690 research outputs found
Intraprofessional, team-based treatment planning for oral health students in the comprehensive care clinic
published_or_final_versio
Maturation of human lactase-phlorizin hydrolase Proteolytic cleavage of precursor occurs after passage through the Golgi complex
AbstractMaturation of human intestinal lactase-phlorizin hydrolase (LPH) requires that a precursor (pro-LPH) be proteolytically processed to the mature microvillus membrane enzyme (m-LPH). The subcellular site of this processing is unknown. Using low-temperature experiments and brefeldin A (BFA), intracellular transport was blocked in intestinal epithelial cells. In Caco-2 cells incubated at 18°C pro-LPH was complex-glycosylated but not cleaved, while at 20°C small amounts of proteolytically processed LPH were observed. These data exclude a pre-Golgi proteolytic event. BFA completely blocked proteolytic maturation of LPH and lead to an aberrant form of pro-LPH in both Caco-2 cells and intestinal explants. Therefore, proteolytic processing of LPH is a post-Golgi event, occuring either in the trans-Golgi network, transport vesicles, or after insertion of pro-LPH into the microvillus membrane
Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival
In obesity, beta cells activate compensatory mechanisms to adapt to the higher insulin demand. Interleukin-1 receptor antagonist (IL-1Ra) prevents obesity-induced hyperglycaemia and is a potent target for the treatment of diabetes, but the mechanisms of its secretion and regulation in obesity are unknown. In the present study, we hypothesise the regulation of IL-1Ra secretion by purinergic P2X7 receptors in islets.
Production and regulation of P2X7 were studied in pancreatic sections from lean and obese diabetic patients, non-diabetic controls and in isolated islets. IL-1Ra, IL-1β and insulin secretion, glucose tolerance and beta cell mass were studied in P2x7 (also known as P2Rx7)-knockout mice.
P2X7 levels were elevated in beta cells of obese patients, but downregulated in patients with type 2 diabetes mellitus. Elevated glucose and non-esterified fatty acids rapidly activated P2X7 and IL-1Ra secretion in human islets, and this was inhibited by P2X7 blockade. In line with our results in vitro, P2x7-knockout mice had a lower capacity to secrete IL-1Ra. They exhibited severe and rapid hyperglycaemia, glucose intolerance and impaired beta cell function in response to a high-fat/high-sucrose diet, were unable to compensate by increasing their beta cell mass in response to the diet and showed increased beta cell apoptosis.
Our study shows a tight correlation of P2X7 activation, IL-1Ra secretion and regulation of beta cell mass and function. The increase in P2X7 production is one mechanism that may explain how beta cells compensate by adapting to the higher insulin demand. Disturbances within that system may result in the progression of diabetes
Robot-assisted pancreatoduodenectomy with preservation of the vascular supply for autologous islet cell isolation and transplantation: a case report
<p>Abstract</p> <p>Introduction</p> <p>For patients with chronic pancreatitis presenting with medically intractable abdominal pain, surgical intervention may be the only treatment option. However, extensive pancreatic resections are typically performed open and are associated with a substantial amount of postoperative pain, wound complications and long recovery time. Minimally invasive surgery offers an avenue to improve results; however, current limitations of laparoscopic surgery render its application in the setting of chronic pancreatitis technically demanding. Additionally, pancreatic resections are associated with a high incidence of diabetes. Transplantation of islets isolated from the resected pancreas portion offers a way to prevent post-surgical diabetes; however, preservation of the vascular supply during pancreatic resection, which determines islet cell viability, is technically difficult using current laparoscopic approaches. With recent advances in the surgical field, robotic surgery now provides a means to overcome these obstacles to achieve the end goals of pain relief and preserved endocrine function. We present the first report of a novel, minimally invasive robotic approach for resection of the pancreatic head that preserves vascular supply and enables the isolation of a high yield of viable islets for transplantation.</p> <p>Case presentation</p> <p>A 35-year old Caucasian woman presented with intractable chronic abdominal pain secondary to chronic pancreatitis, with a stricture of her main pancreatic duct at the level of the ampulla of Vater and distal dilatation. She was offered a robotic-assisted pylorus-preserving pancreatoduodenectomy and subsequent islet transplantation, to both provide pain relief and preserve insulin-secretory reserves.</p> <p>Conclusion</p> <p>We present a novel, minimally invasive robotic approach for resection of the pancreatic head with complete preservation of the vascular supply, minimal warm ischemia time (less than three minutes) and excellent islet recovery (134,727 islet equivalent). Our patient is currently pain-free with normal glycemic control. Robot-assisted pylorus-preserving pancreatoduodenectomy and autologous islet transplantation can be safely performed and has the potential to minimize operative traumas as well as to partially preserve endocrine function. Results from this case report suggest that this dual procedure should be considered as a treatment option for patients with chronic pancreatitis at earlier stages of the disease, before irreversible islet loss occurs.</p
Effect of incoherent scattering on shot noise correlations in the quantum Hall regime
We investigate the effect of incoherent scattering in a Hanbury Brown and
Twiss situation with electrons in edge states of a three-terminal conductor
submitted to a strong perpendicular magnetic field. The modelization of
incoherent scattering is performed by introducing an additional voltage probe
through which the current is kept equal to zero which causes voltage
fluctuations at this probe. It is shown that inelastic scattering can lead in
this framework to positive correlations, whereas correlations remain always
negative for quasi-elastic scattering.Comment: 5 pages latex, 5 eps figure
Shot noise from action correlations
We consider universal shot noise in ballistic chaotic cavities from a
semiclassical point of view and show that it is due to action correlations
within certain groups of classical trajectories. Using quantum graphs as a
model system we sum these trajectories analytically and find agreement with
random-matrix theory. Unlike all action correlations which have been considered
before, the correlations relevant for shot noise involve four trajectories and
do not depend on the presence of any symmetry.Comment: 4 pages, 2 figures (a mistake in version 1 has been corrected
Electrical current noise of a beam splitter as a test of spin-entanglement
We investigate the spin entanglement in the superconductor-quantum dot system
proposed by Recher, Sukhorukov and Loss, coupling it to an electronic
beam-splitter. The superconductor-quantum dot entangler and the beam-splitter
are treated within a unified framework and the entanglement is detected via
current correlations. The state emitted by the entangler is found to be a
linear superposition of non-local spin-singlets at different energies, a
spin-entangled two-particle wavepacket. Colliding the two electrons in the
beam-splitter, the singlet spin-state gives rise to a bunching behavior,
detectable via the current correlators. The amount of bunching depends on the
relative positions of the single particle levels in the quantum dots and the
scattering amplitudes of the beam-splitter. The singlet spin entanglement,
insensitive to orbital dephasing but suppressed by spin dephasing, is
conveniently quantified via the Fano factors. It is found that the
entanglement-dependent contribution to the Fano factor is of the same magnitude
as the non-entangled, making an experimental detection feasible. A detailed
comparison between the current correlations of the non-local spin-singlet state
and other states, possibly emitted by the entangler, is performed. This
provides conditions for an unambiguous identification of the non-local singlet
spin entanglement.Comment: 13 pages, 8 figures, section on quantification of entanglement adde
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