Motor vehicle accidents in Parkinson's disease: A questionnaire study.

OBJECTIVES: Few studies have investigated the risk factors for motor vehicle accidents (MVA) in individuals with Parkinson's disease (PD) in Japan. MATERIALS AND METHODS: We sent an anonymous questionnaire to 1417 patients with PD who had received medical care certificates for Intractable Diseases during the 2014 fiscal year from the Aomori Prefectural Government in Japan. Data from patients with PD who previously or currently held a driving license at the time of the survey were analyzed. RESULTS: Complete datasets were obtained from 384 patients with PD who were either past or present driving license holders. Fifty-seven patients had caused at least one MVA in the last 5 years before the survey. Logistic regression analyses revealed that ergot-dopamine agonist (DA) use and excessive daytime sleepiness (Epworth Sleepiness Scale score ≥ 10) were the best predictors of MVAs. Patients having caused non-sleep-related MVAs had significantly longer disease durations, more frequent ergot-DA use, and higher cognition and communication subscores on the Parkinson's Disease Questionnaire-39 than those without non-sleep-related MVAs (P < .05). The Epworth Sleepiness Scale scores of PD patients with sleep-related MVAs were significantly higher than those of patients without sleep-related MVAs (P < .01). CONCLUSIONS: Excessive daytime sleepiness and ergot-DA use may be important predictive risk factors for MVAs in PD. Daytime sleepiness appears to be related to sleep-related MVAs in PD, whereas disease progression and ergot-DA use may contribute to non-sleep-related MVAs.

[Perioperative targeting brachytherapy for lung cancer invading the chest wall].

We evaluated the efficacy of perioperative targeting brachytherapy for lung cancer invading the chest wall. Between 1998 and 2003, 7 patients underwent perioperative targeting brachytherapy for lung cancer invading the chest wall. There were 5 male and 2 female patients. The mean age was 63.3 years, with a range of 45 to 77 years. All patients underwent complete resection including the chest wall combined resection. During the operation, plastic afterloading catheters fixed on the Vicryl mesh at interval of 1 cm were placed on the site of chest wall resection. From the third to sixth day after the operation, 15 to 32 Gy of radiation was delivered over 3 or 4 days using a high dose rate remote afterloading system. The area targeted for brachytherapy was determined by a computed tomography (CT) scanner translator with a computer program for radiation planning. The median postoperative hospital stay was 35 days. Local recurrences were observed in 2 patients, but there was no evidence of recurrence in the margin of the resected chest wall. We believe that this short period of treatment and the low side effects enhances the quality of the patients. Prevention of local recurrence was achieved in short term follow-up.

Hepatocellular carcinoma with blood supply from omental branches: treatment with transcatheter arterial embolization.

PURPOSE: To evaluate the usefulness of transcatheter arterial embolization (TAE) through the omental branch in the treatment of hepatocellular carcinoma (HCC) with blood supply from the omental branch. MATERIALS AND METHODS: Fifteen patients with HCC fed by the omental branch underwent TAE. All but one had previously undergone several therapies for HCC, including TAE. Three patients had intraperitoneal hemorrhage caused by ruptured HCC fed by the omental branch, and two necessitated emergency TAE. The technical success rate, therapeutic effect, and safety of TAE via the omental branch were evaluated. RESULTS: Twenty-six omental branches that fed HCC were observed angiographically. Attenuation or occlusion of the hepatic artery was observed in 80%. Nineteen omental branches (73%) could be successfully embolized. Hepatic hemostasis was achieved in all patients with ruptured HCC. Tumor recurred in 80% of patients who underwent successful TAE of the omental branch, and additional therapy was performed in six patients. Ten patients died after 2-26 months (mean, 8 mo). Five patients were alive for 3-13 months (mean, 7 mo). Severe complications were not observed in any patient. CONCLUSION: TAE of the omental branch is safe and has become technically feasible in almost all patients, but tumors frequently recur.

Cytotoxic effects of soluble factor in preeclamptic sera on human trophoblasts.

Evidence indicating abnormal biological behavior of trophoblasts has been seen in preeclamptic patients, but the mechanism is still unknown. We have previously shown that endothelial injury and neutrophil activation are induced by certain factors in preeclamptic sera. We investigated the effect of sera from eight preeclamptic and 11 normal pregnant women on cellular proliferation and viability of trophoblasts using 3H-thymidine incorporation and the trypan-blue dye exclusion test, respectively. Five of eight preeclamptic sera, but none of the normal pregnant sera, inhibited 3H-thymidine incorporation. The trypan-blue test revealed the sera reduced cellular viability. Gel permeation showed that the greatest growth-inhibitory activity corresponded to a molecular weight of 50 kDa. The serum-mixing test revealed this permeation and inhibitory preeclamptic sera suppressed the growth-promoting activity of normal pregnant sera in a dose-dependent manner. These results suggested the presence of certain factors in some preeclamptic sera that can affect cellular behavior of human trophoblasts.

Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats.

In an attempt to define the role of the pineal secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px), decreased as a result of CP administration, which was restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats; these changes were prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative capacity, however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co-treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function.

Targeting adjuvant brachytherapy for a superior sulcus tumor: report of two cases.

We report herein the cases of two patients who underwent complete resection of a superior sulcus tumor (SST) plus adjuvant brachytherapy, with the area to be irradiated determined by a computer program system designed to minimize unnecessary irradiation to the normal components and to optimize the effect on the targeted area. Although the efficacy of brachytherapy on the inhibition of local relapse needs to be observed over a long period, the selective and alternative use of delivering adjuvant brachytherapy by this method appears to enhance the quality of life of patients with a SST.

Muscle high-energy metabolites and metabolic capacity in patients with heart failure.

UNLABELLED: OKITA, K., K. YONEZAWA, H. NISHIJIMA, A. HANADA, T. NAGAI, T. MURAKAMI, and A. KITABATAKE. Muscle high-energy metabolites and metabolic capacity in patients with heart failure. Med Sci. Sports. Exerc., Vol. 33, No. 3, 2001, pp. 442-448. BACKGROUND: Various abnormalities in skeletal muscle have been demonstrated by biopsy in patients with chronic heart failure (CHF). In mammalian muscles, high-energy metabolite composition at rest (HEMC) provides data on important metabolic characteristics; however, the significance of HEMC has not been clarified in patients with CHF. Therefore, we investigated HEMC in normal subjects and patients with CHF and examined its relation to muscle metabolic capacity and exercise tolerance. METHODS: High-energy metabolites (phosphocreatine (PCr), inorganic phosphate (Pi), and ATP) in resting calf muscle were measured by 31P-magnetic resonance spectroscopy (31P-MRS), and ratios of Pi to PCr, Pi to ATP, and PCr to ATP were calculated in 34 patients with CHF and 13 age- and size-matched normal subjects. Muscle metabolism was evaluated during local exercise of unilateral plantar flexion by 31P-MRS. Metabolic capacity was estimated by the rate of PCr breakdown in relation to the workload. Systemic exercise capacity was evaluated by a bicycle ergometer. RESULTS: The ratio of PCr to ATP was significantly increased in patients with CHF compared with controls (3.06 +/- 0.43 vs 2.72 +/- 0.36, P < 0.05) and was significantly correlated with metabolic capacity (r = -0.37, P < 0.01) and with peak oxygen uptake (r = -0.45, P < 0.01). There was a significant correlation between metabolic capacity and peak oxygen uptake (r = 0.53, P < 0.001). CONCLUSION: HEMC was altered in patients with CHF, and this change was related to metabolic capacity and exercise capacity. These findings provide new insight into the mechanism of impaired muscle metabolism in CHF.

Atomic force microscopy with carbon nanotube probe resolves the subunit organization of protein complexes.

Among many scanning probe microscopies, atomic force microscopy (AFM) is a useful technique to analyse the structure of biological materials because of its applicability to non-conductors in physiological conditions with high resolution. However, the resolution has been limited to an inherent property of the technique; tip effect associated with a large radius of the scanning probe. To overcome this problem, we developed a carbon nanotube probe by attaching a carbon nanotube to a conventional scanning probe under a well-controlled process. Because of the constant and small radius of the tip (2.5-10 nm) and the high aspect ratio (1:100) of the carbon nanotube, the lateral resolution has been much improved judging from the apparent widths of DNA and nucleosomes. The carbon nanotube probes also possessed a higher durability than the conventional probes. We further evaluated the quality of carbon nanotube probes by three parameters to find out the best condition for AFM imaging: the angle to the tip axis; the length; and the tight fixation to the conventional tip. These carbon nanotube probes, with high vertical resolution, enabled us to clearly visualize the subunit organization of multi-subunit proteins and to propose structural models for proliferating cell nuclear antigen and replication factor C. This success in the application of carbon nanotube probes provides the current AFM technology with an additional power for the analyses of the detailed structure of biological materials and the relationship between the structure and function of proteins.

The cell biological application of carbon nanotube probes for atomic force microscopy: comparative studies of malaria-infected erythrocytes.

We describe the first cell biological application of carbon nanotube (CN) probes for atomic force microscopy studies. Topographic and phase images were collected from Plasmodium falciparum malaria-infected erythrocytes using both TappingMode Etched Silicon Probes (TESP probe) and CN probes. We estimate that the lateral resolution of a CN probe-generated topographic image is at least four-fold higher than that of the TESP probe. Carbon nanotube probe-generated phase images of P. falciparum-induced knobs on the surface of erythrocytes also show a markedly higher lateral resolution than comparable TESP probe-generate phase images of the same area. We conclude that CN probes are useful for cell biological atomic force microscopy studies and should play an increasingly important role in the future of this evolving discipline.

Prevention of nephrotoxicity of cisplatin by repeated oral administration of ebselen in rats.

The ability of ebselen, which exhibits glutathione peroxidase (GSH-Px)-like activity, to prevent cisplatin (CDDP)-induced nephrotoxicity was examined in rats. CDDP (6 mg/kg [20 micromol/kg] body weight) was injected intraperitoneally. In subgroups, daily ebselen doses of 2.75 (10 micromol), 5.5 (20 micromol), or 11.0 mg (40 micromol)/kg body weight were administrated orally 1 hour prior to CDDP treatment. Treatment with CDDP alone resulted in significantly increased plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Repeated administration of 5.5 and 11.0 mg/kg ebselen prevented the CDDP-induced elevation of plasma Cr and BUN levels and protected against kidney damage. Relative to controls, rat that received CDDP treatment displayed a decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), an indicator directly related to oxidative stress, and elevated malondialdehyde (MDA) levels in the kidney. In comparison with controls, activity of GSH-Px activity, which antioxidant enzyme, was also reduced in the kidney of rats treated with CDDP. Repeated administration of 5.5 or 11.0 mg/kg ebselen prevented CDDP-induced alteration of GSH/GSSG ratios, MDA levels, and GSH-Px activity; however, no protection against CDDP was observed with administration of 2.75 mg/kg ebselen. Effective protection of CDDP-induced nephrotoxicity with ebselen was observed only when the molar amount of each daily ebselen treatment equaled or exceeded

Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma.

Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. We present a preliminary report on the results of a new treatment, "radiochemotherapy combined with caffeine" (K3 protocol), for high-grade soft tissue sarcomas. Seventeen patients with various high-grade soft tissue sarcomas were included in this study. Preoperatively, three to five courses of intra-arterial chemotherapy using cisplatin, caffeine and doxorubicin after radiation therapy were administered. Following the preoperative therapy, function-saving surgery was performed for all cases. Complete response was observed in six patients, partial response in six and no change in five. The effectiveness rate of caffeine-potentiated radiochemotherapy was therefore 71%. The histological response for radiochemotherapy was better than that for chemotherapy alone, that is, total tumor necrosis was identified in six patients and over 90% necrosis in another six. Complications resulting from the preoperative radiation comprised of serious inflammation in three patients and skin necrosis in another three. Twelve patients have remained free of disease, two patients are alive with disease and three have died of metastatic disease with a mean follow-up period of 36 months. There was no local tumor recurrence. These preliminary findings suggest that caffeine-potentiated radiochemotherapy contributed to a satisfactory local response and the success of function-saving surgery for high-grade soft tissue sarcomas.

Expression of thrombomodulin in squamous cell carcinoma of the lung: its relationship to lymph node metastasis and prognosis of the patients.

Thrombomodulin (TM) is a type of thrombin receptor that was identified originally on the endothelium and acts as a natural anticoagulant through converting thrombin from a procoagulant protease to an anticoagulant. We reported previously that TM was also expressed in the squamous epithelium mainly at the intercellular bridges. In this study, we examined TM expression in the primary lesions of 81 patients with squamous cell carcinomas (SCCs) of the lung and in the lymph node metastatic lesions of 39 patients using immunohistochemical methods. The carcinoma tissues expressed TM mainly at the cell-cell boundaries and also in the cytoplasm. When TM expression was compared between the primary and metastatic lesions in the 39 patients who had lymph node metastasis, 26 (67%) showed decreased TM expression, 13 (33%) showed no change, and none (0%) showed an increase in the metastatic lesions. Wilcoxon's signed-rank test indicated that tumor cells that were positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.0001). The present study also showed that the patients with TM-negative expression in the primary tumors showed significantly poorer survival than those with TM-positive expression, mainly due to distant metastases of poorly-differentiated SCCs with negative TM expression in the primary tumors. These results indicate that the reduction of TM expression seems to play an important role in the metastatic process of lung SCCs.

Premature chromatin condensation caused by loss of RCC1.

Hamster rcc1 mutant, tsBN2, prematurely enter mitosis during S phase. RCC1 is a guanine nucleotide exchanging factor for a small G protein Ran and localised on the chromatin, whereas RanGTPase activating protein is in the cytoplasm. Consistently, Ran shuttles between the nucleus and the cytoplasm, carrying out nucleus-cytosol exchange of macromolecules, which regulates the cell cycle. The finding that loss of RCC1 which disturbs nuclear protein export due to loss of RanGTP, abrogates the check point control suggests that RCC1 senses the status of the chromatin, such as replication, and couples it to the cell cycle progression through Ran.

Dissociation between muscle metabolism and oxygen kinetics during recovery from exercise in patients with chronic heart failure.

OBJECTIVE: To estimate muscle metabolism and oxygen delivery to skeletal muscle in patients with chronic heart failure. METHODS: 13 patients with chronic heart failure and 15 controls performed calf plantar flexion for six minutes at a constant workload of 50% of one repetition maximum. During recovery from exercise, skeletal muscle content of oxygenated haemoglobin (oxy-Hb) and the level of phosphocreatine (PCr) were measured by near-infrared spectroscopy and (31)P-magnetic resonance spectroscopy, respectively. RESULTS: The mean (SD) time constants of PCr and oxy-Hb during recovery from exercise were significantly greater in patients with chronic heart failure than in normal subjects (tau PCr: 76.3 (30.2) s v 36.5 (5.8) s; tau oxy-Hb: 48.3 (7.3) s v 30.1 (7.7) s; p < 0.01). Both time constants were similar in normal subjects, while the tau PCr was significantly greater than the tau oxy-Hb in patients with chronic heart failure. CONCLUSIONS: The slower recovery of PCr compared with oxy-Hb in patients with chronic heart failure indicates that haemoglobin resaturation is not a major rate limiting factor of PCr resynthesis. It is suggested that muscle metabolic recovery may depend more on oxygen utilisation than on haemoglobin resaturation or oxygen delivery in patients with chronic heart failure.

Mechanisms mediating the vasorelaxing action of eugenol, a pungent oil, on rabbit arterial tissue.

The inhibitory actions of eugenol on intracellular Ca2+ concentration ([Ca2+]i) and the contractions induced by excess extracellular K+ concentration ([K+]o) in rabbit thoracic aorta were investigated. Application of excess [K+]o solution (30-90 mM) produced contraction and increased the intensity of the Ca2+ fluorescence signal. Pretreatment with eugenol (> or =0.1 mM) reduced both the amplitude of contraction and the intensity of the Ca2+ fluorescence signal, but the contraction was more strongly affected than the [Ca2+]i. Application of eugenol (0.3 mM) to tissue precontracted by 90 mM [K+]o solution (immediately after the removal of the 90 mM [K+]o solution) slowed the decay of the [Ca2+]i signal, but it did not change the rate of relaxation. Carbonyl cyanide m-chlorophenylhydrozone (10 microM), a mitochondrial metabolic inhibitor, produced a reduction in tension despite a slight increase in [Ca2+]i when applied to muscle precontracted by 90 mM [K+]o solution. These results indicate that eugenol relaxes the rabbit thoracic aorta while suppressing the Ca2+-sensitivity and both the uptake and extrusion mechanisms for Ca2+. To judge from the similarities between its actions and those of metabolic inhibitors, eugenol may produce its actions at least partly through metabolic inhibition.

The reduced expression of e-cadherin, alpha-catenin and gamma-catenin but not beta-catenin in human lung cancer.

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the histo-architecture. Using a combination of biochemical and immunohistochemical methods, we analyzed the expression of cadherin-catenin complexes in 37 non-small cell lung carcinomas. In 19 cases, decreased expression of E-cadherin protein was observed. In 12 of them, decreased expression of alpha-catenin protein was also observed. Thus, decreased expression of alpha-catenin was apparently preceded by decreased expression of E-cadherin. In no cases was decreased expression of beta-catenin observed. In the 12 cases in which mRNA expression was analyzed by Northern blot analysis, decreased expression of mRNAs for E-cadherin and alpha-catenin was observed in 11 and 9 cases, respectively. In cases with reduced E-cadherin and alpha-catenin expression, immunohistochemistry revealed two types of staining pattern for the proteins. In the first type, almost all the cells in a tumor were stained weakly (homogeneous pattern). In the second type, different percentages of cells were stained strongly, the rest being almost negative for the staining (heterogeneous pattern).

Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure.

BACKGROUND: Several studies have indicated that skeletal muscle is important in determining the exercise capacity of patients with chronic heart failure (CHF). However, this theory has been investigated only in experiments based on local exercise involving a small muscle mass. We investigated skeletal muscle metabolism during maximal systemic exercise to determine whether muscle metabolism limits exercise capacity in patients with CHF. We also studied the relationship between muscle metabolic abnormalities during local and systemic exercise. METHODS AND RESULTS: Skeletal muscle metabolism was measured during maximal systemic exercise on a bicycle ergometer by a combination of the metabolic freeze method and 31P magnetic resonance spectroscopy in 12 patients with CHF and 7 age- and size-matched normal subjects. We also evaluated skeletal muscle metabolism during local exercise while subjects performed unilateral plantar flexion. Muscle phosphocreatine (PCr) was nearly depleted during maximal systemic exercise in patients with CHF and normal subjects (12.5+/-0.04% and 12.3+/-0.07%, respectively, of initial level). PCr depletion occurred at a significantly lower peak oxygen uptake (peak VO2) in patients with CHF than in normal subjects (CHF, 20.2+/-3.0 versus normal, 31.8+/-3.7 mL . min-1 . kg-1, P<0. 0001). Muscle metabolic capacity, evaluated as the slope of PCr decrease in relation to increasing workload, was correlated with peak VO2 during maximal systemic exercise in patients with CHF (r=0.83, P<0.001). Muscle metabolic capacity during local exercise was impaired in patients with CHF and was correlated with capacity during systemic exercise (r=0.76, P<0.01) and with peak VO2 (r=0. 83, P<0.001). CONCLUSIONS: These results suggest that impaired muscle metabolism associated with early metabolic limitation determines exercise capacity during maximal systemic exercise in patients with CHF. There was a significant correlation between muscle metabolic capacity during systemic and local exercise in patients with CHF.

Skeletal muscle metabolism in maximal bicycle and treadmill exercise distinguished by using in vivo metabolic freeze method and phosphorus-31 magnetic resonance spectroscopy in normal men.

This study indicates that skeletal muscle metabolism may affect the results of maximal bicycle and treadmill exercise differently, and that maximal bicycle exercise was limited by quadriceps muscle metabolism rather than by cardiopulmonary capacity. In contrast, maximal treadmill exercise was not limited, eliciting more cardiopulmonary reserve and attaining greater peak oxygen uptake than maximal bicycle exercise.