Development of a direct exposure system for studying the mechanisms of central neurotoxicity caused by volatile organic compounds

Many volatile organic compounds (VOCs) used in work places are neurotoxic. However, it has been difficult to study the cellular mechanisms induced by a direct exposure to neurons because of their high volatility. The objective of this study was to establish a stable system for exposing brain slices to VOCs. With a conventional recording system for brain slices, it is not possible to keep a constant bath concentration of relatively highly volatile solvents, e.g. 1-bromopropane (1-BP). Here we report a new exposure system for VOCs that we developed in which a high concentration of oxygen is dissolved to a perfused medium applying a gas-liquid equilibrium, and in which the tubing is made of Teflon, non adsorptive material. Using our system, the bath concentration of the perfused 1-BP remained stable for at least 2 h in the slice chamber. Both 6.4 and 2.2 mM of 1-BP did not change the paired-pulse response, but fully suppressed long-term potentiation in the dentate gyrus (DG) of hippocampal slices obtained from rats, suggesting that 1-BP decreases synaptic plasticity in the DG at the concentrations tested. Our new system can be applicable for investigating the underlying mechanisms of the neurotoxicity of VOCs at the cellular level.     

ALCOHOL-RELATED SUDDEN DEATH WITH HEPATIC FATTY METAMORPHOSIS: A COMPREHENSIVE CLINICOPATHOLOGICAL INQUIRY INTO ITS PATHOGENESIS

To clarify the pathogenesis of the widely known but obscuresyndrome of sudden death with hepatic fatty metamorphosis observedin alcohol abusers, we have scrutinized both the clinical andpathological data of 11 subjects who died under such circumstancesbetween 1987 and 1993. Death followed several days of uninterrupteddrinking often with little dietary intake. The notable clinicalfeatures on arrival at the emergency room were disturbance ofconsciousness (11/11), hypotension (47/6), hypothermia (3/5),hypoglycaemia (8/11), metabolic acidosis (6/6), renal dysfunction(11/11), and hyperammonaemia (5/5). The common hepatic pathologywas the extensive appearance of numerous microvesicular fattydroplets in the hepatocytes together with varying degrees ofmacrovesicular fatty change; four subjects had an underlyingcirrhosis. Death undoubtedly results from a variety of metabolicdisturbances triggered by the combination of massive ethanolintake and starvation. The appearance of extensive microvesicularfatty change superimposed on macrovesicular fatty change wasconsidered to be an associated phenomenon     

Clonogenic Patterns of Human Pulmonary Adenocarcinoma Cell Lines (PC-9, PC-13 and PC-14) and How They Influence the Results of Test for Chemosensitivity to Cisplatin in the Human Tumor Clonogenic Assay

The clonogenic patterns of three human pulmonary adenocarcinomacell lines (PC-9, PC-13 and PC-l4) were studied by human tumorclonogenic assay (HTCA), and factors which could influence theresults of tests for the chemosensitivity of these tumor cellsto cisplatin in HTCA were determined. The results showed thateach tumor cell line had a characteristic clonogenic pattern.The time intervals for the cells to grow to the plateau phasevaried from 9 to 16 days, depending on the cell line and numberof cells plated. The number of cells plated could substantiallyinfluence the results of chemosensitivity tests. The percentageof surviving colonies increased markedly if too many cells (usually5 x 10⁴ or more/plate) were plated. For continuous exposure,the results of chemosensitivity tests were rather stable after7 days of incubation in each cell line, especially when fewerthan 2 x 10⁴ cells/plate were plated. For 1-hour exposure, theincubation periods for the results to become stable varied from7 to 16 days depending on the cell type, number of cells platedand drug concentration. It was stressed that for the correctevaluation of the chemosensitivity of cultured cell lines inHTCA, the clonogenic pattern of each tumor cell line shouldbe checked in detail before further experiments are conducted.The higher the concentration and the longer the exposure time,the more strongly cis-diamminedichloroplatinum (CDDP) suppressedthe colony growth in each of the three cell lines in HTCA, andit was recommended that CDDP should be used clinically in sucha way as to maintain a high serum level of the active form ofCDDP for a long time.     

Analysis of labour accidents in tunnel construction and introduction of prevention measures

At present, almost all mountain tunnels in Japan are excavated and constructed utilizingthe New Austrian Tunneling Method (NATM), which was advocated by Prof. Rabcewicz ofAustria in 1964. In Japan, this method has been applied to tunnel construction sincearound 1978, after which there has been a subsequent decrease in the number of casualtiesduring tunnel construction. However, there is still a relatively high incidence of labouraccidents during tunnel construction when compared to incidence rates in the constructionindustry in general. During tunnel construction, rock fall events at the cutting face area particularly characteristic of the type of accident that occurs. In this study, weanalysed labour accidents that possess the characteristics of a rock fall event at a worksite. We also introduced accident prevention measures against rock fall events.     

Renal functional measurements in young rats with chronic inhibition of nitric oxide synthase

The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: N^G-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20–80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO₂^?/NO₃^?. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-β-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-β-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.     

Natural Killer (NK) and Lymphokine-Activated Killer (LAK) Cell Activity in Healthy Volunteers with Special Emphasis on the Familial Incidence of Cancer

Natural killer (NK) and lymphokine activated killer (LAK) cellactivities in 133 healthy volunteers were analyzed with regardto the volunteer's sex, age, smoking history and the familialincidence of cancer. None of these factors had any influence on NK and LAK cell activities.It was concluded that identifying individuals with increasedrisk of cancer development by examining NK and LAK activitieswould be difficult.     

A clinical case of neuro-Behçet syndrome without mucocutaneo-ocular symptoms: Relationship with brain stem encephalitis

Abstract The case of a 50 year old man with personality changes, dementia, and brain stem symptoms is presented. Magnetic resonance imaging (MRI) disclosed high signal areas mainly in the brain stem. Both a positive skin prick test and an HLA-B51 were demonstrated. These clinical findings were suggestive of neuro-Behçet syndrome, although there were no mucocutaneo-ocular symptoms characteristically associated with this disease. The relationship between neuro-Behçet syndrome and brain stem encephalitis, including a discrimination from multiple sclerosis, is discussed.     

Induction of Fos expression following anodal polarization in rat brain

Abstract Expression of c-fos immunoreactivity was investigated in rat brain after unilateral application of a weak anodal direct current (anodal polarization) to the sensorimotor cortex of rats. Increases in Fos-immunopositive neurons were observed transiently in the neocortex, cingulate cortex, piriform cortex, and hippocampal formation, which were ipsilateral to the polarization, as a function of the duration and intensity of the currrent applied. It is likely that anodal polarization enhances the neuronal activities in the cortex dependent on polarization paradigms.     

Susceptibility genes for schizophrenia

Abstract  It is well known that genetic factors contribute to the susceptibility for schizophrenia. Recent advances in the molecular genetics of schizophrenia strongly suggest several susceptibility genes (e.g. dysbindin, neuregulin-1, DISC1, COMT, G72, RGS4 and Akt1). We discuss the evidence and biology of these genes. As glutamate transmission is especially implicated in these genes, neurobiological basis of schizophrenia might be elucidated by investigation of functional interactions between susceptibility genes for schizophrenia and the glutamatergic system.