Defect propagation in NiTi rotary instruments: a noncontact optical profilometry analysis.

AIM: To evaluate the presence and propagation of defects and their effects on surfaces of nickel-titanium (NiTi) instruments using noncontact, three-dimensional optical profilometry, and to assess the accuracy of this method of investigation. METHODOLOGY: The flute surface areas of instruments from two commercial instrumentation systems, namely Reciproc R25 (n = 5) and WaveOne Primary (n = 5), were assessed and compared before and after performing two instrumentation cycles in simulated root canals in clear resin blocks. All the analyses were conducted on areas measuring 211 × 211 µm, located 3 mm from the tips of the instruments. A quantitative analysis was conducted before and after the first and second instrumentation cycles, using the Sa (average roughness over the measurement field), Sq (root mean square roughness) and Sz (average height over the measurement field) amplitude parameters. All the data were submitted to statistical analysis at a 5% level of significance. RESULTS: There was a significant increase (P = 0.007) in wear in both groups, especially between baseline and the second instrumentation cycle, with significantly higher wear values being observed on WaveOne instruments (Sz median values = 33.68 and 2.89 µm, respectively, for WO and RP groups). A significant increase in surface roughness (P = 0.016 and P = 0.008, respectively, for Sa and Sq) was observed in both groups from the first to the second instrumentation cycle, mostly in WaveOne specimens. Qualitative analysis revealed a greater number of defects on the flute topography of all the instruments after use. CONCLUSIONS: More defects were identified in WaveOne Primary instruments compared to Reciproc R25, irrespective of the evaluation stage. The investigation method provided an accurate, repeatable and reproducible assessment of NiTi instruments at different time-points.

Generic nature of long-range repulsion mechanism on a bulk insulator?

Dynamic atomic force microscopy measurements are reported that provide evidence for the presence of long-range repulsion in molecular self-assembly on a bulk insulator surface. We present the structures formed from four different benzoic acid derivatives on the (10.4) cleavage plane of calcite kept in ultra-high vacuum. These molecules have in common that they self-assemble into molecular stripes when deposited onto the surface held at room temperature. For all molecules tested, a detailed analysis of the stripe-to-stripe distance distribution reveals a clear deviation from what would be expected for randomly placed, non-interacting stripes (i.e., geometric distribution). When excluding kinetic effects during growth, this result gives evidence for a long-range repulsion mechanism acting during the assembly of these stripes. The fact that this finding is robust against changes in the molecular structure indicates a generic nature of the observed mechanism, implying a ubiquitous origin such as electrostatic repulsion. Finally, we discuss parameters that might affect the unambiguous observation of this generic repulsion under specific experimental conditions.

A new method for the assessment of the surface topography of NiTi rotary instruments.

AIM: To describe a new method for the assessment of nanoscale alterations in the surface topography of nickel-titanium endodontic instruments using a high-resolution optical method and to verify the accuracy of the technique. METHODOLOGY: Noncontact three-dimensional optical profilometry was used to evaluate defects on a size 25, .08 taper reciprocating instrument (WaveOne® ), which was subjected to a cyclic fatigue test in a simulated root canal in a clear resin block. For the investigation, an original procedure was established for the analysis of similar areas located 3 mm from the tip of the instrument before and after canal preparation to enable the repeatability and reproducibility of the measurements with precision. All observations and analysis were taken in areas measuring 210 × 210 µm provided by the software of the equipment. RESULTS: The three-dimensional high-resolution image analysis showed clear alterations in the surface topography of the examined cutting blade and flute of the instrument, before and after use, with the presence of surface irregularities such as deformations, debris, grooves, cracks, steps and microcavities. CONCLUSIONS: Optical profilometry provided accurate qualitative nanoscale evaluation of similar surfaces before and after the fatigue test. The stability and repeatability of the technique enables a more comprehensive understanding of the effects of wear on the surface of endodontic instruments.

What controls plant nutrient use in high elevation ecosystems?

The importance of rock-derived mineral nutrients (P, K, Mn, Mg, and Ca) in plant physiological function is well established. However, one important and relatively unexplored question is whether or not the same rules of plant nutrient use efficiency apply to these essential elements even if they are not limiting to primary production. We examined conifer growth and nutrient use dynamics across sites with contrasting geologies (sedimentary and volcanic) that vary in both rock-derived mineral nutrient and N availability. Differences in bedrock geochemistry generally corresponded to differences in available soil nutrients, such that the volcanic site tended to have greater available nutrients. Foliar nutrient concentrations reflected both differences in bedrock chemistry and indices of available soil nutrients for P, K, and Mn. Aboveground biomass production did not follow expected patterns and was greater for trees growing on low nutrient sites, but only with respect to the annual woody increment. Fine litter production did not differ between sites. Finally, we found evidence for trade-offs between two commonly examined components of nutrient use efficiency (NUE): nutrient productivity (A n) and mean residence time of nutrients. However, we did not find evidence for higher plant NUE in soils with lower nutrient availability for N or rock-derived nutrients.

Are sea otters being exposed to subsurface intertidal oil residues from the Exxon Valdez oil spill?

Twenty years after the Exxon Valdez oil spill, scattered patches of subsurface oil residues (SSOR) can still be found in intertidal sediments at a small number of shoreline locations in Prince William Sound, Alaska. Some scientists hypothesize that sea otters continue to be exposed to SSOR by direct contact when otters dig pits in search of clams. This hypothesis is examined through site-specific examinations where SSOR and otter-dug pits co-occur. Surveys documented the exact sediment characteristics and locations on the shore at the only three subdivisions where both SSOR and otter pits were found after 2000. Shoreline characteristics and tidal heights where SSOR have persisted are not suitable habitat for sea otters to dig pits during foraging. There is clear separation between areas containing SSOR and otter foraging pits. The evidence allows us to reject the hypothesis that sea otters encounter and are being exposed by direct contact to SSOR.

Soil carbon storage responses to expanding pinyon-juniper populations in southern Utah.

Over the past several decades, the expansion and thickening of woodlands in the western United States has caused a range of ecological changes. Woody expansion often leads to increases in soil organic matter (SOM) pools with implications for both biogeochemical cycling and ecological responses to management strategies aimed at restoration of rangeland ecosystems. Here we directly measure C and N stocks and use simple non-steady-state models to quantify the dynamics of soil C accumulation under and around trees of varied ages in southern Utah woodlands. In the two pinyon-juniper forests of Grand Staircase Escalante National Monument studied here, we found approximately 3 kg C/m2 and approximately 0.12 kg N/m2 larger C and N stocks in soils under pinyon canopies compared to interspace sites. These apparent increases in soil C and N stocks under woody plant species were dominated by elevated SOM in the surface 10 cm of soil, particularly within non-mineral-associated organic fractions. The most significant accumulation of C was in the >850 microm fraction, which had an estimated C residence time of <20 yr. Rates of carbon accumulation following pinyon-juniper expansion appear to be dominated by changes in this fast-cycling surface soil fraction. In contrast, we found that after separating >850 microm organic matter from the remaining light fraction (LF), C had residence times of approximately 400 yr and mineral-associated (MA) soil C had residence times of approximately 600 yr. As a result, we calculate that input rates to the LF and MA pools to be 10 +/- 1 and 0.68 +/- 0.15 g m(-2) yr(-1) (mean +/- SE), respectively. These findings suggest that one consequence of management activities aimed at the reduction of pinyon-juniper biomass may be a relatively rapid loss of soil C and N pools associated with the >850 microm fraction. The temporal dynamics of the <850 microm pools suggest that carbon and nitrogen continue to accumulate in these fractions, albeit at very slow rates, and suggest that multidecadal storage of C following tree recruitment is limited to relatively small, subsurface fractions of the total soil C pool.

The earliest stages of ecosystem succession in high-elevation (5000 metres above sea level), recently deglaciated soils.

Global climate change has accelerated the pace of glacial retreat in high-latitude and high-elevation environments, exposing lands that remain devoid of vegetation for many years. The exposure of 'new' soil is particularly apparent at high elevations (5000 metres above sea level) in the Peruvian Andes, where extreme environmental conditions hinder plant colonization. Nonetheless, these seemingly barren soils contain a diverse microbial community; yet the biogeochemical role of micro-organisms at these extreme elevations remains unknown. Using biogeochemical and molecular techniques, we investigated the biological community structure and ecosystem functioning of the pre-plant stages of primary succession in soils along a high-Andean chronosequence. We found that recently glaciated soils were colonized by a diverse community of cyanobacteria during the first 4-5 years following glacial retreat. This significant increase in cyanobacterial diversity corresponded with equally dramatic increases in soil stability, heterotrophic microbial biomass, soil enzyme activity and the presence and abundance of photosynthetic and photoprotective pigments. Furthermore, we found that soil nitrogen-fixation rates increased almost two orders of magnitude during the first 4-5 years of succession, many years before the establishment of mosses, lichens or vascular plants. Carbon analyses (pyrolysis-gas chromatography/mass spectroscopy) of soil organic matter suggested that soil carbon along the chronosequence was of microbial origin. This indicates that inputs of nutrients and organic matter during early ecosystem development at these sites are dominated by microbial carbon and nitrogen fixation. Overall, our results indicate that photosynthetic and nitrogen-fixing bacteria play important roles in acquiring nutrients and facilitating ecological succession in soils near some of the highest elevation receding glaciers on the Earth.

Gene expression profiling of liver metastases and tumour invasion in pancreatic cancer using an orthotopic SCID mouse model.

The prognosis of pancreatic adenocarcinoma is affected by early metastases and local tumour invasion beyond surgical margins. Gene expression profiling in pancreatic cancer tissue is complicated due to the high amount of RNAses being present in human tissue and that of suitable models. In order to demonstrate early metastases, the models should take into account the anatomical environment of the tumour. Using the orthotopic transplantation of pancreatic tumour cells in SCID (severe combined immunodeficiency) mice, these interactions are taken into consideration. In order to identify genes associated with local tumour invasion and metastases in ductal pancreatic cancer, we investigated a human pancreatic tumour cell line derived from an orthopic pancreatic tumour model in SCID mice. Differential gene expression was performed on the basis of microarray technique. The human MiaPaca-2 cell line was implanted orthotopically in SCID mice. Transcriptional profiling was performed on fresh frozen tissue derived from the primary tumour, the tumour invasion front and the liver metastases. Differentially expressed genes were identified using statistical analyses, and were validated with external databases and with immunohistochemistry. A total of 1066 of 14 500 genes were significantly differentially expressed. Comparing the primary tumour with the tumour invasion front, there were 614 statistically significant up- and 348 downregulated genes. Twenty-five statistically significant up- and 181 downregulated genes were identified comparing the liver metastases with the primary tumour. Eight genes (PAI-1, BNIP3l, VEGF, NSE, RGS4, HSP27, GADD45A, PTPN14) were chosen and validated in a semi-quantitative immunohistochemical analysis, which revealed a positive correlation to the array data. Overrepresentation analyses revealed a total of 66 significantly regulated pathways associated with cell proliferation, cell stress, cell communication metabolic and cytokine function. In conclusion, model marker genes for local invasion and liver metastases can be identified using transcriptional profiling in the SCID mouse. Overrepresentation analysis secures a good and fast overview about the significantly regulated genes and can assign genes to certain pathways. These marker genes can be related to the apoptotic cascade, angiogenesis and cell interaction.

The impact of boreal forest fire on climate warming.

We report measurements and analysis of a boreal forest fire, integrating the effects of greenhouse gases, aerosols, black carbon deposition on snow and sea ice, and postfire changes in surface albedo. The net effect of all agents was to increase radiative forcing during the first year (34 +/- 31 Watts per square meter of burned area), but to decrease radiative forcing when averaged over an 80-year fire cycle (-2.3 +/- 2.2 Watts per square meter) because multidecadal increases in surface albedo had a larger impact than fire-emitted greenhouse gases. This result implies that future increases in boreal fire may not accelerate climate warming.

Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study.

BACKGROUND: Cytogenetic studies of malignant peripheral nerve sheath tumours (MPNSTs) and malignant triton tumours (MTTs) are rare. AIMS: To undertake cytogenetic analysis of these tumours. METHODS: Conventional cytogenetic analysis of 21 MPNSTs and MTTs from 17 patients (nine with peripheral neurofibromatosis (NF1)) was carried out using standard culture and harvesting procedures. For a more precise identification of composite structural rearrangements and marker chromosomes, spectral karyotypic analysis (SKY) was applied to a subset of cases. In addition, EGFR gene copy number was assessed by fluorescence in situ hybridisation (FISH) analysis in a subset of cases. RESULTS: Cytogenetic analysis revealed predominantly complex karyotypes. SKY analysis was useful in further defining many structural anomalies. Structural aberrations most frequently involved chromosomal bands or regions 1p31-36, 4q28-35, 7p22, 11q22-23, 19q13, 20q13, and 22q11-13. Overall, loss of chromosomal material was much more common than gain. Loss of chromosomes or chromosomal regions 1p36 (48%), 3p21-pter (52%), 9p23-pter (57%), 10 (48%), 11q23-qter (48%), 16/16q24 (62%), 17(43%), and 22/22q (48%), and gains of 7/7q (29%) and 8/8q (29%) were most prominent. These gains and losses were distributed equally between MPNST and MTT, demonstrating that these entities are similar with respect to recurrent genomic imbalances. Similarly, none of the recurrent chromosomal breakpoints or imbalances was restricted to either NF1 associated or sporadic MPNSTs. FISH analysis was negative for amplification. CONCLUSIONS: These cytogenetic and molecular cytogenetic findings expand the knowledge of chromosomal alterations in MPNST and MTT, and point to possible recurring regions of interest.

Reaching impaired populations with HIV prevention programs: a clinical trial for homeless mentally ill African-American men.

This study tested an intervention to reduce sexual risk behaviors in a high risk impaired population: homeless African-American, Caucasian and Hispanic men with mental illness. In a comparison group clinical trial, men were assigned to an experimental cognitive-behavioral or a control intervention and followed up over 16 months. Men were recruited from a psychiatric program in two shelters for homeless men in Nashville, Tennessee. An ethnically mixed cohort of subjects (54% African-American, 42% Caucasian and 4% Hispanic) were included in the study. Most had a chronic psychiatric disorder and a co-morbid substance abuse disorder. The 257 participants who were sexually active (130 experimental, 127 control) prior to the trial were the main target of the intervention. An experimental intervention (SexG), adapted from Susser and Associates (51), comprised 6 group sessions. The control intervention was a 6-session HIV educational program. Sexual risk behavior was the primary outcome. The experimental and control groups were compared with respect to the mean score on a sexual risk index. Complete follow-up data were obtained on 257 men (100%) for the initial six-month follow-up. These individuals have been followed for the remainder of the 16-month follow-up. This intervention, (SexG), successfully reduced sexual risk behaviors of homeless mentally ill African-American, Caucasian and Hispanic men. Similar approaches may be effective in other impaired high-risk populations.

Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases.

PURPOSE: A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations. METHODS: We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses. RESULTS: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was <5% in 47 (57%) cases and > or =5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined as > or =10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as > or =5% RC; P < 0.01), presence of necrosis (> or =5% of tumor mass; P < 0.05), and overexpression of P53 (P < 0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P < 0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P < 0.01). CONCLUSION: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (> or =5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.

Pfiesteria: review of the science and identification of research gaps. Report for the National Center for Environmental Health, Centers for Disease Control and Prevention.

In connection with the CDC National Conference on Pfiesteria, a multidisciplinary panel evaluated Pfiesteria-related research. The panel set out what was known and what was not known about adverse effects of the organism on estuarine ecology, fish, and human health; assessed the methods used in Pfiesteria research; and offered suggestions to address data gaps. The panel's expertise covered dinoflagellate ecology; fish pathology and toxicology; laboratory measurement of toxins, epidemiology, and neurology. The panel evaluated peer-reviewed and non-peer-reviewed literature available through June 2000 in a systematic conceptual framework that moved from the source of exposure, through exposure research and dose, to human health effects. Substantial uncertainties remain throughout the conceptual framework the panel used to guide its evaluation. Firm evidence demonstrates that Pfiesteria is toxic to fish, but the specific toxin has not been isolated or characterized. Laboratory and field evidence indicate that the organism has a complex life cycle. The consequences of human exposure to Pfiesteria toxin and the magnitude of the human health problem remain obscure. The patchwork of approaches used in clinical evaluation and surrogate measures of exposure to the toxin are major limitations of this work. To protect public health, the panel suggests that priority be given research that will provide better insight into the effects of Pfiesteria on human health. Key gaps include the identity and mechanism of action of the toxin(s), the incomplete description of effects of exposure in invertebrates, fish, and humans, and the nature and extent of exposures that place people at risk.

A genetically modified adenoviral vector exhibits enhanced gene transfer of human smooth muscle cells.

Adenoviral vector-based gene therapy is a promising approach for the treatment of restenosis postangioplasty. However, a high concentration of adenoviral vector can cause cellular activation, damage, and an enhanced immune response. One approach to solving this problem is to increase gene transfer efficiency by directing adenoviral vector entry via an alternate receptor system. We have constructed an adenoviral vector, Av9LacZ, that encodes the beta-galactosidase gene and contains a chimeric fiber protein that redirects viral vector binding to the Ad3 adenoviral receptor on the host cell. We examined the ability of Av9LacZ to transduce primary human smooth muscle cells (SMC) and found that it showed a 10- to 15-fold higher transduction efficiency when compared to the prototypic adenoviral vector currently used for preclinical and clinical studies. While both vectors were able to transduce rabbit, pig and monkey SMCs, the genetically modified vector transduced human SMC with much higher efficiency. SMC obtained from the aorta, coronary, renal, popliteal and pulmonary arteries were all efficiently transduced by Av9LacZ. Consistent with the data obtained from cultured cells, Av9LacZ also transduced fresh human arterial tissues considerably more efficiently than Av1LacZ. We conclude that the large discrepancy between transduction of animal and human cells by conventional vectors supports a cautious extrapolation of the results of in vivo animal studies to man. Furthermore, the genetically modified AV9 vector may deliver better efficacy and studies in large animal models with this vector could be more predictive of therapeutic efficacy in the treatment of human restenosis.

A randomized, double-blind placebo-controlled trial of the effects of the 5-hydroxytriptamine(4) agonist cisapride on the female urinary bladder.

OBJECTIVE: Anecdotal reports have proposed the use of the 5-hydroxytriptamine(4) agonist cisapride as a treatment for female voiding dysfunction on the basis of the known prokinetic actions of the medication. The purpose of our study is to assess the effects of this agent on the normal bladder in vivo. STUDY DESIGN: In this randomized, double-blind placebo-controlled trial, patients were randomized to receive either 20 mg cisapride or an identical placebo. They then underwent urodynamic evaluation that included uroflowmetry, multichannel filling cystometry, pressure-flow studies, and a urethral pressure profile. After a washout period of at least 7 days, subjects were then crossed over to the other arm and the tests were repeated. RESULTS: Twenty women without significant urinary incontinence agreed to participate. There was a decrease in the maximum cystometric capacity from 556 mL for placebo to 496 mL for cisapride (P <.001). There was no difference in the detrusor pressure at maximum flow, the maximum detrusor pressure, the flow rate, or the percentage of maximum cystometric capacity voided. CONCLUSIONS: In healthy women, cisapride caused a significant decrease in the maximum cystometric capacity, which could account for the higher reported rates of urinary frequency and urgency with this medicine. There was no evidence that this prokinetic agent improved voiding function.

Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services.

BACKGROUND: Children with complex chronic conditions (CCCs) might benefit from pediatric supportive care services, such as home nursing, palliative care, or hospice, especially those children whose conditions are severe enough to cause death. We do not know, however, the extent of this population or how it is changing over time. OBJECTIVES: To identify trends over the past 2 decades in the pattern of deaths attributable to pediatric CCCs, examining counts and rates of CCC-attributed deaths by cause and age (infancy: <1 year old, childhood: 1-9 years old, adolescence or young adulthood: 10-24 years old) at the time of death, and to determine the average number of children living within the last 6 months of their lives. DESIGN/METHODS: We conducted a retrospective cohort study using national death certificate data and census estimates from the National Center for Health Statistics. Participants included all people 0 to 24 years old in the United States from 1979 to 1997. CCCs comprised a broad array of International Classification of Diseases, Ninth Revision codes for cardiac, malignancy, neuromuscular, respiratory, renal, gastrointestinal, immunodeficiency, metabolic, genetic, and other congenital anomalies. Trends of counts and rates were tested using negative binomial regression. RESULTS: Of the 1.75 million deaths that occurred in 0- to 24-year-olds from 1979 to 1997, 5% were attributed to cancer CCCs, 16% to noncancer CCCs, 43% to injuries, and 37% to all other causes of death. Overall, both counts and rates of CCC-attributed deaths have trended downward, with declines more pronounced and statistically significant for noncancer CCCs among infants and children, and for cancer CCCs among children, adolescents, and young adults. In 1997, deaths attributed to all CCCs accounted for 7242 infant deaths, 2835 childhood deaths, and 5109 adolescent deaths. Again, in 1997, the average numbers of children alive who would die because of a CCC within the ensuing 6-month period were 1097 infants, 1414 children, and 2548 adolescents or young adults. CONCLUSIONS: Population-based planning of pediatric supportive care services should use measures that best inform our need to provide care for time-limited events (perideath or bereavement care) versus care for ongoing needs (home nursing or hospice). Pediatric supportive care services will need to serve patients with a broad range of CCCs from infancy into adulthood.

Differential N-demethylation of l-alpha-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18, and 3A4.

Incubation of l-alpha-acetylmethadol (LAAM) or norLAAM with cDNA-expressed P450s 3A4, 2B6, and 2C18 produced significant N-demethylation products. P450s 2C19, 2C8, 3A5, 2C9, 3A7, 1A1, and 2D6 (norLAAM only), also produced detectable product. Coexpression of cytochrome b(5) enhanced LAAM N-demethylation, most dramatically for 3A4, but had marginal effects on norLAAM N-demethylation. Modeling total liver metabolism using immunoquantification and relative activity factors of P450s suggests contributions of P450 3A4 > 2B6 > 2C18, with the importance of 2B6 to 2C isozymes enhanced by relative activity factors. The ratio of dinorLAAM to norLAAM plus dinorLAAM formed from LAAM did not exceed 20%, and was isozyme and cytochrome b(5) coexpression dependent. This ratio decreased with concentration with 3A4, but was relatively constant for 2B6 and 2C18. The human liver microsomes substrate-concentration response was similar to cDNA-expressed 3A4, but the ratio was higher. Changes in the environment of cDNA-expressed 3A4 also effected the magnitude of the ratio, but not the concentration-dependent decrease. These studies show that the N-demethylation of LAAM and norLAAM is not restricted to P450 3A4, particularly P450s 2B6 and 2C18, and suggest that the mechanism of sequential metabolism for 3A4 differs from that of 2B6 and 2C18.

Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma.

The cytogenetic findings for two epithelioid hemangioendotheliomas are reported. An identical chromosomal translocation involving chromosomes 1 and 3 [t(1;3)(p36.3;q25)] was detected in both cases of epithelioid hemangioendothelioma, possibly representing a characteristic rearrangement for this histopathologic entity. The presence of clonal karyotypic abnormalities supports a neoplastic origin for the epithelioid variant of hemangioendothelioma. Identification of the 1;3 translocation may be useful diagnostically. Should additional studies confirm these data, this could lead to the identification of the gene(s) central to this neoplastic process.

Cytogenetic instability, predominantly involving chromosome 1, is characteristic of elastofibroma.

Elastofibroma, an unusual pseudotumor composed of excessive collagen and abnormal elastic fibers, has rarely been subjected to cytogenetic analysis. Only two cases have been previously defined, both of which demonstrated nonclonal abnormalities. In the present study, three cases of elastofibroma were cytogenetically analyzed. Abnormalities of the short arm of chromosome 1 were seen in all three cases (either clonally or as the most frequently involved region among nonclonal aberrations). In addition, a translocation involving chromosomes 8 and 12 was detected as a clonal rearrangement in one of the three cases. The observation of clonal abnormalities in elastofibroma suggests that this lesion may represent a neoplastic rather than a reactive process.

Noninvasive control of stochastic resonance.

External feedback can enhance (or depress) the response of a noisy bistable system to monochromatic signals, significantly magnifying its natural stochastic resonance. We compare and contrast a variety of such feedback strategies, using both numerical simulations and analog electronic experiments. These noninvasive control techniques are especially valuable for noisy bistable systems that are difficult or impossible to modify internally.