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    Improvement In Blood Pressure Control With Impedance Cardiography-Guided Pharmacologic Decision Making

    CONGESTIVE HEART FAILURE, Issue 1 2004
    Donald L. Sharman MD
    Previous reports have demonstrated improvement in blood pressure (BP) control utilizing noninvasive hemodynamic measurements with impedance cardiography (ICG). The purpose of this article is to report the effect of utilizing ICG-guided decision making to treat uncontrolled hypertension in a community generalist setting. Patient medical records were retrospectively reviewed for subjects on two antihypertensive agents with systolic blood pressure ,140 mm Hg or diastolic blood pressure ,90 mm Hg. All subjects were treated utilizing a previously published ICG-guided treatment algorithm. Twenty-one subjects met the BP and medication criteria. BP at entry was 157.2±13.9/78.7±9.9 mm Hg. Subjects were treated for 215±85 days (5.0±2.0 visits). After ICG-guided treatment, 12/21 (57.1%) achieved sustained BP control (p<0.001). BP was lowered to 141.6±22.0 (p<0.001)/77.1±10.7 (p>0.05) mm Hg. Antihypertensive agents increased from 2.0±0.0 to 2.5±0.7 (p<0.05). In this series of subjects with uncontrolled BP taking two antihypertensive agents, ICG-guided pharmacologic decision making resulted in significant reduction in BP and improvement in BP control. [source]


    Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USA

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2008
    David E Traul MD PhD
    We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity. [source]


    Proliferation and interleukin,5 production by CD8hiCD57+ T cells

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008

    Abstract CD8hiCD57+ T cells have previously been described as effector memory T cells with minimal expansion capacity and high susceptibility to activation-induced cell death. In contrast, we demonstrate here that CD8hiCD57+ T cells are capable of rapid expansion using multiple techniques including [3H]thymidine uptake, flow cytometric bead-based enumeration and standard haemocytometer counting. Previous reports can be explained by marked inhibition of activation-induced expansion and increased 7-amino-actinomycin,D uptake by CD8hiCD57+ T cells following treatment with CFSE, a dye previously used to measure their proliferation, combined with specific media requirements for the growth of this cell subset. The ability of CD8hiCD57+ T cells to further differentiate is highlighted by a distinct cytokine profile late after activation that includes the unexpected release of high levels of interleukin,5. These data indicate that CD8hiCD57+ T cells should not be considered as "end-stage" effector T cells incapable of proliferation, but represent a highly differentiated subset capable of rapid division and exhibiting novel functions separate from their previously described cytotoxic and IFN-, responses. [source]


    Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats

    ADDICTION BIOLOGY, Issue 4 2003
    María elena Quintanilla
    Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose-response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity. [source]


    Enzymatic control of anhydrobiosis-related accumulation of trehalose in the sleeping chironomid, Polypedilum vanderplanki

    FEBS JOURNAL, Issue 20 2010
    Kanako Mitsumasu
    Larvae of an anhydrobiotic insect, Polypedilum vanderplanki, accumulate very large amounts of trehalose as a compatible solute on desiccation, but the molecular mechanisms underlying this accumulation are unclear. We therefore isolated the genes coding for trehalose metabolism enzymes, i.e. trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) for the synthesis step, and trehalase (TREH) for the degradation step. Although computational prediction indicated that the alternative splicing variants (PvTps,/,) obtained encoded probable functional motifs consisting of a typical consensus domain of TPS and a conserved sequence of TPP, PvTps, did not exert activity as TPP, but only as TPS. Instead, a distinct gene (PvTpp) obtained expressed TPP activity. Previous reports have suggested that insect TPS is, exceptionally, a bifunctional enzyme governing both TPS and TPP. In this article, we propose that TPS and TPP activities in insects can be attributed to discrete genes. The translated product of the TREH ortholog (PvTreh) certainly degraded trehalose to glucose. Trehalose was synthesized abundantly, consistent with increased activities of TPS and TPP and suppressed TREH activity. These results show that trehalose accumulation observed during anhydrobiosis induction in desiccating larvae can be attributed to the activation of the trehalose synthetic pathway and to the depression of trehalose hydrolysis. [source]


    NEMO oligomerization in the dynamic assembly of the I,B kinase core complex

    FEBS JOURNAL, Issue 10 2007
    Elisabeth Fontan
    NF-,B essential modulator (NEMO) plays an essential role in the nuclear factor ,B (NF-,B) pathway as a modulator of the two other subunits of the I,B kinase (IKK) complex, i.e. the protein kinases, IKK, and IKK,. Previous reports all envision the IKK complex to be a static entity. Using glycerol-gradient ultracentrifugation, we observed stimulus-dependent dynamic IKK complex assembly. In wild-type fibroblasts, the kinases and a portion of cellular NEMO associate in a 350-kDa high-molecular-mass complex. In response to constitutive NF-,B stimulation by Tax, we observed NEMO recruitment and oligomerization to a shifted high-molecular-mass complex of 440 kDa which displayed increased IKK activity. This stimulus-dependent oligomerization of NEMO was also observed using fluorescence resonance energy transfer after a transient pulse with interleukin-1,. In addition, fully activated, dimeric kinases not bound to NEMO were detected in these Tax-activated fibroblasts. By glycerol gradient ultracentrifugation, we also showed that: (a) in fibroblasts deficient in IKK, and IKK,, NEMO predominantly exists as a monomer; (b) in NEMO-deficient fibroblasts, IKK, dimers are present that are less stable than IKK, dimers. Intriguingly, in resting Rat-1 fibroblasts, 160-kDa IKK,,NEMO and IKK,,NEMO heterocomplexes were observed as well as a significant proportion of NEMO monomer. These results suggest that most NEMO molecules do not form a tripartite IKK complex with an IKK,,IKK, heterodimer as previously reported in the literature but, instead, NEMO is able to form a complex with the monomeric forms of IKK, and IKK,. [source]


    Repeat Trigeminal Nerve Radiosurgery for Refractory Cluster Headache Fails to Provide Long-Term Pain Relief

    HEADACHE, Issue 2 2007
    Shearwood McClelland III MD
    Objective/Background.,Medically refractory cluster headache (MRCH) is a debilitating condition that has proven resistant to many modalities. Previous reports have indicated that radiosurgery for MRCH provides little long-term pain relief, with moderate/significant morbidity. However, there have been no reports of repeated radiosurgery in this patient population. We present our findings from the first reports of repeat radiosurgery for MRCH. Methods.,Two patients with MRCH underwent repeat gamma knife radiosurgery at our institution. Each fulfilled clinical criteria for treatment, including complete resistance to pharmacotherapy, pain primarily localized to the ophthalmic division of the trigeminal nerve, and psychological stability. Both patients previously received gamma knife radiosurgery (75 Gy) for MRCH with no morbidity, but no long-term improvement of pain relief (Patient 1 = 5 months, Patient 2 = 10 months) after treatment. For repeat radiosurgery, each patient received 75 Gy to the 100% isodose line delivered to the root entry zone of the trigeminal nerve, and was evaluated postretreatment. Pain relief was defined as: excellent (free of MRCH with minimal/no medications), good (50% reduction of MRCH severity/frequency with medications), fair (25% reduction), or poor (less than 25% reduction). Results.,Following repeat radiosurgery, long-term pain relief was poor in both patients. Neither patient sustained any immediate morbidity following radiosurgery. Patient 2 experienced right facial numbness 4 months postretreatment, while Patient 1 experienced no morbidity. Conclusion.,Repeat radiosurgery of the trigeminal nerve fails to provide long-term pain relief for MRCH. Given the reported failures of initial and repeat radiosurgery for MRCH, trigeminal nerve radiosurgery should not be offered for MRCH. [source]


    Amoxicillin Resistance in Helicobacter pylori: Studies from Tokyo, Japan from 1985 to 2003

    HELICOBACTER, Issue 1 2005
    Kazuhiro Watanabe
    ABSTRACT Background., Previous reports revealed no resistant strains of amoxicillin (AMPC), which is usually used in eradication therapy for H. pylori infection. However, the frequency and evolution of natural AMPC-resistant strains in the Japanese population remains unknown. Aim., To assess the prevalence of H. pylori resistance against AMPC in the Tokyo area, a collection of 648 H. pylori strains isolated from patients with GI diseases from 1985 to 2003 was tested for their sensitivity to AMPC. Methods., The susceptibility of the strains was assessed by determination of the minimal inhibitory concentration (MIC) using the E -test and/or the Dry-plate method. The susceptibility breakpoints of AMPC for H. pylori were: sensitive (AMPC-S); MIC < 0.04 µg/ml, intermittent resistance (AMPC-I); 0.04,1, resistant (AMPC-R); > 1. Results., No AMPC-R strains were detected in the strains isolated between 1985 and 1996, while the rate of resistance was determined to be 1.1%, 2.1%, 5.4%, 5.6%, 0%, 8.8%, and 1.5% every year, respectively, from 1997 to 2003. The percentage of AMPC-I strains increased from 2000 to 2003. The total eradication rate of H. pylori in the patients who received triple therapy containing AMPC was 81.4% (214/263). Classified as above, the rates of AMPC-S, AMPC-I, and AMPC-R were 84.6%, 77.8%, 25%, respectively. Conclusion.,H. pylori resistance to AMPC is still rare in Japan, although the percentage of AMPC-I strains has increased over the last 4 years. The frequency of isolation of strains showing true resistance to AMPC may increase in the future, along with an increase in the frequency of isolation of AMPC-I strains. [source]


    Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat

    IMMUNOLOGY, Issue 2 2000
    E. Kenny
    Summary Among peripheral T cells, the expression of CD4 and CD8 is almost mutually exclusive. However, here we show, using flow cytometric analysis, that ex vivo approximately 6% of rat T cells stained for both CD4 and CD8. These double positive cells were also detected by confocal microscopy. Only around 50% of double positive cells expressed the CD8, chain, the remaining cells expressed the CD8, chain alone. Double positive cells were blast-like with a phenotype, distinct from that of either CD4 or CD8 single positive cells, suggestive of an activated state. Previous reports of double positive T cells have also suggested that coexpression of CD4 and CD8 is linked to the activation state of the cell. There was an indication that priming animals with a hapten-carrier complex increased the ratio of CD8,,,:,,, expressing double positive T cells, although we did not detect an increase in the frequency of double positive T cells following priming. We also show that the frequency of double positive cells was reduced following thymectomy and with age. In conclusion, these studies show that peripheral T cells expressing both CD4 and CD8 can be detected in the rat and that they are phenotypically distinct from CD4 and CD8 single positive T cells. [source]


    Proteasome inhibition with bortezomib suppresses growth and induces apoptosis in osteosarcoma

    INTERNATIONAL JOURNAL OF CANCER, Issue 1 2010
    Yuriy Shapovalov
    Abstract Osteosarcomas are primary bone tumors of osteoblastic origin that mostly affect adolescent patients. These tumors are highly aggressive and metastatic. Previous reports indicate that gain of function of a key osteoblastic differentiation factor, Runx2, leads to growth inhibition in osteosarcoma. We have previously established that Runx2 transcriptionally regulates expression of a major proapoptotic factor, Bax. Runx2 is regulated via proteasomal degradation, and proteasome inhibition has a stimulatory effect on Runx2. In this study, we hypothesized that proteasome inhibition will induce Runx2 and Runx2-dependent Bax expression sensitizing osteosarcoma cells to apoptosis. Our data showed that a proteasome inhibitor, bortezomib, increased Runx2 and Bax in osteosarcoma cells. In vitro, bortezomib suppressed growth and induced apoptosis in osteosarcoma cells but not in nonmalignant osteoblasts. Experiments involving intratibial tumor xenografts in nude mice demonstrated significant tumor regression in bortezomib-treated animals. Immunohistochemical studies revealed that bortezomib inhibited cell proliferation and induced apoptosis in osteosarcoma xenografts. These effects correlated with increased immunoreactivity for Runx2 and Bax. In summary, our results indicate that bortezomib suppresses growth and induces apoptosis in osteosarcoma in vitro and in vivo suggesting that proteasome inhibition may be effective as an adjuvant to current treatment regimens for these tumors. Published 2009 UICC. This article is a US Government work and, as such, is in the public domain in the United States of America. [source]


    Ichthyosiform eruption associated with lamivudine in a patient with chronic hepatitis-B infection

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2005
    A. F. Kaptanoglu
    Summary The side-effects of antiretroviral agents have been widely reported in the literature. Lamivudine is an antiretroviral agent, and skin eruption because of this agent has been rarely reported. Previous reports regarding these few side-effects of lamivudine include angioedema, urticaria, anaflactoid reactions, allergic contact dermatitis and alopecia. There is no report of an ichthyosiform eruption associated with lamivudine. The authors present a case of 43-year-old female patient presenting with an ichthyosiform eruption during lamivudine therapy for chronic hepatitis-B for the first time. [source]


    Myelodysplastic syndrome associated with trisomy 2

    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2005
    M. HELLER
    Summary Clinical course and cytogenetic analysis suggest that myelodysplasia (MDS) is one step in a multistep model of malignant transformation of haematopoietic stem cells to acute myeloid leukaemia (AML). We report a further case of MDS associated with trisomy 2, and comment on the significance of the cytogenetic abnormality, which as a sole abnormality only occurs in MDS, but is found in combination with other chromosomal abnormalities in AML. Previous reports on balanced and unbalanced chromosomal abnormalities associated with therapy related MDS and therapy related AML suggest that trisomy 2 is an early chromosomal abnormality in leukaemogenesis. [source]


    Massive epithelioid angiomyolipoma of the kidney in a young girl

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005
    MING-SHAN HUNG
    Abstract, We report the case of a huge right renal tumor in a 17-year-old girl. Absence of fat on preoperative magnetic resonance imaging suggested renal cell carcinoma, and surgery was performed. Pathologic evaluation with HMB-45 immunohistochemical staining con,rmed the diagnosis of epithelioid angiomyolipoma. The tumor consisted predominantly of epithelioid cells, and it could easily be misidenti,ed as a renal cell carcinoma due to the paucity of the fat component. Previous reports have suggested that epithelioid angiomyolipomas have the potential to be malignant, and thus regular postoperative surveillance is recommended. Our patient had no signs of recurrence at her most recent follow up, 12 months after surgery. [source]


    School nursing: costs and potential benefits

    JOURNAL OF ADVANCED NURSING, Issue 5 2000
    Linda Cotton RHV
    School nursing: costs and potential benefits Background. Previous reports that variations in school nursing resources across the UK had no relationship to deprivation; controversy about the changing role of the school nursing service. Objectives. To measure the resources allocated to school nursing, determine whether the variations can be explained by deprivation, and assess whether the allocation of school nursing time to a range of tasks is in line with current evidence and perceptions of changing needs. Study design. Quantitative economic analysis; qualitative descriptive study. Setting. Detailed study of four English districts with diverse characteristics; staffing and service questionnaire and telephone survey of 62 districts. Main measures. Staff resources and their salaries; measures of population and deprivation; activity statistics. Results. There were wide variations in the cost of the school nursing service, but in contrast to previous reports 24% of the variance was explained by deprivation. There were no clear associations with any other social or educational variables. The greatest allocation of time was in routine screening and surveillance tasks. Relatively little time was allocated to other activities such as health promotion, support of special needs or unwell children, or teenage clinics. The expenditure on school nursing is only loosely related to deprivation and the results of this study offer guidance on what districts should spend to achieve equity of provision. Conclusions. The current allocation of resources to school nursing in between districts comparisons is not equitable and the use of school nursing time is out of step with current evidence of need and effectiveness. [source]


    Perspectives on hyperphalangy: patterns and processes

    JOURNAL OF ANATOMY, Issue 3 2004
    Tim J. Fedak
    Abstract Hyperphalangy is a digit morphology in which increased numbers of phalanges are arranged linearly within a digit beyond the plesiomorphic condition. We analyse patterns and processes of hyperphalangy by considering previous definitions and occurrences of hyperphalangy among terrestrial and secondarily aquatic extant and fossil taxa (cetaceans, ichthyosaurs, plesiosaurs and mosasaurs), and recent studies that elucidate the factors involved in terrestrial autopod joint induction. Extreme hyperphalangy, defined as exceeding a threshold condition of 4/6/6/6/6, is shown only to be found among secondarily aquatic vertebrates with a flipper limb morphology. Based on this definition, hyperphalangy occurs exclusively in digits II and III among extant cetaceans. Previous reports of cetacean embryos having more phalanges than adults is clarified and shown to be based on cartilaginous elements not ossified phalanges. Developmental prerequisites for hyperphalangy include lack of cell death in interdigital mesoderm (producing a flipper limb) and maintenance of a secondary apical ectodermal ridge (AER), which initiates digit elongation and extra joint patterning. Factors of the limb-patterning pathways located in the interdigital mesoderm, including bone morphogenetic proteins (BMPs), BMP antagonists, fibroblast growth factors (FGFs), growth/differentiation factor-5 (GDF-5), Wnt-14 and ck-erg, are implicated in maintenance of the flipper limb, secondary AER formation, digit elongation and additional joint induction leading to hyperphalangy. [source]


    Lead-induced alterations of apoptosis and neurotrophic factor mRNA in the developing rat cortex, hippocampus, and cerebellum

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2007
    Shirley L. Chao
    Abstract Previous reports have recently shown the prototypic neurotoxicant, lead, to induce apoptosis in the brains of developing organisms. In the current study, timed-pregnant rats were exposed to lead acetate (0.2% in the drinking water) 24 h following birth at postnatal day 1 (PND 1). Dams and pups were continuously exposed to lead through the drinking water of the dam until PND 20. Postnatal exposure in the pups resulted in altered mRNA levels of the following apoptotic and neurotrophic factors: caspase 2 and 3, bax, bcl-x, brain-derived neurotrophic factor (BDNF). Ribonuclease protection assays were conducted to measure the factors simultaneously at the following postnatal time points: 9, 12, 15, 20, 25, days. Our results suggest a brain region- and time-specific response following lead acetate exposure. The region most vulnerable to alterations occurs in the hippocampus with alterations beginning at PND 12, in which caspase 3, bcl-x, BDNF increase with lead exposure. Significant treatment effects were not observed for both the cortex and cerebellum. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:265,272, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20191 [source]


    Cloning and molecular dissection of the 8.8 kb pig uroplakin II promoter using transgenic mice and RT4 cells

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006
    Deug-Nam Kwon
    Abstract Uroplakin II (UPII) gene expression is highly tissue and cell specific, with mRNA present in the suprabasal cell layers of the bladder and urethra. Previous reports described the mouse UPII (mUPII) promoter as primarily urothelium selective. However, ectopic expression of a transgene under the 3.6 kb mUPII promoter was also detected in brain, kidney, and testis in some transgenic mouse lines. Here, we have cloned an 8.8 kb pig UPII (pUPII) promoter region and investigated which cells within the bladder and urethra express a transgene consisting of the pUPII promoter fused to human erythropoietin (hEPO) or a luciferase gene. pUPII-luciferase expression vectors with various deletions of the promoter region were introduced into mouse fibroblast (NIH3T3), Chinese hamster ovary (CHO), and human bladder transitional carcinoma (RT4). A 2.1 kb pUPII promoter fragment displayed high levels of luciferase activity in transiently transfected RT4 cells, whereas the 8.8 kb pUPII promoter region displayed only low levels of activity. The pUPII-hEPO expression vector was injected into the pronucleus of zygotes to make transgenic mice. To elucidate the in vivo molecular mechanisms controlling the tissue- and cell-specific expression of the pUPII promoter gene, transgenic mice containing 2.1 and 8.8 kb pUPII promoter fragments linked to the genomic hEPO gene were generated. An erythropoietin (EPO) assay showed that all nine transgenic lines carrying the 8.8 kb construct expressed recombinant human erythropoietin (rhEPO) only in their urethra and bladder, whereas two transgenic lines carrying the 2.1 kb pUPII promoter displayed hEPO expression in several organs including bladder, kidney, spleen, heart, and brain. These studies demonstrate that the 2.1 kb promoter contains the DNA elements necessary for high levels of expression, but lacks critical sequences necessary for tissue-specific expression. We compared binding sites in the 2.1 and 8.8 kb promoter sequences and found five peroxisome proliferator responsive elements (PPREs) in the 8.8 kb promoter. Our data demonstrated that proliferator-activated receptor (PPAR)-, activator treatment in RT4 cells induced the elevated expression of hEPO mRNA under the control of the 8.8 kb pUPII promoter, but not the 2.1 kb promoter. Collectively, our data suggested that all the major trans-regulatory elements required for bladder- and urethra-specific transcription are located in the 8.8 kb upstream region and that it may enhance tissue-specific protein production and be of interest to clinicians who are searching for therapeutic modalities with high efficacy and low toxicity. J. Cell. Biochem. 99: 462,477, 2006. © 2006 Wiley-Liss, Inc. [source]


    Red cell exchange transfusion for babesiosis in Rhode Island

    JOURNAL OF CLINICAL APHERESIS, Issue 3 2009
    Joshua Spaete
    Abstract We report four cases of clinically severe tick borne babesiosis treated with chemotherapy and adjunctive red cell exchange (RCE) at two Rhode Island hospitals from 2004 to 2007. All RCE procedures were performed using a Cobe Spectra device and were well tolerated without complications. The volume of allogeneic red cells used in the exchange was determined using the algorithm in the apheresis device with the input variables of preprocedure hematocrit, weight, height, an assumed allogeneic red cell hematocrit of 55 and a desired post procedure hematocrit of 27. The preprocedure level of parasitemia varied between 2.4% and 24% and the postprocedure level of parasitemia between 0.4 and 5.5% with an average overall percent reduction in parasitemia of 74%. Retrospectively, application of a new formula to calculate red cell mass appeared to correlate better with the percent reduction in parasitemia. Previous reports of RCE in babesiosis were reviewed. The reported reduction in parasitemia varied from 50% to >90%. Although a preprocedure level of parasitemia of 10% is sometimes used as a threshold for RCE in clinically severe babesiosis, this threshold does not have a firm empirical basis. No postprocedure desired level of parasitemia is indicated nor the mass of allogeneic red cells needed to achieve such a level. We conclude that current estimates of the dose of allogeneic red cells used in RCE are probably inaccurate, advocate a new formula to estimate this dose and suggest that a 90% reduction in parasitemia should be the minimally desired target of RCE in babesiosis. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source]


    Single cell PCR from archival stained bone marrow slides: A method for molecular diagnosis and characterization

    JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2004
    Stefanie Zanssen
    Abstract Molecular analysis of isolated single cells is a powerful tool for clarifying issues of cell origin and clonality. Previous reports have described PCR amplifications from total DNA and RNA extracted from archival bone marrow and peripheral blood smears and have also shown the feasibility of amplifications from single cells, microdissected from stained histological sections. In this study, a method is described for performing PCR from morphologically defined single cells isolated from archival May-Gruenwald-Giemsa-stained bone-marrow and blood smears. Using three DNA extraction procedures, the organic lysis showed reproducible high efficiencies of amplifications. With this method, we were able to amplify long range amplicons up to 14.5 kb from mitochondrial DNA as well as PCR products of conventional length. The usability of such products for molecular diagnosis is demonstrated by restriction fragment length polymorphism (RFLP)characterization of a mitochondrial disorder. In conclusion, this method has the power to perform molecular diagnosis and characterization of diseases on the single cell level, and should provide valuable information to aid disease treatment and prognosis of hematological disorders. J. Clin. Lab. Anal. 18:176,181, 2004. © 2004 Wiley-Liss, Inc. [source]


    Muscle precursor cells isolated from aged rats exhibit an increased tumor necrosis factor-, response

    AGING CELL, Issue 1 2009
    Simon J. Lees
    Summary Improving muscle precursor cell (MPC, muscle-specific stem cells) function during aging has been implicated as a key therapeutic target for improving age-related skeletal muscle loss. MPC dysfunction during aging can be attributed to both the aging MPC population and the changing environment in skeletal muscle. Previous reports have identified elevated levels of tumor necrosis factor-, (TNF-,) in aging, both circulating and locally in skeletal muscle. The purpose of the present study was to determine if age-related differences exist between TNF-,-induced nuclear factor-kappa B (NF-,B) activation and expression of apoptotic gene targets. MPCs isolated from 32-month-old animals exhibited an increased NF-,B activation in response to 1, 5, and 20 ng mL,1 TNF-,, compared to MPCs isolated from 3-month-old animals. No age differences were observed in the rapid canonical signaling events leading to NF-,B activation or in the increase in mRNA levels for TNF receptor 1, TNF receptor 2, TNF receptor-associated factor 2 (TRAF2), or Fas (CD95) observed after 2 h of TNF-, stimulation. Interestingly, mRNA levels for TRAF2 and the cell death-inducing receptor, Fas (CD95), were persistently upregulated in response to 24 h TNF-, treatment in MPCs isolated from 32-month-old animals, compared to 3-month-old animals. Our data indicate that age-related differences may exist in the regulatory mechanisms responsible for NF-,B inactivation, which may have an effect on TNF-,-induced apoptotic signaling. These findings improve our understanding of the interaction between aged MPCs and the changing environment associated with age, which is critical for the development of potential clinical interventions aimed at improving MPC function with age. [source]


    Translocation of viable Aeromonas salmonicida across the intestine of rainbow trout, Oncorhynchus mykiss (Walbaum)

    JOURNAL OF FISH DISEASES, Issue 5 2006
    F Jutfelt
    Abstract The pathogenic bacterium Aeromonas salmonicida is the causative agent of the destructive disease furunculosis in salmonids. Horizontal transmission in salmonids has been suggested to occur via the skin, gills and/or intestine. Previous reports are contradictory regarding the role of the intestine as a route of infection. The present study therefore investigates the possibility of bacterial translocation across intestinal epithelia using Ussing chamber technology, in vitro. Intestinal segments were exposed for 90 min to fluorescein isothiocyanate-labelled pathogenic A. salmonicida. Sampling from the serosal side of the Ussing chambers showed that bacteria were able to translocate across the intestinal epithelium in both the proximal and distal regions. Plating and subsequent colony counting showed that the bacteria were viable after translocation. During the 90 min exposure to A. salmonicida, the intestinal segments maintained high viability as measured by electrical parameters. The distal region responded to bacterial exposure by increasing the electrical resistance, indicating an increased mucus secretion. This study thus demonstrates translocation of live A. salmonicida through the intestinal epithelium of rainbow trout, suggesting that the intestine is a possible route of infection in salmonids. [source]


    Prevalence, morbidity and service need among South Asian and white adults with intellectual disability in Leicestershire, UK

    JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 4 2002
    C. W. McGrother
    Abstract Background Previous reports have suggested that South Asian and white UK populations have different prevalences of intellectual disability (ID), related psychological morbidity and service use. The aim of the present study was to compare these rates among South Asian and white adults in Leicestershire, UK. Method This cross-sectional study is comprised of two parts. The analysis of prevalence is based on data from all South Asian and white adults known to the Leicestershire Learning Disabilities Register in 1991, with population denominators being drawn from the 1991 census. The other analyses use data collected from the most recent semi-structured home interviews, carried out between 1987 and 1998, with 206 South Asian and 2334 white adults. Results The prevalence of ID in adults in Leicestershire is 3.20 per 1000 in South Asians and 3.62 per 1000 in whites. Among adults with ID, South Asians have similar prevalences of disabilities to whites and significantly lower skill levels. South Asians show similar levels of psychological morbidity, but make significantly lower use than whites of psychiatric services, residential care and respite care. South Asians use community services as extensively as whites, but feel that they have a substantially greater unmet need, especially with regard to social services. Conclusion South Asian and white populations have similar prevalences of ID and related psychological morbidity. Culturally appropriate services for South Asian adults may need to focus on skill development and community care. [source]


    Risk factors and mechanism of transplacental transmission of hepatitis B virus: A case-control study

    JOURNAL OF MEDICAL VIROLOGY, Issue 1 2002
    De-Zhong Xu
    Abstract Intrauterine hepatitis B virus (HBV) infection has been suggested to be caused by transplacental transmission that cannot be blocked by hepatitis B vaccine. This would decrease the effectiveness of hepatitis B vaccine. This study examined the risk factors and mechanism of transplacental HBV transmission. A case-control study included 402 newborn infants from 402 HBsAg-positive pregnant women. Among these, 15 newborn infants infected with HBV by intrauterine transmission were selected as cases, and the rest as controls. A pathology study included 101 full-term placentas from the HBsAg-positive pregnant women above and 14 from HBsAg-negative pregnant women. Immunohistochemistry staining and HBV DNA in situ hybridization were used to estimate the association of intrauterine HBV infection and HBV infection in the placentas. HBeAg positivity in mothers' sera (OR,=,17.07, 95%CI 3.39,86.01) and threatened preterm labor (OR,=,5.44, 95%CI 1.15,25.67) were found to be associated with transplacental HBV transmission. The intrauterine infection rate increased linearly and significantly with maternal serum HBsAg titers (trend test P,=,0.0117) and HBV DNA concentration (trend test P,<,0.01). Results of the pathology study showed that HBV infection rates decreased gradually from the maternal side to the fetal side (trend test P,=,0.0009) in the placental cell layers. There was a significant association between intrauterine HBV transmission and HBV infection in villous capillary endothelial cells (VCEC) in the placenta (OR,=,18.46, P,=,0.0002). The main risk factors for intrauterine HBV infection are maternal serum HBeAg positivity, history of threatened preterm labor, and HBV in the placenta especially the villous capillary endothelial cells. Previous reports of transplacental leakage of maternal blood causing intrauterine infection are confirmed. In addition, there appears to be a "cellular transfer" of HBV from cell to cell in the placenta causing intrauterine infection. This latter hypothesis needs to be confirmed. J. Med. Virol. 67:20,26, 2002. © 2002 Wiley-Liss, Inc. [source]


    Impaired Glucose Tolerance in the R6/1 Transgenic Mouse Model of Huntington's Disease

    JOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2008
    K. Josefsen
    Previous reports have highlighted a possible link between Huntington's disease (HD) and diabetes mellitus (DM), but the association has not been characterised in detail. A transgenic mouse model for HD, the R6/2 mouse, also develops diabetes. In the present study, we examined the R6/1 mouse, which carries a shorter CAG repeat than the R6/2 mouse, and found that, although not diabetic, the mice showed several signs of impaired glucose tolerance. First, following i.p. glucose injection, the blood glucose concentration was approximately 30% higher in young R6/1 mice (10 weeks) compared to wild-type mice (P = 0.004). In older mice (38 weeks), glucose tolerance was further impaired in both R6/1 and wild-type animals. Second, during glucose challenge, the R6/1 mice reached higher plasma insulin levels than wild-type mice, but the peripheral insulin sensitivity was normal as measured by injection of human or mouse insulin or when evaluated by the quantitative insulin sensitivity check index (QUICKI). Third, the beta cell volume was 17% and 39% smaller at 10 and 38 weeks of age, respectively, compared to age-matched wild-type littermates and the reduction was not caused by apoptosis at either age. Finally, we demonstrated the presence of the HD gene product, huntingtin (htt), in both alpha- and beta-cells in R6/1 islets of Langerhans. Since pancreatic beta cells and neurons share several common traits, clarification of the mechanism associating neurodegenerative diseases with diabetes might improve our understanding of the pathogenic events leading to both groups of diseases. [source]


    Mutual effects of caveolin and nerve growth factor signaling in pig oligodendrocytes

    JOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2010
    Matthias Schmitz
    Abstract Signaling of growth factors may depend on the recruitment of their receptors to specialized microdomains. Previous reports on PC12 cells indicated an interaction of raft-organized caveolin and TrkA signaling. Because porcine oligodendrocytes (OLs) respond to nerve growth factor (NGF), we were interested to know whether caveolin also plays a role in oligodendroglial NGF/TrkA signaling. OLs expressed caveolin at the plasma membrane but also intracellularly. This was partially organized in the classically ,-shaped invaginations, which may represent caveolae. We could show that caveolin and TrkA colocalize by using a discontinuous sucrose gradient (Song et al. [1996] J. Biol. Chem. 271:9690,9697), MACS technology, and immunoprecipitation. However, differential extraction of caveolin and TrkA with Triton X-100 at 4°C indicated that caveolin and TrkA are probably not exclusively present in detergent-resistant, caveolin-containing rafts (CCRs). NGF treatment of OLs up-regulated the expression of caveolin-1 (cav-1) and stimulated tyrosine-14 phosphorylation of cav-1. Furthermore, OLs were transfected with cav-1-specific small interfering RNA (siRNA). A knockdown of cav-1 resulted in a reduced activation of downstream components of the NGF signaling cascade, such as p21Ras and mitogen-activated protein kinase (MAPK) after NGF exposure of OLs. Subsequently, increased oligodendroglial process formation via NGF was impaired. The present study indicates that CCRs/caveolin could play a modulating role during oligodendroglial differentiation and regeneration. © 2009 Wiley-Liss, Inc. [source]


    Analysis of the capsular polysaccharide biosynthesis locus of Porphyromonas gingivalis and development of a K1-specific polymerase chain reaction-based serotyping assay

    JOURNAL OF PERIODONTAL RESEARCH, Issue 6 2008
    J. Brunner
    Background and Objective:,Porphyromonas gingivalis is a gram-negative obligate anaerobe that is strongly associated with severe periodontitis. Previous reports showed an association of P. gingivalis capsular polysaccharide with virulence. The K1 capsular polysaccharide was found to be more immunostimulatory than the other serotypes. Our objective was to explore the genetic background of the capsule biosynthesis (K-antigen) locus in a representative group of K1 serotype strains. Material and Methods:, We used restriction fragment length polymorphism, polymerase chain reaction (PCR) and DNA sequencing to study the capsular polysaccharide locus in P. gingivalis K1 strains. For serotyping by double immunodiffusion and PCR we used 32 strains of P. gingivalis, including strains of all six known K serotypes. Results:, All tested K1 strains showed high conservation of the capsular polysaccharide locus, although a DNA re-arrangement was found in two strains. Based on this information a K1-specific PCR-based serotyping assay was designed. The specificity and sensitivity of this test were confirmed using non-K1 P. gingivalis serotypes. Conclusion:, The capsular polysaccharide locus of P. gingivalis is conserved but may vary slightly among K1 strains. The new K1 serotyping assay presented here is much faster than double immunodiffusion and can detect K1 strains in a very selective and sensitive way. This method may therefore be clinically relevant in the detection of the virulent P. gingivalis K1 serotype. [source]


    Increased Consumption but Not Operant Self-administration of Ethanol in Mice Lacking the RII, Subunit of Protein Kinase A

    ALCOHOLISM, Issue 5 2006
    Frank M. Ferraro III
    Background: Accumulating evidence indicates that adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the neurobiological responses to ethanol. Previous reports indicate that mice lacking the RII, subunit of PKA (RII,,/,) voluntarily consume more ethanol than wild-type controls (RII,+/+) using 2-bottle testing procedures. Although such procedures primarily measure consummatory behavior, operant self-administration procedures allow analysis of consummatory as well as appetitive or "ethanol-seeking" behavior (i.e., lever pressing is required to gain access to the ethanol solution). Therefore, we determined whether the high ethanol consumption characteristic of RII,,/, mice would be complemented by increased appetitive ethanol-seeking behavior in an operant paradigm. Methods: RII,,/, (n=8) and RII,+/+ (n=8) mice were initially sucrose-faded until they were lever responding for nonsweetened ethanol (10, 14, and 18%). Following the self-administration testing, RII,+/+ and RII,,/, mice were given access to 2 bottles, one containing water and the other ethanol to replicate the voluntary ethanol drinking data previously from our laboratory. Finally, immediately after voluntary consumption all mice were again tested for self-administration of 10% ethanol. Alterations in the reinforcement schedule were also explored as RII,+/+ and RII,,/, mice were tested for self-administration of 10% ethanol at FR-3 and FR-5 schedules. Results: The RII,,/, mice displayed lower operant responding for ethanol and food reinforcement compared with RII,+/+ controls. However, this effect was driven by a significant increase in lever responses made by female RII,+/+ mice. When the excessive lever responses of the female RII,+/+ mice are accounted for, the RII,,/, mice show ethanol lever responses comparable to controls. Following operant self-administration testing, RII,,/, mice of both sexes consumed more ethanol solution compared with RII,+/+ mice during 2-bottle testing. Conclusions: Increased ingestion of ethanol by RII,,/, mice is likely the result of altered PKA activity within neuronal pathways that control ethanol-consummatory behaviors. Conversely, the RII, subunit of PKA appears not to play a critical role in neuronal pathways that regulate appetitive behaviors directed at obtaining ethanol. Finally, increased operant self-administration of food and ethanol by female wild-type mice was absent in female RII,,/, mice, suggesting that normal PKA signaling may be part of a general, and sex-dependent, mechanism involved with reinforcement-seeking behavior. [source]


    Reduced tear production in three canine endocrinopathies,

    JOURNAL OF SMALL ANIMAL PRACTICE, Issue 5 2007
    D. L. Williams
    Objectives: Previous reports have suggested that hypothyroid and diabetic patients can be predisposed to keratoconjunctivitis sicca. This study aimed to measure tear production in dogs with diabetes, hypothyroidism and hyperadrenocorticism using the Schirmer tear test and to compare these results with Schirmer tear test values for a group of normal dogs. Methods: Schirmer tear tests were performed on 16 dogs with hyperadrenocorticism, 18 with diabetes and 12 with hypothyroidism together with 100 control dogs. Corneal sensitivity was also measured in 12 of the 18 diabetic dogs with a Cochet Bonnet aesthesiometer and compared with age- and breed-matched normal dogs. Results: Schirmer tear test values in dogs with hypothyroidism, hyperadrenocorticism and diabetes were 12·3±3·2, 14·0±4·0 and 12·3±5·3 mm/minutes, respectively. Schirmer tear test values were significantly lower than that for the control group (19·6±4·2 mm/minutes) in all dogs with an endocrinopathy. Only in two hypothyroid dogs and three diabetics, this was manifested as profound keratoconjunctivitis sicca with Schirmer tear test value lower than 5 mm/minutes. Diabetic dogs had significantly reduced corneal sensitivity compared with a matched set of control dogs. Clinical Significance: This study shows a significant reduction in tear production in animals with diabetes mellitus, hypothyroidism and hyperadrenocorticism. Further research is needed to elucidate the mechanisms by which this reduction in tear production occurs. Assessment of tear production should be undertaken in animals diagnosed with these endocrinopathies, as these animals may progress to clinical keratoconjunctivitis sicca. [source]


    POTENTIAL IMPACTS OF CLIMATE CHANGE ON CALIFORNIA HYDROLOGY,

    JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION, Issue 4 2003
    Norman L. Miller
    ABSTRACT: Previous reports based on climate change scenarios have suggested that California will be subjected to increased wintertime and decreased summertime streamflow. Due to the uncertainty of projections in future climate, a new range of potential climatological future temperature shifts and precipitation ratios is applied to the Sacramento Soil Moisture Accounting Model and Anderson Snow Model in order to determine hydrologic sensitivities. Two general circulation models (GCMs) were used in this analysis: one that is warm and wet (HadCM2 run 1) and one that is cool and dry (PCM run B06.06), relative to the GCM projections for California that were part of the Third Assessment Report of the Intergovernmental Panel on Climate Change. A set of specified incremental temperature shifts from 1.5°C to 5.0°C and precipitation ratios from 0.70 to 1.30 were also used as input to the snow and soil moisture accounting models, providing for additional scenarios (e.g., warm/dry, cool/wet). Hydrologic calculations were performed for a set of California river basins that extend from the coastal mountains and Sierra Nevada northern region to the southern Sierra Nevada region; these were applied to a water allocation analysis in a companion paper. Results indicate that for all snow-producing cases, a larger proportion of the streamflow volume will occur earlier in the year. The amount and timing is dependent on the characteristics of each basin, particularly the elevation. Increased temperatures lead to a higher freezing line, therefore less snow accumulation and increased melting below the freezing height. The hydrologic response varies for each scenario, and the resulting solution set provides bounds to the range of possible change in streamflow, snowmelt, snow water equivalent, and the change in the magnitude of annual high flows. An important result that appears for all snowmelt driven runoff basins, is that late winter snow accumulation decreases by 50 percent toward the end of this century. [source]


    Rehires and Unemployment Duration in the Swedish Labour Market , New Evidence of Temporary Layoffs

    LABOUR, Issue 2 2002
    Fredrik JanssonArticle first published online: 7 JAN 200
    The paper investigates temporary layoffs in the Swedish labour market. Previous reports of few temporary layoffs are rejected. About 45 percent of unemployed people who found a job returned to a previous employer. As a stock measure, 10 percent of the unemployed are on temporary layoff. Using new job and recall as distinct exits in a competing risks model, one cannot reject a horizontal duration dependence for new jobs, while the recall hazard shows a strong, negative duration dependence. Clearer predictions of the effect of education on job probabilities are also found. Further, the results probably have implications for the interpretation of several policy parameters, including labour market programme outcomes. [source]