The expression of CD4 and CD8 molecules conditions the behavior of V beta + murine thymocytes upon superantigenic challenge

We investigated the capacity of the Staphylococcal enterotoxin (SE) B, a superantigen (SAg) specific for TCR V beta domain, to modulate V beta 8+ thymocytes selection in adult mice. Thymocytes were collected at various time intervals after SEB injection (10 and 100 micrograms) and V beta 8+ modulation was analysed by three color flow cytometry. SEB failed to affect V beta 8+ thymocytes comprised in the less mature compartments, namely, CD4+8+ and CD4-CD8-, whereas it selectively affected V beta 8+CD4+8+ (downward modulation) and V beta 8+CD4-8+ thymocytes (upward modulation). The different response to SEB challenge between CD4+8- and CD4-8+ thymocytes appeared dependent on the CD4/MHC class II interaction, as V beta 8+CD4-8+ thymocytes carrying a transgenic CD4 molecule capable of interacting with MHC class II showed the same response of V beta 8+CD4+8- thymocytes. At variance with thymocytes, however, V beta 8+CD4+8- and V beta 8+CD4-8+ splenic T lymphocytes responded to SAg challenge in identical manner (upward modulation) highlighting the importance of maturation status and/or microenvironment in SAg response. V beta 8+ thymocytes remaining in the thymus were assessed for their capacity to respond to a SAg challenge. Thus, thymocytes were obtained at various time intervals after SEB injection and cultured in the presence of SEB or SEA, a Sag specific for V beta 10 as control. A reduced mitotic response to SEB but not to SEA was noticed irrespective of the number of V beta 8+ responding cells present in culture. It is concluded that SAgs affect TCR specific thymocytes by conditioning their redistribution and inducing an anergic status.     

Comorbidity of drug dependence and other mental disorders: a two-phase study of prevalence at outpatient treatment centres in Italy

The proposed mechanism of action of the antineoplastic drug 3-nitrobenzothiazolo[3,2-alpha]quinolinium chloride (NBQ-2) involves its interaction with DNA by intercalation and inhibition of topoisomerase II activity by arresting the enzyme in a covalent cleavage complex. In an attempt to identify some structural determinants for activity and develop a molecular structure/cytotoxicity correlation, four new structural analogs of the antitumor NBQ-2 were prepared and their cytotoxic activity and DNA binding properties were investigated. The cytotoxic activity was evaluated against six different human tumor cell lines: U937, K-562, HL-60, HT-29, HeLa, and A431. The results showed that these new drugs elicit pronounced cytotoxic effects against U937, K-562, HL-60 and A431 while HeLa and HT-29 were less sensitive to the new drugs. This apparent selectivity was different to that of m-AMSA, a drug currently used for cancer treatment. Since the interaction of NBQ-2 to DNA by intercalation has been proposed as the initial step leading to its antineoplastic activity, DNA binding and changes in DNA contour length induced by the new NBQ-2 structural analogs were also investigated using calf thymus and human DNA. The drug, 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-alpha]quinolinium chloride (NBQ-59) was the most cytotoxic agent of the analog series (IC50 = 16 microM for HL-60 cells), however, it demonstrated the weakest binding to DNA (Kint = 0.9 x 10[5] M-1 for calf thymus DNA). NBQ-59 was also found to be a poor intercalator into the DNA double helix. Therefore, our results suggest that DNA binding is not the primary mechanism of drug action for this family of compounds. In addition structural determinants important for cytotoxicity of the benzazolo quinolinium chlorides were suggested by our results. In particular, the nitro group in the 3 position does not seem to be necessary for bioactivity, while substitutions in the benzazolo moiety have striking effects on the biological activity of the drugs.     

Incisional hernia after laparoscopic nephrectomy with intact specimen removal: caveat emptor

The choline-containing phosphoglycolipid, MfGL-II, is the major polar lipid of Mycoplasma fermentans PG18. Anti-MfGL-II antisera raised in rabbits using the purified MfGL-II as an immunogen were employed in immunogold electron microscopic and immunofluorescence studies showing that MfGL-II is uniformly distributed and exposed on the cell surface of M. fermentans cells. The specificity of the antibodies was determined by immunostaining of lipid extracts separated by thin layer chromatography. The antibodies recognize lipids specific to M. fermentans but did not cross-react with lipid extracts of M. penetrans, M. capricolum, M. gallisepticum or Acholeplasma laidlawii. As phosphocholine almost completely abolished antibody interaction with MfGL-II in an ELISA assay it is suggested that the anti-MfGL-II repertoire is composed primarily of anti-phosphocholine antibodies. The anti-MfGL-II antisera inhibit the attachment of M. fermentans to Molt-3 lymphocytes suggesting that MfGL-II plays a major role in M. fermentans-host cell interaction.     

Balloon dilatation in acute myocardial infarct in routine clinical practice: results of the register of the Working Society of Leading Cardiologic Hospital Physicians in 4,625 patients

Balloon angioplasty as the treatment of first choice in the setting of an acute myocardial infarction (AMI) is gaining widespread acceptance because of favourable results from specialised centres concerning high patency rates and low mortality. This study reports the results of angioplasty for AMI at large community hospitals during 1992-1995. 4625 procedures were performed at 68 centres of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhaus?rzte (ALKK). The age of the patients was 60.8 +/- 11.3 years, with 75.1% men. The infarct related artery was the left anterior descendent in 43%, the right coronary artery in 37%, the circumflex artery in 16%, a bypass graft in 2.3% and the left main stem in 1.4% of patients. The success rate (residual stenosis < 50%) of the intervention was 86%. There was a wide range of procedures per centre, with a median of 40 AMI angioplasties per year and centre. The amount of angioplasties for AMI in relation to all angioplasties performed during this period rose from 5.2% in 1992 to 5.9% in 1995 (p = 0.01). Local complications at the puncture site occurred in 3.2%, with the need for a surgical intervention in 1.1% of patients. In 273 (5.9%) of the patients a second angioplasty was performed during the hospital stay. Aortocoronary bypass surgery was performed in 3% of the patients. Hospital mortality was 9.5% (438/4625 patients). The mortality rate remained constant during the years investigated (1992: 10.6%; 1993: 8.6%; 1994: 9.7%; 1995: 9.8%; p = ns). Higher mortality was observed in older patients, patients with multiple vessel disease, the left anterior descending artery or a bypass graft as infarct related artery as well as in patients with failed reperfusion (residual stenoses > 50%). Hospitals with a case load of more than 40 angioplasties for AMI per year showed a lower mortality as compared to the others. In clinical practice at large community hospitals results of angioplasty for AMI concerning mortality, complications and technical success rate are comparable to those of highly specialised centres. The absolute numbers of angioplasties for AMI increased constantly over the years.     

Circuit analysis of an ultrafast junction mixing scanning tunnelingmicroscope

A lumped element circuit model for the operation of a junction mixing scanning tunneling microscope (JM-STM) is presented. Fits from this model show excellent agreement with experimental results in the picosecond time regime. The tip sample capacitance employed in the model was calculated to be 33 fF, using the method of images. By varying the capacitance, various tip/sample geometries can be investigated. Testing the response of the model tunnel junction, for faster electrical pulses, suggests how the JM-STM can be pushed into the femtosecond time regime     

Synchronisation of hyperchaotic oscillators

The authors present three different examples demonstrating the possibility of synchronising hyperchaotic oscillators via a single variable     

Peptide YY inhibition of rat gastric enterochromaffin-like cell function

The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency.     

In vitro mutagenesis of PH-20 hyaluronidase from human sperm

The cDNA encoding PH-20 hyaluronidase from human sperm has been mutated at five positions by in vitro mutagenesis. We have changed three acidic amino acids and two arginine residues that are conserved in the sequence of mammalian PH-20 polypeptides as well as in the hyaluronidases from bee and hornet venom. Of the former, the mutants [Gln113]PH-20 and [Gln249]PH-20 had no detectable enzymatic activity; the mutant [Asn111]PH-20 had about 3% activity. The mutant [Thr252]PH-20 was also inactive, while [Gly176]PH-20 had only about 1% activity. This indicates that the PH-20 hyaluronidases, like numerous enzymes that hydrolyze glycosidic bonds, have acidic amino acids in their active site. Moreover, for the binding of the substrate, the polyanion hyaluronan, arginine residues appear to be essential.