calcineurin-inhibitor-free de-novo immunosuppression: Topics by WorldWideScience.org

Synthesis and characterization of new platinum(II) complexes containing oxalate and derivatives of ethylenediamine as ligands; Sintese e caracterizacao de novos complexos de platina (II) contendo oxalato e derivados da etilenodiamina como ligantes

Transformed Drosophila Kc cell lines, resistant to methotrexate, an inhibitor of de novo purine and pyrimidine synthesis, have been obtained by calcium phosphate transfection of plasmids containing...Full Text Available

1983-01-01

Straightforward and de Novo Peptide Sequencing by MALDI-MS/MS Using a Lys-N Metalloendopeptidase*S?

No abstract prepared.

2006-07-01

Replication Stress Induces Genome-wide Copy Number Changes in Human Cells that Resemble Polymorphic and Pathogenic Variants

In this work, we explore the potential of the metalloendopeptidase Lys-N for MALDI-MS/MS proteomics applications. Initially we digested a HEK293 cellular lysate with Lys-N and, for comparison, in parallel...Full Text Available

2009-04-01

De Novo Induction of Genetically Engineered Brain Tumors In Mice Using Plasmid DNA

Copy number variants (CNVs) are an important component of genomic variation in humans and other mammals. Similar de novo deletions and duplications, or copy number changes (CNCs), are now known to be...Full Text Available

2009-03-13

Auxin Biosynthesis during Seed Germination in Phaseolus vulgaris¹

Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required to generate spontaneous...Full Text Available

2009-01-15

The SPIRIT V Study:A Clinical Evaluation of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With De Novo Coronary Artery Lesions

The relative roles of de novo biosynthesis of indoleacetic acid (IAA) and IAA conjugates stored in mature seeds (Phaseolus vulgaris L.) in supplying auxin to germinating bean seedlings...Full Text Available

1992-09-01

British Library Electronic Table of Contents (United Kingdom)

ObjectivesThe SPIRIT V (A Clinical Evaluation of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With De Novo Coronary Artery Lesions) study is a post-market surveillance experience of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) in patients with higher-risk coronary anatomy. BackgroundPrevious pre-approval studies have shown the safety and efficacy of EES in highly selected groups of patients. MethodsThe SPIRIT V trial is a prospective, open label, single arm, multicenter study. Two thousand seven hundred patients with multiple de novo coronary artery lesions suitable for treatment with a planned maximum of 4 EES were enrolled at 93 centers in Europe, Asia Pacific, Canada, and South Africa. Lesions had a referenc...

2011-01-01

Viral suppression of multiple escape mutants by de novo CD8⁺T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

Synthesis and characterization of new platinum(II) complexes with N-alkylated ligands of longer chain containing a hydroxyl group derivatives of 1,2-etano diamine;Sintese e caracterizacao de novos complexos de platina(II) com ligantes N-alquilados de cadeia longa contendo um grupo hidroxila derivados da 1,2-etanodiamina

Elite suppressors or controllers (ES) are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated...Full Text Available

Insect-Induced Conifer Defense. White Pine Weevil and Methyl Jasmonate Induce Traumatic Resinosis, de Novo Formed Volatile Emissions, and Accumulation of Terpenoid Synthase and Putative Octadecanoid Pathway Transcripts in Sitka Spruce1[w

No abstract prepared.

2009-07-01

Designing Human m₁ Muscarinic Receptor-Targeted Hydrophobic Eigenmode Matched Peptides as Functional Modulators

Stem-boring insects and methyl jasmonate (MeJA) are thought to induce similar complex chemical and anatomical defenses in conifers. To compare insect- and MeJA-induced terpenoid responses, we analyzed...Full Text Available

2005-01-01

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

A new proprietary de novo peptide design technique generated ten 15-residue peptides targeting and containing the leading nontransmembrane hydrophobic autocorrelation wavelengths, “modes”,...Full Text Available

2004-03-01

The skin of Osedax (Siboglinidae, Annelida): An ultrastructural investigation of its epidermis

BackgroundPaclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

The symbiotic polychaetes of the genus Osedax living on the bones of whale carcasses have become known as bone-eating worms. It is believed that whale bones are the source of nutrition for those gutless worms and that fatty acids are produced by their symbionts and transferred to the host. However, the symbionts are of the heterotrophic group Oceanospirillales and as such are not able to synthesize organic carbon de novo. Also, they are not housed in close contact to the bone material. We studied the ultrastructure of the integument overlying the symbiont housing trophosome in the ovisac region and the roots region and of the symbiont-free trunk region of Osedax to investigate the hosts possible contribution in feeding for the whole symbiosis. The epidermis differs conspicuously between th...

2010-01-01

Selective changes of retroelement expression in human prostate cancer

British Library Electronic Table of Contents (United Kingdom)

Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their re-expression. Whether this re-expression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA methylation of several classes of retroelements in human prostate cancer tissues and cell lines by quantitative reverse transcription-polymerase chain reaction and pyrosequencing, respectively. The most striking finding was strong and generalized increased expression of the HERV-K_22q11.23 provirus in cancers, including de novo expression of a spliced accessory Np9 transcript in some tumors. In parallel, DNA methylation in the long terminal repeat (LTR) decreased. Conversely, HER...

2011-01-01

Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA

Clinical Evaluation of the Zilver Vascular Stent for Symptomatic Iliac Artery Disease

The Lesch-Nyhan (LN) syndrome is a severe X chromosome-linked disease that results from a deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). The mutations leading to the disease are heterogeneous and frequently arise as de novo events. The authors have identified nucleotide alterations in 15 independently arising HPRT-deficiency cases by direct DNA sequencing of in vitro amplified HPRT cDNA. They also demonstrate that the direct DNA sequence analysis can be automated, further simplifying the detection of new mutations at this locus. The mutations include DNA base substitutions, small DNA deletions, a single DNA base insertion, and errors in RNA splicing. The application of these procedures allows DNA diagnosis and carrier identification by the direct detection of the mutant alleles within individual families affected by LN.

1989-03-01

British Library Electronic Table of Contents (United Kingdom)

PurposeTo evaluate the safety and effectiveness of the Zilver vascular stent in the treatment of de novo or restenotic lesions in the external and common iliac arteries.Materials and MethodsRegardless of the results of an initial percutaneous transluminal angioplasty (PTA), 151 consecutive patients were implanted with Zilver vascular stents (Cook, Bloomington, Ind) in up to two stenotic (?10 cm) or occluded (?5 cm) atherosclerotic lesions of the external or common iliac arteries. The primary endpoint was the rate of major adverse events within 9 months after the procedure. Major adverse events were defined as death, myocardial infarction, target lesion revascularization, and limb loss. Secondary endpoints included acute procedural success, 30-day clinical success, 9-month pat...

2008-01-01

Organisms posses enzymes that function in the repair of DNA damaged by radiations, chemicals and metabolic events

Nanomechanical properties of vimentin intermediate filament dimers

This report briefly describes the studies on the mechanism of in vivo DNA repairing by the author in Research Reactor Institute, Kyoto Univ. for the past 30 years. First, the ability of UV radiation to induce transformation was investigated with viral DNA. The formation of thymine-thymine dimer was found harmful to organisms and such dimers were removable by UV-radiation at a low frequency. The mutability was determined in three different E.coli strains with mutator gene, mutT, mutS or mutL. The ability to excise 8-oxoguanin developed in primer DNA was deficient in mutT and miss-pairing left after DNA replication could not be recovered in mutL and mutS strains. Further, DNA repairing mechanism was investigated in other microorganisms; single-strand cleavage caused by exposure to BNCB radiation (boron-neutron-captured beam) could not be repaired in E. coli. Whereas for Deinococcus radiodurans, of which survival rate was not decreased by #gamma#-ray radiation at 5 kGy or less, it was ...

1998-01-01

Four small puzzles that Rosetta doesn't solve

The cell's cytoskeleton, providing the cell with structure and shape, consists of a complex array of structural proteins, including microtubules, microfilaments and intermediate filaments. Intermediate filaments play a crucial role in mechanotransduction and in providing mechanical stability to cells, in particular under large deformation. By utilizing molecular simulation, here we report a nanomechanical analysis of vimentin intermediate filament dimers, the basic building blocks of intermediate filaments. We describe a detailed analysis of the mechanical properties and associated deformation mechanisms, and find that mechanical stretch induces a transition from alpha-helices to beta-sheets, a phenomenon known as alpha-beta transition. A comparison of the Young's modulus predicted from simulation with experimental measurements is provided, and good agreement is found. We present an analysis of structural changes during deformation, domain unfolding patterns, rate dependence of the ...

2009-10-21

CERN Document Server

A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular ...

2011-01-01

1 2 3

Structural alterations in the seminiferous tubules of rats treated with immunosuppressor tacrolimus

Immunosuppressant calcineurin inhibitors phase shift circadian rhythms and inhibit circadian responses to light

BackgroundTacrolimus (FK-506) is an immunosuppressant that binds to a specific immunophilin, resulting in the suppression of the cellular immune response during transplant rejection....Full Text Available

British Library Electronic Table of Contents (United Kingdom)

PP2B is a Ca2+/calmodulin-dependent protein phosphatase that is ubiquitously expressed in mammals. Among other actions, it is an effector mechanism in NMDA-mediated glutamate neurotransmission as well as a regulator of GSK3? and MAPK signaling cascades. Because all of these mechanisms have demonstrable roles in the control of circadian rhythyms, we hypothesized that PP2B would be a key regulator of rhythm generation and entrainment, and that through inhibition of its phosphatase activity, the circadian system would be affected by immunosuppressant drug therapy. We report here that immunosuppressant drugs (cyclosporin A, FK506) (1) block the circadian responses to light that underlie photic entrainment; (2) produce circadian phase shifts with a characteristic nonphotic profile; and (3) disr...

2008-01-01

Mycophenolic acid inhibits activation of inducible nitric oxide synthase in rodent fibroblasts

Mechanism of Host Defense Suppression Induced by Viral Infection: Mode of Action of Inosiplex as an Antiviral Agent

Mycophenolate mofetil (MMF) is an immunosuppressive drug that acts as a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH). MMF has recently been shown to inhibit the enzymatic activity...Full Text Available

2003-05-01

Legionella tucsonensis sp. nov. isolated from a renal transplant recipient.

The mechanism of influenza virus (INFV)-induced immunosuppression and the mode of inosiplex action against INFV infection were studied. INFV suppressed both anti-lipopolysaccharide and anti-sheep erythrocyte...Full Text Available

1982-10-01

Impaired immunity in harbour seals (Phoca vitulina) exposed to bioaccumulated environmental contaminants: review of a long-term feeding study.

A Legionella-like organism (strain 1087-AZ-H) was isolated from a pleural-fluid specimen from a renal transplant patient undergoing immunosuppressive therapy. Growth characteristics and gas-liquid chromatography...Full Text Available

1989-08-01

Correlates to Increased Lethality of Attenuated Venezuelan Encephalitis Virus Vaccine for Immunosuppressed Hamsters.

Mass mortalities among seals and dolphins inhabiting contaminated marine regions have led to speculation about a possible involvement of immunosuppression associated with environmental pollution. To...Full Text Available

1996-08-01

Anti-albumin antibodies in chronic liver diseases: diagnostic significance of these antibodies in patients with conventional or immunosuppressive therapy.

Splenectomy or pretreatment of adult hamsters with cyclophosphamide (Cytoxan) increased the lethality of the TC-83 vaccine strain of Venezuelan encephalitis virus (VEE), inoculated subcutaneously, from 12% for normal hamsters to 75 and 76% respectively. A...

1974-01-01

Transcriptome sequencing and annotation of the microalgae Dunaliella tertiolecta: Pathway description and gene discovery for production of next-generation biofuels

The two categories of anti-albumin antibodies (AAA), namely precipitins (AA-P) and agglutinins (AA-Aggl), were investigated in 260 patients with morphologically diagnosed chronic liver diseases (CLD)....Full Text Available

1981-02-01

Relative correlation of Jet-REMPI monitoring with adsorption tube sampling followed by TDS-CIS-GC/MS

BackgroundBiodiesel or ethanol derived from lipids or starch produced by microalgae may overcome many of the sustainability challenges previously ascribed to petroleum-based fuels and first generation plant-based biofuels. The paucity of microalgae genome sequences, however, limits gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for the non-model microalgae species, Dunaliella tertiolecta, and identify pathways and genes of importance related to biofuel production.ResultsNext generation DNA pyrosequencing technology applied to D. tertiolecta transcripts produced 1,363,336 high quality reads with an average length of 400 bases. Following quality and size trimming, ~ 45% of the high quality reads were assembled into 33,307 isotigs with a 31-fold coverage and 376,482 singletons. Assembled sequences and singletons were subjected to BLAST similarity searches and annotated with ...

2011-03-14

Post-transplant monitoring of renal allografts: are we there yet?

During earlier work rapid and highly sensitive Jet-REMPI (resonance-enhanced multiphoton ionization) mass spectrometry was applied for monitoring the effluent from thermal treatment of a filter dust during a de novo test under laboratory conditions. The sample, from ESP-Field 2 of an iron ore sintering plant, was already loaded with dioxins ({sigma}PCDD/F = 132 ng/g), their precursors (PCBz, PCPh) and other products of incomplete combustion. Heating filter dust in a temperature window 200-350 C under a flow of air results in further formation of these pollutants. As described elsewhere, on-line detection was mostly carried out using a non-selective ionization mode, to measure a wide range of compounds simultaneously. The changes of output suggest that the reaction products increase in chlorination level with time. Another explanation is that higherchlorinated compounds appear later as a consequence of lower volatility and stronger adsorption. ...

2004-09-15

British Library Electronic Table of Contents (United Kingdom)

Transplantation has emerged as the therapy of choice for many patients with end organ failure. One of the major goals is to tailor immunosuppressive therapy to the individual needs of every patient to balance the risk for rejection and over-immunosuppression. This will require diagnostic tools that can detect harmful processes in the allograft early, and that can be measured repeatedly. This review will consider recent advances in our understanding of the molecular nature of these processes and how this information is being utilized to design novel diagnostic assays to non-invasively monitor allografts. Highlighted is the need for large-scale prospective multi-centre studies to validate assays that show early promise in single centre studies.

2009-01-01

Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects.

Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells

The IgG response to gp41 (envelope glycoprotein of Mr 41,000) of the human immunodeficiency virus (HIV) was studied with eight synthetic peptides derived from three different regions of the protein....Full Text Available

1988-07-01

Clinical aspects of Marburg hemorrhagic fever

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study the authors have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. They find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCV{sub L}, in glial cells. They conclude that the presence of the HIV-1-encoded tat protein may positively affect the JCV lytic cycle ...

1990-05-01

British Library Electronic Table of Contents (United Kingdom)

Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the...

2011-01-01

Studies on adjuvant parenteral nutrition during chemotherapeutic and radiotherapeutic measures in haematological disorders

Severe paraquat poisoning: clinical and radiological findings in a survivor

In patients subjected to bone marrow transplantation the aggressive measures necessarily preceding this treatment lead to drastic metabolic changes which, in turn, are a cause of marked disturbances of homeostasis. The general preparatory measures in the form of cytoreduction by cytostatic drugs are broadened for leukaemic patients to include wholebody irradiation. During the study described here investigations were carried out into the resulting strain on the metabolism. One of the most essential changes observed in those patients was a nitrogen loss of up to approx. 20 g/day that occurred during the immunosuppressive phase. This was accompanied by markedly pronounced variations in fluid elimination, which partly were of an iatrogenic nature. An immediate and sufficient substitution of amino acids in connection with complete parenteral nutrition rapidly acted to compensate for the nitrogen losses, even though these could not be totally reversed to achieve a ...

Severe paraquat poisoning: clinical and radiological findings in a survivor

Paraquat is a nonselective contact herbicide of great toxicological importance, being associated with high mortality rates, mainly due to respiratory failure. We report the case of a 22-year-old male admitted to the emergency room with a sore throat, dysphagia, hemoptysis, and retrosternal pain after the ingestion of 50 mL of a paraquat solution, four days prior to admission. Chest CT scans revealed pulmonary opacities, pneumomediastinum, pneumothorax, and subcutaneous emphysema. The patient was submitted to two cycles of immunosuppressive therapy with cyclophosphamide, methylprednisolone, and dexamethasone. The pulmonary gas exchange parameters gradually improved, and the patient was discharged four weeks later. The clinical and tomographic follow-up evaluations performed at four months after discharge showed that there had been further clinical improvement. We also present a brief review of the literature, as well as a discussion of the therapeutic algorithm for ...

Setting the standard in T-cell-depleted haploidentical transplantation and beyond

2010-07-01

British Library Electronic Table of Contents (United Kingdom)

Much progress has been made in the clinical, biological and technical aspects of the T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). Our experience demonstrates that infusing a megadose of extensively T-cell-depleted hematopoietic peripheral blood stem cells after an immuno-myeloablative conditioning regimen in acute leukemia patients ensures sustained engraftment with minimal GvHD without the need of any post-transplant immunosuppressive treatment. Since our first successful pilot study, our efforts have concentrated on developing new conditioning regimens, optimizing the graft processing and improving the post-transplant immunological recovery. The results we have so far achieved in high risk acute leukemia patients show that haploidentical transplantation ...

2011-01-01

Rapamycin (sirolimus) protects against hypoxic damage in primary heart cultures via Na^+/Ca^2^+ exchanger activation

British Library Electronic Table of Contents (United Kingdom)

Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...

2011-01-01

Adoptive immunotherapy with virus-specific T cells

British Library Electronic Table of Contents (United Kingdom)

Viral infections are still common causes of morbidity and mortality in immunosuppressed patients after allogeneic hematopoietic stem cell transplantation. Infections caused by virus such as cytomegalovirus, adenovirus and Epstein-Barr virus are well-known. In addition, several other viruses such as polyomavirus and human herpesvirus 6 have been recently reported to be causes of significant complications. As the delay in recovery of virus-specific cellular immune response after transplant is associated with viral reactivation and viral disease, adoptive immunotherapy to restore virus-specific cellular immunity is an attractive option. Recent clinical trials showed the safety and effectiveness of adoptive immunotherapy against viral diseases. In this review, we summarize the current status o...

2011-01-01

1 2 3

The diagnosis of inflammatory muscular and vascular conditions using MRT with STIR sequences

Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis

The role of MRT in the prebiopsy diagnosis of muscular and vascular inflammatory conditions was evaluated prospectively and an optimal method of examination was investigated. 92 patients with a suspected diagnosis of myositis (60 cases) or vasculitis (32 cases) were examined, in each case two extremities were studied using transverse T_1 and T_2 weighted SE sequences and double echo STIR sequences on a 0.5 Tesla (56 patients) or 1.5 Tesla magnet (36 patients; T5/S15 Gyroscan, Philips). The site of the biopsy depended on the MRT findings. In 41 patients the suspected diagnosis was confirmed histologically, in two patients an infective myositis was diagnosed on clinical grounds despite negative histology. MRT demonstrated muscle oedema in 86% of patients. There were negative findings after immuno-suppressive therapy (two patients), in focal myositis (3 out of 4 patients) and in one of 7 patients with untreated vasculitis. Amongst 49 patients in whom the suspected ...

2000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis

Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt ...

Validation of immune function testing during a 4-week oral toxicity study with FK506.

Because toxicity with the use of 3000 centiGray (cGy) of total lymphoid irradiation (TLI) was observed in an earlier study, 2000-cGy treatments were delivered in a 2-portal format to 7 patients and in a modified 3-portal fashion to 6 patients, as part of a randomized, investigator-blinded trial of TLI treatment for refractory rheumatoid arthritis. Analysis of combined data from the 13 patients revealed statistically significant improvement in 5 clinical indicators of disease activity at the end of TLI and 6 and 12 months later, accompanied by T4-specific immunosuppression. Management considerations resulted in the introduction of prednisone therapy in 5 patients, methotrexate in 4, and azathioprine in 1 during the interval of 8-12 months post-TLI. Herpes zoster occurred in 5 patients prior to the initiation of this additional therapy. These data indicate that, in patients with rheumatoid arthritis, a TLI dose of 2000 cGy is sufficient to produce measurable benefit ...

Native kidney reincarnation following a failed transplant

Assessment of the immune system's capability to respond to antigens with the generation of specific antibodies, whilst under the influence of a test article, is required in toxicity tests according to the European guideline for repeated dose toxicity testing of medicinal products. The purpose of this study in rats was to validate methodology for the determination of Keyhole Limpet Haemocyanin (KLH)-specific antibodies under the influence of an immunologically active compound. The immunosuppressant FK506, commercially available as Prograf, was administered orally (gavage) to five rats per sex per group at dosages of 0.5mg/kg per day or 3mg/kg per day, for a period of 4 weeks. On days 14 and 22, KLH was administered subcutaneously, with an adjuvant (AluGel), to the two treated groups and a control (i.e. without FK506 treatment) approximately 1h following administration of FK506. Terminal investigations included haematology parameters, titration of KLH-specific ...

2004-04-01

Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG rats fed herring from the contaminated Baltic Sea

Full text: A 51-year-old woman with end stage renal failure secondary to Haemolytic Uraemic syndrome underwent a cadaveric renal transplant. A routine post transplant DTPA scan was performed which demonstrated satisfactory renal transplant perfusion and function. Incidental note was made of tracer uptake in the pelvis in the mid-line, which was suspected to be a uterine fibroid. This was confirmed on ultrasonography and at surgery. One week post transplantation the patient became acutely unwell and at laparotomy a perforated diverticular abscess was drained. Intraoperatively the transplant kidney was examined and the surgeon thought there was a area of infarction. This was confirmed on biopsy. As the patient's creatinine was rising a repeat DTPA study was performed. Perfusion and function of the transplant kidney was virtually absent while Doppler studies showed no flow. The patient however continued to produce urine and the creatinine was stable. Subsequently a ...

2002-05-04

Honokiol-mediated inhibition of PI3K/mTOR pathway: a potential strategy to overcome immunoresistance in glioma, breast, and prostate carcinoma without impacting T cell function.

We carried out a feeding study in rats aimed at extending our aboservations of contaminant-induced immunosuppression in harbour seals. Two herring batches were freeze-dried, supplemented and fed to female adult PVG rats for a period of 4 1/2 months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg in the Atlantic and Baltic groups, respectively. At the end of the feeding experiment, no contaminant-related changes in spleen CD{sub 4}{sup +}/CD{sub 8}{sup +} cellularity, natural killer cell activity, or mitogen-induced proliferative responses of thymus or spleen cells could be detected. However, total thymocyte numbers and thymus CD{sub 4}{sup +}/CD{sub 8}{sup +} ratios were reduced in the Baltic group. A novel model was established to assess the specific T-cell response to rat cytomegalovirus (RCMV). When applied to the feeding study, no differences between the ...

1996-08-01