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Discusses the prevailing view on conventional force disparity and NATO's sense of inferiority to the Warsaw Pact's numerical superiority. NATO to Warsaw Pact comparison; Analysis. INSET: In the gift horse's mouth (Israeli acquisition of Soviet tanks)..

Discusses the meeting between Secretary of State James Baker and Soviet Foreign Minister Eduard Shevardnadze that was held in late September in Jackson Hole, Wyoming. Overcoming impediments to a strategic arms reduction treaty (START); Sea-launched cruise missiles; Air-launched cruise missiles; Mobile missiles; Verification and stability; Timetables.

The article discusses modern medical case histories published between 1600 and 1900, focusing on the use of seriality by the hospital system and its use of tables. The condensing of narrative patient information into tabular form allowed for the creation of quantitive data reporting which would support rhetorical arguments. Other subjects considered include the impact of the history of printing technologies on the history of science, the development of scientific specialization, and the creation of indexes to access knowledge and information in books.

The article focuses on the science of bacteria in its golden age of 1880. On February 9, 1880, Louis Pasteur reported that he had produced a weakened or attenuated culture of microorganism of fowl cholera, which conferred immunity to the disease when inoculated in chickens. According to his principle, a first infection protects against a subsequent one. The article finally argues that, far from excluding variation, much of early bacteriology consisted in manipulating, checking and controlling variability of virulence and other bacterial properties, and that these variations were impressive enough to demand explanation through biological theory and to appear to explain, in turn, aspects of the behavior of infectious disease.

We previously reported that exposure of DiFi human colon cancer cells to the anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 resulted in apoptosis, but the mechanisms remain to be elucidated. In the present study, we investigated the effects of a panel of four anti-EGF receptor mAbs, each of which binds to different epitopes of the EGF receptor in DiFi cells, on the induction of apoptosis. We found that each of these mAbs induced apoptosis in DiFi cells. Exposure of DiFi cells to mAb 225 activated the initiation caspase-8, which was detectable between 8 and 16 h after exposure of the cells to the antibody. There was also an activation of the initiation caspase-9, which lagged a few hours behind the activation of caspase-8. Exposure of DiFi cells to mAb 225 also activated the execution caspase-3, which was accompanied temporally by evidence of cleavage of a well-characterized caspase-3 substrate, poly(ADP)ribosepolymerase (PARP). Pre-exposure of the cells to the caspase-3-specific inhibitor DEVD-CHO partially reduced the mAb 225-induced PARP cleavage and apoptosis, whereas pre-exposure of the cells to the caspase pan-inhibitor z-VAD-fmk completely inhibited mAb 225-induced apoptosis. Caspases-3, -8 and -9 were not activated in the cell lines in which mAb 225 only induced G1 phase arrest of the cell cycle. In contrast to the apoptosis of DiFi cells induced by ultraviolet irradiation, which strongly activated the c-jun N-terminal kinase-1 (JNK1) and the caspase cascade, mAb 225-induced apoptosis and activation of the caspase cascade in DiFi cells were not associated with activation of JNK1. [ABSTRACT FROM AUTHOR]

The steroid hormones estradiol, progesterone and testosterone, in addition to cortisol, inhibited stimulation of human peripheral blood lymphocytes by phytohaemagglutinin (PHA) and Con A. This effect upon lymphocyte transformation was assayed by three methods: quantitation of [³H]thymidine incorporation into acid precipitable material, microscopic assessment of blastic transformation and determination of the labelling index. Addition of steroid hormones at the initiation of culture resulted in a marked inhibition in all three parameters, which was observed with lower concentrations of cortisol than the other hormones. The inhibition was not attributable to cell death and could be partially reversed by removing hormones from the incubation medium after culture for 48-72 hr. Late addition of steroid hormones, 52 hr after addition of mitojien and 18 hr prior to pulse-labelling with [³H]thymidine, also resulted in reduced [³H]thymidine incorporation, accompanied by a nearly 50% reduction in the labelling indices and only a minimal decrease in the per cent transformed cells. Inhibition of lymphocyte stimulation by steroid hormones operates by the following cytokinetic mechanisms: (1) suppressed recruitment of cells from Go to G1 phase of the cell cycle, as indicated by the diminished per cent blasts; (2) inhibition of profession from G1 phase into S phase, as evidenced by the reduced ratio [labelling index/blasts]; and, in the case of estradiol and progesterone, (3) reduced rate of DNA replication or altered intracellutar [³H]thymidine specific activity, as shown by the decreased ([³H]thymidine incorporation/labelling index) ratio. Late addition of steroid hormones to stimulated cultures reduced the per cent of cells in S phase, but did not revert previously transformed cycling lymphocytes to the Go state. [ABSTRACT FROM AUTHOR]

Argues that typhoid policy in early twentieth-century New York City was humane but not social. Intensification of bacteriological hygiene; Choice between the individual and the social as the focus of attention; Social definition of disease and danger; Contest between the concept of powers and liberties.

Background: The expression of epidermal growth factor receptor (EGFR) and type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is associated with neoplastic transformation. By use of human renal cancer cell lines (i.e., 769-P, ACHN, A498, and SW839), we investigated the antiproliferative activity and the antitumor activity of an anti-EGFR humanized chimeric mouse monoclonal antibody, MAb C225, and a novel mixed backbone 18-mer antisense oligonucleotide, HYB 190, that targets expression of the RIalpha regulatory subunit of PKAI.Methods: The antiproliferative activity of MAb C225 and oligonucleotide HYB 190, alone or in combination, on different renal cancer cell lines was determined by monitoring cell growth in soft agar. In addition, the induction of apoptosis by treatment with the anti-EGFR antibody and/or antisense PKAI oligonucleotides was evaluated by flow cytometric analysis of fragmented DNA. The antitumor activity of MAb C225 and oligonucleotide HYB 190 was determined in athymic mice bearing established ACHN tumor xenografts. Cell proliferation and tumor growth data were evaluated for statistical significance using Student's t test; reported P values are two-sided.Results: MAb C225 and oligonucleotide HYB 190 inhibited colony formation in soft agar in a dose-dependent manner for all renal cancer cell lines tested. We observed a potentiation of growth inhibition and induction of apoptosis when 769-P cells and ACHN cells were treated with both agents. Combination treatment with MAb C225 and oligonucleotide HYB 190 caused regression of ACHN tumor xenografts, whereas single-agent treatment only delayed tumor growth.Conclusion: The combination of anti-EGFR MAb C225 and ited cooperative antiproliferative effects and cooperative antitumor effects on EGFR and PKAI-expressing human renal cancer cell lines. [ABSTRACT FROM AUTHOR]

Background: A variety of human tumors frequently express high levels of epidermal growth factor (EGF) receptor and its ligand, transforming growth factor alpha (TGF-alpha), which in some tumors is associated with poor prognosis. Monoclonal antibodies (MAbs) that block the binding of TGF-alpha or EGF to the receptor can inhibit proliferation of tumor cells that express the receptor. Studies suggest that these MAbs may enhance the antitumor effects of chemotherapy.Purpose: Our purpose was to study, in vitro and in vivo, the antitumor effects of doxorubicin in combination with anti-EGF receptor MAbs against tumor cells expressing high levels of EGF receptor. Our goal was to achieve maximum initial cytoreduction with high-dose doxorubicin in association with prolonged blockade of EGF receptor with MAbs.Methods: Anti-EGF receptor MAbs 528 (isotype IgG2a) and 225 (isotype IgG1) were used in combination with doxorubicin against cells from human A431 squamous cell carcinoma and human MDA-468 breast adenocarcinoma. Both A431 and MDA-468 cells express high levels of EGF receptors and TGF-alpha. Cultured cells were treated with doxorubicin (range, 0-10 nM) in the presence or absence of MAb 528 or 225 (range, 0-30 nM). At 48 hours, doxorubicin-containing medium was removed, and treatment with antibody was continued for 5 days, when cell proliferation assays were performed. The activity of the agents and the combinations against well-established xenografts in BALB/c nude mice was also studied. In nude mice, doxorubicin was given at doses of 50-100 micrograms/20 g body weight on 2 successive days, and MAbs 528 and 225 were given at a dose range of 0-2 mg intraperitoneally twice a week.Results: MAbs 528 and 225 both enhanced the antitumor effects of doxorubicin against A431 and MDA-468 tumor cells, producing additive growth suppression in cell cultures. MAb 528 increased the antitumor effects of doxorubicin by 32%-42%, and similar results were obtained with MAb 225. In BALB/c athymic mice, the treatment of well-established xenografts with either doxorubicin or anti-EGF receptor MAb alone temporarily inhibited growth, but the combination of both agents substantially enhanced antitumor activity over that of doxorubicin alone in A431 and MDA-468 cell xenografts. The combination treatment of mice bearing A431 xenografts resulted in tumor eradication of 40%-100% in the surviving mice in several independent experiments. The enhanced antitumor activity was dose dependent.Conclusions: Our results suggest that anti-EGF receptor MAbs substantially enhance the effects of doxorubicin against well-established xenografts of tumor cells expressing high levels of EGF receptors.Implications: Clinical trials with anti-EGF receptor MAbs are being conducted, and trials with anti-EGF receptor MAbs combined with doxorubicin are planned. [ABSTRACT FROM AUTHOR]

Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner. [J Natl Cancer Inst 83:97–104, 1991] [ABSTRACT FROM PUBLISHER]

Peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia of T cell origin (T-CLL PBL), were found to lack PHA and Con A responsiveness and to have a very poor responder activity in mixed lymphocyte cultures. In spite of the presence of la-like antigens on 36%, of the T-CLL PBL, negligible stimulator capacity in MLC was observed. Proliferation of the T-CLL PBL could be induced and maintained both by exogenous T cell growth factor (TCGF) containing PHA, and mitogen-free TCGF. In addition, restoration of the responder and stimulator capacity in MLC was obtained In the presence of mitogen-free TCGF. These results indicate that the lack of response to mitogens and alloantigens of the T-CLL PBL has to be attributed to the failure of these cells to produce TCGF upon activation. [ABSTRACT FROM AUTHOR]

Patients with Hodgkin's disease have increased numbers of spontaneously proliferating circulating lymphocytes. In order to test the relationship between this phenomenon and the in vitro mitogenic response, both spontaneous lymphocyte proliferation and the response to stimulation with phytohaemagglutinin were quantified. In addition, the proliferating lymphocytes were identified autoradiographically and characterized for the presence of lymphocyte surface markers and monocyte markers. Spontaneous thymidine incorporation by lymphocytes from patients with Hodgkin's disease was increased compared with normal controls, and the phytohaemagglutinin response was depressed. A significant inverse relationship was demonstrated between the spontaneous thymidine incorporation on day 0 and the phytohaemagglutinin response on day 3 (P < 0.01). The activated lymphocytes were heterogeneous with respect to both morphology and surface markers. These data suggest that the circulating proliferating lymphocytes in Hodgkin's disease are reactive cells and that the quantitative depression in cellular immunity demonstrable in these patients may be related to this chronic reactivity. [ABSTRACT FROM AUTHOR]