Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant

Simian immunodeficiency virus (SIV) induces an immunodeficiency syndrome similar to human AIDS. Although the disease course of SIV-induced immunodeficiency is generally measured in months to years, a disease syndrome that results in death in 5 to 14 days has been described in pig-tailed macaques infected with the SIVsmmPBj (PBj) strain. The purpose of this study was to derive an acutely lethal PBj molecular clone in order to study viral genes involved in pathogenesis. Six infectious molecular clones were generated; acutely fatal disease was induced by experimental inoculation of pig-tailed macaques with virus stocks derived from either of two clones, PBj6.6 or PBj14.6. Molecular chimeras were constructed by exchange of regions of the genome of PBj6.6 and a nonlethal, related clone, SIVsmH4. Only a chimera expressing the PBj genome under the control of a SIVsmH4 long terminal repeat induced death soon after inoculation. These studies suggest that multiple viral genes of PBj are critical for development of acute disease. More specifically, the env gene but not the long terminal repeat PBj was required for acute disease induction; however env must act in concert with another gene(s) of the PBj genome.     

Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer

Serum anti-p53 antibodies (p53-Abs) may be surrogate markers for both p53 alterations and preclinical cancer. Ancillary to a prospective trial to abate progressive development of clinical stages of chronic obstructive pulmonary disease, we conducted a retrospective, nested case-control study. Twenty-three cases were diagnosed with cancer during the trial. Enzyme immunoassay, immunoblotting, and immunoprecipitation were used to detect p53-Abs in serum, immunohistochemistry (IHC) to detect p53 accumulation, and single-strand conformation polymorphism and DNA sequencing to detect p53 mutations in tumor samples. p53-Abs were detected by three types of assays in five (23%) of the cancer patients, 80% of whom had detectable p53-Abs before diagnosis: 2 lung cancers (7 and 6 months before), 1 prostate cancer (11 months), and 1 breast cancer (5 months). Four Ab-positive patients had IHC-positive tumors. Two of 4 Ab-positive patients and 2 of 14 Ab-negative had p53 missense mutations or base pair deletion and IHC-positive tumors. The 44 noncancer COPD controls, matched with the cancer cases for age, gender, and smoking habits, were negative for p53-Abs. These results indicate that p53-Abs may facilitate the early diagnosis of cancer in a subset of smokers with chronic obstructive pulmonary disease who are at an increased cancer risk.     

Choice of metal ion and formulation concentration for first-pass brain perfusion studies with magnetic resonance imaging at 1.5 tesla

RATIONALE AND OBJECTIVES: Gadolinium (Gd) and dysprosium (Dy) analogues, chelated with HP-DO3A, were compared at both 0.5- and 1.0-mol/L concentrations for efficacy in first-pass brain studies on magnetic resonance (MR) imaging at 1.5 tesla (T). METHODS: Ten healthy cats were examined with a dose of 0.3 mmol/kg, using two concentrations of each agent (0.5 mol/L and 1.0 mol/L, 20 examinations). Gadolinium-HP-DO3A (gadoteridol or ProHance) or Dy-HP-DO3A was injected at 9 mL/second, with acquisition of 64 sequential steady-state free precession (SSFP) images at a rate of one each 0.6 second. RESULTS: The change in white matter signal intensity, at the peak of the first pass of the contrast agent bolus in the brain, was -231 +/- 68 for the 0.5-mol/L formulation of Gd-HP-DO3A, compared with -267 +/- 57 for the 1.0-mol/L formulation. Using the 0.5-mol/L formulation of Dy-HP-DO3A, the change at peak was -318 +/- 42, a result statistically improved compared with both the 0.5-mol/L (P < 0.02) and 1.0-mol/L (P < 0.04) Gd-HP-DO3A formulations. A further improvement was observed with the 1.0-mol/L Dy-HP-DO3A formulation, with the change being -368 +/- 33. CONCLUSIONS: First-pass brain MR studies at 1.5 T are improved by use of higher concentration Gd chelate formulations (1.0 versus 0.5 mol/L) and by substitution of the Dy ion for the Gd ion in the chelate. Injection of higher-concentration formulations results in higher initial arterial metal ion concentration. Incomplete blood mixing on transit during first pass causes the higher initial concentration, which then results in a greater susceptibility effect on imaging. The superiority of the Dy formulation compared with the Gd formulation is anticipated because of the higher magnetic moment of Dy. The curves for tissue signal intensity versus time during first pass return artifactually to near baseline after Gd chelate injection (when SSFP imaging techniques are used), a differentiating feature from results with the Dy chelate. This difference can be explained by a substantial T1 effect of the Gd chelate, despite acquisition of images that are predominantly susceptibility weighted.     

Experience in using ultrasonic and laser therapy in surgical diseases

Experience is presented gained with the use of ultratonotherapy, low-intensity laser radiation of infrared actions, and a number of drug electrophoreses in the treatment of 358 surgical patients over 1994-1996. A complex of combinations of different techniques common in physiotherapy has been designed with those of drug therapy during different phases of surgical disorders. Methods and complexes of the therapy treatments to be administered are submitted together with relevant indications. The proposed variants of complex physiotherapy make for earlier recovery, shorter treatment courses, longer remission.     

DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies

This review summarizes reports of recurrent DNA sequence copy number amplifications in human neoplasms detected by comparative genomic hybridization. Some of the chromosomal areas with recurrent DNA copy number amplifications (amplicons) of 1p22-p31, 1p32-p36, 1q, 2p13-p16, 2p23-p25, 2q31-q33, 3q, 5p, 6p12-pter, 7p12-p13, 7q11.2, 7q21-q22, 8p11-p12, 8q, 11q13-q14, 12p, 12q13-q21, 13q14, 13q22-qter, 14q13-q21, 15q24-qter, 17p11.2-p12, 17q12-q21, 17q22-qter, 18q, 19p13.2-pter, 19cen-q13.3, 20p11.2-p12, 20q, Xp11.2-p21, and Xp11-q13 and genes therein are presented in more detail. The paper with more than 150 references and two tables can be accessed from our web site http://www.helsinki.fi/lglvwww/CMG.html. The data will be updated biannually until the year 2001.     

Summary of a symposium on natriuretic and digitalis-like factors

An international symposium on natriuretic and digitalis-like factors was convened for the first time since 1992. Topics discussed included structures and biosynthesis of endogenous digitalis-like factors (EDLF), biologic activities, physiology function and role of EDLF in hypertension, and novel natriuretic factors. Progress was reported in determining the exact structure of an isomer of ouabain isolated from bovine hypothalamus. Evidence was presented supporting the existence of a second mammalian EDLF that resembles steroids found in toads (bufodienolides). Support for endogenous synthesis of mammalian EDLF was also presented. Mammalian EDLF were reported to have effects which are different from those possessed by digitalis like steroids derived from plants. New evidence was presented implicating EDLF in various forms of hypertension in humans and animal models. Finally, several unique natriuretic factors that do not inhibit Na, K ATPase and that appear to play a role in mammalian volume regulation were discussed.