Increased carbonyl protein level in the stratum corneum of inflammatory skin disorders: A non‐invasive approach

The stratum corneum (SC) is the interface of body and environment, and is continuously exposed to oxidative stress, resulting in carbonyl modification of proteins. We have developed a simple and non‐invasive method to assess carbonyl protein (CP) level in the SC, applied it to various kinds of skin, and revealed a link between the stratum corneum carbonylated protein (SCCP) level and water content in the SC. The purpose of the present study is to examine the SCCP level in inflammatory skin disorders associated with xerosis. Psoriasis vulgaris (PV) and atopic dermatitis (AD) are typical inflammatory skin disorders, of which the stratum corneum shows markedly low water content. SC samples were non‐invasively collected from the lesional and non‐lesional areas of PV and AD by adhesive tape stripping, and their carbonyl groups were determined by reaction with fluorescein‐5‐thiosemicarbazide. The average fluorescence intensity of the SC was calculated as SCCP level. Higher SCCP level was observed in the lesional area of PV as compared with non‐lesional area or healthy control. Lesional area of AD also exhibited higher SCCP level than corresponding non‐lesional area, of which SCCP level was slightly higher than the healthy control. These data suggest the involvement of oxidative modification of the SC protein, at least in part, in generation of xerotic skin in inflammatory skin disorders as well as dry skin in healthy subjects.     

Circumscribed myxoedema of lichen myxoedematosus as a sign of faulty formation of the proteoglycan macromolecule

Using a new method devised by our laboratory, the ultrastructure of dermal glycosaminoglycan in an involved area of lichen myxoedematosus was examined. Although histochemical and biochemical studies have indicated simply an accumulated deposition of hyaluronic acid in the lesion, the glycosaminoglycan ultrastructure within it was distinaly different from that in normal skin. The glycosaminoglycan structure of normal skin was similar to the proteoglycan aggregate model described by Rosenberg (1975). As confirmed by the enzymatic digestion procedure, it represents the ultrastructure of hyaluronic acid bound to glycosaminoglycans such as dermatan sulphate or chondroitin sulphate. In contrast, hyaluronic acid filaments observed in lesions of lichen myxoedematosus contained no glycosaminoglycan subunits.     

Wavelength and Conduction Inhomogeneity in Each Atrium in Patients with Isolated Mitral Valve Disease and Atrial Fibrillation

INTRODUCTION: Patients with mitral valve disease frequently have atrial fibrillation (AF), and the left atrium is presumed to be the primary atrium that develops AF. However, it is still not clear whether the electrophysiologic abnormalities responsible for AF are confined to the left atrium in this subset of patients. METHODS AND RESULTS: To examine the AF vulnerability of each atrium, we measured the wavelength and inhomogeneity of the conduction at the lateral right atrium, lateral left atrium, and Bachmann's bundle after defibrillation of AF in seven patients undergoing the maze procedure and mitral valve surgery for AF and isolated mitral valve disease, respectively (AF group). The data were compared with five coronary surgery patients in sinus rhythm (SR group). The wavelength in the AF group was significantly shorter (P < 0.05) than in the SR group not only at the lateral left atrium (225 +/- 62 vs 285 +/- 36 mm) but also at the lateral right atrium (214 +/- 54 vs 254 +/- 34 mm). The variation coefficient of the local maximum activation phase difference in the AF group (1.9 +/- 0.8 at the right atrium, 2.1 +/- 0.8 at the lateral left atrium, and 2.0 +/- 0.6 at Bachmann's bundle) was significantly greater (P < 0.05) than in the SR group at all atrial regions. CONCLUSION: AF vulnerability was not confined to the left atrium immediately after defibrillation in AF patients with isolated mitral valve disease. Electrical remodeling resulting from perpetuation of AF, pathological changes extending to the right atrium, geometric changes caused by the atrial interactions occurring across the interatrial septum, or a combination of these may explain the results.     

Evaluation of Liver Function by Co-administration Methodology Using 13C-Labelled Benzoic Acid and Hippuric Acid Coupled with Nuclear Magnetic Resonance Spectroscopy

The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-¹³C]Benzoic acid and [glycine carbonyl-¹³C]hippuric acid ([gly-¹³C]hippuric acid), each 0.4–0.6 mmol kg^?1 were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz ¹³C NMR spectroscopy. Consequently, urinary excretion of [7-¹³C]hippuric acid formed from [7-¹³C]benzoic acid and [gly-¹³C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-¹³C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-¹³C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-¹³C]hippuric acid and the glycine carbonyl carbon of [gly-¹³C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-¹³C]Hippuric acid was excreted more slowly than [gly-¹³C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (V_max) (4.8–5.8 μmol min^?1 kg^?1) and the renal elimination rate constants of hippuric acid (K_re) (0.010–0.021 min^?1) in the liver-injured rats were lower than those (V_max 6.7–11.8 μmol min^?1 kg^?1; K_re 0.026–0.045 min^?1) in the normal rats. These results have demonstrated that liver function can be evaluated from the V_max value even though the renal function of hippuric acid excretion (K_re) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.     

Effects of Sulfur Dioxide and Ozone on Hypertension Sensitive and Resistant Rats

Effects of Sulfur Dioxide and Ozone on Hypertension Sensitiveand Resistant Rats. Drew, R.T., Kutzman, R.S., Costa, D.L.,and Iwai, J. (1983). Fundam. Appl Toxicol 3: 298–302.Two lines of Dahl rats, one resistant to salt-induced hypertension(DR) and one susceptible to salt-induced hypertension (DS) weresubchronically exposed to SO₂ (50 ppm, 6 hr/d, 5 d/wk for 31weeks) or ozone (2.0 ppm, 6 hr/d, 5 d/wk for 20 weeks). Subgroupsof rats were maintained on either high or low salt diets. Inrats not expected to develop hypertension, exposure to SO₂ causeda slight but consistent decrease in blood pressure. In DS ratson a high salt diet exposure to SO₂ resulted in an increasein blood pressure over that of their air exposed counterparts.All exposure-related differences in blood pressure disappearedafter the last exposure to SO₂. Exposure to ozone was fatalto all DS rats, regardless of the amount of salt in the diet.The DR rats were more resistant to ozone, with most animalssurviving the 20-week exposure. Ozone-exposed rats exhibiteda decrease in both growth rate and blood pressure in all groupswhen compared to their air-exposed counterparts. It is not knownif exposure-related blood pressure differences would persistafter ending ozone exposures. After brief exposures, ozone causedincreased lung weights in both groups, but there were no consistentchanges in pulmonary nonprotein sulfhydryl groups. Hepatic nonpro-teinsulfhydryl levels were consistently, but not significantly,lower in ozone-exposed rats.     

Long-term effects of bone marrow transplantation for inborn errors of metabolism: A study of four patients with lysosomal storage diseases

Long-term effects of bone marrow transplantation (BMT) were evaluated in patients with I-cell disease, metachromatic leukodystrophy (MLD), Maroteaux-Lamy syndrome or Hunter syndrome (mild form). Donors were human leukocyte antigen (HLA)-matched siblings, and the follow-up periods were 24–71 months after BMT. The enzyme activities were increased in leukocytes, plasma or liver tissues compared with pre-BMT levels. A patient with I-cell disease acquired development of 4–8 month old infants and showed no further progression in cardiac dysfunctions. A patient with MLD showed a decelerated disease progression and an improved peripheral neuropathy, but progressive brain atrophy was not prevented. Patients with Maroteaux-Lamy syndrome or Hunter syndrome showed improvements in hepatomegaly, joint contractures, short stature and tight skin, and this greatly increased their quality of life. These results indicated that the long-term therapeutic effects achieved by BMT were subject to multiple factors including biochemical improvements, a reversibility of affected tissues, or advanced states of disease and central nervous system impairments in inborn errors of metabolism.     

Pulmonary myoepithelial carcinoma resembling matrix‐producing carcinoma of the breast: case report and review of the literature

Tanahashi J, Kashima K, Daa T, Yada N, Tanaka K‐I, Kawano Y, Yokoyama S. Pulmonary myoepithelial carcinoma resembling matrix‐producing carcinoma of the breast: case report and review of the literature. APMIS 2010; 118: 401–6. We report a case of pulmonary myoepithelial carcinoma with extensive myxohyaline stroma, resembling matrix‐producing carcinoma of the breast. A 76‐year‐old Japanese man presented with a nodular lesion in the left lung (S8), and underwent partial resection of the left lower lobe. Microscopically, the resected tumor was relatively well circumscribed with central hypocellular myxohyaline and peripheral hypercellular area. In the central area, eosinophilic and clear polygonal cells proliferated in a cord‐like or reticulated pattern with extensive myxohyaline stroma, while the peripheral area was composed of solid lobules of different shapes and sizes with occasional comedonecrosis. The tumor cells were markedly atypical with frequent mitotic figures. Vascular and lymphatic invasion was evident with regional lymph node metastasis. No squamous or glandular differentiation was evident in the tumor. Immunohistochemical staining implied myoepithelial differentiation. The patient developed multiple brain metastases, and died of the disease 11 months after the surgery. In this report, we discuss the histopathologic uniqueness of the present case together with a review of the literature.     

Effect of diisopropyl 1,3-dithiol-2-ylidinemalonate on rat liver and AFP-positive cells in 3'-Me-DAB hepatocarcinogenesis

The simultaneous administration of diisopropyl, 1,3-dithiol-2-ylidinemalonate (malotilate) suppressed the proliferation of AFP-positive oval cells, the formation of hyperplastic nodules and the appearance of clusters of AFP-positive cells in rat liver with hyperplastic nodules in 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) hepatocarcinogenesis. The development of hepatocarcinoma, induced by 3′-Me-DAB, was delayed in rats treated with malotilate; therefore, the simultaneous administration of malotilate worked as an inhibitory effect on 3′-Me-DAB hepatocarcinogenesis.