Conformal proton therapy for prostate carcinoma

The suppression of apoptosis may contribute to the carcinogenicity of the peroxisome proliferators (PPs), a class of non-genotoxic rodent hepatocarcinogens. Our previous work demonstrated that the PP nafenopin suppressed both spontaneous and transforming growth factor beta1 (TGFbeta1)-induced hepatocyte apoptosis both in vivo and in vitro. Here, we extend these observations by demonstrating the ability of nafenopin to suppress apoptosis induced by other major candidates for the signalling of cell death in the liver. Treatment of rat or mouse hepatocyte monolayers with TGFbeta1 or the DNA damaging drugs etoposide or hydroxyurea induced high levels of apoptosis. Western blot analysis did not support a role for either p53 or p21waf1 in etoposide-induced apoptosis in rat hepatocytes. Treatment of mouse hepatocytes with an agonistic anti-Fas antibody also resulted in an induction of high levels of apoptosis. Pre-addition and continued exposure to nafenopin suppressed apoptosis induced by all three stimuli. Overall, our studies demonstrate that the ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus. It is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways. However, it seems more likely that nafenopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism.     

Injections of D-amphetamine into the ventral pallidum increase locomotor activity and responding for conditioned reward: a comparison with injections into the nucleus accumbens

The nucleus accumbens and ventral pallidum receive dopamine (DA) projections from the mesencephalon. Although DA inputs to the nucleus accumbens are implicated in both locomotion and reward processes, little is known of the behavioural significance of DA in the ventral pallidum. These studies examined the effects of D-amphetamine injected into the nucleus accumbens or ventral pallidum on locomotor activity and responding for a conditioned reward (CR). In the nucleus accumbens D-amphetamine dose dependently (1, 3 and 10 microg) increased locomotion within 5-10 min of injection. Intra-ventral pallidum microinjections of D-amphetamine also increased activity in this dose range, but the effect occurred with a longer latency (5-20 min). The magnitude of the response evoked by ventral pallidum injections was lower than that evoked by nucleus accumbens injections. The GABAA antagonist picrotoxin (0.1 microg) stimulated activity when injected into the ventral pallidum but not the nucleus accumbens, providing a pharmacological dissociation between the two injection sites. In the CR studies, D-amphetamine injected into both sites potentiated responding for a CR previously paired with food delivery, without altering responding on an inactive lever. Picrotoxin injected into the ventral pallidum reduced responding and abolished the selectivity of responding for CR. The results show that DA release in the ventral pallidum enhances locomotion and responding for a CR, providing evidence that DA in the ventral pallidum plays a significant role in the mediation of the effects of D-amphetamine. The failure of picrotoxin to elevate responding for CR despite increasing locomotor activity indicates that pharmacologically-induced blockade of GABAA receptors in the ventral pallidum disrupts goal-directed responding.     

Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130

It has previously been reported that in resting T-lymphocytes the protein tyrosine kinase p59 constitutively co-precipitates with four phosphoproteins of 43, 55, 85, and 120 kDa, respectively. We have recently cloned the 55-kDa protein that was termed Src kinase-associated phosphoprotein of 55 kDa (SKAP55). Here we demonstrate that the recently characterized SH2-domain-containing leukocyte protein 76-associated phosphoprotein of 130 kDa (SLAP-130) is one of the components of the Fyn complex and that it also co-precipitates with SKAP55 in human T-cells. We establish that SKAP55 and SLAP-130 associate with each other when both molecules are co-expressed in COS cells. By co-transfection of truncated mutants of SKAP55 and SLAP-130 as well as by using the two-hybrid selection system, we further demonstrate that the association between SLAP-130 and SKAP55 is direct and involves the Src homology 3 domain of SKAP55 and the proline-rich sequence of SLAP-130.     

Pre-incision infiltration with lidocaine reduces pain and opioid consumption after reduction mammoplasty

BACKGROUND: The main purpose of the reconstruction of the cranium is the protection of the brain. Besides we have to consider important functional and aesthetic necessities in order to achieve satisfactory results. METHODS: Thirty-six clinical cases, operated from November 1991 to June 1996, in which the reconstruction of the cranial vault is carried out by a polymethylmethacrylate acrylic resin are analysed. The causes and locations of the most common bone defects and the main indications for reconstruction are examined. While the repair of the osseous gaps caused by neoplasms is immediate, in the traumatic occurrences, in order to reduce the probability of infectious complications, an average time of 11 months elapsed from the first operation. The surgical technique, with slightest alterations, is the same in all the presented cases, preparing the acrylic resin straight on the operating table. The resin, moulded and adapted to the defect until its complete hardening, presents, thanks to its properties, manifold advantages (and few real disadvantages). RESULTS: The results, in terms of complications, are very satisfactory, with an infectious rate of 2.7%. Besides, in one third of the patients, a considerable clinical improvement after the repair has been observed. CONCLUSIONS: According to personal experience, it is possible to affirm that polymethylmethacrylate, with its remarkable plasticity and stability in time, can always guarantee a satisfactory functional and aesthetic result.     

Influence of receptor number on the stimulation by salmeterol of gene transcription in CHO-K1 cells transfected with the human beta2-adrenoceptor

We investigated the behavior of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APx), in potato tubers during storage at low temperature. SOD activity increased temporarily within 3 weeks and was higher at 1 degree C than at 20 degrees C. APx activity also increased more at low (1 degree C) than at higher temperatures (5 and 20 degrees C). The contents of ascorbic acid (AsA), which is the substrate of APx, decreased immediately within 3 weeks and then gradually decreased until 15 weeks. The activity of CAT, the other enzyme which can scavenge hydrogen peroxide, decreased once in the first six weeks and thereafter increased to 15 weeks. Thus, the enhancement of the active oxygen-scavenging system that was induced by low temperature in potato tubers could result not only in a decrease of AsA but also in combined increases in APx and CAT activity whose manners were different.     

Penicillin vs. erythromycin in the treatment of diphtheria

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.     

Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene

Genetic variation among malaria parasites has important consequences with regard to drug resistance, pathogenicity, immunity, transmission, and speciation. In this regard, malaria parasites have been shown to display a high degree of inter- and intra-species genetic divergence. The nuclear genomes of Plasmodium falciparum, Plasmodium yoelii, and Plasmodium gallinaceum are vastly divergent yet share a similar codon usage and total A/T content of approximately 82%. This is in contrast to other primate-specific species including P. vivax which have an A/T content of approximately 67%. To assess the effects of this evolutionary divergence on the conservation of gene content, organization, and codon usage in the mitochondrial DNA (mtDNA) of malaria parasites, we have cloned and sequenced the mitochondrial genome of Plasmodium vivax, and compared it with the mtDNAs of P. falciparum, P. yoelii, and P. gallinaceum. The P. vivax mitochondrial genome was found to be 5990 base pairs in length, and displayed a gene organization identical to that of P. falciparum, P. yoelii, and P. gallinaceum. Furthermore, there was a remarkable 90% conservation of sequence identity between the mitochondrial genomes of all four species. As an example of intra-species conservation, comparison of mtDNAs from two independently cloned P. falciparum isolates, Malay Camp and C10, revealed only a single nucleotide substitution. A/T content of the P. vivax mitochondrial genome was found to be identical to other species of Plasmodium, hence, we have postulated that the mitochondrial genomes of malaria parasites were refractory to the evolutionary shifts in nucleotide content seen among the nuclear genomes of malaria parasites. Among different Plasmodium species, the second position of mitochondrial codons were found to be the least prone to substitutions and displayed a significant bias in pyrimidines. These aspects of mitochondrial codon usage were distinct from the nuclear genome and may reflect functional aspects of decoding by the mitochondrial translational system.     

Cbf5p, a potential pseudouridine synthase, and Nhp2p, a putative RNA-binding protein, are present together with Gar1p in all H BOX/ACA-motif snoRNPs and constitute a common bipartite structure

The eukaryotic nucleolus contains a large number of small nucleolar RNAs (snoRNAs) that are involved in preribosomal RNA (pre-rRNA) processing. The H box/ACA-motif (H/ACA) class of snoRNAs has recently been demonstrated to function as guide RNAs targeting specific uridines in the pre-rRNA for pseudouridine (psi) synthesis. To characterize the protein components of this class of snoRNPs, we have purified the snR42 and snR30 snoRNP complexes by anti-m3G-immunoaffinity and Mono-Q chromatography of Saccharomyces cerevisiae extracts. Sequence analysis of the individual polypeptides demonstrated that the three proteins Gar1p, Nhp2p, and Cbf5p are common to both the snR30 and snR42 complexes. Nhp2p is a highly basic protein that belongs to a family of putative RNA-binding proteins. Cbf5p has recently been demonstrated to be involved in ribosome biogenesis and also shows striking homology with known prokaryotic psi synthases. The presence of Cbf5p, a putative psi synthase in each H/ACA snoRNP suggests that this class of RNPs functions as individual modification enzymes. Immunoprecipitation studies using either anti-Cbf5p antibodies or a hemagglutinin-tagged Nhp2p demonstrated that both proteins are associated with all H/ACA-motif snoRNPs. In vivo depletion of Nhp2p results in a reduction in the steady-state levels of all H/ACA snoRNAs. Electron microscopy of purified snR42 and snR30 particles revealed that these two snoRNPs possess a similar bipartite structure that we propose to be a major structural determining principle for all H/ACA snoRNPs.