Clinical impact of cyclosporine cellular pharmacodynamics in minimal change nephrotic syndrome.

BACKGROUND: Cellular pharmacodynamics of cyclosporine (INN, cyclosporin) is considered to be closely implicated in clinical efficacy of the drug in kidney transplantation and other immunologic disorders. We applied this strategy to patients with minimal change nephrotic syndrome to predict individual clinical efficacy of cyclosporine. METHODS: Drug sensitivity tests were carried out with peripheral blood mononuclear cells from 31 patients with minimal change nephrotic syndrome. The 50% lymphocyte-mitosis inhibition of cyclosporine on in vitro blastogenesis of peripheral blood mononuclear cells stimulated with concanavalin A were estimated, and interpatient variations of 50% lymphocyte-mitosis inhibition were evaluated. The relationship between cyclosporine-50% lymphocyte-mitosis inhibition and clinical outcomes indicated a decrease of urinary protein and the period required for complete remission under cyclosporine therapy was examined in 14 patients. We also evaluated the correlation between cyclosporine-50% lymphocyte-mitosis inhibition and interleukin-2 production and percentages of interleukin 2 receptor-positive peripheral blood mononuclear cells in vitro. RESULTS: Cyclosporine 50% lymphocyte-mitosis inhibition on peripheral blood mononuclear cell blastogenesis deviated largely between patients from 0.2 to 86.0 ng/mL. We found a statistically significant negative correlation between cyclosporine-50% lymphocyte-mitosis inhibition in vitro and decreasing rates of urinary protein at 1 week after onset of cyclosporine administration (r = -0.655, P < .02). When we arbitrarily divide the 14 patients who received cyclosporine therapy according to their median 50% lymphocyte-mitosis inhibition of cyclosporine into two groups, that is, a high-sensitivity group (50% lymphocyte-mitosis inhibition < 18.1 ng/mL, n = 6) and a low-sensitivity group (50% lymphocytemitosis inhibition > 18.1 ng/mL, n = 8), the period required for complete remission was significantly shorter in the high-sensitivity group (P < .03). The 50% lymphocyte-mitosis inhibition of cyclosporine on interleukin-2 production in culture medium was correlated with 50% lymphocyte-mitosis inhibition of the drug on peripheral blood mononuclear cell blastogenesis (r = 0.806, P < .02). Decreasing rates of interleukin-2R-positive cells by cyclosporine treatment in vitro were negatively correlated with peripheral blood mononuclear cells blastogenesis in the presence of the drug (r = -0.694, P < .02). CONCLUSIONS: Peripheral blood mononuclear cell response to cyclosporine in vitro is closely related to clinical efficacy of the drug in minimal change nephrotic syndrome. Peripheral blood mononuclear cell resistance to cyclosporine was correlated with ability of the cells to express interleukin 2 and interleukin 2R.

Prognosis of accidental low back pain at work.

Accidental low back pain at the workplace was classified into two groups; 177 cases of the organic type and 176 cases of the non-specific type. Concerning the recuperation period, the length of leave, and the amount of compensation for recuperation, medical cost and leave of absence, a comparison was made between two groups. Regarding age, sex, and the type of work, no difference was found between the organic and the non-specific groups. However, the non-specific group showed lower values than the organic one for the duration of recuperation and leave and the amount of compensation for medical cost and leave of absence. Multiple regression analysis showed that the difference in the type of low back pain had more influence on the duration and cost than that in sex and age. The prognosis of non-specific low back pain is better than that of organic one in terms of cost and duration.

Magnetometric evaluation for the effect of chrysotile on alveolar macrophages.

Alveolar macrophages are thought to play an important role in fibrogenesis due to asbestos exposure. In this experiment, we evaluated the effect mainly by unique magnetometry and also by conventional methods such as lactate dehydrogenase (LDH) activity measurement and morphological observations. Alveolar macrophages obtained from Syrian golden hamsters by bronchoalveolar lavages were exposed 18 hours in vitro to Fe3O4 as an indicator for magnetometry and chrysotile for experiments. A rapid decrease of the remanent magnetic field, so called "relaxation", was observed after the cessation of an external magnetic field in macrophages phagocytizing Fe3O4 alone, while relaxation was delayed in those concurrently exposed to chrysotile. Since relaxation is thought due to the cytoskeleton-driven random rotation of phagosomes containing iron oxide particles, chrysotile is considered to interfere with the cytoskeletal function of macrophages. Release of LDH from chrysotile-exposed macrophages into the medium was recognized, but it was not significantly higher than the controls. Apoptosis was negligible in macrophages exposed to chrysotile by the DNA ladder detection, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method and morphological observations. Electron microscopical examinations revealed early necrotic changes in macrophages exposed to chrysotile. These findings indicate that cell magnetometry detects impaired cytoskeletal function due to in vitro exposure to chrysotile.

Adverse effects of colophony.

Regarding colophony, the use in industries, adverse effects, diagnosis, pathophysiology and control are reviewed. Colophony is an unhomogeneous mixture of resin acids as like abietic acid and neutral substances. Colophony is used everywhere, in industry, daily life and medical supplies. Soldering workers are exposed to the colophony fumes heated up to the temperature of soldering irons. The effects of exposure to colophony are classified into bronchial asthma and contact dermatitis. Colophony fumes cause bronchial asthma by its nonspecific irritation. Inhalation challenge test and repeated spirometry during working day may help the diagnosis of colophony induced asthma. Improvement of working environment for soldering and development of new flux instead of colophony will be necessary. A study on contact dermatitis revealed that colophony and its related compounds are one of major causes for contact dermatitis. Cases of dermatitis by depilatory agents used to remove hair from slaughtered swine, anti-slipping cream for ballet shoes or resin for cello strings have been reported. Patch test may contribute to the diagnosis of dermatitis caused by colophony.

Intrinsic fluorescence of mitochondrial F1-ATPase.

The emission maximum of the fluorescence spectrum of mitochondrial F1-ATPase is shifted from 305 to 334 nm when the excitation wavelength is altered from 270 to 300 nm. This indicates that both tyrosine and tryptophan contribute to the intrinsic fluorescence of the F1-ATPase.

A novel packing of the hydrocarbon chains in lipids. The low temperature phases of dipalmitoyl phosphatidyl-glycerol.

The system dipalmitoyl phosphatidylglycerol-water displays several phases in the temperature-concentration range explored in this work. All the phases are lamellar; they differ by the organization of the hydrocarbon chains. In the high temperature phase the conformation of the chains is liquid-like. In the low temperature phases the chains are stiff and parallel and they interdigitate (in other words the CH3 ends of the chains of one layer are near to the polar groups of the opposite layer). Moreover, several types of packings of the stiff chains are observed which differ by the symmetry of the two-dimensional lattices. The observed lattices are p6, cmm and pgg.