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PubMed1995

Disease activity courses in a regional cohort of Crohn's disease patients.

BACKGROUND: The study was a follow-up of an inception cohort of 373 patients with Crohn's disease. METHODS: Annual assessments, life table analyses, and Markov chain analyses, estimating the probability for remission and relapse with time, and working capacity were carried out. RESULTS: The clinical course of Crohn's disease differs markedly over time, from ever-relapsing cases to a quiescent course with remission for several years, interrupted by years with relapse. No predictive factors have been found for the subsequent course with regard to age, sex, extent of disease at diagnosis, and treatment in the year of diagnosis. The relapse rate within the year of diagnosis and the following 2 years, however, does correlate positively (p = 0.00001) with the relapse rate in the following 5 years. Furthermore, the relapse rate for 1 year during the disease course influences the relapse rate the following year, indicating a disease pattern over time with waves of at least 2 years' duration. A slight tendency towards burning out was found. The disease course reflected in working capacity for the patients showed that a minor part--up to 15% after 15 years--will become incapable and obtain disablement pension, while 75% of the patients each year are fully capable of work. Within 10 years 50% of the patients will not have experienced any year with impaired capacity for work.

Activities of Daily Living↗

PubMed1994

Body mass index and economic productivity.

The paper reviews the evidence to date on the nutritional links with productivity and then goes on to provide results from a multi-country study on the effects of increasing body mass index (BMI) on productivity. The research relating nutritional status to work capacity is more consistent than the research linking nutritional status to productivity. None of the studies to date elucidate the pathways through which improved nutrition improves economic productivity. In addition, many of the studies that have been conducted on the nutrition/wage links have been based on samples that contained a disproportionate number of male subjects. The few studies that have disaggregated data by gender report different results for men and women. Research conducted at IFPRI is presented to examine the trends in BMI for men and women across countries and for Kenya to examine the relationships between various measures of nutritional status--BMI and height--and energy expenditures in women. BMIs of men show a more consistent relationship with increasing household income than do the BMIs of women. In the case of the Gambia and Kenya, the mean BMI of women decreases with increasing household income. One reason for the apparently low response of BMI to increasing household income in Kenya is the time allocation patterns of women. Women in the Kenya sample spend the largest proportion of their day in home production activities which are energy intensive. In examining the relationship between nutritional indicators and the time devoted to work, the results suggest a significant, positive association between both BMI and height and the amount of time devoted to work. In the models presented, both BMI and height appear to increase the capacity to carry out work. It is difficult to value much of this work time since a disproportionate share is devoted to home production activities. Some of the more classic methods of measuring economic productivity, such as measuring wage rates, are not relevant for women in this setting. The data from Kenya suggest that more appropriate measures for specifying the value of women's work need to be developed in order to capture some of the nutrition/productivity links which may exist.

Body Mass Index↗

PubMed1999

Erythrocyte membrane transport.

Erythrocytes are endowed with functional entities that support either cellular functions or the systemic delivery of O2 from lung to tissue and removal of CO2 from tissue to lung. The latter depend largely on the blood's circulatory capacity. They are associated, respectively, with cytosolic haemoglobin and the major membrane polypeptide band 3 (anion exchanger 1, AE1). As a membrane transporter, AE1 mediates Cl-/HCO3- exchange, thus enhancing the blood capacity for carrying CO2 and for acid-base homeostasis. By interacting with lipids and proteins, the multifunctional AE1 tethers the membrane cytoskeleton multiprotein complex to the membrane and confers upon erythrocytes both mechanical and viscoelastic properties. Those in turn allow cells to withstand the shear forces of circulation and squeeze through capillaries. Most other major membrane transporters are apparently essential for maintaining a stable erythrocyte cell shape and flexibility via a functional membrane cytoskeleton. These include the membrane transporters of glucose, nucleoside and purine for fueling the Na/K and Ca pumps via ATP production, and of amino acid and oxidized glutathione transport for maintaining the cell redox status. All membrane transporters detected in mature erythrocytes are synthesized early in erythrocyte differentiation. Their contribution to erythrocyte and to systemic physiology is presently being re-assessed by targeted gene disruption and replacement. For example, organisms with reduced or disrupted AE1 gene expression showed major erythrocyte instabilities and defective anion exchange capacity and acidosis, but remain alive.

Animals↗

PubMed1998

Research on the human brain in an epilepsy surgery setting.

Recent advances in our understanding of the fundamental mechanisms of epilepsy have derived, to a large extent, from improvements in designing parallel human and animal studies. This is the result not only of better animal models of human epileptic phenomena, but of an increasing ability to carry out detailed invasive studies on patients in the course of surgical treatment for medically refractory epilepsy. In addition to interictal and ictal video-EEG recordings with chronic depth and subdural electrodes, it is also possible to sample single-unit activity with chronically implanted microelectrodes, and measure constituents of extracellular fluid with chronically implanted microdialysis probes, using protocols that in the past were possible only in the experimental animal laboratory. Subsequent surgical resection provides tissue that can be used for electrophysiological, morphological, biochemical, and molecular biological investigations. Patients in epilepsy surgery facilities represent a precious resource for research that should be utilized to the fullest extent possible by basic scientists interested in mechanisms of epilepsy. It is particularly important that invasive research be pursued now, because improved diagnostic technology is greatly reducing the need for chronic intracranial electrode recordings, and surgical approaches that do not yield tissue could be used more commonly in the future. Therefore, the capacity to carry out invasive research in the context of epilepsy surgery may diminish greatly over time. To take full advantage of these opportunities, carefully designed iterative experimental protocols are necessary to characterize abnormalities in the human epileptic brain, to create appropriate experimental animal models to study these phenomena in greater detail, and to return to the human brain to validate the clinical relevance of observations made on animals. It is also important, however, to recognize certain unavoidable limitations of human research, including ethical considerations, variability inherent in the clinical setting, imprecision in defining target areas, lack of control data, and small subject numbers, which continue to make animal investigations essential to the achievement of our goals of defining fundamental mechanisms of human epileptic phenomena.

Animals↗

PubMed1997

Transfection of the inner cell mass and lack of a unique DNA sequence affecting the uptake of exogenous DNA by sperm as shown by dideoxy sequencing analogues.

PURPOSE: The purpose of this study was to determine whether exogenous DNA internalized into blastocysts after transference from DNA-carrier sperm are localized at the inner cell mass or trophoblast cells and to identify differences in uptake of exogenous DNA fragments by sperm due to unique DNA sequences. METHODS: Mouse blastocysts at the hatching stage were exposed to migrating human sperm cells carrying exogenous DNA fragments synthesized from the E6-E7 conserved gene regions of human papillomavirus (HPV) types 16 and 18. After an interaction period of 2 hr, the transfected blastocysts were washed several times to remove extraneous sperm and the blastocysts were dissected into groups of cells derived from the inner cell mass and trophoblasts. The cells were analyzed by polymerase chain reaction (PCR) for the presence of HPV DNA fragments. In the second part of the experiment, thawed donor (N = 10) sperm cells were pooled, washed, and divided into two fractions. The first (control) fraction was added with formalin and further divided and added with a 35S-radiolabeled G, A, T, or C sequencing mixture. The second fraction was similarly treated but the formalin step was omitted from the treatment. After an hour of incubation at 37 degrees C, the sperm specimens were washed several times by centrifugation and DNA extracted by the GeneReleaser method. The extracted DNA were processed on sequence gels, and the autoradiographs analyzed. RESULTS: Mouse blastocysts transfected by carrier sperm with DNA from HPV types 16 and 18 showed localization of the HPV DNA to both the inner cell mass and trophoblast cells. Negative controls consisting of untreated human sperm and untreated mouse blastocysts did not reveal any evidence of HPV DNA. The positive sperm control generated expected DNA fragments from HPV types 16 and 18. In the second experiment, the intensities of the DNA fragments in the G, A, T, and C columns from low to high molecular weights were not different from the positive control bands. Band intensities of the four sequencing columns were similar. Formalin pretreatment of the sperm inhibited uptake of the DNA fragments from the smallest to the largest DNA molecules. CONCLUSIONS: Exogenous DNA taken into blastocysts are localized to both the inner cell mass and trophoblast cells. Only live sperm exhibited the capacity to carry various sizes of exogenous DNA, suggesting the involvement of active cell membrane mechanism in the transference process. The results showed that DNA fragments terminating in any of the four nucleotides were equally taken up by the sperm cell. Fragments of DNA produced by the sequencing reaction failed to identify a unique DNA sequence that would facilitate or inhibit the sperm from taking up exogenous DNA.

Animals↗

PubMed1983

Clinical and physiological outcomes of a university-hospital pulmonary rehabilitation program.

Pulmonary rehabilitation programs have resulted in improvements in quality of life, capacity for carrying out daily activities, and physical conditioning, as well as reduced hospitalization and cost of care. In our retrospective study, we reviewed the data of 75 patients who had participated in Loma Linda University Medical Center's pulmonary rehabilitation program--in order to determine its effect on survival, progression of disease, and quality of life for a selected group of patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary rehabilitation team evaluated each patient and developed for him a plan of care that included a 2-week inpatient education program. The cumulative survival rate of our group computed by the life table methods was 86.5% at 5 years of rehabilitation, and 64% at 10 years. The mean FEV1 at the beginning of the program was 1.53 1 and the mean FVC was 2.87 1; the mean change in FEV1 was - 45 ml/yr, and in FVC, - 70 ml/yr. By use of a questionnaire, we also found that most of our responding patients felt that their quality of life had improved. Our findings compare favorably with other published data and suggest that it is possible to improve the survival of patients with COPD by early diagnosis, comprehensive treatment, continuing medical care, and home visitation.

California↗

PubMed1975

Chronic obstructive airway diseases. Current concepts in diagnosis and comprehensive care.

Physicians and paramedical personnel often find the early diagnosis and differentiation of obstructive airway diseases to be a challenging problem. The history and physical examination are often not enough to allow the physician to detect either the presence of, or determine the type of, disease present. Patterns of pulmonary function abnormality to determine the presence of obstructive or restrictive defects are discussed. Guidelines useful in the differentiation of obstructive airway diseases are presented. Once a patient with COAD is assessed, the physician needs to outline a therapeutic program after establishing goals with the patient. These goals include (1) improved ability for the patient to achieve relief from symptoms and (2) improved capacity to carry out the activities of daily living. The therapeutic modalities available for the comprehensive care of patients with COAD are discussed. These include general factors such as patient and family education, avoidance of smoking and other inhaled irritants, avoidance of infection, a minimum stress environment, high fluid intake, and proper nutrition. The appropriate use of the medications most commonly employed in the teatment of these patients, eg, bronchodilators, expectorants, antimicrobials, corticosteroids, cromolyn, digitalis, and diuretics, are individually discussed. The use of such respiratory therapy techniques as aerosol therapy, intermittent positive pressure breathing, and oxygen therapy are considered. Application of the specialty of rehabilitation medicine to patients with obstructive airway disease is described. This includes physical therapy with breathing retraining, clapping and postural drainage, and exercise reconditioning, occupational therapy with attention to energy conservation in activities of daily living, psychological considerations, and vocational rehabilitation. Definite benefits that can be demonstrated if the physician employs this type of systematic respiratory care program include a decrease in the frequency and duration of hospital admissions, socioeconomic gains from reduced hospitalizations, a reduction in anxiety, depression and somatic concern, the return of patients to positions of employment and the establishment of a better quality of life. Persistence in making sure the patient continues in a systematic program, including both pharmacological and nonpharmacological modalities, may be the means of assuring maintenance or even improvement in his health. The day-to-day treatment for the majority of patients should remain in the hands of the primary physician. However, community resources must be established to allow the primary physician to provide these patients with adequate comprehensive respiratory care. Development of three levels of care (the primary physician, community respiratory rehabilitation units, and the regional respiratory center) should make superior respiratory care available to every patient with obstructive airway disease.

Adrenal Cortex Hormones↗

PubMed2005

Interactive Health Communication Applications for people with chronic disease.

BACKGROUND: Interactive Health Communication Applications (IHCAs) are computer-based, usually web-based, information packages for patients that combine health information with at least one of social support, decision support, or behaviour change support. These are innovations in health care and their effects on health are uncertain. OBJECTIVES: To assess the effects of IHCAs for people with chronic disease. SEARCH STRATEGY: We designed a four-part search strategy. First, we searched electronic bibliographic databases for published work; second, we searched the grey literature; and third, we searched for ongoing and recently completed clinical trials in the appropriate databases. Finally, researchers of included studies were contacted, and reference lists from relevant primary and review articles were followed up. As IHCAs require relatively new technology, the search time period commenced at 1990, where possible, and ran until 31 December 2003. SELECTION CRITERIA: Randomised controlled trials (RCTs) of IHCAs for adults and children with chronic disease. DATA COLLECTION AND ANALYSIS: One reviewer screened abstracts for relevance. Two reviewers screened all candidate studies to determine eligibility, apply quality criteria, and extract data from included studies. Authors of included RCTs were contacted for missing data. Results of RCTs were pooled using random-effects model with standardised mean differences (SMDs) for continuous outcomes and odds ratios for binary outcomes; heterogeneity was assessed using the I(2 )statistic. MAIN RESULTS: We identified 24 RCTs involving 3739 participants which were included in the review.IHCAs had a significant positive effect on knowledge (SMD 0.46; 95% confidence interval (CI) 0.22 to 0.69), social support (SMD 0.35; 95% CI 0.18 to 0.52) and clinical outcomes (SMD 0.18; 95% CI 0.01 to 0.35). Results suggest it is more likely than not that IHCAs have a positive effect on self-efficacy (a person's belief in their capacity to carry out a specific action) (SMD 0.24; 95% CI 0.00 to 0.48). IHCAs had a significant positive effect on continuous behavioural outcomes (SMD 0.20; 95% CI 0.01 to 0.40). Binary behavioural outcomes also showed a positive effect for IHCAs, although this result was not statistically significant (OR 1.66; 95% CI 0.71 to 3.87). It was not possible to determine the effects of IHCAs on emotional or economic outcomes. AUTHORS' CONCLUSIONS: IHCAs appear to have largely positive effects on users, in that users tend to become more knowledgeable, feel better socially supported, and may have improved behavioural and clinical outcomes compared to non-users. There is a need for more high quality studies with large sample sizes to confirm these preliminary findings, to determine the best type and best way to deliver IHCAs, and to establish how IHCAs have their effects for different groups of people with chronic illness.

Adaptation, Psychological↗

PubMed1993

Reproductive health, population growth, economic development and environmental change.

World population will increase by 1000 million, or by 20%, within 10 years. Ninety-five per cent of this increase will occur in the South, in areas that are already economically, environmentally and politically fragile. Morbidity and mortality associated with reproduction will be greater in the current decade than in any period in human history. Annually, 40-60 million pregnancies will be terminated and 5-10 million children will die within one year of birth. AIDS-related infections, e.g. tuberculosis, will undermine health care in Africa (and elsewhere) and in places AIDS-related deaths will decimate the work-force. The growth in population and associated morbidity will inhibit global economic development and spawn new problems. The key issues are migration, the spread of disease, the supply of water and the degradation of land, and fiscal policies with respect to family planning, pharmaceuticals and Third-World debt. Full education, particularly of women, and more effective family planning in the South have the power to unlock the problem. Failure will see the developed countries, with their 800 million population, swamped by the health, economic and environmental problems of the South, with its projected population of 5400 million people for the year 2000.

Demography↗

PubMed1980

Ultrastructural effects of riboflavin deficiency on rat hepatic mitochondria.

The hepatic mitochondria of rats fed a riboflavin-deficient diet were examined by electron microscopy. Discoidal mitochondria with elongated cristae increased in frequency from day 4 to day 12 of the test diet. At day 22, sheaves of closely packed cristae were present in many otherwise typical mitochondria. At day 53, numerous cupshaped mitochondria appeared; these often nested one inside the other. From this day onward, the mitochondria showed a tendency towards increasing size. By day 82, some had a diameter greater than 8 micrometer. These and other, smaller mitochondria often contained extremely prominent matrix granules. The production by riboflavin-deficiency of giant mitochondria in the rat liver appears to be unrelated to their capacity to carry out oxidative metabolism.

Animals↗

PubMed1991

YACs and the C. elegans genome.

During the past decade, it has become apparent that it is within our grasp to understand fully the development and functioning of complex organisms. It is widely accepted that this undertaking must include the elucidation of the genetic blueprint - the genome sequence - of a number of model organisms. As a prelude to the determination of these sequences, clone-based physical maps of the genomes of a number of multicellular animals and plants are being constructed. Yeast artificial chromosome (YAC) vectors, by virtue of their relatively unbiased cloning capabilities and capacity to carry large inserts, have come to play a central role in the construction of these maps. The application of YACs to the physical map of the Caenorhabditis elegans genome has enabled cosmid clone 'islands' to be linked together in an efficient manner. The long-range continuity has improved the linkage between the genetic and physical maps, greatly increasing its utility. Since the genome can be represented by a relatively small number of YACs, it has been possible to make replica filters of genomically ordered YACs available to the community at large.

Animals↗

PubMed1994

Endocytosis of the beta chain of interleukin-2 receptor requires neither interleukin-2 nor the gamma chain.

Interleukin-2 (IL-2) and IL-2 receptors (IL-2R) critically regulate the magnitude and duration of T cell expansion required in an immune response. Modulation occurs at the level of receptor number and affinity. IL-2R is a multisubunit receptor which contains at least three chains, IL-2R alpha (p55), IL-2R beta (p70) and IL-2R gamma (p64). Some components of high-affinity receptors (alpha beta gamma) are continuously internalized in the absence as well as in the presence of IL-2. From studies on other receptors, it is known that endocytosis of ligand-receptor complexes is due to an intrinsic property of the receptor. However, the specific chains responsible for endocytosis of high-affinity IL-2 receptors have not been fully elucidated. IL-2R gamma has been reported to be necessary for IL-2 internalization, based on the fact that fibroblasts transfected with IL-2R alpha and -beta do not internalize IL-2. However, IL-2 dissociates too rapidly from IL-2R alpha beta receptors to allow for its internalization. From the reported results on IL-2 internalization in transfected fibroblasts, it cannot be concluded as to the respective roles of IL-2R beta and/or IL-2R gamma in endocytosis. As modulation of receptor number is important for biological activity, we have attempted to define the chains responsible for receptor internalization. In this work, we have studied the endocytic properties of IL-2R beta. We demonstrate that IL-2R beta is constitutively endocytosed in a B cell line, derived from a X-linked severe combined immunodeficiency patient, which lacks expression of IL-2R gamma. IL-2R beta was also constitutively internalized in T and natural killer cell lines independently of IL-2R gamma. These results suggest that IL-2R beta is endowed with endocytic capacity and carries internalization signals.

Antibodies, Monoclonal↗

PubMed2001

A single (6-4) photoproduct inhibits plasmid DNA replication in xeroderma pigmentosum variant cell extracts.

The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in the human RAD30 gene, which encodes the lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV-irradiation. Using extracts of an XPV lymphoblast cell line (GM2449C) that has a truncating mutation in the RAD30 gene, we investigated the effect of a (6-4) photoproduct and a cyclobutane pyrimidine dimer (CPD), at a unique -TT- site on either the leading or lagging strand, on plasmid DNA replication. Compared to normal cell extracts, XPV cell extracts have a reduced capacity to carry out complete replication of DNA containing either a (6-4) photoproduct or a CPD on the leading strand, whereas there is little difference between the two cell extracts in replication of DNA containing a lesion on the lagging strand. Inhibition of replication in the presence of a (6-4) photoproduct is attributed to arrest of nascent DNA strand synthesis at the lesion site; in XPV cell extracts, the proportion of arrested products is increased compared to that of normal cell extracts. These results are consistent with a requirement for functional DNA polymerase eta in the replication of a double-stranded plasmid containing either a (6-4) photoproduct or a CPD, on the leading but not the lagging strand.

Base Sequence↗

PubMed1985

Induction of DNA polymerase alpha in senescent cultures of normal and Werner's syndrome cultured skin fibroblasts.

DNA polymerase alpha activity was determined following serum stimulation of early and late passages of human diploid fibroblast-like (HDFL) cultures derived from apparently normal donors (two strains) and from a patient with Werner's syndrome (one strain). Induction of this enzyme was observed in both low passage, actively proliferating cultures and in postmitotic "senescent" cultures from all three strains. The maximal polymerase activity of early and late passage cells of each strain were nearly identical when normalized to the number of cells present. However, the activity of the enzyme was observed to be significantly lower in late passage cultures when normalized to total protein content apparently because of enlargement of the senescent cells. The behavior of Werner derived cells was similar to that of the normal cells. The induction of DNA polymerase alpha in senescent cultures indicates that they retain the capacity to carry out some complex metabolic responses to mitogen stimulation. In addition, these results suggest the possibility that dilution of DNA polymerase alpha and/or other DNA replication factors may play a role in the onset or maintenance of the postmitotic state in the enlarged senescent HDFL cells.

Aphidicolin↗

PubMed1988

Stable variant of LM fibroblast defective in fluid-phase but competent in receptor-mediated endocytosis.

The F-40 cell line, a stable variant of LM fibroblasts selected for its resistance to polyethylene glycol (PEG)-induced fusion (Roos and Davidson: Somatic Cell and Molecular Genetics 6:381-391, 1980), has a decreased capacity to internalize fluid-phase markers and nonspecifically surface-bound macromolecules. It is not defective in exocytosis since, after a short sucrose pulse, it releases the same fraction of ingested sucrose into the medium as does the parental line. F40 cells have a normal capacity to carry out receptor-mediated endocytosis, as tested with 125I-alpha-2 macroglobulin (alpha-2 MG) and 125I-transferrin (Tf), and to recycle Tf receptor to the cell surface. These data demonstrate that receptor-mediated and non-receptor mediated endocytosis are distinct processes that can be altered independently. Of the many membrane fusions occurring in the course of endocytosis, the only one that appears associated with the defect in cell fusion characteristic of F40 cells is the formation of primary endocytotic vesicles engaged in non-receptor-mediated internalizations.

Animals↗

PubMed2004

An engineered EBV vector expressing human factor VIII and von Willebrand factor in cultured B-cells.

BACKGROUND: Hemophilia A is a congenital disorder caused by a deficiency of the blood-clotting factor VIII (FVIII) and is an attractive candidate for gene therapy. Most of the studies have only explored the potential of hepatocytes and muscle cells as the targets for gene transfer. Attempts to transfer the genes into hematopoietic cells have so far been mostly unsuccessful due to inefficiency of most viral vectors to transduce these cells and the supposed inability of the cells to express FVIII. METHODS: We demonstrate the generation of an engineered Epstein-Barr virus (EBV) vector with a BAC backbone that has the unique capacity to carry either the full-length FVIII cDNA or its B-domain-deleted form; a modified version of the vector that carries B-domain-deleted FVIII along with the von Willebrand factor (vWF) cDNA or the reporter gene DsRed2 was also used. All these vectors have been safety modified with viral thymidine kinase cDNA to transduce human B-cells in culture. RESULTS: Low-level expression of FVIII in the order of 5-8 ng FVIIIC/ml were observed in the cells stably transduced with full-length FVIII, while cells with the B-domain-deleted version expressed 8-16 ng FVIIIC/ml. Expression of vWF and B-domain-deleted FVIII resulted in a moderate expression of 18-30 ng FVIIIC/ml. Long-term expression for 12-16 weeks was observed in these cells regardless of selection pressure. CONCLUSIONS: These results support the development of an episomal engineered EBV vector for treatment of hemophilia A using the hematopoietic cells as a target for providing immediate secretion of functionally active product in the circulating bloodstream.

B-Lymphocytes↗

PubMed2006

Gene therapy for BCR-ABL+ human CML with dual phosphorylation resistant p27Kip1 and stable RNA interference using an EBV vector.

BACKGROUND: BCR-ABL-mediated chronic myelogenous leukemia (CML) CD34(+) cell proliferation mostly depends on the nucleo-cytoplasmic ratio of the cyclin-dependent kinase inhibitor p27. The ubiquitin-ligase SCF(Skp2) promotes degradation of phosphorylated p27 at T187 in the nucleus, resulting in G1/S progression of the cells. On the other hand, phosphatidylinositol-3-kinase (PI3K)-directed T157 nuclear localization signal (NLS) phosphorylation results in cytoplasmic sequestration of p27, leading to abnormal integrin-mediated proliferation of CD34(+) CML cells. METHODS: We demonstrate the generation of an engineered Epstein-Barr virus (EBV) vector with a BAC backbone that has the unique capacity to carry doubly modified (DM) p27 (i.e. T187A, T157A p27) along with the BCR-ABL siRNA expression construct. The HSV-tk suicide gene has also been incorporated in the same vector, which promotes apoptosis in a BCR-ABL-independent pathway. RESULTS: Expression of DM p27 markedly inhibits proliferation of BCR-ABL(+) primary human CML cells. Moreover, DM p27 strongly inhibits the growth of imatinib-resistant CML cells, compared to the T157A p27 (SM p27). The CML growth inhibition is found to be the result of significant G1/S arrest with concomitant increase in hypophosphorylated retinoblastoma (Rb). Moreover, the EBV vector mediated stable RNA interference induces apoptosis in K562 cells and reduces myeloid colony forming units. CONCLUSIONS: We therefore propose a multi-gene delivery strategy for BCR-ABL(+) CML cells by targeting not only the fusion transcript, but also the downstream signaling, to overcome drug resistance in the acute phase of CML.

Active Transport, Cell Nucleus↗

PubMed2004

Structural properties of perfluorinated linear alkanes: a 19F and 13C NMR study of perfluorononane.

Liquid perfluorocarbons exhibit unique physical-chemical characteristics such as extraordinary stability, combined hydrophobia and lipophobia, low surface tension and a capacity to carry large quantities of gas. They have found widespread use in industry, medicine and biology even though the molecular origin of these properties is not fully understood. The objective of the present work was to elucidate the physical behavior of perfluorinated linear alkanes by investigating their intramolecular electronic environment using 13C and 19F NMR techniques in combination with theoretical calculations of molecular orbitals. Particular advantage was taken of 19F-19F through-space couplings, which led us to propose a molecular model in which delocalized p-electrons of the fluorines cover the entire surface of the molecule in two pairs of intertwined helices. Experimental data are presented for n-perfluorononane and supported by corresponding measurements with shorter and longer perfluorinated alkanes.

Algorithms↗