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.     

Differential Expression of Subspecies of Polyomavirus and Murine Leukemia Virus Enhancer Core Binding Protein, PEBP2, in Various Hematopoietic Cells

The core sequence of the enhancer of murine leukemia virus (MuLV) long terminal repeat is highly conserved in a large number of MuLV strains and appears to play an essential role when SL3-3 or Moloney strains induce T cell lymphoma in mice. We found by using the electrophoretic mobility shift assay that a polyomavirus enhancer core-binding protein, PEBP2, bound to this core motif of MuLV. We also noted that PEBP2 in several hematopoietic cell lines derived from B lymphocyte, macrophage and myelocyte lineages migrated significantly faster than the authentic PEBP2 detected in NIH3T3 (ibroblasts. Interestingly, PEBP2 detected in the cell lines of T lymphocyte lineage appeared to contain both types, which were indistinguishable in electrophoretic mobility from those of NIH3T3 and of B lymphocyte, macrophage and myelocyte lineages. The treatment of the nuclear extract containing PEBP2 with phosphatase generated PEBP3, which is a subcomponent of PEBP2 and retained the same DNA-binding specificity as PEBP2. The altered mobility of hematopoietic cell-derived or T lymphocyte-derived PEBP2 was found to be due to the alteration of the mobility of PEBP3. Based on the distinct mobility of PEBP2/3 of T lymphocytes from those of other hematopoietic cells, we discuss the implication of PEBP2 in MuLV-induced T cell leukemia and T cell-specific gene expression.     

Strain Difference of Susceptibility to 4-Nitroquinoline 1-Oxide-induced Tongue Carcinoma in Rats

Strain difference of susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced squamous cell carcinomas of the tongue among Dark-Agouti, Long-Evans, Sprague-Dawley, ACI/Ms, Fischer 344, Donryu and Wistar/Furth rats was surveyed by evaluating the survival times, incidences and sizes of developed tumors as markers of susceptibility. Administration of 4NQO dissolved in drinking water induced squamous cell carcinomas in various sites of the upper digestive tract mucosa of all the experimental male and female rats of the seven strains. Regarding the mean survival times, Wistar/Furth rats survived much longer than any other strain of rats, and Dark-Agouti showed the shortest survival. The incidence of large, mass-type carcinomas of the tongue of Dark-Agouti rats was higher than in any other strain of rats, while that of Wistar/Furth rats was the lowest. Subsequently the mitotic activity and bromodeoxyuridine incorporation in the tongue epithelium of Dark-Agouti and Wistar/Furth rats were estimated after a short-term administration of 4NQO. There was a pronounced difference between the two strains of rats, because the proliferative responses of the tongue epithelium of Dark-Agouti rats to the 4NQO stimulation were much higher than those of Wistar/Furth rats. These results indicated that there are marked differences in the susceptibility to 4NQO-induced tongue carcinoma among the seven strains of rats, and that Dark-Agouti and Wistar/Furth rats could be useful as models of highly and poorly susceptible strains, respectively, for further genetic analysis.     

Cell-killing Activity and Kinetic Analysis of a Novel Antitumor Compound NC-190, a Benzo[a]phenazine Derivative

A novel antitumor compound, N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190), was evaluated for antitumor activity in vitro against cultured tumor cell lines, and the kinetics of cell killing was elucidated. NC-190 strongly inhibited the growth of all of 3 murine tumor cell lines, 7 human tumor cell lines and 2 normal cell lines. With continuous exposure, the 50% inhibition concentrations were in the range of 0.005–0.06 μg/ml, except for KATO-III (2.15 μ g/ml). By colony-forming assay, concentrations of NC-190 giving 90% cell kill (IC₉₀) at various exposure times were obtained with HeLa S3 cells. The plot of IC₉₀exposure time on a log-log scale was linear for NC-190 with a slope of -1, which is typical for cell cycle phase-nonspecific agents. A 2 h treatment with NC-190 induced a rapid reduction in cell viability at doses of more than 3 μ g/ml. At the dose where colony formation was completely inhibited, cell viability was persistently reduced to below 20% during the cell culture period. NC-190 cauced a dose- and time-dependent reduction in DNA synthesis. The inhibitions of RNA and protein synthesis were less than that of DNA synthesis. Spectroscopic studies of NC-190 mixed with calf thymus DNA demonstrated that NC-190 was capable of interacting with DNA. However, DNA thermal denaturation studies suggested that intercalation of NC-190 was weak in comparison with those of classical intercalating drugs.     

Notes on the use of low magnification telescopes in low vision care

Several areas related to the use of telescopes in low vision are reviewed. These include: contrast sensitivity function; eccentric viewing through a telescope; field of view; telescope used in reverse; and IOL-spectacle lens telescopic systems. Experimental data are included to support selected clinical observations routinely made by low vision clinicians.     

Cortical Distribution of Eeg Activity for Component Processes During Mental Rotation

Alpha power (8–12 Hz) was monitored over the frontal, temporal, parietal and occipital lobes of the left and right cerebral hemispheres while participants mentally rotated three-dimensional shapes to match a specified target. By comparing the activational patterns generated during three experimental conditions, each designed to systematically isolate the involvement of the various subcomponents comprising this mental rotation task, it was suggested that the right frontal lobe mediates encoding and comparison/decision processes, while the left parietal and the left temporal region appear most involved in the generation of images and their mental rotation. A preliminary model describing the cooperative interaction of these cortical regions during mental rotation tasks is proposed.     

Aggressive behaviour in elderly psychiatric inpatients.

We describe the types of aggressive behaviour and determine their prevalence in a sample of hospitalized elderly psychiatric patients. Data were obtained by nurse ratings of aggressive behaviour using the recently developed Rating Scale for Aggressive Behaviour in the Elderly; 90 patients were rated over a 3-d period. Nearly half the sample were at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries and the use of restraints and medication for aggressive behaviour were low. Some correlates of the aggressive behaviour were also analysed.     

Autoradiographic Analysis of Radiolabeled Anti-carcinoembryonic Antigen Monoclonal Antibody CEA102 in Colorectal Cancer Using Computed Radiography

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with ¹³¹I-labeled intact CEA102 or its F(ab')₂. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of ¹³¹I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.     

Preparation and Characterization of a Murine Monoclonal Antibody (MDR3M) Reactive with mdr3 Gene Product

A murine monoclonal antibody (MDR3M) (isotype: IgM) reactive with mdr3 gene product was generated by immunizing mice with mdr3 -specific peptide (H₂N-¹²WRPTSAEGDFELGISSKQKRKKTKTVKMI⁴¹G-COOH) and hybridizing the primed mouse splenic B cells with X63-Ag8,6.5.3 mouse plasmacytoma cells. MDR3M did not cross-react with mdr1 gene product. This monoclonal antibody may be useful for analyzing the role of mdr3 gene product in cells and tissues.