Efficacy of Lung Cancer Screening; Comparison of Results from a Case-Control Study and a Survival Analysis

A case-control study to evaluate the efficacy of lung cancer screening conducted by us showed that lung cancer screening may reduce the mortality of the disease up to 28%. Assuming this efficacy is unbiased, and that the screening rate is 51.6%, which was observed in the control group in the above study, the number of lung cancer deaths prevented by screening in the study period was calculated to be 47 for males and females combined. In the same study population, screen-detected lung cancer patients (N = 207) in the same study period were followed and the 7-year survival rate (46.9%) was compared to the 5-year survival rate (11.3%) obtained by the Osaka Cancer Registry, in which screen-detected lung cancer patients were only 1.8%. The number of lung cancer deaths prevented by screening, estimated by the difference in the above two survival rates, was 74 (95% confidence interval; 55–93). The number of lung cancer deaths prevented by screening estimated from the case-control study was significantly lower than that estimated from the survival analysis. This indicates that the efficacy of lung cancer screening estimated by the case-control study was within the range that could be explained by the actual long-term survivors among the screen-detected patients in the study population.     

Clinico-pathological aspects of a residual natal tooth: a case report

A Japanese girl was referred to Osaka University Dental Hospital for examination of a tooth-like structure that had erupted following spontaneous exfoliation of a natal tooth in the lower left primary central incisor region. The structure had erupted at 6 months of age, and radiographic and clinical examination showed composition of pulp and dentin, but no enamel. On histological examination, the majority of the dentin area had a tubular dentin-like appearance, while the outer area of the root appeared to be composed of an osteodentin-like substance. Most of the dentin was covered by cementum. These findings suggest that the structure had originated from a developing remnant of the extracted natal tooth, which must have remained in the gingival tissues. We termed this calcified structure a residual natal tooth.     

Central motor and sensory conduction in X-linked recessive bulbospinal neuronopathy.

Central conduction was studied in 12 patients with X-linked recessive bulbospinal neuronopathy (XBSN) using percutaneous electrical cortical, cervical and lumbar stimulation and somatosensory evoked potentials (SEPs). The central motor conduction time from the motor cortex to the cervical and lumbar segments of the spinal cord was normal in XBSN. SEPs, however, were abnormal or central sensory conduction time was prolonged in patients with XBSN. These results are consistent with the clinicopathological findings of XBSN in which the primary sensory neurons are involved as well as the lower motor neurons in the CNS, whereas the upper motor neurons are well preserved.     

Dorfin localizes to the ubiquitylated inclusions in Parkinson's disease,dementia with Lewy bodies,multiple system atrophy,and amyotrophic lateral sclerosis

In many neurodegenerative diseases, the cytopathological hallmark is the presence of ubiquitylated inclusions consisting of insoluble protein aggregates. Lewy bodies in Parkinson's disease and dementia with Lewy bodies disease, glial cell inclusions in multiple system atrophy, and hyaline inclusions in amyotrophic lateral sclerosis (ALS) are representative of these inclusions. The elucidation of the components of these inclusions and the mechanisms underlying inclusion formation is important in uncovering the pathogenesis of these disorders. We hypothesized that Dorfin, a perinuclearly located E3 ubiquitin ligase, participates in the formation of ubiquitylated inclusions in a wide range of neurodegenerative diseases. Here, we report that affinity-purified anti-Dorfin antibody labeled ubiquitylated inclusions of Parkinson's disease, dementia with Lewy bodies disease, multiple system atrophy, and sporadic and familial ALS. A double-immunofluorescence study revealed that Dorfin shows a distribution pattern parallel to that of ubiquitin. Furthermore, by a filter trap assay, we detected that Dorfin is present in the ubiquitylated high-molecular weight structures derived from these diseases. These results suggest that Dorfin plays a crucial role in the formation of ubiquitylated inclusions of alpha-synucleinopathy and ALS. However, because we failed to show the direct binding of alpha-synuclein with Dorfin, future investigations into the binding partner(s) of Dorfin will be needed to deepen our understanding of the pathophysiology of alpha-synucleinopathy and ALS.     

Low uptake of [H]2-deoxy-d-glucose by cultured rat Schwann cells

[³H]2-Deoxy-d-glucose (2-DG) was used to investigate the glucose uptake in cultured rat Schwann cells from postnatal Sprague-Dawley rat sciatic nerves. The glucose uptake of Schwann cells slightly increased in a time- and dose-dependent manner. However, the maximal uptake level was much lower than that of ethylnitrosourea (ENU)-induced transformed rat schwannoma-like cells and fibroblasts. By autoradiography of the cultured system, we were able to visualize the accumulation of [³H]2-DG grains in the schwannoma-like cells and fibroblasts, but not in Schwann cells.     

Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death

We generated transgenic mice that expressed a highly expanded 239 polyglutamine (polyQ) repeat under the control of the human androgen receptor promoter. These transgenic mice developed progressive neurological phenotypes of muscular weakness and ataxia, small body size and short life-span. PolyQ nuclear inclusions (NIs) were remarkable and widespread but found in selective regions of the central nervous system (CNS) such as the spinal cord, cerebrum and cerebellum as well as in selective peripheral visceral organs. This distribution pattern resembled that of spinal and bulbar muscular atrophy somewhat, but was more widespread. In neuronal tissues, NIs were present in astrocytes as well as neurons. Cytoplasmic and axonal inclusions were not observed. In the CNS regions with abundant NIs, neuronal populations were well-preserved, and neither neuronal cell death, reactive astrogliosis nor microglial invasions were detected. These findings suggest that polyQ alone can induce the neuronal dysfunction that precedes gross neuronal degeneration and provides a clue for investigating molecular mechanisms that underly the pathway to neuronal dysfunction from polyQ expansion.