Combined aerobic and resistance training improves physical and executive functions in women with systemic lupus erythematosus.

Objectives: Exercise is considered as an adjuvant therapeutic modality to alleviate symptoms of several rheumatic diseases. However, data regarding the benefits of exercise to patients with systemic lupus erythematosus (SLE) are relatively scant.

Methods: This study aimed to assess the effects of regular, moderate-intensity, aerobic exercise combined with resistance training on women with SLE who had no regular exercise.

Vernonia patula (Dryand.) Merr. and Leucas chinensis (Retz.) R. Brown exert anti-inflammatory activities and relieve oxidative stress via Nrf2 activation.

Ethnopharmacological Relevance: Vernonia patula (Dryand.) Merr. and Leucas chinensis (Retz.

Haemophilia B curative FIX production from a low dose UCOE-based lentiviral vector following hepatic pre-natal delivery.

The ubiquitous chromatin opening element from the human HNRPA2B1-CBX3 housekeeping gene locus (A2UCOE) is able to provide stable and cell-to-cell reproducible levels of transgene expression regardless of target cell genome integration site with efficacy demonstrated in adult, embryonic and induced pluripotent stem cells and their differentiated progeny in vitro and in vivo. Here we evaluate the ability of A2UCOE-based lentiviral vectors to confer stable expression following pre-natal delivery in mice. Our results show stable post-natal A2UCOE-eGFP and A2UCOE-luciferase lentiviral vector presence in both the liver and haematopoietic system with concomitant persistence of expression demonstrating efficient transduction of both fetal hepatocytes and haematopoietic stem cells.

Calorimetric and Spectroscopic Analysis of the Thermal Stability of Short Duplex DNA-Containing Sugar and Base-Modified Nucleotides.

Base- and sugar-modified analogs of DNA and RNA are finding ever expanding use in medicine and biotechnology as tools to better tailor structured oligonucleotides by altering their thermal stability, nuclease resistance, base-pairing specificity, antisense activity, or cellular uptake. Proper deployment of these chemical modifications generally requires knowledge of how each affects base-pairing properties and thermal stabilities. Here, we describe in detail how differential scanning calorimetry and UV spectroscopy may be used to quantify the melting thermodynamics of short dsDNA containing chemically modified nucleosides in one or both strands.

Association of sleep duration and insulin resistance in Taiwanese vegetarians.

Background: Short sleep duration has been reported to associate with increased insulin resistance. However, no studies have investigated whether such association exists in vegetarians. The aim of this study was to investigate the association between sleep duration and insulin resistance in Taiwanese vegetarians.

Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells.

Pharmacological targeting of individual ErbB receptors elicits antitumor activity, but is frequently compromised by resistance leading to therapeutic failure. Here, we describe an immunotherapeutic approach that exploits prevalent and fundamental mechanisms by which aberrant upregulation of the ErbB network drives tumorigenesis. A chimeric antigen receptor named T1E28z was engineered, in which the promiscuous ErbB ligand, T1E, is fused to a CD28 + CD3ζ endodomain.

RU486-inducible recombination in the salivary glands of lactoferrin promoter-driven green fluorescent Cre transgenic mice.

When compared with the many tamoxifen-activated Cre mouse lines available for gene manipulation studies, relatively few RU486-inducible Cre mice are in use, due to leakiness issues. Here, we report the generation of an RU486-inducible triple fusion gene (GCrePR1e), consisting of green fluorescent protein, Cre, and the progesterone receptor ligand-binding domain (F642-L901). We sought to improve the GCrePR1e by selecting a truncated human lactoferrin (Lf) promoter to drive its expression, based on the promoter's low basal activity and innate sensitivity to RU486.

Detection of experimentally induced pulmonary granuloma inflammation in monocyte chemoattractant protein-1 reporter mice.

Purpose: Among different chemokines, monocyte chemoattractant protein-1 (MCP-1) plays an important role in inflammatory disorders of lung. In response to stimuli, MCP-1 increases its transcription as an immediate early gene. In this paper, we describe the MCP-1-enhanced green fluorescent protein(EGFP) transgenic mouse in which EGFP expression is driven by human MCP-1 promoter and mimics the MCP-1 expression in situ.

Death From Liver Disease and Development of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection: A Prospective Study.

Patients with chronic hepatitis B virus (HBV) infection are at risk for death from complications of liver disease and development of hepatocellular carcinoma (HCC). To identify the time course and risk factors associated with these events, we conducted a prospective study in chronic hepatitis B patients referred to our clinic. From January 1989 to March 1998, 400 hepatitis B surface antigen (HBsAg)-positive patients were classified into three categories: inactive carriers (N=110), chronic hepatitis (N=151), and cirrhosis (N=139).

A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon alpha-2a in adenocarcinoma of the large bowel.

We have reported that increasing the length of infusion from 5 min to 1 h appeared to substantially reduce the toxicity associated with fluorouracil (5-FU) modulated by leucovorin (LV) and interferon alpha-2a (IFN-alpha). This phase II study assessed the antitumor efficacy of this regimen. Patients (n=38) with colorectal cancer received IFN-alpha 5 MU/m(2) SC on days 1-6; on days 2-6, LV 200 mg/m(2) IV was given with 5-FU at initial doses of 370-425 mg/m(2)/h.

Myocyte protection by 10 kD heat shock protein (Hsp10) involves the mobile loop and attenuation of the Ras GTP-ase pathway.

Heat shock proteins (hsp), hsp60 and hsp10, are involved in the folding of imported mitochondrial proteins and the refolding of denatured proteins after stress. We examined whether hsp10 can reduce myocyte death by its mitochondrial function or by interacting with cytoplasmic signaling pathways. Overexpression of hsp10 by adenoviral infection decreased myocyte death induced by hydrogen peroxide, sodium cyanide, and simulated ischemia and reoxygenation (SI/RO).

A phase I pharmacologic and pharmacodynamic study of pyrazoloacridine given as a weekly 24-hour continuous intravenous infusion in adult cancer patients.

Purpose: Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases I and II through a mechanism distinct from other topoisomerase poisons. PZA shows schedule-independent cytotoxicity against tumor cells, whereas host toxicity is greater with shorter infusions. We assessed the clinical toxicities and pharmacologic effects of PZA given as a 24-h i.

Biochemical and molecular effects of UCN-01 in combination with 5-fluorodeoxyuridine in A431 human epidermoid cancer cells.

Concurrent and pre-exposure of A431 human epidermoid cancer cells to UCN-01, an investigational anticancer drug, with 5-fluoro--2'-deoxyuridine (FdUrd), which targets thymidylate synthase, produced more than additive cytotoxicty. A 24-h exposure to 10 nM FdUrd led to inhibition of TS, a 2.5-fold increase in total thymidylate synthase protein content, profound dTTP depletion and a 6.

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.

Background: Measurement of serum alpha-fetoprotein (AFP) and abdominal ultrasound (US) examination are used for the early detection of hepatocellular carcinoma (HCC) in chronic liver disease patients. However, the accuracy and usefulness of these tests in a clinical setting in the United States of America have not been clarified.

Methods: We conducted a 7-year prospective surveillance study by using both AFP and US to detect HCC in 602 patients with chronic viral hepatitis.

A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity.

As part of a large scale effort to discover novel secreted proteins, a cDNA encoding a novel cytokine was identified. Alignments of the sequence of the new protein, designated IL-17B, suggest it to be a homolog of the recently described T cell-derived cytokine, IL-17. By Northern analysis, EST distribution and real-time quantitative polymerase chain reaction analysis, mRNA was detected in many cell types.

Sequence-dependent antagonism between fluorouracil and paclitaxel in human breast cancer cells.

The effects of 24-hr exposures to 5-fluorouracil (FUra) and paclitaxel in various sequences were studied in MCF-7 breast cancer cells to determine an optimal schedule for possible clinical use. In clonogenic assays, pre-exposure to FUra followed by paclitaxel resulted in marked antagonism, while sequential paclitaxel followed by FUra was optimal. Concurrent or pre-exposure to paclitaxel did not affect [3H]FUra metabolism, [3H]FUra-RNA incorporation, or the extent of FUra-mediated thymidylate synthase inhibition.

Cytotoxicity and DNA fragmentation associated with sequential gemcitabine and 5-fluoro-2'-deoxyuridine in HT-29 colon cancer cells.

The combined cytotoxic effects of the antimetabolites gemcitabine (dFdCyd) and 5-fluoro-2'-deoxyuridine (FdUrd) were studied. Cytotoxicity, biochemical perturbations, and DNA damage seen with dFdCyd and FdUrd alone and in combination were evaluated in HT-29 human colon cancer cells. A 4-h exposure to dFdCyd followed by FdUrd for 24 h produced more than additive cytotoxicity and marked S-phase accumulation.

Vascular endothelial growth factor and basic fibroblast growth factor present in Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to promote vascular permeability and KS lesion development.

All forms of Kaposi's sarcoma (KS) are characterized by spindle cell proliferation, angiogenesis, inflammatory cell infiltration, and edema. We have previously reported that spindle cells of primary KS lesions and KS-derived spindle cell cultures express high levels of basic fibroblast growth factor (bFGF), which is promoted by the inflammatory cytokines identified in these lesions. These cytokines, namely, tumor necrosis factor, interleukin-1, and interferon-gamma, induce production and release of bFGF, which stimulates angiogenesis and spindle cell growth in an autocrine fashion.

Block of AIDS-Kaposi's sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonucleotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS.

Kaposi's sarcoma (KS) is the most frequent tumor of HIV-1-infected individuals (AIDS-KS). Typical features of KS are proliferating spindle-shaped cells, considered to be the tumor cells of KS, and endothelial cells forming blood vessels. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is highly expressed by KS spindle cells in vivo and after injection in nude mice it induces vascular lesions closely resembling early KS in humans.

Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines.

Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat.

Role of the carboxy-terminal portion of the HIV-1 transmembrane protein in viral transmission and cytopathogenicity.

The transmembrane glycoprotein (gp41) of human immunodeficiency virus type-1 (HIV-1) has a long cytoplasmic domain of unknown functional significance. To investigate the role of the carboxy-terminal (C-terminal) portion of the HIV-1 envelope protein in viral replication, infectivity, and cytopathogenicity, we examined the properties of a panel of mutants with variable deletions in the 3'-env region. Deletion of the C-terminal 76 amino acids did not abolish production of reverse transcriptase upon transfection of COS-1 cells.

Sialic acid analysis and tritium-labelling of sialoglycoproteins of mouse erythrocytes infected with Plasmodium berghei.

Schizont-infected red blood cells (SI-RBC) from Plasmodium berghei-infected mice contain between 2 and 10 times as much sialic acid as uninfected RBC from the same blood (99-550 micrograms/10(10) RBC versus 33-65 micrograms/10(10) RBC). Total RBC samples from infected animals containing up to 63% ring- and trophozoite-infected cells had identical sialic acid contents to purified RBC samples (of less than 3% parasitaemia) from the same blood (52-64 micrograms/10(10) RBC). We conclude that RBC containing immature parasites have the same sialic acid content as uninfected RBC from infected blood and that total cellular sialic acid increases during maturation to the schizont stage.

N-terminal amino acid sequence of the histidine-rich protein from Plasmodium lophurae.

We have determined the N-terminal amino acid sequence of the first 25 amino acids of the histidine-rich protein (HisRP) isolated from granules of the avian malaria parasite Plasmodium lophurae. The protein was purified from cytoplasmic granules and shown to be 65.2 mol % histidine, close to the previously described value of 73 mol % histidine (Kilejian (1974) J.

Protein antigens of Plasmodium knowlesi clones of different variant antigen phenotype.

Mature asexual stages of the malaria parasite Plasmodium Knowlesi synthesize proteins of Mr 180 000-225 000 that are expressed on the outer membrane of infected erythrocytes and which vary antigenically such that different parasite clones are specifically agglutinated with homologous antibody. Other non-agglutinable clones have been prepared which fail to express variant antigen on infected cells. Two agglutinable clones of different variant antigen phenotypes and a non-agglutinable cone were examined to determine the proportion of total malarial proteins represented by variant antigens.

Antigenic variation of Plasmodium knowlesi malaria: identification of the variant antigen on infected erythrocytes.

Erythrocytes infected with mature asexual stages of Plasmodium knowlesi express a new surface antigen such that rhesus monkey antisera specifically agglutinate these cells. Cloned parasites can express different antigenic variants of this antigen. The variant antigen has been identified by comparison of the surface membrane antigens of a clone and of an antigenic variant of that clone of different agglutination phenotype.