Blood lead (Pb) levels: Further evidence for an environmental mechanism explaining the association between socioeconomic status and psychophysiological dysregulation in children.

Objective: The authors recently reported that blood lead (Pb) was a significant mediator for the positive association between socioeconomic status (SES) and peripheral vascular responses to acute stress in children (B. B. Gump et al., 2007). The present study considers the possibility that Pb may also mediate an association between SES and cortisol responses to acute stress. Design: Early childhood Pb exposure was tested as a mediator for cross-sectional associations between SES and cortisol responses. Main Outcome Measures: The primary outcome was cortisol responses to acute stress in 9.5-year-old children (N = 108). Results: Lower family income was associated with significantly greater cortisol levels following an acute stress task. A mediational analysis confirmed that Pb was a significant mediator for this association. Conclusion: These results reaffirm the importance of considering the chemical environment as well as social and psychological environment when evaluating psychophysiological effects of low SES. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identifying the dominant failure mode in the hot extrusion tooling used to forge nickel based superalloy

The dies used in the extrusion of nickel based super alloys are subject to severe mechanical and thermal stresses, resulting in shortened life and high manufacturing costs. It is necessary to understand the dominant damage mode in order to guide improvements for increased tool life. The operation under examination consists of the hot extrusion of a nickel based superalloy using nitrided hot work tool steel, glassed workpieces and graphite lubrication. The investigation was conducted through a combination of metallurgical analysis, metrology and finite element analysis. Out of the damage modes observed under these conditions, the plastic deformation of the substrate was found to be the cause for tool failure. This paper discusses the relationship between plastic deformation of the substrate and the formation of scoring marks, which fail the die.     

Chronic illness, pain and health behaviors of community behavioral health clients.

Persons with comorbid medical disorders, along with substance use disorders and mental illness, present complex treatment needs that are seldom addressed. Chronic physical illness negatively affects treatment participation and retention, decreasing effectiveness. Studies documenting higher medical morbidity and mortality in such persons have long been available. Less is known about their health behaviors. Respondents (n = 418) at a community behavioral health center were surveyed for prevalence of illness, pain, health behaviors, and interest in lifestyle change. A total of 73% reported at least one chronic health problem, and nearly half rated their health between fair and very poor. Most reported at least one negative health indicator or behavior (e.g., smoking). Encouragingly, nearly 50% desired lifestyle changes including smoking cessation, exercise, and stress management. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Confocal laser scanning ophthalmoscope and spherical harmonics used as a possible aid to detect glaucoma

We present a procedure whereby the confocal laser scanning ophthalmoscope can be used to extract information about the three-dimensional structure of the central excavated area or the cup of the optic nerve head of the eye. The data are analyzed in terms of spherical harmonics. It is hypothesized that the shape of the cup of the optic nerve head for a normal eye can be parameterized by a specific set of spherical harmonic coefficients and is different from the set of coefficients describing a glaucomatous eye. The sets of coefficients are analyzed by using multivariate statistics and can in turn be used to classify new observations. Preliminary results indicate that there are significant differences in the coefficients and that the procedure might have potential as a diagnostic aid for the detection or the screening of glaucoma.     

Observations of the Effects of Oxide Skins on the Oscillations of Electromagnetically Levitated Metal Droplets

The surface tensions of liquid metals can be derived from measurements of the natural oscillation frequencies of levitated drops through the Rayleigh relation, In general, during terrestrial measurements, a spectrum consisting of three to five dominant oscillation frequencies (in the range of 30 to 60 Hz) are found, rather than the single one predicted by Rayleigh, due to deformation of the drop shape by gravity and the supporting magnetic field. Cummings and Blackburn have derived a correction factor to align the measured frequencies with the Rayleigh frequency, which has been shown to hold through micro-gravity experiments by Egry et al., for the majority of metals that have a liquid surface. Work at the NPL on more complex, commercial alloys has found that, in some cases, oscillation frequencies may be split into more complex spectra exhibiting seven to nine oscillation frequencies. This has been attributed to formations of oxide from the metal collecting on the surface of the droplet. Observations of the frequency spectra and high speed video images of the levitated drops are discussed.     

Induction of human breast cancer cell apoptosis from G2/M preceded by stimulation into the cell cycle by Z-1,1-dichloro-2,3-diphenylcyclopropane

We have shown previously that Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a. Analog II, A(II)) inhibits human breast cancer cell proliferation regardless of estrogen receptor status or estrogen sensitivity, and that its cellular targets include microtubules. In the present study, we investigated the apoptosis-inducing effects of A(II). MCF-7, MCF-7/LY2, and MDA-MB-231 cells all showed nuclear fragmentation in response to 100 microM A(II) when stained with Hoechst 33342 and examined by fluorescence microscopy. Pulsed field gel electrophoretic analysis showed that each of the cell lines also developed specific high molecular weight DNA fragments: a low level of 1-2 Mb fragments appeared after 6 hr, while 30-50 kb fragments accumulated subsequently. At 24 hr of drug exposure, the majority of cells became nonadherent, and the 30-50 kb fragments were restricted to detached MCF-7 and MDA-MB-231 cells. Both adherent and detached MCF-7/LY2 cells exhibited these fragments. A previous study by single-color (propidium) flow cytometry demonstrated that A(II) blocks MDA-MB-231 cells in G2/M of the cell cycle. More refined analyses in the present study showed this same result for MDA-MB-231 cells, but MCF-7 and MCF-7/LY2 cells did not reveal apparent drug-induced cell cycle block. A(II) demonstrated growth inhibitory, cell cycle-perturbing, and hypodiploidy-inducing activity against other human breast carcinoma lines, i.e. BT-20, CAMA-1, and SKBR-3, but no such actions in the non-tumorigenic, "normal" human breast epithelial line MCF-10A. Bromodeoxyuridine labeling and two-color flow cytometric analysis, however, suggested that A(II) caused stimulation into S phase, and that G2/M was the phase of the cell cycle from which cells apoptosed. A(II) caused cell rounding, detachment from the growth matrix, and nuclear shrinkage and fragmentation in parallel with biochemical changes. Cycloheximide inhibited A(II)-induced cell death, indicating that its toxicity requires de novo protein synthesis.     

Management of recurrent meningeal hemangiopericytoma

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.     

T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel has been identified in the cardiac muscle of a number of mammalian species, including humans. The goal of this study was to begin quantifying the structural requirements necessary for arylaminobenzoate block of the CFTR channel. The cardiac cAMP-dependent Cl- current (ICl) was measured using the whole-cell arrangement of the patch-clamp technique in guinea pig ventricular myocytes during stimulation of protein kinase A with forskolin. At drug concentrations below the IC50 value for channel block, reduction of ICl by the arylaminobenzoates occurred in a strongly voltage-dependent manner with preferential inhibition of the inward currents. At higher drug concentrations, block of both the inward and outward ICl was observed. Increasing the length of the carbon chain between the benzoate and phenyl rings of the arylaminobenzoates resulted in a marked increase in drug block of the channel, with IC50 values of 47, 17, and 4 microM for 2-benzylamino-5-nitro-benzoic acid, 5-nitro-2-(2-phenylethylamino)-benzoic acid, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), respectively. Increasing the carbon chain length further with the compound 5-nitro-2-(4-phenylbutylamino)-benzoic acid, caused no additional increase in the potency of drug block (IC50 = 4 microM). Inhibition of ICl by the arylaminobenzoates was modulated by the pH of the external solution; increasing the pH from 7.4 to 10.0 greatly weakened NPPB block, whereas decreasing the pH to 6.4 enhanced block. In addition, block of ICl was observed during intracellular dialysis of NPPB, and this action was not affected by raising the external pH.     

Chitinolytic activity in Chromobacterium violaceum: substrate analysis and regulation by quorum sensing

Quorum sensing control mediated by N-acyl homoserine lactone (AHL) signaling molecules has been established as a key feature of the regulation of exoenzyme production in many gram-negative bacteria. In Chromobacterium violaceum ATCC 31532 a number of phenotypic characteristics, including production of the purple pigment violacein, hydrogen cyanide, antibiotics, and exoproteases are known to be regulated by the endogenous AHL N-hexanoyl-L-homoserine lactone (HHL). In this study we show that C. violaceum produces a set of chitinolytic enzymes whose production is regulated by HHL. The chitinolytic activity was induced in strains grown in the presence of chitin as the sole carbon source and quantitated in the secreted proteins by using p-nitrophenol analogs of disaccharide, trisaccharide, and tetrasaccharide oligomers of N-acetylglucosamine. By using 4-methylumbelliferyl analogs of the same oligomers of N-acetylglucosamine as substrates for proteins separated and renatured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least six enzymes were detected: a chitobiase with high specificity to a dimeric substrate of 87 kDa, two N-acetylglucosaminidases with apparent molecular masses of 162 and 133 kDa, two endochitinases of 108 and 67 kDa, and a chitobiosidase of 56 kDa. In addition, two unidentified bands of >205 kDa were found where a tetrameric chitin derivative was used as a substrate. A pleiotropic mini-Tn5 mutant of C. violaceum (CV026) that is defective in HHL production and other quorum-sensing-regulated factors was also found to be completely deficient in chitinolytic activity. Growth of this mutant on minimal medium with chitin supplemented with culture supernatant from the C. violaceum wild-type strain or 10 microM synthetic HHL restored chitinase production to the level shown by the parental strain. These results constitute the most complete evidence so far for regulation of chitinolytic activity by AHL signaling in a gram-negative bacterium.