Oxidants are released directly from smoke and also as a result of the airways inflammation that occurs after smoke injury. We determined the relation between the degree of tissue oxidant change with the use of malondialdehyde content to measure lipid peroxidation and the degree of lung and systemic organ damage and resulting damage mortality 24 hours after a controlled smoke exposure in a rat model. We also monitored changes in the key tissue antioxidant catalase. We found that the degree of lung lipid peroxidation and the decrease in catalase activity directly correlated with mortality caused by respiratory failure and with the degree of lung inflammation but that they did not correlate with the peak carboxyhemoglobin level, a marker of smoke gas phase exposure. The lung oxidant changes also directly correlated with increased systemic lipid peroxidation and decreased catalase in liver and kidney tissue. We conclude that the initial smoke insult causes lung and in turn systemic inflammation with resulting release of oxidants, which leads to tissue oxidant injury. The degree of lung oxidant change significantly correlates with the degree of lung tissue injury, respiratory failure, and mortality, and the major source of the oxidant changes is tissue inflammation rather than oxidants in the smoke itself.

Animals↗

PubMedDate not supplied

Selective expression of Ser 199/202 phosphorylated tau in a case of frontotemporal dementia.

We examined a 65-year-old patient with clinicopathological features that met the criteria of frontotemporal dementia (FTD), particularly frontal lobe degeneration (FLD). He came from a family with concentrated occurrence of dementia symptoms in the presenium. Neuropathological examination disclosed brain atrophy locally pronounced on the frontotemporal lobes with characteristic neuronal loss, microvacuolation and astrocytic gliosis. There were no pathological hallmarks such as senile plaques, Pick bodies (PBs), achromatic cells and neurofibrillary tangles. Precise separation of FTD from Pick disease (PD) and motor neuron disease with dementia (MNDD) has not yet been established, and they are included in one spectrum. Antibodies against paired helical filament tau protein demonstrated immunopositive cytoskeletal structures within the neurons as well as the glial cells in the brain of the present case. They were selectively stained with tau 199/202 but not tau 396, which were provided newly to recognize phosphorylation at Ser 199/202 or Ser 396 in tau, respectively. We investigated tau pathology in the present case in comparison to 8 cases with PD that were clinicopathologically confirmed. Neither tau 199/202 nor tau 396 stained the CNS structures in PD cases with few PBs, while both stained evidently those as well as PBs in PD cases associated with many PBs; so that the present case could be distinguished from PD on the basis of the immunoreactivity to site-specific phosphorylated tau. Our result suggests that FTD, especially familial FLD type might involve unique tau pathology, no matter whether FLD is a distinct entity from PD, or a variant form in the wide FTD spectrum including PD and MNDD and other related disorders.

Adult↗

PubMedDate not supplied

Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments.

It has been reported that many tau sites in neurofibrillary tangles (NFT) are abnormally phosphorylated. We investigated the phosphorylation of tau in the hippocampus of nondemented patients and Alzheimer's disease patients by immunostaining with five site-specific antibodies against phosphorylated tau. In the pretangle stage, tau in neuropil threads was phosphorylated at serines 199, 202 and 409, numbered according to the longest human tau isoform, whereas tau in some neuronal soma was phosphorylated at serines 199, 202, 409 and 422. Tau at the stage of NFT was phosphorylated at serine 396 and threonine 231 in addition to serines 199, 202, 409 and 422. In the advanced stage, tau in ghost tangles was phosphorylated mainly at serine 396. These results suggest that the phosphorylation of each site in tau differs among the maturing stages of neurofibrillary change and that abnormal phosphorylation of tau in the neuronal soma occurs at 199, 202, 409 and 422 earlier than at threonine 231 and serine 396.

Adult↗

PubMedDate not supplied

Voided urine cytology of papillary renal cell carcinoma and renal calculus: report of a case with emphasis on the importance of cytologic screening in high-risk individuals.

BACKGROUND: Preoperative diagnosis of cases of renal calculus complicated with papillary renal cell carcinoma (RCC) by image analysis is usually difficult. CASE: A 50-year-old man who had a past history of renal calculus suffered from macrohematuria and abdominal pain for one month was admitted to our hospital. Ultrasonographic examination revealed a 4-cm tumor shadow in the right kidney; it was hypovascular in arteriography. Papillary cell clusters with abundant cytoplasm were found by the cytologic examination of voided urine. Their nuclei were oval and situated eccentrically in the cytoplasm. The nuclear/cytoplasmic ratio was increased. Fine, granular chromatin was distributed evenly, and the nuclear membrane was thin and nearly smooth. Several small nucleoli were evident. All these findings were indicative of a diagnosis of papillary RCC. Histology of nephrectomy specimens confirmed the diagnosis. CONCLUSION: Voided urine cytology can be useful for screening and follow-up of patients with papillary RCC.

Carcinoma, Papillary↗

PubMedDate not supplied

Hetrazepine PAF antagonists.

Hetrazepines such as WEB-2086 or WEB-2170 are potent, specific, competitive PAF antagonists binding at the same site as the PAF molecule. Despite their structural similarity to known hypnotic drugs they lack hypnotic actions. They almost certainly bind not only cell-surface but also intracellular PAF receptors, which may explain their activity in disease models in which adherence of neutrophils or other cell types to the vascular endothelium plays a role.

Animals↗

PubMedDate not supplied

Effect of nizofenone on experimental head trauma in mice.

The therapeutic effect of nizofenone, a cerebroprotective drug, on experimental traumatic head injury was investigated in mice. The animals under halothane anaesthesia were subjected to a severe concussive head trauma and their neurological status was assessed by a string grip-test for 6 consecutive days. The neurological function of the control groups fell markedly 1 hr after trauma and slowly recovered day by day, but some animals failed to restore to the normal level, even on the 6th day. The post-treatment of the head-injured mice with nizofenone (3 mg/kg/day, i.p.) significantly improved the neurological function. The neurological improvement by nizofenone was dose-dependent and a significant amelioration was observed at 0.3 mg/kg/day. Methylprednisolone (30 mg/kg/day, i.v.) did not exert any significant neurological improvement in this therapeutic, experimental condition. In this study, nizofenone treatment was found to beneficially influence the recovery of the neurological function, maybe by reducing the progress of brain injury following head trauma.

Animals↗