Adv Exp Med Biol
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The myocardium is well protected against chronic hypoxia. In chronic hypoxia stroke volume falls both at rest and on exercise. The fall in stroke volume is associated with reduction in left ventricular dimensions and filling pressure. ⋯ The relative importance of different mechanisms which reduce stroke volume probably depends whether hemodynamics are measured at rest or on exercise. Intervention with sildenafil to ameliorate hypoxic pulmonary vasoconstriction is associated with both an increase in exercise capacity and stroke volume in hypoxia. Whether these have a causal association remains to be demonstrated.
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The cytotoxic RNase, Onconase (ONC), isolated from amphibian oocytes, was used to study its effect on the radiation response in A549 human NSCLC in vitro and in vivo. In cell culture studies, we found that ONC increased the radiation response by ONC-induced inhibition of O2 consumption (QO2). The occurrence of apoptosis was increased by ONC and was dependent on dosages and time exposure (measured by a Tunnel in situ cell death detection assay). ⋯ Using a non-invasive DCE-MRI technology, ONC-induced changes of perfusion were observed in A549 tumors. We concluded that the ONC-induced enhancement in tumor oxygenation was mainly due to the reduction in QO2 rather than an increase in tumor blood flow. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients.
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Patients who undergo pelvic or abdominal radiotherapy may develop side effects that can be life threatening. Tissue complications caused by radiation-induced stem cell depletion may result in structural and functional alterations of the gastrointestinal (GI) tract. Stem cell therapy using mesenchymal stem cells (MSC) is a promising approach for replenishment of the depleted stem cell compartment during radiotherapy. ⋯ In this study, we show that radiation-induced small intestinal injury may play a role in the recruitment of MSC for the improvement of tissue recovery. This work supports, the use of MSC infusion to repair damaged GI tract in patients subjected to radiotherapy. MSC therapy to avoid extended intestinal crypt sterilization is a promising approach to diminish healthy tissue alterations during the course of pelvic radiotherapy.
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We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. ⋯ On the other hand, we have developed SARS DNA vaccines that induce human neutralizing antibodies and human monoclonal antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor (angiotensin converting enzyme 2) are also under development. These vaccines are expected to induce immune responses specific for SARS CoV in human and should provide useful tool for development of protective vaccines.