This study compared changes in oxygen uptake (VO), heart rate (HR), blood lactate concentration (BLa), affective valence, and rating of perceived exertion (RPE) between sessions of high intensity interval exercise (HIIE) performed on the arm (ACE) and leg cycle ergometer (LCE). Twenty three active and non-obese men and women (age and BMI=24.7±5.
View Article and Find Full Text PDFMaximal oxygen uptake (VOmax) is strongly associated with endurance performance as well as health risk. Despite the fact that VOmax has been measured in exercise physiology for over a century, robust procedures to ensure that VOmax is attained at the end of graded exercise testing (GXT) do not exist. This shortcoming led to development of an additional bout referred to as a verification test (VER) completed after incremental exercise or on the following day.
View Article and Find Full Text PDFThe aim of the EU Drugs Strategy 2013-2020 is to contribute to a reduction in drug demand and drug supply within the EU. The Strategy has so far been implemented by an Action Plan covering the period 2013-2016. This article sets out the findings of an evaluation that assesses the degree of implementation of the Strategy and the Action Plan in terms of outputs and, where possible, impacts.
View Article and Find Full Text PDFPhosphonium salts are part of a class of lipophilic cationic molecules that accumulate preferentially in mitochondria and inhibit the growth of human and rodent carcinoma cells in vitro and in animal models. The delocalized cations tested previously such as dequalinium have exhibited considerable cross resistance against multiple drug-resistant cells expressing gp 170. In order to overcome this cross resistance, we have developed two novel phosphonium salts which contain haloalkyl moieties with potential protein alkylating capabilities.
View Article and Find Full Text PDFObjective: To report on the in vitro and in vivo inhibitory effects of LH-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75; Asta Medica, Frankfurt-Main, Germany) against a panel of human ovarian carcinomas.
In Vitro Studies: the effect of SB-75 was measured using a standardized chemosensitivity assay in the following ovarian cancer cell lines: UCI 101; UCI 107; PA-1; NIH: OVCAR 3; UCLA: 222; A2780, parental; A2780-CR, cisplatin resistant; A2780-DR, doxorubicin resistant; and the human breast cancer cell line, MCF-7. Results were expressed as percent growth inhibition determined by crystal violet photometric analysis.
Objectives: Our purpose was to determine whether the sequence of rotation disciplines taken can effect medical student examination scores on the National Board of Medical Examiners Subject Exam score for obstetrics and gynecology.
Study Design: A retrospective study was conducted of 439 student files for the academic years 1987 through 1991. The final clerkship grades and subject examination scores for internal medicine, pediatrics, psychiatry, surgery, and obstetrics and gynecology were reviewed.
Due to preferential uptake and retention, the small molecular weight lipophilic, cationic antimicrobial agent dequalinium chloride (DECA) displays potent in vitro and in vivo antitumor activity against carcinoma cells. The primary mechanism of DECA activity is directed against the mitochondria where it disrupts cellular energy production. One of the direct antitumor effects of tumor necrosis factor (TNF) is also targeted against the mitochondria.
View Article and Find Full Text PDFThe shed portion of the 55 and 75 kDa membrane receptors for tumor necrosis factor (TNF) and lymphotoxin (LT) have been described in the serum of patients with cancer. This study was designed to determine whether serum levels of the 55 and 75 kDa soluble TNF/LT receptors (sTNFr) had clinical significance in patients with gynecologic malignancies. Serum samples from 79 patients with ovarian, endometrial, or cervical cancer were assayed for CA 125 levels by RIA and the 55 and 75 kDa sTNFr levels by ELISA.
View Article and Find Full Text PDFDequalinium chloride (DECA) is a cationic, lipophilic compound with structure similar to the dye rhodamine 123. DECA is selectively accumulated and retained within the mitochondria of carcinoma cells where it acts as a mitochondrial poison by blocking mitochondrial enzymes which can then disrupt cellular energy production, eventually resulting in cell death. In this manner it is similar to the antimitochondrial effects observed with tumor necrosis factor (TNF).
View Article and Find Full Text PDFDequalinium chloride (DECA), a cationic, lipophilic mitochondrial poison, selectively targets the mitochondrial membrane of certain epithelial carcinoma cells, in which it inhibits cellular energy production. It has demonstrated potency as a cytotoxic agent specific for carcinomas and may provide a novel approach for cancer therapy, either as a single agent or as an adjunct to conventional chemotherapy. The purpose of this study was to determine the toxicity of DECA in the murine model.
View Article and Find Full Text PDFA new epithelial ovarian carcinoma cell line (UCI 101) has been established from the ascitic fluids and solid tumor of a patient with progressive papillary adenocarcinoma of the ovary shown previously to be refractory to combination chemotherapy consisting of cyclophosphamide, Adriamycin, and cisplatin as well as single-agent chemotherapy of taxol and high-dose cisplatin. The UCI 101 cell line grows well with an in vitro doubling time of 24 hr. The cell line expresses the B 72.
View Article and Find Full Text PDFThe management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins.
View Article and Find Full Text PDFAm J Obstet Gynecol
February 1992
Objective: This study compares the perioperative morbidity and mortality following radical hysterectomy of patients older than 65 years with a younger age group who underwent radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma stage IB or IIA.
Study Design: A retrospective analysis of morbidity and mortality for the first 60 postoperative days was conducted. The study population of 45 women greater than 65 years of age with cervical cancer treated by radical hysterectomy was compared with a control population of 90 women less than 65 years treated similarly.
We examined the effect of levamisole (LMS) on the proliferative response and interleukin-2 (IL-2) concentration in OKT3-, phytohemagglutinin-, and concanavalin-A-stimulated lymphocyte cultures. Although proliferative response was enhanced in lymphocyte cultures stimulated in the presence of LMS, similar levels of IL-2 were observed in stimulated and unstimulated cultures. The mechanism of the enhancement effect of LMS on proliferative response was further characterized by studying its effects on the growth of IL-2-dependent CTLL-2 cells in culture.
View Article and Find Full Text PDFWe have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines.
View Article and Find Full Text PDFTo establish the histogenetic identity of the predominant cell type in monolayer cultures of normal human adult brain, eight brain specimens were placed into culture and characterized according to cell kinetics, karyotype, antigenic expression, and ultrastructural features. The protein profiles of both the cell layer and the medium were analyzed in selected cultures using sodium dodecyl sulfate polyacrylamide gel electrophoresis and diethylaminoethyl cellulose chromatography. All cultures displayed a limited life span in vitro; marked contact inhibition at confluence; a normal karyotype; an intracytoplasmic and extracellular glycoprotein profile consisting of fibronectin, procollagen type III, laminin, and collagen type IV; specialized intercellular junctions; and interstitial collagen chain synthesis.
View Article and Find Full Text PDFGrowth of the Lewis lung (LLca) tumor in BDF1 mice was found to be accompanied by a marked expansion of the multipotential stem (CFUs-8) and committed erythroid (BFUe) and myeloid (CFU-gm) progenitor cells of the marrow with a concomitant depression of more differentiated compartments. The long-term effects of adriamycin (AdR), busulfan (BU), cis-diaminedichloroplatinum II (DDP), and 5-fluorouracil (5-FU) on the LLca-induced expansion of the CFUs-8 and CFU-gm were investigated at eight weeks after drug treatment. Of the four drugs studied, only BU demonstrated a reduction of CFUs-8 at eight weeks after treatment and prior to tumor inoculation.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
November 1985
The long-term effect of adriamycin (AdR) on the radiation response of hematopoietic marrow was studied at 16 weeks after treatment with a MTD (10 mg/kg) for the BDF1 mouse. The radiation response was monitored in both the "stem cell" (CFUs-8) and myeloid (CFU-gm, granulocyte, WBC) compartments, as well as the erythroid (BFUe, CFUe, HcT) compartments of the marrow for 14 days following a whole body dose (TBI) of 4.5 Gy X ray.
View Article and Find Full Text PDFAltered haematopoiesis in the femoral marrow was observed in mice bearing the Lewis lung carcinoma (LLca). During tumour growth, a marked reduction was observed in the myeloperoxidase-positive cells (granulocytes) of the marrow 7 days after inoculation of the LLca tumour reaching a nadir (17% of control) by day 28. Accompanying this suppression of mature white cells was a gradual expansion of the CFUc-GM compartment followed by an increase in the number of femoral CFUs.
View Article and Find Full Text PDFThe long-term effects of a maximum tolerated dose of doxorubicin (ADR) (10 mg/kg, LD10/60) on the recovery of the hematopoietic compartments of the femoral marrow from radiation (450 rad) were investigated over a 32-week interval using a mouse model. Comparative radiation response curves, estimating hematopoietic proliferative potential, were used to establish response deficits (RD) for individual compartments of ADR-treated marrow. The RD data suggest that two potentially discrete lesions result from ADR treatment: one lesion associated with acute toxicity and a second developing 8-16 weeks after drug treatment.
View Article and Find Full Text PDFThe effect of the H-4-II-E2 (H4) rat tumor cell line on murine granulocyte/macrophage colony-forming units (CFU-gm) was studied in vitro using a bilayer (agar/methylcellulose) culture system over the tumor cell feeder and 10% colony-stimulating activity (CSA). The H4 cells demonstrated an amplification of CSA from several sources and of CFU-gm growth of murine marrow, including the CSA present in L-cell-conditioned medium (L-CSA; 200% of control). The amplification did not result from CSA produced by the H4 cell line, nor was cell-to-cell contact necessary for enhanced CFU-gm growth.
View Article and Find Full Text PDFCan J Genet Cytol
September 1976
Polyethylene glycol (PEG) has been utilized to induce homokaryocyte formation in avian and mammalian erythrocytes previously treated with proteolytic enzymes. PEG of molecular weight 6,000-7,5000 was found superior to 1,500 and 20,000 MW PEG. Cells exposed to protease alone, prior to PEG treatment, fused to a high degree (60-95% multinucleated cells), whereas trypsin or pepsin treatment alone allowed very little fusion (2.
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