Carcinogenic action of nickel and cadmium powders in the same rat

Powders of nickel and cadmium metals were compared for their relative carcinogenic action when injected in contra thigh muscles of legs in the same Fischer-344 rat. For negative controls, rats of both sexes were injected im with 0.2 mL of the suspending vehicle, trioctanoin, once a month for 12 m. The two positive controls were treated once a month with either a suspension of powdered nickel (10 mg/mL for 5 m) or powdered cadmium (5 mg/mL twice). These dose levels were those found previously in the authors' laboratories to yield fibrosarcomas in 50–70% of the treated animals. For the combined experiment where the animals were injected with Ni and Cd in contra legs, the doses were about one-half of that used for the positive controls. Individual vehicle controls were used for each group. The fibrosarcoma yields for the experiments with individual positive metal controls were: vehicle alone, 0%; for both nickel and cadmium injected individually, between 60 and 80% for both males and females. In the combined metal experiment, one male and one female vehicle control developed tumors at the site of injection. The yield in the nickel leg was 14% for the females and 57% for the males; in the cadmium leg, the values were 93 and 50%, respectively. Only one male and one female developed sarcomas in both legs; in each case, the cadmium-induced tumor appeared first and grew seven to eight times larger than that induced by nickel.     

Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year

Introduction

Clinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by comparing baseline characteristics and one-year clinical outcomes of patients with active RA, grouped by baseline APR levels.

Methods

This was an observational study of 9,135 RA patients who had both ESR and CRP drawn and a visit at which CDAI was >2.8 (not in remission).

Results

Of 9,135 patients with active RA, 58% had neither elevated ESR nor CRP; only 16% had both elevated ESR and CRP and 26% had either ESR or CRP elevated. Among the 4,228 patients who had a one-year follow-up visit, both baseline and one-year follow-up modified Health Assessment Questionnaire (mHAQ) and CDAI scores were lowest for patients with active RA but with neither APR elevated; both mHAQ and CDAI scores increased sequentially with the increase in number of elevated APR levels at baseline. Each individual component of the CDAI followed the same trend, both at baseline and at one-year follow-up. The magnitude of improvement in both CDAI and mHAQ scores at one year was associated positively with the number of APRs elevated at baseline.

Conclusions

In a large United States registry of RA patients, APR levels often do not correlate with disease activity as measured by joint counts and global assessments. These data strongly suggest that it is appropriate to obtain both ESR and CRP from RA patients at the initial visit. Requiring an elevation in APR levels as a criterion for inclusion of RA patients in studies of experimental agents may exclude some patients with active disease.     

The F1-F2 vowel chart for Czech whispered vowels a, e, i, o, u

Aim: The aim of this contribution is to present the formant chart of the Czech vowels a, e, i, o, u and show that this can be achieved by means of digital methods of sound processing. Method: A group of 35 Czech students of the Pedagogical Faculty of Palacky University was tested and a record of whispered vowels was taken from each of them. The record was digitalized and processed by the Discrete Fourier Trasform. The result is the power spectrum of the individual vocals - the graphic output consists of a plot of the relative power of individual frequencies in the original sound. The values of the first two maxima which represent the first and the second formants were determined from the graph. The values were plotted on a formant chart. Results: Altogether, 175 spectral analyses of individual vowels were performed. In the resulting power spectrum, the first and the second formant frequencies were identified. The first formant was plotted against the second one and pure vocal formant regions were identified. Conclusion: Frequency bands for the Czech vowel "a" were circumscribed between 850 and 1150 Hz for first formant (F1) and between 1200 and 2000 Hz for second formant (F2). Similarly, borders of frequency band for vowel "e" they were 700 and 950 Hz for F1 and 1700 and 3000 Hz for F2. For vowel "i" 300 and 450 Hz for F1 and 2000 and 3600 Hz for F2, for vowel "o" 600 and 800 Hz for F1 and 600 and 1400 Hz for F2, for vowel "u" 100 and 400 Hz for F1 and 400 and 1200 Hz for F2. Discussion: At low frequencies it is feasible to invoke the source-filter model of voice production and associate vowel identity with frequencies of the first two formants in the voice spectrum. On the other hand, subject to intonation, singing or other forms of exposed voice (such as emotional speech, focused speech), the formant regions tend to spread. In spectral analysis other frequencies dominate, so specific formant frequency bands are not easily recognizable. Although the resulting formant map is not much different from the formant map of Peterson, it carries basic information about specific Czech vowels. The results may be used in further research and in education.     

Rapid, high resolution screening of biomaterial hydrogelators by μ2rheology

A combination of sample manipulation and rheological characterization at the microscale is used to identify the gelation of poly(ethylene glycol)-heparin hydrogels over a wide range of compositions. A microfluidic device produces 50-100 droplet samples, each with a different composition. Multiple particle tracking microrheology is used to measure the rheological state of each sample. This combination requires little material and enables efficient and rapid screening of gelation conditions. The high resolution data identifies the gelation reaction percolation boundaries and a lower limit of the total hydrogelator concentration for gelation to occur, which can be used for the subsequent engineering, testing, and processing of these materials.     

Fusion pore expansion is a slow, discontinuous, and Ca2+-dependent process regulating secretion from alveolar type II cells

In alveolar type II cells, the release of surfactant is considerably delayed after the formation of exocytotic fusion pores, suggesting that content dispersal may be limited by fusion pore diameter and subject to regulation at a postfusion level. To address this issue, we used confocal FRAP and N-(3-triethylammoniumpropyl)-4-(4-[dibutylamino]styryl) pyridinium dibromide (FM 1-43), a dye yielding intense localized fluorescence of surfactant when entering the vesicle lumen through the fusion pore (Haller, T., J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl. 1998. Proc. Natl. Acad. Sci. USA. 95:1579-1584). Thus, we have been able to monitor the dynamics of individual fusion pores up to hours in intact cells, and to calculate pore diameters using a diffusion model derived from Fick's law. After formation, fusion pores were arrested in a state impeding the release of vesicle contents, and expanded at irregular times thereafter. The expansion rate of initial pores and the probability of late expansions were increased by elevation of the cytoplasmic Ca2+ concentration. Consistently, content release correlated with the occurrence of Ca2+ oscillations in ATP-treated cells, and expanded fusion pores were detectable by EM. This study supports a new concept in exocytosis, implicating fusion pores in the regulation of content release for extended periods after initial formation.