Mechanism of methylmercury cytotoxicity

Although a large number of epidemiological, clinical, and pathological studies on methylmercury intoxication have been published, these investigations have not been able to elucidate the detailed mechanisms by which the metal alkyl causes a wide variety of biological dysfunctions. Thus, the cultured cells which are free from the influence of whole body complexities, such as absorption, distribution, metabolism, etc., which complicate the interpretation of in vivo experimental results, attract the attention of many scientists who are interested in clarifying the mode of toxic action of methylmercury. The aim of this article is to review the recent studies on the toxicity of methylmercury at the cellular level and to outline the mechanisms which have been proposed to be responsible for cell injuries.     

Effects of nitrogen dioxide and ozone in combination on xenobiotic metabolizing activities of rat lungs

Male Jcl:Wistar rats were exposed continuously to 0.2 ppm ozone (O3) and 4 ppm nitrogen dioxide (NO2), alone and in combination, for 1 and 2 months to examine the effects of combined gas on the xenobiotic metabolizing systems of lung microsomes. The cytochrome P-450 content increased to 200% and 253% of the control values during 2-month exposures to O3, while it was not increased by NO2 exposures. Addition of NO2 to O3 reduced the increased level of cytochrome P-450 to 179% and 178% of the control values. The activities of cytochrome P-450-dependent monooxygenase, benzo[a]pyrene hydroxylase and 7-ethoxycoumarin O-deethylase were changed in the same fashion by exposures to NO2 and O3. The 7-ethoxycoumarin O-deethylase activity was increased to 147% and 142% of the control values by O3 exposure, whereas it was decreased to 71% and 75% of the control values by NO2 exposures. This activity was decreased to 124% and 97% of the control values by combination of O3 with NO2 after 1 and 2 months, respectively. Similarly, the benzo[a]pyrene hydroxylase activity was increased to 157% and 153% of the control values during O3 exposures, while it was not changed by NO2 exposures. Addition of NO2 to O3 reduced the activity to 140% and 115% of the control values after 1 and 2 months, respectively. The alteration of coumarin hydroxylase activity was different from those of others. This activity decreased to 44% and 29% of the control values after 1- and 2-month exposures to NO2, respectively, and was also decreased by O3 exposures. However, the magnitude of decrease was not reinforced by combination of NO2 with O3. These results indicate that an increased level of xenobiotic metabolizing activity produced by O3 exposures is lowered by combination with NO2. These phenomena may be antagonistic effects of these gases on the xenobiotic metabolizing systems of lung microsomes.     

Cerebral type of Lewy body disease

A cerebral type of Lewy body disease (LBD) is proposed. Lewy body disease was split formerly into three types: brainstem type, transitional type and diffuse type. The diffuse type is now called diffuse Lewy body disease (DLBD). These three types are characterized pathologically by the presence of a large number of Lewy bodies in the CNS. In the brainstem type, Lewy bodies are numerous in the brainstem and diencephalon nuclei, and in DLBD, a vast number are present not only in these nuclei but also in the cerebral cortex and amygdala. In the cerebral type of LBD, as many Lewy bodies are found in the cerebral cortex and in the amygdala as there are in DLBD, but only rarely are they present in the brainstem and diencephalon nuclei. Thus, this type of LBD is different from other types in that it has no parkinson pathology. Therefore, parkinsonism fails to occur throughout the whole clinical course of this disease. The existence of a cerebral type of LBD suggests that Lewy bodies occur in the cerebral cortex earlier than in the brainstem nuclei and that cortical Lewy bodies appear even when the mesocortical dopaminergic system is intact. In addition, this might explain why dementia frequently precedes parkinsonism in DLBD.     

Video-assisted thoracoscopic wedge resection of solitary pulmonary metastasis from hepatocellular carcinoma

We report a metastatic pulmonary tumor resected by video-assisted thoracoscopic surgery. A 63-year-old female was found to have four nodules of hepatocellular carcinoma (HCC) in January 1991; after non-surgical treatment, the tumors had become necrotic. In June 1992, a new HCC nodule was found. After infusion chemotherapy, it became necrotic. In September 1993, a solitary lung tumor, 2.4 cm in diameter, appeared at the periphery of the right lung. Because the tumor was considered to be a metastatic HCC rather than a primary lung cancer, it was removed by thoracoscopic wedge resection. Although whether metastasectomy contributes to prolongation of survival is still controversial, thoracoscopic pulmonary resection may be indicated for solitary peripheral metastasis, if the primary HCC is well controlled by multidisciplinary treatment.     

Quantitation and identification of human monocytic colony-stimulating factor in human serum by enzyme-linked immunosorbent assay

An enzyme-linked immunosorbent assay (ELISA) system for the quantitation of human monocytic colony-stimulating factor (hM-CSF) was established, which was based on the "dual antibody immunometric sandwich" principle using horse and rabbit polyvalent antibodies against human urinary colony-stimulating factor (CSF-HU). The minimal detectable level of hM-CSF was 10 U/mL, and the assays showed good reproducibility. As measured by this method, the average serum hM-CSF level of 20 normal adults was 540 +/- 110 U/mL (range, 300 to 800 U/mL). The peak of hM-CSF measured by ELISA was identical to that measured by bioassay when semipurified CSF-HU was fractionated by reversed-phase high performance liquid chromatography (HPLC). This method detected two types of hM-CSF, which had approximate molecular weights of 85 Kd (CSF-HU) and 45 Kd in human serum and urine; the ratio of 85:45 Kd was very high in serum and the amounts of the two types were nearly equal in urine. After anticancer chemotherapy, the serum hM- CSF level of one half of the patients with hematological malignancy was elevated according to the reduction in neutrophil number, while it was almost in the normal range in the other half of the patients, indicating the possibility that anticancer chemotherapy damaged the hM- CSF-producing cells. This ELISA method may be useful for monitoring the serum hM-CSF level after anticancer chemotherapy.     

MR imaging of dural arteriovenous malformations with ocular signs

Summary Four patients with dural arteriovenous malformation (AVMs) draining into the cavernous sinus, who presented ophthalmic manifestations, were studied by magnetic resonance (MR) imaging. In all patients signal decrease in the involved cavernous sinus was demonstrated in coronal spinecho (SE) imaging. It is attributable to rapid venous flow in the sinus, and this high velocity signal loss is a fairly pathognomonic finding in this condition. We stress the validity of MR imaging in the primary diagnosis of dural AVMs with ophthalmic symptoms.     

Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.