67Ga scanning in the evaluation of esophageal carcinoma.

Eighty-nine patients with histologically proved esophageal carcinoma were scanned with 67Ga to screen for extramural tumor extension and lymph-node involvement. Radiation dose and reduction of uptake were correlated. 67Ga accumulation indicated extramural extension with a sensitivity of 67% and a specificity of 93%. Marked uptake in an extraprimary site in the mediastinum or upper abdomen indicated lymph-node involvement with a sensitivity of 27% and a specificity of 100%. Irradiation with more than 20 Gy (2,000 rad) reduced uptake (P less than 0.05). 67Ga scanning appears to be useful in the evaluation of esophageal carcinoma.     

Carcinogenesis in tissue culture. 13. Binding of 4-nitroquinoline 1-oxide- 3 H to nucleic acids and proteins of L-P3 and JTC-25-P3 cells

The effect of a chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO), on two mammalian cell strains of tissue culture was investigated with special reference to its binding to macromolecular constituents of cells by the use of cell strains L.P3, a substrain of L-929 mouse fibroblasts, and JTC-25.P3, a substrain of rat liver cells transformed by Nagisa culture. Both substrains have been cultivated in a protein-free synthetic medium. Population-dependent inhibition of growth by 4NQO was detected. This was due to the population-dependent incorporation of the carcinogen into cells, i.e. the lower the population density in a culture vessel, the higher was the amount of carcinogen incorporated into cells, resulting in the amplification of the inhibitory effect. On addition to culture medium, 4NQO-³H was readily incorporated into the cold acid-soluble pool of cells attaining the maximum within 30 min. This labelling value, however, gradually decreased during a few hours, more than 90% being metabolized and excreted into the medium. On the other hand, the binding of 4NQO-³H to the cold acid-insoluble macro-molecular fraction rapidly reached the maximum within 30 min and was kept unreleased for several hours. On removal of the carcinogen from the medium, the value of the bound label decreased with a half-life time of about 5 h. In binding to cellular proteins the carcinogen was found to have bound uniformly to every fraction of various soluble proteins but it was released from each fraction with a half-life of approximately 5 h, as revealed by the fractionation on Sephadex G-100 columns. Three successive additions of 4NQO-³H to the medium brought about the binding of the carcinogen to tRNA, DNA and rRNA, molar ratios of the carcinogen to 10,000 nucleotides of each nucleic acid fraction being 2.6, 3.3, and 5.3, respectively. In 24 h of recovery incubation, specific activities in these nucleic acid fractions decreased to 27.4%, 39.1% and 22.0%, respectively.     

Protective effects of melatonin against low- and high-LET irradiation

To investigate the protective effects of melatonin against high-LET ionizing radiation, V79 Chinese hamster cells were irradiated with 100 keV/microm carbon beam. Parallel experiments were performed with 200 kV X-rays. To avoid the impact from extra solvents, melatonin was dissolved directly in culture medium. Cells were cultured in melatonin medium for 1 hr before irradiation. Cell inactivation was measured with conventional colony forming assay, medium containing 6-thioguanine was used for the selection of mutants at hprt locus, and the cell cycle was monitored by flow cytometry. Both carbon beam and X-rays induced cell inactivation, hprt gene mutation and cell cycle G2 block dose-dependently. But carbon beam showed stronger effects as indicated by all three endpoints and the relative biological effectiveness (RBE) was 3.5 for cell killing (at 10% survival level) and 2.9 for mutation induction (at 5 x 10(-5) mutants/cell level). Melatonin showed protective effects against ionizing radiation in a dose-dependent manner. In terms of cell killing, melatonin only increased the survival level of those samples exposed to 8Gy or larger of X-rays or 6 Gy or larger of carbon beam. In the induction of hprt mutation and G2 block, melatonin reduced such effects induced by carbon beam but not by X-rays. The results suggest that melatonin reduces the direct interaction of particles with cells rather than an indirect interaction. Further studies are required to disclose the underlying mechanisms.     

Frequent immune response to a melanocyte specific protein KU-MEL-1 in patients with Vogt-Koyanagi-Harada disease

AIM: To isolate autoantigens possibly involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS: Autoantigens recognised by immunoglobulin G antibodies (IgG Ab) in sera from VKH patients were isolated by screening the lambda phage cDNA libraries made from melanocytes and a highly pigmented melanoma cell line with the patients' sera. Presence of IgG specific for the autoantigens in sera from patients with various panuveitis and healthy individuals was evaluated. Relation between the specific IgG and various clinicopathological features was examined. RESULTS: KU-MEL-1 was found to be one of the 81 isolated positive clones representing 35 distinct genes, which is a previously isolated melanoma antigen preferentially expressed in melanocytes. The IgG Ab specific for KU-MEL-1 was detected in sera from patients with VKH in significantly higher amounts than in sera from patients with Beh?et's disease, sarcoidosis, and from healthy individuals. Positive serum KU-MEL-1 Ab was significantly associated with HLA-DRB1*0405 and male VKH patients. CONCLUSION: KU-MEL-1 was identified as a new autoantigen for VKH. The highly frequent induction of IgG Ab for KU-MEL-1 in HLA-DRB1*0405 positive VKH patients may suggest the possible involvement of KU-MEL-1 specific CD4(+) T cells in the pathogenesis of VKH, suggesting the possible use in the development of diagnostic and therapeutic treatments for VKH patients.     

Taraxasterane- and ursane-type triterpenes from Nerium oleander and their biological activities

Two new taraxasterane-type triterpenes, 20beta,28-epoxy-28alpha-methoxytaraxasteran-3beta-ol (1) and 20beta,28-epoxytaraxaster-21-en-3beta-ol (2), were isolated from an ethyl acetate extract of the leaves of Nerium oleander, together with ursane-type triterpenes, 28-nor-urs-12-ene-3beta,17beta-diol (3) and 3beta-hydroxyurs-12-en-28-aldehyde (4). The structures of 1 and 2 were established on the basis of their spectroscopic data. Anti-inflammatory activity of 1-4 was examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1). Cytotoxic activity of 1-4 was evaluated against four human cell lines, A-549, WI-38, VA-13, and HepG2 cells.     

Is ulnar variance suitable for a parameter of Colles' fracture pre-operatively?

BACKGROUND: To evaluate ulnar variance (UV) as a parameter for Colles' fracture as a measure of the true length of the distal radius pre-operatively, we measured UV pre-operatively in 20 patients with Colles' fractures being treated surgically using the method of perpendiculars. Because the distal fragment is by definition dorsi-flexed, the dorsal edge of the most distal part of the radius is seen proximally and the volar edge of it is seen distally on true postero-anterior x-ray of the wrist. METHODS: We measured three different UVs in x-rays. UVd is the distance from the dorsal edge of the distal radius to the distal end of the ulnar head. UVv is the distance from the volar edge of the distal radius to the distal end of the ulnar head. We calculated UVc using lateral x-ray of the wrist at the midpoint of the lunate fossa to describe the true length of the distal radius. We compared UVd with UVv or UVc in 20 patients as well as in 11 patients who had dorsal tilt over 15 degrees. RESULTS: UVv was -3.8 +/- 2.5 mm (average+/-SD). UVd was 2.2 +/- 2.4 mm. UVc was 1.7 +/- 2.2 mm. Statistically, there was a significant difference between UVv and UVd (p < 0.0001). There was no statistically significant difference between UVd and UVc. However, in 11 cases with dorsal tilt over 15 degrees, UVd was 2.2 +/- 2.8 mm and UVc was 1.1 +/- 2.7 mm. There was a statistically significant difference between both groups (p = 0.003). CONCLUSIONS: The length of the distal radius can be described by measuring UVd pre-operatively in Colles' fracture patient in general. However, the true length of the distal radius can not be described by measuring UVd pre-operatively in cases with marked dorsi-flexion of the distal fragment.