Cytogenetic abnormalities of chromosome 9p21 are characteristic of malignant melanomas, gliomas, lung cancers and leukaemias. From a panel of 46 human malignant cell lines, we localized by positional cloning the most frequently deleted region on 9p21. Sequence analysis of the isolated fragment reveals two open reading frames identical to the recently described complementary DNA for the inhibitor of cyclin-dependent kinase 4 (CDK4). Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. One carcinoma had a deletion entirely within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line nonsense mutation. The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation.

The phase diagram of LiMn2Q over a wide oxygen pressure-temperature region was determined, and the thermodynamics of the oxygen extraction (the heat of reaction, AH, etc.) were estimated using thermal analysis, x-ray diffraction, sample quenching, and a high pressure oxygen treatment. The oxygen stoichiometry, 8, in LiMn204_+a varied with the selection of treatment conditions. The extent of the cooperative Jahn-Teller effect in the LiMn204 8 and various kinds of spinel Mn oxides are discussed in terms of the Madelung potential and Mn valency using the DV-Xa calculation. The performance of coin-type cells containing cathodes of the synthesized spinel was investigated and compared to that of cells containing standard LiMn20~ spinel cathodes.

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It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer.

A protein, isolated and purified from the unheated culture filtrate of Mycobacterium bovis BCG (substrain Tokyo 172) and designated MPB70, elicited a delayed skin reaction in guinea pigs sensitized with viable cells of BCG but not in those sensitized with heat-killed cells. The skin reaction reached the maximum 4 to 8 weeks after the inoculation of the BCG and then decreased gradually, resulting in conversion to negative after 20 weeks, whereas the skin reaction to purified protein derivative (PPD) continued to be positive. Guinea pigs immunized with viable cells of various substrains of BCG were skin tested with MPB70 and PPD. Guinea pigs immunized with the BCG substrain Tokyo 172 and the substrain Moreau (Brazil) showed strong delayed skin reactions to both MPB70 and PPD. On the other hand, guinea pigs immunized with the Pasteur substrain 1173P2, the Glaxo substrain 1077, the Copenhagen substrain 1331, the Tice substrain, or the Beijing substrain 64-42 showed negative skin reactions to MPB70, whereas they were strongly positive to PPD. In a two-dimensional acrylamide gel electrophoretic analysis of proteins from the culture filtrates of the BCG substrains, the culture filtrates of the Tokyo and Moreau substrains showed the spot of MPB70 on the gel slabs, whereas those of the other BCG substrains did not.

Summary HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 106 ml-X) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ngml-' within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-1L6 cells were transplanted into C57BL/6 mice subcutaneously, the mean ± s.d. of survival times of these mice were 33.3 ± 9.7, 34.3 ± 7.1 and 17.0 ± 3.1 days, respectively. The survival time of LLC-1L6 cells transplanted mice was significantly shorter than that of LLC (P<0.01) or LLC-Neo (P<0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-1L6 transplanted mice than in LLC transplanted mice. Mouse IL-la and mouse TNF-a were not detected in the plasma of LLC-1L6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-Ia and TNF-a in the plasma. This state may be responsible for the shortened survival of LLC-1L6 tumour-bearing mice.

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