Complete nucleotide sequence of HTLV-II isolate NRA: comparison of envelope sequence variation of HTLV-II isolates from U.S. blood donors and U.S. and Italian i.v. drug users

Seven cardiac electrophysiology stimulators from four manufacturers (Biotronik, Bloom, Digitimer and Medtronic) in common current use are reviewed. The stimulators differ in the features provided and the design adopted to achieve these features. The number of output channels ranges from one to four, the number of extra-stimuli available ranges from two to six, and these can be delivered as a variety of sequences. Some of the stimulators (Digitimer and Bloom) are modular while others (Biotronik and Medtronic 532 series) are of an integrated design comprising a single physical unit. The design of the Medtronic EP-2 has both integrated and modular characteristics. The features of the stimulators associated with input, output, control and the user interface are specifically reviewed. The features are also compared against the published recommendations of the American Heart Association. In addition, a summary of stimulator user comments from a number of electrophysiology centres is presented. All of the stimulators fulfil, or are close to fulfilling, basic electrophysiological requirements, but some provide more complex facilities such as would be required by specialist centres.     

Panic disorder in cardiac outpatients

OBJECTIVE: Continuing the long history of interest in the relation of anxiety disorders to cardiovascular function and symptoms, this study investigated the level of anxiety and prevalence of panic disorder in cardiac patients and the possible associations between specific abnormal ECG results and a diagnosis of panic disorder. METHOD: Consecutive patients referred for ambulatory ECG recordings were assessed with the seven anxiety items of the Hospital Anxiety and Depression Scale. Then, 50 patients with scores higher than 8 (the anxious group) were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version Modified for the Study of Anxiety Disorders (SADS-LA). RESULTS: Of the 50 anxious patients (26 male and 24 female) interviewed with the SADS-LA, 62% (N = 31) met the DSM-III-R criteria for panic disorder. Patients with panic disorder had a higher mean maximal heart rate and a shorter P-R interval than patients without panic disorder. Unlike the patients without panic disorder, the patients with panic disorder showed no correlation between maximal heart rate and minimal P-R interval. CONCLUSIONS: The rate of panic disorder was high in the patients referred for ECG. Moreover, the prevalence of panic disorder was similar in the patients with and without ECG abnormalities, indicating that in anxious patients the presence of panic disorder does not rule out organic cardiac disease. On the other hand, the higher maximal heart rate and shorter P-R interval of the panic patients may be attributable to hypersensitivity of beta-adrenergic receptors in panic disorder.     

Chronic hypertrophic gastropathy in a child resembling adult Menetrier''s disease

N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial.     

A major isoform of the maize plasma membrane H(+)-ATPase: characterization and induction by auxin in coleoptiles

The plasma membrane (PM) H(+)-ATPase has been proposed to play important transport and regulatory roles in plant physiology, including its participation in auxin-induced acidification in coleoptile segments. This enzyme is encoded by a family of genes differing in tissue distribution, regulation, and expression level. A major expressed isoform of the maize PM H(+)-ATPase (MHA2) has been characterized. RNA gel blot analysis indicated that MHA2 is expressed in all maize organs, with highest levels being in the roots. In situ hybridization of sections from maize seedlings indicated enriched expression of MHA2 in stomatal guard cells, phloem cells, and root epidermal cells. MHA2 mRNA was induced threefold when nonvascular parts of the coleoptile segments were treated with auxin. This induction correlates with auxin-triggered proton extrusion by the same part of the segments. The PM H(+)-ATPase in the vascular bundies does not contribute significantly to auxin-induced acidification, is not regulated by auxin, and masks the auxin effect in extracts of whole coleoptile segments. We conclude that auxin-induced acidification in coleoptile segments most often occurs in the nonvascular tissue and is mediated, at least in part, by increased levels of MHA2.     

Characterization of Rev function using subgenomic and genomic constructs in T and COS cells

The effects of extracellular Ca2+ on cytotoxicity induced by cardiotoxin (CTX), isolated from Chinese cobra venom, were investigated in cultured rabbit aortic endothelial cells (RAECs). In Hank's buffered saline solution (HBSS) containing 1.2 mM Ca2+, CTX (1-30 microM) caused cell necrosis and cell death in a concentration-dependent manner, as determined by trypan blue exclusion test performed after a 20-min CTX treatment. The concentration of CTX that caused 50% cell death was about 6.5 microM. CTX (10 microM)-induced RAEC damage was also evident but less prominent in Ca2+-free medium and almost completely prevented in medium containing 7-10 mM Ca2+. Therefore, Ca2+ appears to provoke CTX-induced injury at physiological concentrations, but protects against it at high concentrations. The protection of RAECs from CTX-induced injury could also be achieved by high concentrations of Ni2+ and Mg2+. Using the fura-2 fluorescence technique to measure the cytosolic free Ca2+ concentration ([Ca2+]i) of single RAEC, it was shown that in 1.2 mM Ca2+-containing HBSS, treatment of RAECs with 10 microM CTX for 7-35 min resulted in a tremendous and irreversible [Ca2+]i elevation, suggestive of cell membrane damage and extracellular Ca2+ entry. Ni2+ could also enter the cytosol of these damaged RAECs. However, there was no [Ca2+]i elevation or Ni2+ entry in RAECs that were preincubated in HBSS containing 7 mM Ca2+ or Ni2+ before CTX exposure. In RAECs protected with 7 mM Ca2+, the intracellular Ca2+ signals triggered by 100 microM extracellular ATP or 10 microM bradykinin in CTX-treated groups were similar to those in the untreated control groups. Taken together, the results indicate that high extracellular Ca2+ concentrations protected RAECs from CTX-induced injury, and preserved the ability of CTX-treated RAECs to generate Ca2+ signals in response to physiological stimuli.     

Comparative molecular field analysis of the antitumor activity of 9H-thioxanthen-9-one derivatives against pancreatic ductal carcinoma 03

The present study establishes correlations of in vivo growth inhibition of a solid tumor, pancreatic ductal adenocarcinoma (Panc03), of mice with the steric and electrostatic fields and the hydrophobic parameter log P of a series (32) of 1-[[2-(dialkylamino)alkyl]amino]- 9H-thioxanthen-9-ones by the 3D-QSAR method comparative molecular field analysis (CoMFA). The template molecular model was hycanthone methanesulfonate (19), the structure of which had been established previously by X-ray crystallography. The hycanthone base is protonated at the terminal nitrogen N(2), and an intramolecular hydrogen bond is present between the proximal nitrogen N(1) and carbonyl oxygen O(1) atoms. Crystallographic data also indicate a planar arrangement of bonds around N(1). However, the molecular geometry of 19, optimized by semiempirical molecular orbital methods (PM3, MNDO, AM1), showed the expected trigonal-pyramidal configuration for N(1). A comparison of MO and ab initio methods applied to a model compound, 1-amino-9H-thioxanthen-9-one, led to the selection of PM3 as the method for full geometry optimization of first the cationic and then the neutral forms of 1-32, whereas AM1 provided atomic charges for these same structures save those incorporating a sulfonamide moiety (5, 7, 20, 25, 26, 29, 31, and 32). Acceptable values for the latter were obtained from ab initio calculations. Structures were aligned by minimizing root-mean-square (rms) differences in the fitting of structures to 19 using the FIT option of SYBYL. An alternative strategy of alignment, steric and electrostatic alignment (SEAL), was invoked to provide a comparison of statistical data generated with the rms alignment. The rms-fit alignment of structures produced slightly better cross-validated and conventional r2 values than those generated with the SEAL method. In addition, the rms-fit data indicate that a shift in the lattice of one-half of its spacing has a much smaller effect on the CoMFA data for a lattice of 1 A than one of 2 A. Inclusion of log P in a CoMFA of the neutral structures effected a small (ca. 8-10%) but significant improvement in cross-validated r2 values. The relative contributions of the hydrophobic effects and the steric and electrostatic fields to the conventional r2 values were 16%, 42%, and 42%, respectively. By contrast, incorporation of frontier molecular orbital (HOMO and LUMO) energies or their gaps in the PLS analyses failed to enhance correlation coefficients derived for either the charged or uncharged compounds.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cytoplasmic tail deletion of T cell receptor (TCR) beta-chain results in its surface expression as glycosylphosphatidylinositol-anchored polypeptide on mature T cells in the absence of TCR-alpha

Surface expression of the T cell antigen receptor (TCR) in mature T cells requires the association of a variable heterodimer (alpha.beta or gamma.delta) with six invariant CD3 polypeptides (gamma, delta, epsilon-epsilon, zeta-zeta, or zeta-eta). We described here that deletion of the cytoplasmic tail polypeptide sequence (Lys-Lys-Lys-Asn-Ser) of TCR beta-chain (beta CT) results in expression of the truncated beta-chain on the surface of a mature T cell hybridoma line, in the absence of TCR-alpha, as a glycophosphatidylinositol (GPI)-anchored monomeric polypeptide. The GPI-anchored TCR-beta CT is not associated with CD3-epsilon and is incapable of conventional signal transduction. Association with TCR-alpha prevents beta CT from GPI-linkage formation. The alpha beta CT heterodimer binds the CD3 polypeptides, and the resultant TCR alpha beta CT/CD3 complex is capable of signal transduction. Our data show that a signal sequence for GPI-linkage formation is present in TCR-beta, and this alternative membrane anchoring mechanism can be utilized by beta-chain polypeptide lacking the CT sequence. We conclude therefore that in the absence of TCR-alpha expression, the beta-chain CT sequence plays an essential function in hindering GPI-linkage formation, thereby preventing escape of incompletely assembled TCR beta-chain to the cell surface of mature T cells.