A Phase 1 Trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion

Background  

The selective MAO-B inhibitor selegiline has been evaluated in clinical trials as a potential medication for the treatment of cocaine dependence. This study evaluated the safety of and pharmacologic interactions between 7 days of transdermal selegiline dosed with patches (Selegiline Transdermal System, STS) that deliver 6 mg/24 hours and 2.5 mg/kg of cocaine administered over 4 hours.     

Ecological and Morphological Differentiation Among COI Haplotype Groups in the Plant Parasitic Nematode Species Mesocriconema Xenoplax

DNA barcoding with the mitochondrial COI gene reveals distinct haplotype subgroups within the monophyletic and parthenogenetic nematode species, Mesocriconema xenoplax. Biological attributes of these haplotype groups (HG) have not been explored. An analysis of M. xenoplax from 40 North American sites representing both native plant communities and agroecosystems was conducted to identify possible subgroup associations with ecological, physiological, or geographic factors. A dataset of 132 M. xenoplax specimens was used to generate sequences of a 712 bp region of the cytochrome oxidase subunit I gene. Maximum-likelihood and Bayesian phylogenies recognized seven COI HG (≥99/0.99 posterior probability/bootstrap value). Species delimitation metrics largely supported the genetic integrity of the HG. Discriminant function analysis of HG morphological traits identified stylet length, total body length, and stylet knob width as the strongest distinguishing features among the seven groups, with stylet length as the strongest single distinguishing morphological feature. Multivariate analysis identified land cover, ecoregion, and maximum temperature as predictors of 53.6% of the total variation (P = 0.001). Within land cover, HG categorized under “herbaceous,” “woody wetlands,” and “deciduous forest” were distinct in DAPC and RDA analyses and were significantly different (analysis of molecular variance P = 0.001). These results provide empirical evidence for molecular, morphological, and ecological differentiation associated with HG within the monophyletic clade that represents the species Mesocriconema xenoplax.     

Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions

We have determined the nucleotide sequence of a 1,200-base pair (bp) genomic fragment that includes the kappa-chain constant-region gene (C kappa) from two species of native Australian rodents, Rattus leucopus cooktownensis and Rattus colletti. Comparison of these sequences with each other and with other rodent C kappa genes shows three surprising features. First, the coding regions are diverging at a rate severalfold higher than that of the nearby noncoding regions. Second, replacement changes within the coding region are accumulating at a rate at least as great as that of silent changes. Third, most of the amino acid replacements are localized in one region of the C kappa domain--namely, the carboxy-terminal "bends" in the alpha-carbon backbone. These three features have previously been described from comparisons of the two allelic forms of C kappa genes in R. norvegicus. These data imply the existence of considerable evolutionary constraints on the noncoding regions (based on as yet undetermined functions) or powerful positive selection to diversify a portion of the constant-region domain (whose physiological significance is not known). These surprising features of C kappa evolution appear to be characteristic only of closely related C kappa genes, since comparison of rodent with human sequences shows the expected greater conservation of coding regions, as well as a predominance of silent nucleotide substitutions within the coding regions.      

CYCLIC CHANGES IN THE CELL SURFACE : II. The Effect of Cytochalasin B on the Surface Morphology of Synchronized Chinese Hamster Ovary Cells

The surface morphology of Chinese hamster ovary cells treated with cytochalasin B (CB) has been examined using the scanning electron microscope. The cells respond to treatment with CB by retracting peripheral processes, rounding up, and assuming a smooth or gently convoluted surface. This response occurs within minutes. Cells in different stages of the cell cycle all respond in a similar manner. When CB is removed from treated cells by washing with conditioned medium, the cells regain their normal surface conformation within minutes. The surface topography of these released cells is characteristic of their stage in the cell cycle. Because CB causes an alteration in the morphology of the cell surface and because of the speed of the response and recovery, it is proposed that the primary site of action of CB is the cell surface.     

Characterization of monoclonal antibodies raised toStreptococcus mutans

Monoclonal antibodies (MAb) to whole cells ofStreptococcus mutants P-4 (serotype e) were generated. Of the four MAb used in this investigation, three were found to cross-react with mouse heart tissue (MAb-HT) in the solid-phase ELISA, while the remaining MAb was found to be specific forS. mutants only (MAb-SM). Serotypic characterization has shown that MAb-SM as well as MAb-HT recognize strains ofS. mutans representing all of the eight currently known serological groups. In addition, MAb-HT showed reactivity withStreptococcus pyogenes, a Lancefield group-A streptococcus frequently implicated in rheumatic fever. Western blot analysis has shown that MAb-SM recognizes a 14,000-dalton component present in a partially purified membrane fraction recovered following glass-bead breakage ofS. mutans P-4 cells. Two of the MAb-HT were found to react with a 35,000-dalton component from this same preparation.     

Anti-Streptococcus mutans ribosome monoclonal antibodies recognize a cell surface antigen on different serotypes

We have produced a panel of murine monoclonal antibodies to a ribosomal preparation fromStreptococcus mutans NCTC 10449 (serotypec). Ribosomal preparations were isolated from homogenized cells by differential centrifugation and consisted of approximately 17% protein and 83% RNA. Splenocytes from immunized animals were fused to NS-1 myeloma cells using polyethylene glycol and dimethyl sulfoxide. Four stable hybridomas have been currently established, two of which secrete the IgG-k isotype and the other two the IgM-k isotype. All of the monoclonal antibodies react with wholeS. mutans cells representing different serotypes, while not with other bacteria. In Western blot analysis of the ribosomal preparation resolved by one-dimensional electrophoresis, the nmonoclonal antibodies recognize a specific component with an apparent molecular weight of 65,000. These results indicate that theS. mutans ribosomal preparation contains an immunogenic site that is serologically indistinguishable from a species-specific surface determinant common to different serotypes.     

One new genus and three new species of Orsillinae (Hemiptera: Lygaeidae) from Australia

Abstract  Two new species of Nysius Dallas, N. orarius sp. n. and N. tasmaniensis sp. n. are described from New South Wales and Tasmania (Australia), respectively. A new monotypic genus, Reticulatonysius , with type-species R. queenslandensis sp. n. is described from Queensland, and its systematic relationship with other orsilline genera is discussed.     

Treatment with tumour infiltrating lymphocytes and interleukin-2 in patients with metastatic melanoma: A pilot study

Tumour infiltrating lymphocytes (TIL) were isolated and expanded from biopsy samples of 4 patients with metastatic melanoma. The patients were treated with autologous expanded TIL and continuous or bolus infusion of Interleukin 2 (IL-2) at a dose of 18 × 10⁶ International Units/m²/day for 5 days starting 36–48 hours after administration of cyclophosphamide at a dose of 1 g/m². The number of TIL infused ranged from 10¹⁰ to 5,56 × 10¹⁰ cells. Two patients had stable disease (SD) lasting for 2 1/2 and 4 months respectively and they died 24 and 13 months after therapy. One patient died during therapy due to a pseudomonas septicaemia and another patient developed progressive disease (PD). He died 3 months after the start of therapy. The side effects were substantial but most of them were reversible upon cessation of the treatment.The majority of the expanded TIL of all patients were of the CD8+ phenotype. Cutaneous metastases from two patients, removed after treatment with IL-2 and TIL, showed moderate lymphocytic infiltration also mainly of CD8+ T cells.The treatment with IL-2 and TIL is feasible, but further investigations should continue in an attempt to improve the efficacy of the therapy, to reduce toxicity and to diminish the costs and labour of the culture methods.     

Phylogenetic isolation of host trees affects assembly of local Heteroptera communities

A host may be physically isolated in space and then may correspond to a geographical island, but it may also be separated from its local neighbours by hundreds of millions of years of evolutionary history, and may form in this case an evolutionarily distinct island. We test how this affects the assembly processes of the host''s colonizers, this question being until now only invoked at the scale of physically distinct islands or patches. We studied the assembly of true bugs in crowns of oaks surrounded by phylogenetically more or less closely related trees. Despite the short distances (less than 150 m) between phylogenetically isolated and non-isolated trees, we found major differences between their Heteroptera faunas. We show that phylogenetically isolated trees support smaller numbers and fewer species of Heteroptera, an increasing proportion of phytophages and a decreasing proportion of omnivores, and proportionally more non-host-specialists. These differences were not due to changes in the nutritional quality of the trees, i.e. species sorting, which we accounted for. Comparison with predictions from meta-community theories suggests that the assembly of local Heteroptera communities may be strongly driven by independent metapopulation processes at the level of the individual species. We conclude that the assembly of communities on hosts separated from their neighbours by long periods of evolutionary history is qualitatively and quantitatively different from that on hosts established surrounded by closely related trees. Potentially, the biotic selection pressure on a host might thus change with the evolutionary proximity of the surrounding hosts.