Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.     

Ca2+ differentially regulates conventional protein kinase Cs' membrane interaction and activation

The regulation of conventional protein kinase Cs by Ca2+ was examined by determining how this cation affects the enzyme's 1) membrane binding and catalytic function and 2) conformation. In the first part, we show that significantly lower concentrations of Ca2+ are required to effect half-maximal membrane binding than to half-maximally activate the enzyme. The disparity between binding and activation kinetics is most striking for protein kinase C betaII, where the concentration of Ca2+ promoting half-maximal membrane binding is approximately 40-fold higher than the apparent Km for Ca2+ for activation. In addition, the Ca2+ requirement for activation of protein kinase C betaII is an order of magnitude greater than that for the alternatively spliced protein kinase C betaI; these isozymes differ only in 50 amino acids at the carboxyl terminus, revealing that residues in the carboxyl terminus influence the enzyme's Ca2+ regulation. In the second part, we use proteases as conformational probes to show that Ca2+dependent membrane binding and Ca2+-dependent activation involve two distinct sets of structural changes in protein kinase C betaII. Three separate domains spanning the entire protein participate in these conformational changes, suggesting significant interdomain interactions. A highly localized hinge motion between the regulatory and catalytic halves of the protein accompanies membrane binding; release of the carboxyl terminus accompanies the low affinity membrane binding mediated by concentrations of Ca2+ too low to promote catalysis; and exposure of the amino-terminal pseudosubstrate and masking of the carboxyl terminus accompany catalysis. In summary, these data reveal that structural determinants unique to each isozyme of protein kinase C dictate the enzyme's Ca2+-dependent affinity for acidic membranes and show that, surprisingly, some of these determinants are in the carboxyl terminus of the enzyme, distal from the Ca2+-binding site in the amino-terminal regulatory domain.     

Localized CO<Subscript>2</Subscript> corrosion propagation at moderate FeCO<Subscript>3</Subscript> supersaturation initiated by mechanical removal of corrosion scale

The propagation of localized CO₂ corrosion was investigated at moderate iron carbonate supersaturation using an artificial defect method with re-formed corrosion scale. A mechanical tool was developed which locally removed pre-formed iron carbonate scale and initiated localized corrosion at a FeCO₃ supersaturation of 3–10. The localized corrosion rate was calculated based on electrochemical measurement using a simplified algorithm and was also measured at the deepest part of the defect using scanning electron microscopy. Localized corrosion was driven by a galvanic cell established between the two surfaces exposed in the artificial defect where an open circuit potential difference was maintained.     

Transient behavior of run-around heat and moisture exchanger system. Part IІ: Sensitivity studies for a range of initial conditions

Part І of this paper [17] developed and verified the numerical model for simultaneous heat and moisture transfer in the run-around membrane energy exchanger (RAMEE) system to determine the transient behavior of the system under different initial and operating conditions.This paper presents the transient response of the RAMEE system for step changes in the inlet supply air temperature and humidity ratio. Also the system quasi-steady state operating conditions are predicted as the system approaches its asymptotic operating condition. The transient responses are predicted with changes in various parameters. These include: the number of heat transfer units, thermal capacity ratio, heat loss/gain ratio, storage volume ratio and the normalized initial salt solution concentration. It is shown that the storage volume ratio and the initial salt solution concentration have significant impacts on the transient response of the system and heat transfer between the RAMEE system and the surrounding environment can change the system quasi-steady conditions substantially.     

Cross-Well Radar. I: Experimental Simulation of Cross-Well Tomography and Validation

This paper explains and evaluates the potential and limitations of conducting cross-well radar (CWR) in sandy soils. Implementing the experiment and data collection in the absence of any scattering object, and in the presence of an acrylic plate [a representative of dielectric objects, such as dense nonaqueous phase liquid (DNAPL) pools, etc.], as a contrasting object in a water-saturated soil is also studied. To be able to image the signature of any object, more than one pair of receiving and transmitting antennas are required. The paper describes a method to achieve repeatable, reliable, and reproducible laboratory results for different transmitter-receiver combinations. Different practical methods were evaluated for collecting multiple-depth data. Similarity of the corresponding results and problems involved in each method are studied and presented. The data show that the frequency response of a saturated coarse-grained soil is smooth due to the continuous and dominant nature of water in saturated soils. The repeatability and potential symmetry of patterns across some borehole axes provide a valuable tool for validation of experimental results. The potential asymmetry across other borehole axes is used as a tool to evaluate the strength of the perturbation on the electromagnetic field due to hidden objects and to evaluate the feasibility of detecting dielectric objects (such as DNAPL pools, etc.) using CWR. The experimental simulation of this paper models a real-life problem in a smaller scale, in a controlled laboratory environment, and within homogeneous soils that are uniformly dry or fully water saturated, with a uniform dielectric property contrast between the inclusion and background. The soil in the field will not be as homogeneous and uniform. The scaling process takes into consideration that as the size is scaled down; the frequency needs to be scaled up. It is noteworthy that this scaling process needs to be extensively studied and validated for future extension of the models to real-field applications. For example, to extend the outcome of this work to the real field, the geometry (antenna size, their separation and inclusion size) needs to be scaled up back to the field size, while soil grains will not. Therefore, soil, water, and air coupling effects and interactions observed at the laboratory scale do not scale up in the field, and may have different unforeseen effects that require extensive study.     

Clinical management of carpal tunnel syndrome: a 12-year review of outcomes

Carpal tunnel syndrome (CTS) is a disorder frequently encountered by occupational health care specialists. The health care management of this disorder has involved a diverse set of clinical procedures. The present article is a review of the literature related to CTS with an emphasis on occupational-related CTS. MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycLIT, and NIOSHTIC databases from 1985-1997 were searched for treatment outcome studies related to CTS. Treatments of interest included surgery, physical therapy, drug therapy, chiropractic treatment, biobehavioral interventions, and occupational rehabilitation. A systematic review of the effects of these interventions on symptoms, medical status, function, return to work, psychological well-being, and patient satisfaction was completed. Compared to other treatments, the majority of studies assessed the effects of surgical interventions. Endoscopic release was associated with higher levels of physical functioning and fewer days to return to work when compared to open release. Limited evidence indicated: 1) steroid injections and oral use of B6 were associated with pain reduction; 2) in comparison to splinting, range of motion exercises appeared to be associated with less pain and fewer days to return to work; 3) cognitive behavior therapy yielded reductions in pain, anxiety, and depression; and, 4) multidisciplinary occupational rehabilitation was associated with a higher percentage of chronic cases returning to work than usual care. Workers' compensation status was associated with increased time to return to work following surgery. Conclusions are preliminary due to the small number of well-controlled studies, variability in duration of symptoms and disability, and the broad range of reported outcome measures. While there are several opinions regarding effective treatment, there is very little scientific support for the range of options currently used in practice. Despite the emerging evidence of the multivariate nature of CTS, the majority of outcome studies have focused on single interventions directed at individual etiological factors or symptoms and functional limitations secondary to CTS.     

Race--Social, Biological, or Lemonade?

Comments on an article by R. L. Sternberg, E. L. Grigorenko, and K. K. Kidd (see record 2005-00117-006) and another article by H. Tang, T. Quertermous, B. Rodriguez, S. L. Kardia, X. Zhu, X., A. Brown, et al. (2005). On the day that I read Sternberg, Grigorenko, and Kidd's (January 2005) article on race, an article from the American Journal of Human Genetics (Tang et al., 2005) also crossed my desk. As part of their research, the latter authors compared the results of a cluster analysis of people using many genetic markers with the respondent's self-identified race/ethnicity: "Of 3,636 subjects of varying race/ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity" (Tang et al., 2005, p. 268). I would very much like to hear a response to this finding from Sternberg et al. (2005), who maintained that "race is a socially constructed concept, not a biological one" (p. 49), that reifies those physical correlates of ancient population dispersions "as deriving from some imagined natural grouping of people that does not in fact exist, except in our heads" (p. 51). My take is that if we psychologists could use genetics (or any other biological variables) to distinguish those with schizophrenia from those with bipolar disorder with an error rate even a hundredfold greater than that of Tang et al. (2005), we would announce--and do it with no small fanfare--that there are valid, biological differences between the two disorders. I suspect that much of the difficulty in discussing this issue stems from a tendency to treat "social" and "biological" (or "genetic" and "environmental") phenomena as mutually exclusive. Placing a complicated construct like race into a discrete "social" or "biological" box makes as much sense as asking whether lemonade is (a) lemon juice, (b) water, or (c) sugar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concerns of the dry-cleaning industry: a qualitative investigation of labor and management

BACKGROUND: Occupational scientists agree there are hazards associated with dry-cleaning, but do dry-cleaning owners and workers concur? Knowledge of owners' and workers' perceptions can help guide intervention efforts to reduce worker exposure. To better understand these issues, a qualitative study was conducted using focus group methodology and constant comparative analysis. METHODS: Two owner and four worker focus groups were held. RESULTS: Findings suggest that overall, health and safety issues were not of great concern. Owners were primarily concerned with the economic impact of regulations. Workers did express some anxiety about solvent exposure and burns, but most felt that these hazards were "just part of the job." Also, other than the installation of air-conditioning in the shops and the provision of health benefits, workers could not think of ways health and safety on the job could be improved. CONCLUSIONS: These findings will be used to develop comprehensive safety and health interventions (e.g., engineering plus education and training) in dry-cleaning shops.     

Peer reviewed: environmental sleuth at work

A combination of technical approaches and forensic tools can determine historic causes, timing, and impacts of site contamination.     

Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus

Leptin, the protein product of the adipose tissue-specific ob (obese) gene (1), reduces the body weight, adiposity and food intake of obese ob/ob mice on peripheral or central injection (2, 3, 4). [125I]leptin binding has been detected in mouse choroid plexus (5), from which a leptin receptor gene was expression cloned (5). The gene has at least 6 splice variants (6, 7). Leptin receptor mRNA was localized in the hypothalamus by in situ hybridization being particularly abundantly expressed in the arcuate nucleus (8). There is evidence linking the physiological effects of injected leptin with hypothalamic neuropeptide Y (9, 10) (NPY), which has potent central effects on food intake and energy balance (11), and is also expressed in the arcuate nucleus. Here we report dual in situ hybridization studies for leptin receptor and NPY gene expression in the mouse arcuate nucleus, where the majority of cells examined expressed both genes. This provides the first direct evidence that leptin acts on cells that express NPY mRNA.