20 min, then the patients were interviewed regarding their acceptance of taste. RESULTS: The sedation scores in the sublingual group were higher than in the oral group at 30 and 60 min after drug administration. (P = 0.0054 and P = 0.008) Seventy-two percent of the sublingual group had complete drug dissolution within 10 min and 64% of the patients in the sublingual group found the tablet acceptable with regard to its taste. CONCLUSION: Midazolam 7.5 mg sublingual is a more effective pre-anaesthetic sedative than by the oral route.     

Aluminium speciation in cerebrospinal fluid of acutely aluminium-intoxicated dialysis patients before and after desferrioxamine treatment; a step in the understanding of the element's neurotoxicity

BACKGROUND: The association between aluminium and dialysis encephalopathy and deterioration of the neurological state during desferrioxamine treatment of dialysis patients is well established. At present little is known about the speciation and the mechanisms underlying the element's neurotoxicity. METHODS: Aluminium speciation was performed in cerebrospinal fluid samples of acutely aluminium-intoxicated dialysis patients using a recently developed high-performance liquid chromatographic/electrothermal atomic absorption spectrometric hybrid method. RESULTS: Baseline cerebrospinal fluid aluminium levels of samples taken shortly after the intoxication were low but elevated (5.0 +/- 2.0 micrograms/l, n = 3) as compared to subjects with normal renal function (< 1 microgram/l). In contrast to the situation noted in serum and to the iron speciation in cerebrospinal fluid, aluminium was not bound to transferrin but appeared as two distinct compounds, the main fraction eluting at the elution volume of aluminium-citrate/silicate. The second compound was not identified. Forty-four hours after desferrioxamine administration the cerebrospinal fluid aluminium levels had increased up to a concentration of 10.3 +/- 2.5 micrograms/l (n = 3). This was accompanied by a change in the speciation profile with aluminium appearing at the elution volume of aluminoxamine. CONCLUSIONS: Our findings may contribute to a better understanding of the neurotoxic effects of aluminium and its desferrioxamine chelate in dialysis patients.     

Endovascular treatment of abdominal aortic aneurysms: case report and review of literature

A case of endovascular treatment of abdominal aortic aneurysm is discussed along with a review of the literature. This recently introduced Food and Drug Administration Phase II treatment modality may have a significant impact on the approach to the treatment of aneurysmal disease. This discussion details the treatment of one typical patient and reviews the current status of endovascular therapy as it applies to infrarenal abdominal aortic aneurysms.     

A dissociation between perceptual explicit and implicit memory processes

Patient M.S., who underwent right-occipital lobe resection to treat intractable epilepsy, has intact recall and recognition memory for words, but impaired repetition priming in word identification and visual stem-completion tasks. This mirror dissociation to amnesia suggests that explicit recognition and visuoperceptual repetition priming are mediated by distinct neural systems. In prior studies, however, M.S.' recognition memory was tested only with tasks that drew upon his intact verbal knowledge. The present study examined M.S.' recognition memory for nonverbal perceptual information, namely, the modality and font of word presentation and line patterns. M.S.' recognition memory was intact, providing further evidence that perceptual explicit and implicit memory processes are subserved by functionally and neurally independent memory systems.     

Farnesol-derived dicarboxylic acids in the urine of animals treated with zaragozic acid A or with farnesol

Farnesyl diphosphate, the substrate for squalene synthase, accumulates in the presence of zaragozic acid A, a squalene synthase inhibitor. A possible metabolic fate for farnesyl diphosphate is its conversion to farnesol, then to farnesoic acid, and finally to farnesol-derived dicarboxylic acids (FDDCAs) which would then be excreted in the urine. Seven dicarboxylic acids were isolated by high performance liquid chromatography (HPLC) from urine of either rats or dogs treated with zaragozic acid A or rats fed farnesol. Their structures were determined by nuclear magnetic resonance analysis. Two 12-carbon, four 10-carbon, and one 7-carbon FDDCA were identified. The profile of urinary dicarboxylic acids from rats fed farnesol was virtually identical to that produced by treating with zaragozic acid A, establishing that these dicarboxylic acids are farnesol-derived. By feeding [1-14C]farnesol and comparing the mass of the dicarboxylic acids produced with the ultraviolet absorption of the HPLC peaks, a method to quantitate the ultraviolet-absorbing FDDCAs was devised. When rats were treated with zaragozic acid A, large amounts of FDDCAs were excreted in the urine. The high level of FDDCAs that were found suggests that their synthesis is the major metabolic fate for carbon diverted from cholesterol synthesis by a squalene synthase inhibitor. A metabolic pathway is proposed to explain the production of each of these FDDCAs.     

Complementation of integrase function in HIV-1 virions

Proviral integration is essential for HIV-1 replication and represents an important potential target for antiviral drug design. Although much is known about the integration process from studies of purified integrase (IN) protein and synthetic target DNA, provirus formation in virally infected cells remains incompletely understood since reconstituted in vitro assays do not fully reproduce in vivo integration events. We have developed a novel experimental system in which IN-mutant HIV-1 molecular clones are complemented in trans by Vpr-IN fusion proteins, thereby enabling the study of IN function in replicating viruses. Using this approach we found that (i) Vpr-linked IN is efficiently packaged into virions independent of the Gag-Pol polyprotein, (ii) fusion proteins containing a natural RT/IN processing site are cleaved by the viral protease and (iii) only the cleaved IN protein complements IN-defective HIV-1 efficiently. Vpr-mediated packaging restored IN function to a wide variety of IN-deficient HIV-1 strains including zinc finger, catalytic core and C-terminal domain mutants as well as viruses from which IN was completely deleted. Furthermore, trans complemented IN protein mediated a bona fide integration reaction, as demonstrated by the precise processing of proviral ends (5'-TG...CA-3') and the generation of an HIV-1-specific (5 bp) duplication of adjoining host sequences. Intragenic complementation between IN mutants defective in different protein domains was also observed, thereby providing the first evidence for IN multimerization in vivo.     

Protein-RNA interactions in the U5 snRNP of Saccharomyces cerevisiae

We present here the first insights into the organization of proteins on the RNA in the U5 snRNP of Saccharomyces cerevisiae. Photo-crosslinking with uniformly labeled U5 RNA in snRNPs reconstituted in vitro revealed five contacting proteins, Prp8p, Snu114p, p30, p16, and p10, contact by the three smaller proteins requiring an intact Sm site. Site-specific crosslinking showed that Snu114p contacts the 5' side of internal loop 1, whereas Prp8p interacts with five different regions of the 5' stem-loop, but not with the Sm site or 3' stem-loop. Both internal loops in the 5' domain are essential for Prp8p to associate with the snRNP, but the conserved loop 1 is not, although this is the region to which Prp8p crosslinks most strongly. The extensive contacts between Prp8p and the 5' stem-loop of U5 RNA support the hypothesis that, in spliceosomes, Prp8p stabilizes loop 1-exon interactions. Moreover, data showing that Prp8p contacts the exons even in the absence of loop 1 indicate that Prp8p may be the principal anchoring factor for exons in the spliceosome. This and the close proximity of the spliceosomal translocase, Snu114p, to U5 loop 1 and Prp8p support and extend the proposal that Snu114p mimics U5 loop 1 during a translocation event in the spliceosome.     

Validation of left ventricular volume measurements by gated SPECT 99mTc-labeled sestamibi imaging

BACKGROUND: Originally, the authors used a combined transcranial-transmalar approach for removal of sphenoorbital tumors. METHODS: More recently, when computed tomography (CT) scanning became available, surgical management of sphenoorbital meningiomas included resection of the hyperostosis in the pterional region, orbital roof and lateral wall, and middle fossa floor. Thereafter, intradural and intraorbital components are removed, as well as infiltrated dura mater. Finally, a periosteal flap is placed over the dural defect and bone reconstructed with methylmethacrylate. RESULTS: Of 25 patients, there was only one death and all but one showed very good to moderate response to treatment. Four recurrences were observed. CONCLUSIONS: Surgical management cannot be uniform in all cases, but must be adapted to each form of presentation. On the basis of the satisfactory results achieved, we feel justified in advising the technique described above with its current modifications.