Reflectivity and spectral shift from laser plasmas generated by high-contrast, high-intensity KrF laser pulses.

The energy and spectrum of the reflected 248 nm radiation are studied from solid targets up to 1.15 × 1018 W cm-2 intensity. The experiments used the 700 fs directly amplified pulses of the KrF system which was cleaned from prepulses with the new Fourier-filtering method providing 12 orders of magnitude temporal contrast. Increasing the intensity from 1015 W cm-2 results in increasing absorption up to more than 90% above 1018 W cm-2. This is accompanied by increasing x-ray conversion exhibiting a less steep power law dependence for low-Z matter than for gold. Strong blue shift of the reflected radiation from the backward propagating plasma was observed. It is shown that in the case of KrF laser pulses of highest contrast, vacuum heating can be one of the dominant absorption mechanisms. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

Next Generation Driver for Attosecond and Laser-plasma Physics.

The observation and manipulation of electron dynamics in matter call for attosecond light pulses, routinely available from high-order harmonic generation driven by few-femtosecond lasers. However, the energy limitation of these lasers supports only weak sources and correspondingly linear attosecond studies. Here we report on an optical parametric synthesizer designed for nonlinear attosecond optics and relativistic laser-plasma physics. This synthesizer uniquely combines ultra-relativistic focused intensities of about 1020 W/cm2 with a pulse duration of sub-two carrier-wave cycles. The coherent combination of two sequentially amplified and complementary spectral ranges yields sub-5-fs pulses with multi-TW peak power. The application of this source allows the generation of a broad spectral continuum at 100-eV photon energy in gases as well as high-order harmonics in relativistic plasmas. Unprecedented spatio-temporal confinement of light now permits the investigation of electric-field-driven electron phenomena in the relativistic regime and ultimately the rise of next-generation intense isolated attosecond sources.

Analysis of thymidine kinase activity and glucocorticoid-binding capacity in the thymuses of healthy and tumor-bearing chickens.

Thymidine kinase activity in the lymphoid organs of healthy and tumor-bearing chickens was studied after hydrocortisone or dexamethasone treatment. Glucocorticoid hormones (10 mg/100 g body wt) administered twice in 48 hours resulted in an 80% decrease in thymidine kinase activity in the thymuses of healthy chickens, whereas birds with transplantable MC 29 chicken hepatoma failed to respond to the hormones. In the bursae of Fabricius of healthy or tumor-bearing chickens, thymidine kinase activity did not change considerably after administration of hydrocortisone or dexamethasone. The steroid-binding capacity in cellfree systems prepared from thymuses of tumor-bearing birds was significantly decreased. Thus the difference in steroid-binding capacity between thymuses of healthy and tumor-bearing chickens correlated well with, and could account for, the failure of hydrocortisone and dexamethasone to reduce the thymidine kinase level in tumor-bearing birds.

Homologies between a brain-specific identifier (ID) sequence and regions of Harvey murine sarcoma virus and Rous sarcoma virus genomes. Putative role of identifier sequences in the tissue specificity of malignant transformation by RNA tumor viruses.

As a step toward understanding of the tissue specificity of cellular transformation by RNA tumor viruses were looked for the presence of a putative brain specific regulatory (identifier) sequence (C82B) in the genome of various oncornaviruses. The genomes of Harvey murine sarcoma virus and Rous sarcoma virus contain sequences flanking the viral oncogenes with greater than 80% and greater than 60% homology to C82B, respectively. We suggest that identifier sequences acquired by oncoviruses may determine the potential target cells of malignant transformation after virus penetration.

Antiviral activity of phorbol myristate acetate and possible relationships with interferon action.

Signal-induced turnover of membrane phospholipids represents a fundamental transducing mechanism that induces a signal cascade resulting in mobilization of calcium, activation of protein kinase C by diacylglycerol, release of arachidonic acid and stimulation of cyclic GMP production. In this pathway tumor-promoting phorbol esters such as phorbol myristate acetate (PMA) may substitute for diacylglycerol. The interferon-like antiviral effect of PMA described here suggests that the inositol phospholipid-diacylglycerol-protein kinase C signal-transducing mechanism may be involved in interferon action.

Inositol phospholipid turnover and protein kinase C translocation are stimulated by poly(I).poly(C) in human amnion cells (UAC).

Polyinosinic-polycytidylic acid, a potent inducer of inducer of interferon (IFN) production and activator of some IFN-induced enzymes, inhibits [3H]uridine incorporation into the RNA of vesicular stomatitis virus even in the absence of IFN synthesis, transiently triggers the breakdown of inositol phospholipids and activates the translocation of protein kinase C. Since IFNs also have similar activities these results suggest that IFN induction and IFN function are realised through common biochemical pathways.

Interferon (IFN)-like antiviral effect is induced by unspecific cross-linking of cell surface receptors.

Treatment of human amniotic cells (UAC) with Cytodex 1 (DEAE-dextran) results in the development of an antiviral state of the cells, as proven by studying (i) the cytopathic effect and (ii) [3H]uridine incorporation into the RNA of vesicular stomatitis virus (VSV) after VSV infection. The same treatment transiently triggers the breakdown of inositol phospholipids and activates the translocation of protein kinase C (PKC). On the basis of these data it can be suggested that cross-linking of cell surface receptors by a solid carrier bearing covalently bound positive charges may result in IFN-like effects.

Phospholipase C and phospholipase A2 are involved in the antiviral activity of human interferon-alpha.

Treatment of human amniotic cells (UAC) with human interferon-alpha (Hu-IFN alpha) or phorbol myristate acetate (PMA) resulted in translocation of protein kinase C (PK-C) activity from the cytosol fraction to that of the membranes. Analysis of 32P incorporation into phospholipid fractions and studies of alterations in fatty acid content for the major phospholipids of IFN-treated cells suggest that phospholipases C and A2 are activated by Hu-IFN alpha. Addition of neomycin (an inhibitor of phospholipase C), as well as mepacrine (an inhibitor of phospholipase A2) to IFN-treated cells inhibited the antiviral activity of Hu-IFN alpha in the vesicular stomatitis virus (VSV)-UAC system used. These observations indicate that (i) activation of PK-C and (ii) diacylglycerol formation, arachidonic acid and/or lysophosphatidylcholine release are important steps in the mechanism of action of IFN.

Sulfhydryl groups generated by macrophages into the culture medium.

Previous data showing that thiols can functionally replace macrophages in certain in vitro lymphocyte reactions have raised the possibility that macrophages generate SH groups in the medium. The SH activity of cell-free medium decreases considerably due to auto-oxidation. The presence of macrophages inhibited the spontaneous decrease of SH activity and even increased the number of free SH groups in the culture media. This was designated as SH generation. Resident as well as in vivo stimulated (NaIO4, thioglycollate medium, paraffin oil or BCG) macrophages have nearly the same capacity to generate SH groups when cultured in vitro. The SH-generating ability of macrophages depends on the viability and density of cells, and is greatly influenced by the serum concentration of the media. The majority of SH groups produced by macrophages could be demonstrated as albumin SH groups and proved to be more resistant to autooxidation than non-protein thiols. Moreover albumin could replace whole serum in respect of SH generation. It is suggested that macrophages by generating SH activity, may exert a non-specific helper function to lymphocytes or other cells in their environment.

Association between HLA B7, DR2 and dysfunction of natural- and antibody-mediated cytotoxicity without connection with the deficient interferon production in multiple sclerosis.

In this study, 133 patients with MS were investigated for HLA-A,B,C,DR antigens, natural killer (NK) cell activity, and antibody-mediated cytotoxicity (ADCC). A higher frequency of HLA B7 and DR2 was found in this group of patients than in the healthy control group, as can be observed in other caucasoid populations as well. In Gypsies living in the same geographic area, almost a complete absence of the disease was observed, corresponding to a lack of B7; however, HLA DR2 was present in 56% of this population. NK activity and ADCC measured against the K-562 tumor cell line was found to be significantly lower in MS patients, most pronounced in the group of male patients. Interferon augmentation of NK activity showed similar impairment in the patient group, and their lymphocytes produced a significantly lower amount of interferon. A correlation was demonstrated between both killer cell function and HLA B7, DR2 in MS patients, however, it was significant only in the case of ADCC and DR2. No other correlations were found in relation to interferon augmentation, interferon production, and HLA antigens. The above finding underscores a possible HLA-linked pathogenetic role of NK and K cell dysfunction in MS. This is consistent with other, similar observations that a possible defect in virus immunity may exist in MS patients.

Interactions of glucocorticoids and heparin on the humoral immune response of mice.

Interactions of glucocorticoids and heparin on the humoral immune response of mice to SRBC have been studied. Heparin injected subcutaneously in a depot-form 2 hours before immunization restores the antibody-forming ability of mice immuno-suppressed by hydrocortisone, through pretreatment of mice only with heparin 3 days before immunization decreases the PFC-count in the spleen. Cortisone (ip) and heparin (sc) per se injected at about the time of immunization with suboptimal doses of SRBC resulted only in a slight stimulating or no effect on spleen PFC count and serum antibody level. Cortisone and heparin applied in combination, however, exerted a stimulatory effect on the humoral immune response to SRBC. The route of steroid administration pointed to the significance of macrophages in this phenomenon. As the cooperative effect of heparin + cortisone on the humoral immune response shows a good correlation with their cooperative effect on in vivo (3H)dThd incorporation and thymidine kinase activity of spleen, it was hypothesized that an in vivo mitogenic activity for the spleen cells was responsible for the adjuvant effect observed.

A kinetic study of glucocorticoid-heparin interaction on the in vivo DNA-synthesis of mouse lymphatic organs.

The effect of glucocorticoids and heparin (in depot form) on the DNA-synthesis of thymus and spleen of mice was investigated by measuring (3H)dThd incorporation in a four day period. The kinetics of glucocorticoid action was similar whether the hormones were applied in 11 beta-hydroxy-, or keto-form and was characterized by a suppressive effect with a maximum on the first two days after administration. The suppressive effect of glucocorticoids proved to be more marked in the thymus than in the spleen. Heparin per se did not change thymidine incorporation into the lymphoid organs, but injected 3 hours prior steroid administration inhibited the suppressive effect of cortisone, but not that of hydrocortisone. In addition, heparin even reversed the suppressing effect of cortisone on splenic (3H)dThd uptake. The effects of heparin on glucocorticoid action could be only observed when the steroid was applied intraperitoneally. This observation and other data discussed suggest the involvement of peritoneal cells (macrophages) in glucocorticoid-heparin interactions on DNA-synthesis of lymphoid organs.

A solid phase reverse transcriptase micro-assay for the detection of human immunodeficiency virus and other retroviruses in cell culture supernatants.

A simple and rapid solid-phase reverse transcriptase assay was developed based on the use of poly(rA):oligo(dT)12-18 as template primer immobilized on DEAE cellulose paper squares to detect human immunodeficiency virus (HIV) and/or other retroviruses in cell culture supernatants. It was found that PEG (per se) -up to 4% concentrations (w/v)--did not inhibit reverse transcriptase activity. Optimal conditions of the assay were determined. This solid-phase technique is much faster and more convenient than the methods described previously.

The efficacy of long term thyrostatic treatment in elderly patients with toxic nodular goitre compared to radioiodine therapy with different doses.

The objective of the study was to investigate the efficacy of long term thyrostatic versus radioiodine treatment of hyperthyroidism in old age. Our study is a retrospective analysis of the therapeutical outcome in 66 patients over 60 years of age with toxic nodular goitre. The patients were divided in two groups: Group A: 28 patients on methimazole treatment: starting dose 5-30, median (M) 10 mg, maintenance dose 2.5-15 (M = 5) mg, follow up 6 to 240 months (M = 23.5 months). Group B: 38 patients treated by either 100-300 MBq (N = 14, subgroup B1) or 325-1000 MBq (N = 24, subgroup B2) 131I, follow up: 18 to 156 months (M = 48 months). The efficacy of the different therapeutical approaches were compared by calculating the occurrence rate of persisting and relapsing thyroid dysfunctions and associated side effects. The 28 patients on methimazole treatment became euthyroid after 1-16 (M = 5) months but numerous relapses occurred in the follow up: hyperthyroidism, clinical: 5, subclinical 13, (relapse duration: M = 8 months; associated symptoms: hypertension in 4, cardiac arrhythmia in 3, cerebral embolism in 1, angina pectoris in 2, weight loss in 2 cases). Poor patient's compliance (9/28) or dose reduction by the physician (5/28) were the main causes of the relapses. Transient clinical (3 cases) or subclinical (6 cases) hypothyroidism also occurred (duration: 1-3 M = 2 months, no clinical symptoms). In 7 out of 14 (50%) patients receiving 100-300 MBq 131I (Group B1) hyperthyroidism persisted (versus 4/24 -16.7%- in Group B2 following 325-1000 MBq 131I; chi2(1) = 4.78 P = 0.028), methimazole treatment had to be continued in 9/14 patients (64.3%) (versus 5/24 -20.8%)- in Group B2., chi2(1) = 7.18 P = 0.0074) and in 5/14 (35.7%) the radiotherapy had to be repeated (versus 5/24 -020.8%- in Group B2, not sign.). Our conclusions are: 1) long term thyrostatic treatment is not safe in elderly patients with toxic nodular hyperthyroidism, mainly because of poor compliance or dose reduction by the physician; 2) radioiodine treatment as the first choice should be recommended for these patients and higher doses should be preferred.

Non-local-thermodynamical-equilibrium effects in the x-ray emission of radiatively heated materials of different atomic numbers.

X-ray self-emission of radiatively heated materials with different values of Z has been investigated. Thin foils were uniformly heated by a 120-eV Hohlraum radiation of 400-ps duration in order to study the self-emission of a homogeneous, optically thin material. The x-ray emission spectra were followed for more than 2 ns. The spectrally integrated emission shows not only a strong Z dependence, but different temporal behaviors for different values of Z. The lower is the value of Z of the x-ray heated matter, the longer is the duration of self-emission. Theoretical comparison with a hydrocode and FLY post-processing shows a non-local-thermal equilibrium behavior caused by direct photoionization due to the thermal pumping radiation, which has a higher brightness temperature than the matter temperature of the heated material.

Enhanced take of spontaneous murine tumors in mice treated with inhibitors of macrophage and/or NK cell function.

Both macrophages and NK cells have been suggested to play a role in recognizing and eliminating early, in situ neoplasms. Therefore we studied the effect of inhibitors of macrophage and/or NK cell function on the take of transplantable spontaneous murine tumors in syngeneic mice. The treatment of animals with trypan blue, a selective inhibitor of macrophage function, decreased considerably the period of latency of BSP3 adenocarcinoma; however, it did not increase the take of SP4, SP82 and SP84 adenocarcinomas. The treatment of recipients with neutral red, a selective inhibitor of NK cell function, enhanced the take of SP4 adenocarcinoma. The treatment of mice with agents depressing both macrophage and NK cell function (silica or carrageenan) decreased the both macrophage and NK cell function (silica or carrageenan) decreased the period of latency and/or increased the take of SP4, SP82 and SP84 adenocarcinomas. Carrageenan or a combined treatment with both trypan blue and neutral red also enhanced the take of BaF1, a benzo(a)pyrene-induced fibrosarcoma. We concluded that both macrophages and NK cells may function as effector cells of an antitumoral surveillance system.

Immunodiffusion analysis of the antigenic structure of the transplantable MC 29 tumor.

By the use of specific anti-chicken liver sera it could be proved with immunodiffusion techniques that the transplantable MC 29 tumor line contains liver-specific antigens. Production of chicken serum-proteins by the tumor could also be demonstrated. Thus, the transplantable MC 29 tumor line can be regarded as a hepatoma.

Ethanol-induced signal transducing mechanism associated with a transient antiviral state in human amniotic cells.

Short-term effects of ethanol on human amnion cells were investigated by studying the cellular signaling processes and the replication of vesicular stomatitis virus. Treatment of human amniotic cells with ethanol transiently triggers the breakdown of inositol phospholipids, stimulates intracellular [Ca2+]i mobilization and activates the translocation of protein kinase C. Activation of this signal transduction mechanism is associated with the development of an antiviral state, as proven by studying 3H-uridine incorporation into the RNA of vesicular stomatitis virus. Induction of the antiviral state in human amniotic cells correlates with the solubility of the alcohols in the lipid membrane of the cells.

Nuclear factor 1 (NF-1) binding sites in the genomes of human oncoviruses: a hypothetic role for reintegrated cellular origins of replication in malignant transformation.

We have found that genomes of human T cell leukemia-lymphoma virus type I (HTLV-I), BK virus (BKV), and a hepatitis B virus (HBV) DNA sequence integrated into DNA of a hepatoma-derived cell line contain binding sites for nuclear factor 1 (NF-1), a cellular protein which binds to adenoviral and putative cellular origins of DNA replication. We suggest that cellular origins of DNA replication acquired by oncoviruses may play a role in malignant transformation after reintegration into the cellular genome by providing new targets for cellular factors initiating DNA replication and by perturbing the temporal order of replication.

Homologies between small nuclear RNAs and LAV/HTLV-III sequences and their possible role in the cytopathic effect of the virus.

The mechanism of action of LAV/HTLV-III resulting in a pronounced cytopathic effect is still unknown. We demonstrate that the long terminal repeat (LTR) sequence and env gene of LAV/HTLV-III contain regions of 70-80% homology and/or complementarity with regions of small nuclear (sn) RNAs U1 and U2. On this basis, we hypothesize that the cytotoxic effect of LAV/HTLV-III is due - at least partly - to the inhibition of processing of cellular hnRNAs by competing for splice junction sites and/or by complexing with U1 and especially U2 RNAs.