The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.

Event-related potentials were recorded in 2 experiments while participants read sentences in a word-byword congruency judgment task. Sentence final words were either congruent, semantically anomalous (Experiments 1 and 2), or neutral (Experiment 2) with respect to sentence context. Half of all final words referred to concrete and half to abstract concepts. A different scalp distribution of the N400 to concrete and abstract final words was found for anomalous and neutral, but not congruent sentences. Although the interaction of context and concreteness is consistent with the context-availability model, the differential scalp distribution of effects for concrete and abstract words, as well as larger context effects for concrete words, was interpreted as being more consistent with an extended dual-code account of semantic processing.

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To determine the significance of the immunophenotypic heterogeneity of B-cell chronic lymphocytic leukaemia (CLL), surface immunoglobulins (SIgs), mouse rosette assays (MR), and a panel of monoclonal antibodies for B cells, T cells and myeloid cells were performed on peripheral blood samples from 61 newly diagnosed cases. Four groups were observed: group I (SIg+, MR+, CD19/20+, CD5+, T antigen (Ag)-; 27 cases); group II (SIg+, MR+, CD19/20+, CD5+, T Ag+; 17 cases); group III (SIg+, MR+ CD19/20+, CD5-, T AG-; 12 cases); and group IV (SIg-, MR+, CD19/20+, Cd5+, T Ag-; 5 cases). Groups were compared according to French-American-British Cooperative Group subtypes, clinical and laboratory features, Rai staging, and survival. Typical CLL morphology (greater than 90% small lymphocytes) was present in 20/20 (100%) of group I cases and 23/27 (85%) group II, III and IV cases (P = 0.09). Expression of a myeloid antigen was seen in 5/27 group I cases (18%) and 1/16 group II cases (6%), but was not predictive of survival (P = 0.36). The CD5- group III had a lower haemoglobin level (P less than 0.0001), higher Rai stage (P less than 0.002), and poorer survival at 5 years (P less than 0.02) than the other groups. We conclude that at least four distinct immunophenotypic subgroups of B-cell CLL can be determined. Expression of myeloid or T-cell antigens does not appear to predict for patient survival; however, lack of CD5 antigen may be associated with more advanced stage of disease and poor patient survival.

Summary We examined the reactivity of four p53-specific monoclonal antibodies -PAb 1801, p53-BP-12, D07 and CMI -on sections of formalin-fixed tissue collected from 245 breast carcinomas. Immunodetection of p53 varied between 37.6% and 46.6%. The greatest variation was observed among lobular carcinomas and low-grade tumours in which immunodetection varied between 8.3% and 27.3%. In contrast, immunodetection of p53 in invasive ductal carcinomas was subject to a lower degree of variability with between 40.6% and 49.7% of these tumours proving to be positive. In general, we found antibodies PAb 1801 and D07 to be the most effective in immunolocalising p53. Immunodetection of p53 with each of the four antibodies was found to correlate strongly with tumour grade. In survival analysis, the results gained using antibody PAb 1801 proved to be of greatest statistical significance and to provide the strongest index of prognosis. A significant relationship was observed between immunodetection of p53 with each of the four antibodies and poor responsiveness to endocrine therapy. In addition, relationships were also observed between p53 immunostaining and tumour oestrogen receptor (ER) (Iwaya et al., 1991; Sawan et al., 1992;Barnes et al., 1993; Yamashita et al., 1993).The p53 gene is located on the short arm of chromosome 17 and it encodes a 53 kDa nuclear phosphoprotein involved in the control of cell proliferation (Baker et al., 1989). The exact function of the p53 protein is not fully understood but it may play a role in DNA replication and regulation of transcription (Levine et al., 1991). Recent studies have shown that p53 in its 'wild' form may act as a tumour-suppressor gene (Lane and Benchimol, 1990). The precise mechanism of p53 tumour suppression is not known. Recent evidence suggests that p53 indirectly inhibits cell proliferation by regulating the transcription of other unidentified genes (Kern et al., 1992). The p53 gene has been found mutated and/or deleted in a wide range of tumours (Mulligan et al., 1990;Levine et at., 1991). Functional inactivation of the p53 gene by mutation or allelic loss appears to be one of the commonest genetic abnormalities in human cancer (Lane, 1992

Isolates of Staphylococcus aureus (106) from bovine mastitis were tested for susceptibility to antimicrobial agents. beta-lactamase was produced by 69.8 per cent of isolates and 7.5 per cent were resistant to streptomycin (minimum inhibitory concentration more than 32 micrograms/ml). Resistance to other agents was rare. Intrinsic resistance or tolerance to beta-lactam antibiotics was not found.

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A wastewater‐treatment facility at Ford (Dearborn, Michigan) was recently upgraded from chemical de‐emulsification to ultrafiltration (UF) followed by a membrane‐biological reactor (MBR). This paper describes the design, startup, and initial operational performance of the facility. Primary findings are as follows: (1) the MBR proved resilient; (2) the MBR removed approximately 90% of chemical‐oxygen demand (COD) after primary UF; (3) the removal of total Kjeldahl nitrogen by MBR appeared to be more sensitive to operating conditions than COD removal; (4) nitrification and denitrification were established in one month; (5) the MBR removed oil and grease and phenolics to below detection levels consistently, in contrast to widely fluctuating concentrations in the past; (6) permeate fluxes of the primary and MBR UF were adversely affected by inadvertent use of a silicone‐based defoamer; and (7) zinc concentrations in the effluent increased, which might have been a result of ethylenediaminetetraacetic acid used in membrane washing solutions and/or might have been within typical concentration ranges.