Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Temperament and substance abuse in schizophrenia: is there a relationship?

Dyspnea may be easily appreciated during exercise with dyspneic scales, but methodological standardisation still needs to be specified. Authors review the basic physiological mechanism relating dyspnea to indices obtained during a stress test. They propose to use the dyspnea/VE relationship. With the concept of dyspneic threshold (close to the ventilatory threshold) and the ramp that both could be modified (for instance by rehabilitation programmes including exercise training). Interpretation of dyspnea during an exercise test obviously needs to be integrated with other parameters studied during exercise.     

An Information Security Strategy for Networkable Devices

Networkable Windows-based operating system devices present information security challenges to both vendors and users of such devices. This article highlights some of those threats and offers measures to improve the link between a firm's business strategy, its operational activities, and its information security strategy.     

A new method for seed oil body purification and examination of oil body integrity following germination

Plant seeds store triacylglycerols as energy sources for germination and postgerminative growth of seedlings. The triacylglycerols are preserved in small, discrete, intracellular organelles called oil bodies. A new method was developed to purify seed oil bodies. The method included extraction, flotation by centrifugation, detergent washing, ionic elution, treatment with a chaotropic agent, and integrity testing by use of hexane. These processes subsequently removed non-specifically associated or trapped proteins within the oil bodies. Oil bodies purified by this method maintained their integrity and displayed electrostatic repulsion and steric hindrance on their surface. Compared with the previous procedure, this method allowed higher purification of oil bodies, as demonstrated by SDS-PAGE using five species of oilseeds. Oil bodies purified from sesame were further analyzed by two-dimensional gel electrophoresis and revealed two potential oleosin isoforms. The integrity of oil bodies in germinating sesame seedlings was examined by hexane extraction. Our results indicated that consumption of triacylglycerols reduced gradually the total amount of oil bodies in seedlings, whereas no alteration was observed in the integrity of remaining oil bodies. This observation implies that oil bodies in germinating seeds are not degraded simultaneously. It is suggested that glyoxisomes, with the assistance of mitochondria, fuse and digest oil bodies one at a time, while the remaining oil bodies are preserved intact during the whole period of germination.     

Isoforms p69 and p100 of 2'',5''-oligoadenylate synthetase induced differentially by interferons in vivo and in vitro

There is no better place to test life-saving resuscitation interventions than in the prehospital setting. Patients rarely survive cardiac arrest if resuscitation techniques have failed before leaving the scene. Also, paramedics are usually very experienced in key initial resuscitative techniques, and they routinely operate under strict paramilitary protocol, resulting in better study compliance. In addition, the large study populations that are derived from emergency medical services (EMS) systems lead to faster study completion and statistically stronger data. Most important, by reinforcing standardized care, rigidly scrutinized trials improve patient care, regardless of the effect of the study intervention. The success of productive EMS research centers requires routine communication between hospital and EMS administrators and their medical directors, designation of mutually acceptable data collectors who guarantee confidentiality, reciprocal exchange of study data provided as educational seminars to the hospitals, commitments to support the budget requests of an EMS program and appropriate system modifications, inclusion of EMS personnel in study design from the very beginning, prospective education of the medical community and media before protocol implementation, an authoritative grassroots medical director, and a paramedic supervisor system.     

Molecular mechanism of base excision repair of uracil-containing DNA in yeast cell-free extracts

Base excision repair (BER) constitutes a ubiquitous excision repair mechanism, which is responsible for the removal of multiple types of damaged and inappropriate bases in DNA. We have employed a yeast cell-free system to examine the biochemical mechanism of the BER pathway in lower eukaryotes. Using uracil-containing DNA as a model substrate, we demonstrate that yeast BER requires Apn1 protein, an Escherichia coli endonuclease IV homolog. In extracts of an apn1 deletion mutant, the 5'-incision at AP (apurinic/apyrimidinic) sites is not detectable, supporting the notion that yeast contains only one major 5'-AP endonuclease. The processing of the 5'-deoxyribose phosphate moieties was found to be a rate-limiting step. During BER of uracil-containing DNA, repair patch sizes of 1-5 nucleotides were detected, with single nucleotide repair patches predominant.     

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.     

The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3

We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy.