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Careful assessment of the safety and efficacy of islet transplantation should guide the selection process of a small number of children with type 1 diabetes who may be eligible for [...]

The Edmonton Protocol for islet transplantation has provided hope for type 1 diabetic patients. However, this protocol requires lifelong immunosuppression, specifically sirolimus, a cellular antiproliferate. The effect of sirolimus on human pancreatic ductal cells (HDCs) is not known. This may be important since HDCs are believed to be islet precursors. Since neonatal porcine islets (NPIs), which contain many ductal precursor cells, could be a potential clinical source of islets, we also tested the effects of sirolimus on this tissue. HDCs ( n=4), NPIs ( n=9) and human islets ( n=5) were cultured with and without sirolimus (20 ng/ml) for 6 days. HDCs and NPIs cultured with sirolimus showed a 50 and 28% decrease, respectively, in cell number relative to control ( p<0.05). Control cultures expanded 1.65- and 2.44-fold relative to time 0. Decreases in cell number of sirolimus-treated HDCs were not due to apoptosis as measured by TUNEL staining. No functional effects on human islets or NPIs were observed following static incubation with high glucose. Treatment of syngeneically transplanted and naïve BALC/c mice with sirolimus resulted in altered OGTT profiles with prolonged elevation of hyperglycaemia and weight gain. There was no difference in graft and organ insulin content between treatment groups. Our results indicate that sirolimus decreases ductal cell numbers in culture and alters glucose-stimulated insulin secretion in vivo. The administration of sirolimus to islet transplant recipients is likely to impair graft function as a result of decreasing ductal neogenesis and induction of insulin resistance. [ABSTRACT FROM AUTHOR]

Gelfand–Shilov spaces are spaces of entire functions defined in terms of a rate of growth in one direction and a concomitant rate of decay in an orthogonal direction. Gelfand and Shilov proved that the Fourier transform is an isomorphism among certain of these spaces. In this article we consider mapping properties of fractional Fourier transforms on Gelfand–Shilov spaces. Just as the Fourier transform corresponds to rotation through a right angle in the phase plane, fractional Fourier transforms correspond to rotations through intermediate angles. Therefore, the aim of fractional Fourier estimates is to set up a correspondence between growth properties in the complex plane versus decay properties in phase space. [ABSTRACT FROM AUTHOR]

Surgical correction in severe cases of AIS is often hampered by insufficient autograft bone to facilitate the fusion. The development of other sources of bone generating cells would greatly enhance the surgical. Bone marrow derived stem cells were harvested from femoral reaming during total hip arthroplasty for the purpose of differentiating into osteoblasts. Stem cells were isolated from the marrow and successfully differentiated into three cell lines (osteoblasts, chondrocytes and adipocytes) to confirm multilineage potential. Osteoblasts were developed from the stem cells and demonstrated the ability to be cultured to possibly provide a source of bone generating cells to augment surgical fusions. It is anticipated that the addition of osteoblasts created from stem cells (combined with appropriate matrix) will have significant influence on the success of AIS surgery through improvement of bone fusion. [ABSTRACT FROM AUTHOR]

We ask what conditions can be placed on generators φ of principal shift invariant spaces to ensure the validity of analogues of the classical sampling theorem for bandlimited signals. Critical rate sampling schemes lead to expansion formulas in terms of samples, while oversampling schemes can lead to expansions in which function values depend only on nearby samples. The basic techniques for validating such schemes are built on the Zak transform and the Poisson summation formula. Validation conditions are phrased in terms of orthogonality, smoothness, and self-similarity, as well as bandlimitedness or compact support of the generator. Effective sampling rates which depend on the length of support of the generator or its Fourier transform are derived. [ABSTRACT FROM AUTHOR]

Islet transplantation has surpassed whole pancreas transplantation as a cure for diabetes mellitus since the success of the Edmonton group. It is a safer procedure and requires minimal surgical intervention, yet offers excellent results in terms of achieving insulin independence. It also offers a more physiological insulin profile than current insulin replacement therapy. The UK Islet Transplant Consortium, founded by Diabetes UK, is in the process of establishing a programme of clinical islet transplantation in the UK. The immunosuppression required to protect islet grafts remains a threat to the long-term health of transplant recipients and research into the possibility of circumventing the need for immunosuppression continues. The main areas under investigation include immunoisolation of islet grafts, HLA class II mismatching between donor and recipient, destruction of immune-reactive dendritic cells in culture, in vitro pre-treatment of islets to reduce their immunogenicity and genetic modification of islets to produce localised immunosuppression and prevent the release of MHC molecules. Because of the shortage of donors, researchers are looking toward alternative sources of glucose-responsive insulin-secreting tissue. Xenotransplantation would offer an attractive solution if the risk of transferring animal endogenous retroviruses can be eliminated. The expansion of mature beta-cells, beta-cell progenitors in pancreatic ducts or embryonic stem cells into viable tissue for transplant is also being researched in the hope of finding a solution for the tissue shortage issue. Encouraging advances have been made in many of these areas, creating a sense of anticipation and excitement for the future. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation. [ABSTRACT FROM AUTHOR]

Psychometric functions were obatained for the interaural conditions NoSo and NoSπ in both forward and backward masking using masks of different durations. In addition, data were collected for the Sm, Sπ and So conditions without an external mask. The slope parameter k and the signal level required for 76% correct detection were computed with a least-squares technique. The results were that both temporal masking and temporal masking-level differences (MLDs) increased monotonically with longer mask durations. This mask-duration effect was more pronounced for forward masking than for backward masking. Without an external mask, the signal was about 3 dB more detectable in the So configuration than in the Sπ configuration, and it was about 4 dB more detectabe in the Sπ configuration than in the Sm configuration. The psychometric functions were generally steeper for the NoSπ condition than for the NoSo condition in forward masking, but not in backward masking. They were also steeper for the Sπ condition than for either the Sm or So conditions without an external mask. The temporal properties of a typical detection model consisting of a filter centered at the stimulus frequency followed by a rectifier and a final ''leaky'' integrator were found to explain much of existent temporal masking data. Signal:500Hz, 8 msec; interstimulus interval: 5-10 msec; mask: wide-band noise; method: two-interval forced choice. Subject Classification: [43]65.62, [43]65.58, [43]65.68. [ABSTRACT FROM AUTHOR]

The porins of Gram-negative bacteria are responsible for the 'molecular sieve' properties of the outer membrane. They form large water-filled channels which allow the diffusion of hydrophilic molecules into the periplasmic space. Owing to the strong hydrophilicity of their amino acid sequence and the nature of their secondary structure (beta strands), conventional hydropathy methods for predicting membrane topology are useless for this class of protein. The large number of available porin amino acid sequences was exploited to improve the accuracy of the prediction in combination with tools detecting amphipathicity of secondary structure. Using the constraints of β-sheet structure these porins are predicted to contain 16 membrane-spanning strands, 14 of which are com-mon to the two (enteric and the neisserial) porin sub-families. [ABSTRACT FROM AUTHOR]