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Several Reports (several + report)
Selected AbstractsEvaluation of apoptosis in cytologic specimensDIAGNOSTIC CYTOPATHOLOGY, Issue 9 2010Viktor Shtilbans Ph.D. Abstract A hallmark of neoplasia is dysregulated apoptosis, programmed cell death. Apoptosis is crucial for normal tissue homeostasis. Dysregulation of apoptotic pathways leads to reduced cytocidal responses to chemotherapeutic drugs or radiation and is a frequent contributor to therapeutic resistance in cancer. The literature pertaining to detection of apoptotic pathway constituents in cytologic specimens is reviewed herein. Virtually all methods for detecting apoptosis, including classic cytomorphologic evaluation, TUNEL assay, immunocytochemistry, and gene sequence analysis, may be applied to cytologic samples as well as tissue. Components of both intrinsic and extrinsic apoptotic pathways have been studied, including many reports examining p53 and bcl-2, as well as studies of caspase inhibitory proteins XIAP and survivin, death receptors and ligands such as Fas, Fas-ligand, and TRAIL. p53 undergoes oncogenic alteration more than any other protein; its immunocytochemical detection almost always connotes loss of its physiologic role as an inducer of apoptosis in response to a damaged genome. Several reports establish cytologic sampling as being as useful as tissue sampling. In one respect cytologic sampling is superior to tissue sampling in particular, by allowing clinicians to repeat sampling of the same tumor before and after administration of therapy; a number of reports use this approach to attempt to predict tumor response by assaying the effect of chemotherapy on the induction of apoptosis. Diagn. Cytopathol. 2010;38:685,697. © 2010 Wiley-Liss, Inc. [source] ,,, T cells inhibit in vitro growth of the asexual blood stages of Plasmodium falciparum by a granule exocytosis-dependent cytotoxic pathway that requires granulysinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2004Salah Abstract Several reports have stated the ability of ,,, T cells to inhibit the growth of the asexual blood stages of Plasmodium falciparumin vitro. However, little information is available about the mechanisms involved. In this study, in vitro systems were used to study the role of the granule exocytosis-dependent cytotoxic pathway in the growth inhibition/killing of P. falciparum by human ,,, T cells. Our results show that the inhibition requires cell-to-cell contact and that ,,, T cells kill the asexual blood stages of P. falciparum through a granule exocytosis-dependent cytotoxic pathway after recognition of certain ligands or molecules expressed on the surface of infected erythrocytes or merozoites. The in vitro inhibitory capacity of ,,, T cells was strongly correlated with the expression of granulysin in the cytotoxic granules, while non-inhibitory CD4+ and CD8+ T cells expressed very little, implicating a role for granulysin in parasite inhibition. This was further suggested by the addition of neutralizing anti-granulysin antibodies, which abrogated the parasite inhibitory capacity of the ,,, T cells. Taken together, our results suggest that the capacity of ,,, T cells for inhibition/killing of P. falciparum is based on the granule exocytosis-dependent cytotoxic pathway and that the presence of granulysin is essential to maintain efficient killing. [source] Enhanced expression of Mcm proteins in cancer cells derived from uterine cervixFEBS JOURNAL, Issue 6 2003Yukio Ishimi Minichromosome maintenance proteins (Mcm) 2,7 play essential roles in eukaryotic DNA replication. Several reports have indicated the usefulness of Mcm proteins as markers of cancer cells in histopathological diagnosis. However, their mode of expression and pathophysiological significance in cancer cells remain to be clarified. We compared the level of expression of Mcm proteins among human HeLa uterine cervical carcinoma cells, SV40-transformed human fibroblast GM00637 cells and normal human fibroblast WI-38 cells. All the proteins examined were detected in HeLa and GM cells at 6,10 times the level found in WI-38 cells on average. This increase was observed both in total cellular proteins and in the chromatin-bound fraction. Consistently, Mcm2 mRNA was enriched in HeLa cells to approximately four times the level in WI-38 cells, and the synthesis of Mcm4, 6 and 7 proteins was accelerated in HeLa cells. Immunohistochemical studies of surgical materials from human uterine cervix showed that Mcm3 and 4 are ubiquitously expressed in cancer cells. Further, the positive rate and level of Mcm3 and 4 expression appeared to be higher in cancer cells than in normal proliferating cells of the uterine cervix and dysplastic cells, suggesting that they can be useful markers to distinguish these cells. [source] Significant activity of a modified ribozyme with N7-deazaguanine at G10.1: the double-metal-ion mechanism of catalysis in reactions catalysed by hammerhead ribozymesGENES TO CELLS, Issue 8 2000Yuka Nakamatsu Background Several reports have appeared recently of experimental evidence for a double-metal-ion mechanism of catalysis in reactions catalysed by hammerhead ribozymes. In one case, hammerhead ribozyme-mediated cleavage was analysed as a function of the concentration of La3+ ions in the presence of a fixed concentration of Mg2+ ions so that the role of metal ions that are directly involved in the cleavage reaction could be monitored. The resultant bell-shaped curve for activation of cleavage was used to support the proposed double-metal-ion mechanism of catalysis. However, other studies have demonstrated that the binding of a metal ion (the most conserved P9 metal ion) to the pro-Rp oxygen (P9 oxygen) of the phosphate moiety of nucleotide A9 and to the N7 of nucleotide G10.1 is critical for efficient catalysis, despite the large distance (,20 Å) between the P9 metal ion and the labile phosphodiester group in the ground state. In fact, it was demonstrated that an added Cd2+ ion binds first to the pro-Rp phosphoryl P9 oxygen but not with the pro-Rp phosphoryl oxygen at the cleavage site. Results In earlier discussions, it was difficult to completely exclude the possibility that La3+ ions might have replaced the P9 metal ion and, as a result, created conditions represented by the bell-shaped curve. In order to clarify this situation, we examined a chemically synthesized hammerhead ribozyme (7-deaza-R34) that included a minimal modification, namely, an N7-deazaguanine residue in place of G10.1. We compared the kinetic properties of this ribozyme with those of the parental ribozyme (R34). Kinetic analysis revealed that, unlike the cases of added Cd2+ ions, the added La3+ ions did not replace the pre-existing P9 metal ion, and that the replacement of N7 by C7 at G10.1 reduced the catalytic activity to a limited extent. This result indicates that the binding of a Mg2+ ion to N7 at G10.1 is catalytically important but not indispensable. Most importantly, 7-deaza-R34 also yielded a bell-shaped curve upon addition of La3+ ions to the reaction mixture. Conclusions Since the data based on our experiments with 7-deaza-R34 are completely free from potential artefacts, due to the binding of a La3+ ion to N7 at G10.1, our results, that 7-deaza-R34 yielded a bell-shaped curve following the addition of La3+ ions to the Mg2+ -background reaction mixture, strongly supports the proposal that a double-metal-ion mechanism is operative in the cleavage reaction which is catalysed by hammerhead ribozymes. [source] Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy,HEPATOLOGY, Issue 5 2007Marco Binder Hepatitis C virus (HCV) has been known to replicate with extremely varying efficiencies in different host cells, even within different populations of a single human hepatoma cell line, termed Huh-7. Several reports have implicated the retinoic-acid inducible gene I (RIG-I)/ interferon regulatory factor 3 (IRF-3) pathway of the innate antiviral response with differences in host cell permissiveness to HCV. To investigate the general impact of the IRF-3 response onto HCV replication in cell culture, we generated an ample array of stable Huh-7 cell lines with altered IRF-3 responsiveness. Neither blocking IRF-3 activation in various host cells by expression of dominant negative RIG-I or HCV NS3/4A protease nor reconstitution of RIG-I signaling in Huh7.5, a cell clone known to be defective in this pathway, had any impact on HCV replication. Only by overexpressing constitutively active RIG-I or the signaling adaptor Cardif (also known as interferon-beta promoter stimulator 1, mitochondrial anti-viral signaling protein, or virus-induced signaling adaptor), both leading to a stimulation of the IRF-3 pathway in the absence of inducers, was HCV replication significantly inhibited. We therefore assessed the extent of RIG-I, dependent IRF-3 activation by different species of RNA, including full-length HCV genomes and HCV RNA duplexes, and observed strong induction only in response to double-stranded RNAs. Conclusion: Based on these findings, we propose a refined model of innate immune escape by HCV involving limited initial induction and stringent subsequent control of the IRF-3 response. (HEPATOLOGY 2007.) [source] Open Heart Surgery in Patients 85 Years and OlderJOURNAL OF CARDIAC SURGERY, Issue 1 2004Wellington J. Davis III M.D. Several reports have documented acceptable morbidity and mortality in patients 80 years and older. The results from surgical patients 85 years and older were analyzed. Methods: The records of 89 consecutive patients 85 years and older having cardiac operations between June 1993 and May 1999 were retrospectively reviewed. For purposes of statistical analysis follow-up was considered as a minimum of one office visit to the surgeon, cardiologist, or internist at least 1 month postoperatively. Results: Eighty-seven patients underwent coronary artery grafting and two patients had mitral valve replacement. Follow-up was 100% complete. The operative mortality rate was 12.3%; probability of in-hospital death was 8.2%; risk-adjusted mortality rate was 3.2%. The complication rate was 31.5%. The actuarial 1-, 3-, and 5-year survivals were as follows: 75%, 67%, and 40%. Multivariate predictors of 30-day mortality were preoperative EF, less than 30% (p = 0.029) and postoperative renal failure (p = 0.0039). Conclusions: Cardiac surgery can be performed in patients 85 years and older with good results. There is an associated prolonged hospital stay for elderly patients. Consistent successful outcomes can be expected in this patient population with selective criteria identifying risk factors. (J Card Surg 2004;19:7-11) [source] Polyamines Contribute to Ethanol Withdrawal-Induced Neurotoxicity in Rat Hippocampal Slice Cultures Through Interactions With the NMDA ReceptorALCOHOLISM, Issue 7 2003D. Alex Gibson Background: Several reports demonstrate that withdrawal from long-term ethanol exposure is associated with significant central nervous system neurotoxicity, produced at least in part by increased activity of N -methyl-d-aspartate receptors (NMDARs). Recent evidence suggests that elevations in the synthesis and release of the polyamines spermidine and spermine, which are known modulators of NMDARs, contribute to the increased activity of the receptor during ethanol withdrawal. Therefore, the goal of this investigation was to examine what role, if any, spermidine and spermine have in the generation of ethanol withdrawal-induced neurotoxicity. Methods: Neurotoxicity (measured as fluorescence of the cell death indicator propidium iodide, PI), glutamate release (measured by high-performance liquid chromatography analysis), and polyamine concentrations (by high-performance liquid chromatography) were measured in rat hippocampal slice cultures undergoing withdrawal from chronic (10 day) ethanol exposure (100 mM). In addition, the effects of the polyamine synthesis inhibitor di-fluoro-methyl-ornithine (DFMO, 0.1,100 nM) and NMDAR polyamine-site antagonists ifenprodil, arcaine, and agmatine (1 nM-100 ,M) on ethanol withdrawal- and NMDA-induced neurotoxicity were measured. Results: Ethanol withdrawal significantly increased glutamate release (peaking at 18 hr with a 53% increase), increased concentrations of putrescine and spermidine (136% and 139% increases, respectively, at 18 hr), and produced significant cytotoxicity in the CA1 hippocampal region (56% increase in PI staining relative to controls) of the cultures. The cell death produced by ethanol withdrawal was significantly inhibited by ifenprodil (IC50= 14.9 nM), arcaine (IC50= 37.9 nM), agmatine (IC50= 41.5 nM), and DFMO (IC50= 0.6 nM). NMDA (5 ,M) significantly increased PI staining in the CA1 region of the hippocampal cultures (365% relative to controls), but ifenprodil, arcaine, agmatine, and DFMO all failed to significantly affect this type of toxicity. Conclusions: These data implicate a role for polyamines in ethanol withdrawal-induced neurotoxicity and suggest that inhibiting the actions of polyamines on NMDARs may be neuroprotective under these conditions. [source] Multidetector row computed tomography for diagnosing intraductal extension of breast carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2005Takeo Fujita Abstract Objectives Several reports supported the association of higher ipsilateral breast tumor recurrence rates with positive or intermediate margins compared with negative pathologic margins. Precise evaluation of intraductal component and adequate surgical margin are important factors affecting the tumor recurrence after breast conserving surgery. Numerous studies have reported the utility of magnetic resonance imaging for diagnosing developing intraductal extension of breast cancer, but few have investigated multidetector-row computed tomography (MD-CT). The present study evaluated the clinical utility of MD-CT for detecting intraductal extension of breast carcinoma, and analyzed clinical parameters affecting the detection of intraductal extension under MD-CT. Methods Subjects comprised 44 patients grouped into three categories according to degree of intraductal extension of the main tumor under MD-CT (Intraductal spread grade 1,3: IDS 1,3). Tumors were also categorized histopathologically (p-IDS 0,3), and CT-pathological correlations were examined retrospectively. Clinical parameters were evaluated to determine the affect on detection of intraductal components. Results MD-CT detected 44 breast lesions (100%). Sensitivity for detection of intraductal component was 81.2%, specificity was 67.8%, and accuracy was 72.7%. Regarding extent of intraductal components, significant correlations were found between histopathological and MD-CT findings. A strong correlation was found in postmenopausal women between T2 tumor and high histological grade. Conclusions MD-CT findings of intraductal extension from breast carcinoma correlate with histological degree of intraductal extension, and MD-CT may be useful for preoperative assessment of breast-conserving surgery, particularly for postmenopausal women with histological high nuclear grade and T2 tumor. J. Surg. Oncol. 2005;91:10,16. © 2005 Wiley-Liss, Inc. [source] Ultraviolet A1 phototherapy for treatment of acrosclerosis in systemic sclerosis: controlled study with half-side comparison analysisPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2007F. Durand Background: Treatments currently used in acrosclerosis for patients with systemic sclerosis (SS) are not very efficient and are associated with adverse effects. Several reports concern the efficacy of ultraviolet A1 (UVA1) phototherapy for localized scleroderma. Recent studies appear to indicate the interest of UVA1 in acrosclerosis for patients with SS. However, these studies are uncontrolled. Objective: To determine whether UVA1 phototherapy is effective for acrosclerosis in SS with a randomized, investigator-blinded, controlled study. Methods: Nine patients with SS completed the study. The duration of disease ranged from 6 to 21 years. None of them had received glucocorticoids or immunosuppressive agents. Low-dose UVA1 phototherapy (40 J/cm2) of the randomized hand was performed three times weekly over a period of 14 weeks. The other hand served as control. The clinical evaluation used a modified semiquantitative skin scoring system, the index flexion and extension, and a visual analog scale (VAS) was performed at baseline and after treatment. Results: The mean of skin score and VAS improved significantly (P<0.05), but this improvement does not appear to be different between the treated or the untreated hands. There was no modification of the index flexion or extension. Two patients noticeably improved the functions of the treated hand. No side effects were observed. Conclusions: These results suggest that UVA1 phototherapy does not improve cutaneous thickness in acrosclerosis even if few functional improvements, and some ulcerations healings can be occasionally observed. However, a larger scale trial is necessary to confirm this inefficiency. [source] Presence of prostate cancer metastasis correlates with lower lymph node reactivity,THE PROSTATE, Issue 16 2006Gannon Philippe Olivier Abstract BACKGROUND Several reports suggest that the dissemination of neoplastic cells and cancer progression are associated with the generation of an immunosuppressive environment. METHODS In this report, we investigated immunological effects of prostate cancer by comparing metastastic and non-metastatic pelvic lymph nodes (LNs) from 25 patients with carcinomatous involvement of LNs to the non-metastatic LNs from 26 control patients with no metastatic involvement by immunohistochemistry and histological analyses. RESULTS Our results showed a decreased abundance of CD20+ B lymphocytes (P,=,0.031), CD38+ activated lymphocytes (P,=,0.038), and CD68+ macrophages (P,<,0.001), and less evidence of follicular hyperplasia (P,=,0.014), sinus hyperplasia (P,<,0.001), and fibrosis (P=0.028) in metastatic LNs comparatively to control LNs. Finally, we observed that metastatic LNs were significantly smaller than control LNs (P,=,0.005). CONCLUSIONS Our results suggest that the development of prostate cancer LN metastasis is accompanied with smaller LN size and decreased LN reactivity suggesting the development of an immununosuppressive microenvironment. © 2006 Wiley-Liss, Inc. [source] Prospects of stellar abundance studies from near-IR spectra observed with the E-ELTASTRONOMISCHE NACHRICHTEN, Issue 4 2010N. Ryde Abstract In 2006 ESO Council authorized a Phase B study of a European AO-telescope with a 42 m segmented primary with a 5-mirror design, the E-ELT. Several reports and working groups have already presented science cases for an E-ELT, specifically exploiting the new capabilities of such a large telescope. One of the aims of the design has been to find a balance in the performances between an E-ELT and the James Webb Space Telescope, JWST. Apart from the larger photon-collecting area, the strengths of the former is the higher attainable spatial and spectral resolutions. The E-ELT AO system will have an optimal performance in the near-IR, which makes it specially advantageous. High-resolution spectroscopy in the near-infrared has, however, not been discussed much. This paper aims at filling that gap, by specifically discussing spectroscopy of stellar (mainly red giant), photospheric abundances. Based on studies in the literature of stellar abundances, at the needed medium to high spectral resolutions in the near-infrared (0.8,2.4 ,m), I will try to extrapolate published results to the performance of the E-ELT and explore what could be done at the E-ELT in this field. A discussion on what instrument characteristics that would be needed for stellar abundance analyses in the near-IR will be given (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] High-dose cyclophosphamide does not eradicate paroxysmal nocturnal haemoglobinuria haematopoiesis in mice carrying a Piga gene mutationBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Anne Schaefer Summary. Recently, high-dose cyclophosphamide (HD CY) has been used in the treatment of aplastic anaemia. Several reports have suggested that the treatment may either eradicate or suppress mutant clonal haematopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH). We therefore treated mice that have a proportion of blood cells deficient in GPI-anchor molecules (PIGA,) with HD CY, and monitored their peripheral blood counts during and after treatment. HD CY produced a transient myelosuppression; however, the contribution of PIGA, haematopoiesis to the peripheral blood remained unchanged, suggesting that HD CY is unlikely to eliminate an existing PNH clone in patients treated for aplastic anaemia. [source] No allelic association between harm avoidance and the debrisoquine 4-hydroxylase geneACTA NEUROPSYCHIATRICA, Issue 5 2002Adriaan H Veefkind Background: Several reports suggest that variance in personality traits is inherited, but little is known about the genes responsible. It has been suggested that there is a relationship between personality characteristics and the gene responsible for the activity of the enzyme debrisoquine 4-hydroxylase (CYP2D6). Objective: To examine the proportion of poor metabolizers in a group of personality disordered patients. Methods: Blood samples were obtained from 23 patients with a high or very high score on the dimension ,harm avoidance' of the Temperament and Character Inventory (TCI). The samples were genotyped for the null alleles CYP2D6*3 and*4 by performing an allele-specific polymerase chain reaction. Results: The frequencies of genotypes in the sample were very similar to the frequencies found in a general white population. Conclusions: The investigation produced no support for the idea that the CYP2D6 gene is related to personality by means of variations in the temperament dimension of harm avoidance. [source] Prophylaxis of posttraumatic endophthalmitisACTA OPHTHALMOLOGICA, Issue 2009A ABU EL ASRAR Infectious endophthalmitis is a devastating complication of open globe injuries. The incidence of culture-positive endophthalmitis after open globe injuries varies between 0.5% and 17%. Several reports have demonstrated that delayed primary repair, dirty wound, breach of lens capsule, retained intraocular foreign body (IOFB), grade 4 injury (presenting visual acuity of worse than 5/200 to light perception), placement of primary intraocular lens, and rural setting are associated with an increased risk of posttraumatic endophthalmitis. Posttraumatic endophthalmitis is associated with its own microbiologic spectrum which is distinct from other subgroups of exogenous endophthalmitis. Posttraumatic endophthalmitis still carries a poor prognosis. Reasons for guarded prognosis include polymicrobial infection and the virulence of the infecting microorganisms. In addition, concomitant injuries may directly result in ocular damage that limits ultimate visual recovery. Because of the substantial incidence of endophthalmitis after open globe injuries, careful consideration should be given to the use of prophylactic antimicrobial therapy. The purpose of prophylaxis is to provide effective antibiotic levels as rapidly as possible against a broad range of organisms. Good coverage for most organisms is obtained with intravenous vancomycin coupled with a third generation cephalosporin, such as ceftazidime, which can penetrate the vitreous cavity in effective levels in inflamed aphakic experimental eyes. Recently, the use of prophylactic intravitreal antibiotic administration in high-risk cases was recommended. [source] Insulino-mimetic and anti-diabetic effects of vanadium compoundsDIABETIC MEDICINE, Issue 1 2005A. K. Srivastava Abstract Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes. [source] Intracytoplasmic lumina in invasive micropapillary carcinoma of the lungDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2006Naoto Kuroda M.D. Abstract Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3,20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site. Diagn. Cytopathol. 2006;34:224,226. © 2006 Wiley-Liss, Inc. [source] Echocardiographic Parameters in Athlete and Nonathlete Offspring of Hypertensive ParentsECHOCARDIOGRAPHY, Issue 1 2008Patrícia Horváth M.D. Background: According to several reports, some cardiovascular signs of hypertension (left ventricular [LV] hypertrophy, impaired diastolic filling) can be found in the normotensive offspring of hypertensive parents. It is also well known that regular physical exercise decreases the risk of hypertension. Aim: The aim of the present study is to determine whether or not regular physical training influences these early hypertensive traits in the offspring of hypertensive parents. Methods: Echocardiographic data of 215 (144 males, 71 females) 22- to 35-year-old nonathlete and athlete offspring of hypertensive (positive family history, FH+) and normotensive parents (negative family history, FH,) were compared in a cross-sectional design. Results: In the nonathlete FH+ males and females, LV dimensions were not larger than in the FH, subjects. The E/A quotient was lower in the FH+ subjects in both genders. Absolute and heart rate adjusted isovolumetric relaxation times were slightly longer in the FH+ men than in their FH, peers. No differences were seen between athlete FH, and FH+ subjects. Conclusion: Regular physical exercise decreases the incidence of the adverse cardiac signs, which can be associated with hypertension in the normotensive offspring of hypertensive parents. [source] Seasonal dynamics and toxicity of Cylindrospermopsis raciborskii in Lake Guiers (Senegal, West Africa)FEMS MICROBIOLOGY ECOLOGY, Issue 3 2006Céline Berger Abstract Cylindrospermopsis raciborskii is a toxic bloom-forming cyanobacterium that occurs at tropical and temperate latitudes. Despite several reports from Africa, no data were previously available about its dynamics or toxic potential there. We therefore carried out a 1-year survey of the dynamics of C. raciborskii in the main water reservoir in Senegal, Lake Guiers. Cylindrospermopsis raciborskii never formed a bloom in this lake during the period studied, but was dominant during the dry season. The only observed bloom-forming species was a diatom, Fragilaria sp., which displayed a seasonal pattern contrary to that exhibited by C. raciborskii. Principal component analysis applied to environmental and phytoplankton data showed that high C. raciborskii biomasses were mainly related to high temperature and water column stability. Tests for C. raciborskii species-related toxicity and/or toxin synthesis were performed on 21 isolated clones. All the strains isolated tested negative in mouse toxicity bioassays, toxin analysis (MS/MS) and tests for known cylindrospermopsin genes (ps, pks). The limited number of isolates studied, and the occurrence of toxic and nontoxic clones in natural cyanobacterial populations, mean that we cannot conclude that there is no C. raciborskii- associated health risk in this drinking water reservoir. [source] Bell's palsy during interferon therapy for chronic hepatitis C infection in patients with haemorrhagic disordersHAEMOPHILIA, Issue 2 2000Ogundipe Two adult patients with life-long severe haemorrhagic disorders commenced on interferon-,2b therapy for chronic hepatitis C infection. Both developed Bell's palsy several weeks after commencing therapy, They were started on steroids and, in addition, the first patient discontinued interferon-,2b therapy while the second patient elected to continue with therapy. In both cases facial paralysis improved over the ensuing weeks. Bell's palsy is often idiopathic but has been reported. in association with herpesviruses. It is not a recognised complication of chronic hepatitis B or C infection, or interferon-,2b therapy. However, the interferons are associated with numerous adverse reactions including various neuropsychiatric manifestations and neurological syndromes. There are several reports of nerve palsies, including optic tract neuropathy, occurring during interferon therapy, and immune-based mechanisms are thought to play a role in the aetiopathogenesis. No reports of Bell's palsy in association with interferon therapy were identified in our literature search, although one possible case has been reported to the Committee of Safety in Medicine. Although Bell's palsy in our patients may have occurred by chance, a neuropathic effect of interferon-,2b on the facial nerve cannot be excluded and we urge physicians using interferons to be aware of this potential side-effect. [source] Importance of comorbidity in hypopharyngeal cancer,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2010Akihiro Homma MD Abstract Background. Comorbidity has an impact on survival in laryngeal cancer in several reports. However, the importance of comorbidity in hypopharyngeal cancer (HPC) has not been reported. Methods. A retrospective medical record review of 156 patients with HPC treated between 1995 and 2005 was performed. Comorbid illness was measured by the Adult Comorbidity Evaluation-27. A Cox proportional hazards model was used to determine the factors related to overall survival. Results. Comorbidity was absent in 55 (35.2%) of the patients, mild in 39 (25%), moderate in 28 (17.9%), and severe in 34 (21.8%). There were statistically significant differences between the survival rates in accord with age, stage, subsite, and comorbidity (45.1% for none or mild vs 27.7% for moderate or severe; p = .0073). Age, stage, and comorbidity were identified as independent prognostic factors in the multivariate analysis. Conclusion. Comorbidity, along with the clinical stage, should be considered in treatment planning for patients with HPC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Hypoxia in head and neck cancer: How much, how important?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2005H. L. Janssen MD Abstract Background. Hypoxia develops in tumors because of a less ordered, often chaotic, and leaky vascular supply compared with that in normal tissues. In preclinical models, hypoxia has been shown to be associated with treatment resistance and increased malignant potential. In the clinic, several reports show the presence and extent of tumor hypoxia as a negative prognostic indicator. This article reviews the biology and importance of hypoxia in head and neck cancer. Methods. A review of literature was carried out and combined with our own experience on hypoxia measurements using exogenous and endogenous markers. Results. Hypoxia can increase resistance to radiation and cytotoxic drugs and lead to malignant progression, affecting all treatment modalities, including surgery. Hypoxia measurements using electrodes, exogenous bioreductive markers, or endogenous markers show the presence of hypoxia in most head and neck cancers, and correlations with outcome, although limited, consistently indicate hypoxia as an important negative factor. Each hypoxia measurement method has disadvantages, and no "gold standard" yet exists. Distinctions among chronic, acute, and intermediate hypoxia need to be made, because their biology and relevance to treatment resistance differ. Reliable methods for measuring these different forms in the clinic are still lacking. Several methods to overcome hypoxia have been tested clinically, with radiosensitizers (nimorazole), hypoxic cytotoxins (tirapazamine), and carbogen showing some success. New treatments such as hypoxia-mediated gene therapy await proper clinical testing. Conclusions. The hypoxia problem in head and neck cancer needs to be addressed if improvements in current treatments are to be made. Increased knowledge of the molecular biology of intermediate, severe, and intermittent hypoxia is needed to assess their relevance and indicate strategies for overcoming their negative influence. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Klinefelter's syndrome and rheumatoid arthritis: report of a case and review of the literatureINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2010Hussein F. AL-ARFAJ Abstract Kilnefelter's syndrome (KFS) tends to be associated with autoimmune diseases. Although several reports describe association of KFS with different autoimmune diseases, association with rheumatoid arthritis is very rare. We report a case of (KFS) who had seropositive erosive rheumatoid arthritis, and discuss the role of sex hormones/X chromosome in the pathogenesis of disease. [source] Changing concepts of bladder regenerationINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2007Akihiro Kanematsu Abstract: During the last decade, there has been a dramatic increase in studies aimed at regeneration of the urinary bladder. Many studies employed animal-derived or synthetic materials as grafts for experimental bladder augmentation models, with or without additional measures to promote regeneration, such as autologous cell transplantation or growth factor loading. However, in spite of encouraging results in several reports, few methodologies have shown proven definitive clinical utility. One major problem in these studies is the lack of a clear distinction between native and regenerated bladder in total bladder function after augmentation. Another crucial problem is the absorption and shrinkage of larger grafts, which may result from insufficient vascular supply and smooth muscle regeneration. In contrast, researchers have recently attempted to establish alternative regenerative strategies for treating bladder diseases, and have employed far more diverse approaches according to the various pathological conditions to be treated. For total replacement of the bladder after cystectomy for invasive bladder cancer, urothelium-covered neobladder with non-urinary tract backbone remains a viable choice. In addition, functional bladder diseases such as urinary incontinence, weak detrusor, or non-compliant fibrotic bladder have also been major targets for many leading research groups in this field. These conditions are studied much more from different therapeutic standpoints, aiming at the prevention or reversal of pathological conditions in muscle remodeling or neural control. Such altered research direction would inevitably lead to less surgically based basic biological research, and also would include a far wider spectrum of adult and pediatric bladder diseases, from overactive bladder to dysfunctional voiding. [source] Ionic Basis of Pharmacological Therapy in Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2007MANLIO F. MÁRQUEZ M.D. An implantable cardioverter-defibrillator is considered the only effective therapy to terminate ventricular arrhythmias in symptomatic patients with Brugada syndrome. However, it does not prevent future arrhythmic episodes. Only antiarrhythmic drug therapy can prevent them. There have been several reports of a beneficial effect of oral quinidine in both asymptomatic and symptomatic patients. Other possible beneficial oral agents could be Ito blockers. Intravenous isoproterenol has been reported to be especially useful in abolishing arrhythmic storms in emergency situations. Also, isolated case reports on the usefulness of cilostazol, sotalol, and mexiletine have been described. The present article reviews the mechanisms by which these drugs may act and their possible role in the pharmacotherapy of this disease. [source] Isolation and identification of 1,-hydroxy-3-epi-vitamin D3, a potent suppressor of parathyroid hormone secretionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2005Alex J. Brown Abstract Since our original demonstration of the metabolism of 1,,25(OH)2D3 into 1,,25(OH)2 -3-epi-D3 in human keratinocytes, there have been several reports indicating that epimerization of the 3 hydroxyl group of vitamin D compounds is a common metabolic process. Recent studies reported the metabolism of 25OHD3 and 24(R),25(OH)2D3 into their respective C-3 epimers, indicating that the presence of 1, hydroxyl group is not necessary for the 3-epimerization of vitamin D compounds. To determine whether the presence of a 25 hydroxyl group is required for 3-epimerization of vitamin D compounds, we investigated the metabolism of 1,OHD3, a non-25 hydroxylated vitamin D compound, in rat osteosarcoma cells (ROS 17/2.8). We noted metabolism of 1,OHD3 into a less polar metabolite which was unequivocally identified as 1,OH-3-epi-D3 using the techniques of HPLC, GC/MS, and 1H-NMR analysis. We also identified 1,OH-3-epi-D3 as a circulating metabolite in rats treated with pharmacological concentrations of 1,OHD3. Thus, these results indicated that the presence of a 25 hydroxyl group is not required for 3-epimerization of vitamin D compounds. Furthermore, the results from the same studies also provided evidence to indicate that 1,OH-3-epi-D3, like 1,OHD3, is hydroxylated at C-25. We then evaluated the biological activities of 1,OH-3-epi-D3. Treatment of normal rats every other day for 7 days with 2.5 nmol/kg of 1,OH-3-epi-D3 did not raise serum calcium, while the same dose of 1,OHD3 increased serum calcium by 3.39,±,0.52 mg/dl. Interestingly, in the same rats which received 1,OH-3-epi-D3 we also noted a reduction in circulating PTH levels by 65,±,7%. This ability of 1,OH-3-epi-D3 to suppress PTH levels in normal rats without altering serum calcium was further tested in rats with reduced renal function. The results indicated that the ED50 of 1,OH-3-epi-D3 for suppression of PTH was only slightly higher than that of 1,,25(OH)2D3, but that the threshold dose of the development of hypercalcemia (total serum Ca >,10.5 mg/dl) was nearly 80 times higher. These findings indicate that 1,OH-3-epi-D3 is a highly selective vitamin D analog with tremendous potential for treatment of secondary hyperparathyroidism in chronic renal failure patients. © 2005 Wiley-Liss, Inc. [source] Antimalarial drug quality in AfricaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2007A. A. Amin PhD Abstract Background and objective: There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. Methods: A search was conducted in PubMed in English using the medical subject headings (MeSH) terms: ,Antimalarials/analysis'[MeSH] OR ,Antimalarials/standards'[MeSH] AND ,Africa'[MeSH]' to include articles published up to and including 26 February 2007. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarized the data under the following themes: content and dissolution; relative bioavailability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. Results and discussion: The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that (i) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets, (ii) most antimalarial drugs pass the content test and (iii) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine,pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisinin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. Conclusions: There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the continent have access to antimalarial drugs that are safe, of the highest quality standards and that retain their integrity throughout the distribution chain through adequate enforcement of existing legislation and enactment of new ones if necessary, and provision of the necessary resources for drug quality assurance. [source] Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shorteningAGING CELL, Issue 1 2010Chen-Yu Liao Summary Chronic dietary restriction (DR) is considered among the most robust life-extending interventions, but several reports indicate that DR does not always extend and may even shorten lifespan in some genotypes. An unbiased genetic screen of the lifespan response to DR has been lacking. Here, we measured the effect of one commonly used level of DR (40% reduction in food intake) on mean lifespan of virgin males and females in 41 recombinant inbred strains of mice. Mean strain-specific lifespan varied two to threefold under ad libitum (AL) feeding and 6- to 10-fold under DR, in males and females respectively. Notably, DR shortened lifespan in more strains than those in which it lengthened life. Food intake and female fertility varied markedly among strains under AL feeding, but neither predicted DR survival: therefore, strains in which DR shortened lifespan did not have low food intake or poor reproductive potential. Finally, strain-specific lifespans under DR and AL feeding were not correlated, indicating that the genetic determinants of lifespan under these two conditions differ. These results demonstrate that the lifespan response to a single level of DR exhibits wide variation amenable to genetic analysis. They also show that DR can shorten lifespan in inbred mice. Although strains with shortened lifespan under 40% DR may not respond negatively under less stringent DR, the results raise the possibility that life extension by DR may not be universal. [source] Cerebral Embolism of Iodized Oil (Lipiodol) after Transcatheter Arterial Chemoembolization for Hepatocellular CarcinomaJOURNAL OF NEUROIMAGING, Issue 4 2009Joon-Tae Kim MD ABSTRACT Cerebral lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). Its pathological mechanism remains ambiguous despite several investigations. In Case 1, a 67-year-old man with hepatocellular carcinoma (HCC) experienced neurological deficits soon after undergoing a fourth session of TACE. Computed tomography (CT) scan showed multiple hyperdense lesions along the gyrus of frontal lobes and in the subcortical white matter. Transcranial Doppler (TCD) and transesophageal echocardiogram performed during the intravenous injection of agitated saline documented the presence of a right-to-left shunt (RLS) by demonstrating microbubbles in the left middle cerebral artery and left atrium. In Case 2, a 63-year-old woman underwent a third TACE due to a large HCC. After the procedure, her mental status deteriorated. Brain CT showed multiple hyperdense lesions on the cerebral and cerebellar cortex. TCD with agitated saline showed multiple microembolic signals shortly after the injection of agitated saline. The risk of cerebral lipiodol embolism may increase with recurrence and progression of HCC in patients who have a pre-existing RLS in the heart or lung. A test for the detection of an RLS may be necessary to identify patients with a heightened risk of cerebral embolism when multiple TACE procedures are required. TACE for HCC can cause pulmonary embolism or infarction.1,2 However, cerebral lipiodol embolism is rare after TACE. There have been several reports of cerebral embolism after TACE, but their exact mechanism has not yet been fully elucidated. We report herein 2 patients who developed cerebral lipiodol embolism after undergoing multiple TACE procedures for remnant HCC through a pre-existing RLS. [source] Impaired SDF1/CXCR4 signaling in glial progenitors derived from SOD1G93A miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2007Yongquan Luo Abstract Mutations in the superoxide dismutase 1 (SOD1) gene are associated with familial amyotrophic lateral sclerosis (ALS), and the SOD1G93A transgenic mouse has been widely used as one animal model for studies of this neurodegenerative disorder. Recently, several reports have shown that abnormalities in neuronal development in other models of neurodegeneration occur much earlier than previously thought. To study the role of mutant SOD1 in glial progenitor biology, we immortalized glial restricted precursors (GRIPs) derived from mouse E11.5 neural tubes of wild-type and SOD1G93A mutant mice. Immunocytochemistry using cell lineage markers shows that these cell lines can be maintained as glial progenitors, because they continue to express A2B5, with very low levels of glial fibrillary acidic protein (astrocyte), ,III-tubulin (neuron), and undetected GalC (oligodendrocyte) markers. RT-PCR and immunoblot analyses indicate that the chemokine receptor CXCR4 is reduced in SOD1G93A GRIPs. Subsequently, SOD1G93A GRIPs are unable to respond to SDF1, to activate ERK1/2 enzymes and the transcription factor CREB. This may be one pathway leading to a reduction in SOD1G93A cell migration. These data indicate that the abnormalities in SOD1G93A glial progenitor expression of CXCR4 and its mediated signaling and function occur during spinal cord development and highlight nonneuronal (glial) abnormalities in this ALS model. © 2007 Wiley-Liss, Inc. [source] Coexistence of Sjögren's syndrome and sarcoidosis: a report of five casesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2007M. J. Mansour Background:, Sjögren's syndrome (SS) and sarcoidosis are diseases that can affect the salivary glands and result in the loss of salivary gland function. Most of the criteria used for the diagnosis of SS exclude sarcoidosis before establishing the diagnosis of SS. However, several reports have suggested the coexistence of both SS and sarcoidosis in the same patient. Objective:, The purpose of this study was to present five cases that support a true coexistence of sarcoidosis and SS. Methods:, Clinical and laboratory findings of patients with evidence of having both SS and sarcoidosis were reviewed. The diagnosis of SS was based on the European community criteria; the diagnosis of sarcoidosis was based on the presence of serological, radiographic and/or histopathologic findings that are consistent with sarcoidosis. Results:, All patients fulfilled the criteria for the diagnosis of both diseases. Conclusion:, Our findings appear to support a true coexistence of sarcoidosis with SS. Therefore, it is reasonable to suggest removing the exclusion of sarcoidosis from the diagnostic criteria for SS. [source] | |||||||||||||||||||||||||||||||||||||