475 research outputs found
The molecular defect of albumin Tagliacozzo: 313 Lys → Asn
AbstractAlbumin Tagliacozzo is a fast-moving genetic variant of human serum albumin found in 19 unrelated families. The protein was isolated from the serum of a heterozygous healthy subject. Analysis of CNBr fragments by isoelectric focusing allowed us to localize the mutation to CNBr fragment IV (residues 299–329). This fragment was isolated on a preparative scale and subjected to tryptic digestion. Sequential analysis of the abnormal tryptic peptide, purified by RP-HPLC, revealed the variant was caused by 313 Lys → Asn substitution, probably due to a point mutation in the structural gene. The lack of a lysine residue accounts for the electrophoretic behavior of albumin Tagliacozzo
Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: clinical and immunological data of a phase I/II clinical trial
Vaccination with priming and expansion of tumour
reacting T cells is an important therapeutic option to be used
in combination with novel checkpoint inhibitors to increase
the specificity of the T cell infiltrate and the efficacy of the
treatment. In this phase I/II study, 14 high-risk disease-free
ovarian (OC) and breast cancer (BC) patients after completion
of standard therapies were vaccinated with MUC1, ErbB2
and carcinoembryonic antigen (CEA) HLA-A2+-restricted
peptides and Montanide. Patients were subjected to 6 doses
of vaccine every two weeks and a recall dose after 3 months.
ECOG grade 2 toxicity was observed at the injection site. Eight
out of 14 patients showed specific CD8+ T cells to at least one
antigen. None of 4 patients vaccinated for compassionate use
showed a CD8 activation. An OC patient who suffered from
a lymph nodal recurrence, showed specific anti-ErbB2 CD8+
T cells in the bulky aortic lymph nodes suggesting homingof the activated T cells. Results confirm that peptide vaccination
strategy is feasible, safe and well tolerated. In particular
OC patients appear to show a higher response rate compared
to BC patients. Vaccination generates a long-lasting immune
response, which is strongly enhanced by recall administrations.
The clinical outcome of patients enrolled in the trial
appears favourable, having registered no deceased patients
with a minimum follow-up of 8 years. These promising data,
in line with the results of similar studies, the high compliance
of patients observed and the favourable toxicity profile, support
future trials of peptide vaccination in clinically disease-free
patients who have completed standard treatments
Dependence of e-cloud on the longitudinal bunch profile: studies in the PS & extension to the HL-LHC
Recent studies have shown that the prospects for significantly increasing
bunch intensities in the LHC for the luminosity upgrade (HL-LHC) may be
severely limited by the available cryogenic cooling capacity and the
electron-cloud (EC) driven beam instability. However, it is planned that during
the HL-LHC era the bunch intensities in the LHC will go up by nearly a factor
of two compared to the LHC-design values. This motivates the exploration of
additional EC mitigation techniques that can be adopted in addition to those
already in place. Preliminary simulations indicated that long flat bunches can
be beneficial over Gaussian bunches to reduce the EC build up. Rigorous studies
using realistic bunch profiles have never been done. Therefore, we have
undertaken an in-depth investigation in the CERN 26 GeV PS to see if we can
validate the previous findings and, in particular, if flattening the bunch can
mitigate the EC. Here we present the results from dedicated EC measurements in
the PS using a variety of bunch shapes and a comparison with simulations.
Finally, we investigate if reshaping the bunch profiles using a 2nd harmonic rf
cavity can mitigate EC in the HL-LHC
Methods of purification and application procedures of alpha1 antitrypsin: a long-lasting history
The aim of the present report is to review the literature addressing the methods developed for the purification of alpha1-antitrypsin (AAT) from the 1950s to the present. AAT is a glycoprotein whose main function is to protect tissues from human neutrophil elastase (HNE) and other proteases released by neutrophils during an inflammatory state. The lack of this inhibitor in human serum is responsible for the onset of alpha1-antitrypsin deficiency (AATD), which is a severe genetic disorder that affects lungs in adults and for which there is currently no cure. Being used, under special circumstances, as a medical treatment of AATD in the so-called "replacement" therapy (consisting in the intravenous infusion of the missing protein), AAT is a molecule with a lot of therapeutic importance. For this reason, interest in AAT purification from human plasma or its production in a recombinant version has grown considerably in recent years. This article retraces all technological advances that allowed the manufacturers to move from a few micrograms of partially purified AAT to several grams of highly purified protein. Moreover, the chronic augmentation and maintenance therapy in individuals with emphysema due to congenital AAT deficiency (current applications in the clinical setting) is also presented.Pathogenesis and treatment of chronic pulmonary disease
Production of serine chymotrypsin - like elastase by aspergillus fumigatus strains
Thirty-four Aspergillus fumigatus strains isolated from air, horse-hair; agricultural soil and human samples were screened to evaluate the production of elastase. Aspergillus fumigatus strains were grown in elastin solid medium, showing a widespread elastin solubilization. However, isolates from human and agricultural soil samples were found to be the highest elastase producers. Then, eight out of 34 strains were grown in four different liquid media, on wich we investigated total and specific proteolytic activity. Results from this experiments suggest that the elastase production is induced by the presence of elastin as a substrate and that the elastase is a chymotrypsin like enzyme. Inhibitory profile showed that the A.fumigatus elastase is a serine proteinase
Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation
BACKGROUND: Spinal cord N-methyl-D-aspartate (NMDA) receptors are intimately involved in the development and maintenance of central sensitization. However, the mechanisms mediating the altered function of the NMDA receptors are not well understood. In this study the role of phosphorylation of NR1 splice variants and NR2 subunits was examined following hind paw inflammation in rats. We further examined the level of expression of these proteins following the injury. RESULTS: Lumbar spinal cord NR1 subunits were found to be phosphorylated on serine residues within two hours of the induction of hind paw inflammation with carrageenan. The enhanced NR1 serine phosphorylation reversed within six hours. No phosphorylation on NR1 threonine or tyrosine residues was observed. Likewise, no NR2 subunit phosphorylation was observed on serine, threonine or tyrosine residues. An analysis of NR1 and NR2 protein expression demonstrated no change in the levels of NR1 splice variants or NR2A following the inflammation. However, spinal cord NR2B expression was depressed by the hind paw inflammation. The expression of NR2B remained depressed for more than one week following initiation of the inflammation. CONCLUSION: These data suggest that NR1 serine phosphorylation leads to an initial increase in NMDA receptor activity in the spinal cord following peripheral injury. The suppression of NR2B expression suggests compensation for the enhanced nociceptive activity. These data indicate that spinal cord NMDA receptors are highly dynamic in the development, maintenance and recovery from central sensitization following an injury. Thus, chronic pain therapies targeted to NMDA receptors should be designed for the exact configuration of NMDA receptor subunits and post-translational modifications present during specific stages of the disease
Progress with the Upgrade of the SPS for the HL-LHC Era
The demanding beam performance requirements of the High Luminosity (HL-) LHC
project translate into a set of requirements and upgrade paths for the LHC
injector complex. In this paper the performance requirements for the SPS and
the known limitations are reviewed in the light of the 2012 operational
experience. The various SPS upgrades in progress and still under consideration
are described, in addition to the machine studies and simulations performed in
2012. The expected machine performance reach is estimated on the basis of the
present knowledge, and the remaining decisions that still need to be made
concerning upgrade options are detailed.Comment: 3 p. Presented at 4th International Particle Accelerator Conference
(IPAC 2013
Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates
<p>Abstract</p> <p>Background</p> <p>Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy.</p> <p>Results</p> <p>RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7- 8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal.</p> <p>Conclusion</p> <p>Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.</p
A New Luminescence Assay for Autoantibodies to Mammalian Cell–Prepared Insulinoma-Associated Protein 2
OBJECTIVE—Insulinoma-associated protein 2 (IA-2) is a major autoantigen in type 1 diabetes, and IA-2 autoantibodies are routinely detected by a liquid-phase radioimmunoprecipitation assay. The present experiments were initiated to develop a new assay that does not require the use of radioisotopes or autoantigens prepared in bacteria or by in vitro transcription/translation
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