The preservation of order: the use of common approach among staff toward clients in long-term psychiatric care

The authors performed this grounded theory study to gain a deeper understanding of the kinds of social processes that lead to a need among psychiatric nursing staff to reach a common approach on how to act toward individual clients in long-term psychiatric care. They present a theory about the development of such common approaches among staff. The main findings were that in psychiatric group dwellings, when the internal order is perceived as having been disturbed, the staff preserve or restore the internal order by formulating and reaching a common approach. The staff negotiated with each other to achieve an agreement on how to act and behave toward the individual client. The authors isolate and describe different types of order-disturbing incidents and the common approaches taken by the staff in dealing with them. However, their data also show that staff often had difficulties in maintaining a common approach over time.     

Distribution of intraportally implanted microspheres and fluorescent islets in mice

The aim of the study was to evaluate the distribution of intraportally transplanted islets in mice. We initially administered 2000 polystyrene microspheres with a diameter of 50 microm intraportally into normoglycemic C57BL/6 mice. In separate experiments other mice were injected similarly with 300 microspheres each with a diameter of 100 or 200 microm. One week later the animals were killed, and the lungs and livers were removed and divided into lobes. The number of microspheres in each individual liver lobe and in the lungs was counted using a stereomicroscope. In other experiments, athymic C57BL/6 mice were similarly implanted with 250 islets isolated from transgenic mice expressing the enhanced yellow fluorescent protein in the islet cells. The distribution of microspheres and islets was independent of size, and fairly homogenous within the liver, with the exception of the caudate lobe, which contained fewer microspheres and islets, respectively. Approximately one third of all microspheres and islets were present as aggregates. Eighty-five to 90% of the implanted microspheres were identified in the liver sections, whereas 60-65% of the implanted islets were recovered. Aggregates or single fluorescent cells were observed in the liver of islet-implanted mice. We conclude that islets and microspheres implanted into the liver distribute fairly homogenously and quite a few of them exist as aggregates or, with respect to islets, as fragments.     

Nephrin Is Expressed on the Surface of Insulin Vesicles and Facilitates Glucose-Stimulated Insulin Release

OBJECTIVE

Nephrin, an immunoglobulin-like protein essential for the function of the glomerular podocyte and regulated in diabetic nephropathy, is also expressed in pancreatic β-cells, where its function remains unknown. The aim of this study was to investigate whether diabetes modulates nephrin expression in human pancreatic islets and to explore the role of nephrin in β-cell function.

RESEARCH DESIGN AND METHODS

Nephrin expression in human pancreas and in MIN6 insulinoma cells was studied by Western blot, PCR, confocal microscopy, subcellular fractionation, and immunogold labeling. Islets from diabetic (n = 5) and nondiabetic (n = 7) patients were compared. Stable transfection and siRNA knockdown in MIN-6 cells/human islets were used to study nephrin function in vitro and in vivo after transplantation in diabetic immunodeficient mice. Live imaging of green fluorescent protein (GFP)-nephrin–transfected cells was used to study nephrin endocytosis.

RESULTS

Nephrin was found at the plasma membrane and on insulin vesicles. Nephrin expression was decreased in islets from diabetic patients when compared with nondiabetic control subjects. Nephrin transfection in MIN-6 cells/pseudoislets resulted in higher glucose-stimulated insulin release in vitro and in vivo after transplantation into immunodeficient diabetic mice. Nephrin gene silencing abolished stimulated insulin release. Confocal imaging of GFP-nephrin–transfected cells revealed nephrin endocytosis upon glucose stimulation. Actin stabilization prevented nephrin trafficking as well as nephrin-positive effect on insulin release.

CONCLUSIONS

Our data suggest that nephrin is an active component of insulin vesicle machinery that may affect vesicle-actin interaction and mobilization to the plasma membrane. Development of drugs targeting nephrin may represent a novel approach to treat diabetes.In the U.S. alone, diabetes affects >20 million people. Although advances have been made in the clinical care of diabetes, one of the major limitations for finding a cure is that the mechanisms regulating the function of insulin-producing cells have not yet been fully characterized.Nephrin is an immunoglobulin-like protein with important structural and signaling properties (1,2). It was initially described in podocytes, highly specialized cells in the kidney glomerulus (3,4). Nephrin is heavily downregulated in human diabetic nephropathy (5), and nephrin mutations are responsible for the congenital nephrotic syndrome of the Finnish type (6).Nephrin expression has been reported in pancreatic β-cells (7), where its function remains unknown. In immortalized human podocytes, the COOH-terminal portion of nephrin appears to bind VAMP-2, a vesicle-associated membrane protein involved in exocytosis (8). The interaction of nephrin with VAMP-2, together with its well-known interaction with the actin cytoskeleton (9–13), suggests that nephrin may play an important role in vesicles trafficking, a recently described feature of podocyte biology (14).In pancreatic β-cells, glucose stimulation affects actin reorganization, and redistribution of cortical actin is essential for proper β-cell function (15). However, the pathways responsible for the regulated targeting of vesicles to the plasma membrane have not yet been fully characterized. The aim of this study was to understand the regulation of pancreatic nephrin expression in patients with type 2 diabetes and the role of nephrin in the regulation of glucose-stimulated insulin release (GSIR).     

Differential effects of dopamine melanin on norharman-induced toxicity in PC12 cells

Summary The food contaminant norharman structurally resembles MPTP a compound that selectively damages pigmented brain areas. Both compounds are sequestered and retained in melanin-containing neurons. The aim of the study was to examine whether intracellular melanin can modulate the toxicity of norharman in melanin-loaded PC12 cells. Dopamine melanin protected against norharman-induced upregulation of grp78, activation of caspase 3 and necrosis at low concentrations (5 and 50 μM). In contrast, at a high conentration (500 μM) there was a significantly increased expression of grp78, hsp90 and caspase 3 and a disassociation of melanin aggregates leading to dispersal of granules to swollen neurite terminals. In human populations, a long-term low-level exposure to toxicants with a high affinity to melanin will probably result in accumulation in melanin-containing neurons in vivo. Our data suggest that accumulation of a neurotoxicant in melanin-loaded cells may lead to increased cell stress, apoptotic signaling and disassociation of melanin aggregates.     

Quality of fixed prosthodontics after twenty-two years

After an observation period of 22 years, this study was conducted to clinically examine and interview patients who in 1984 and 1989 had participated in similar investigations regarding the quality, over time, of treatments with fixed partial dentures. The patients were examined by two standardized and experienced clinicians using the California Dental Association quality rating system, their results indicating that after 22 years the overall survival rates were 46.5% and 41.1% for the originally placed crowns and pontics, respectively. However, a continuing decrease of the crown quality rating was noted during the more than 20-year-long observation period. Restorative treatments with common types of fixed partial dentures can therefore be regarded as both safe and reliable over long periods of time.