Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease

Allogeneic bone marrow transplantation is limited by the availability of suitable marrow donors and risk of graft-versus-host disease (GVHD) and opportunistic infection. In an attempt to ameliorate these limitations, umbilical cord blood has been postulated as an alternative source of allogeneic haemopoietic stem cells for transplantation. From September, 1994, umbilical cord blood from sibling donors has been used to reconstitute haemapoiesis in 44 children with acquired or congenital lympho-haemapoietic disorders, neuroblastoma, or metabolic diseases. Patients who had HLA-identical and HLA-1 antigen disparate grafts, had a probability of engraftment at 50 days after transplantation of 85%. No patient had late graft failure. The probability of grade II-IV GVHD at 100 days was 3% and the probability of chronic GVHD at one year was 6%. With a median follow-up of 1.6 years, the probability of survival for recipients of HLA-identical or HLA-1 antigen disparate grafts is 72%. We conclude that umbilical cord blood is a sufficient source of transplantable haemopoietic stem cells for children with HLA-identical or HLA-1 antigen disparate sibling donors with very low risk of acute or extensive chronic GVHD. The feasibility of umbilical-cord-blood transplantation with HLA-2 and HLA-3 antigen disparate sibling donors remains to be determined.     

Quality-of-Service Based Protection in MPLS Control WDM Mesh Networks

Intelligent methods for automatic protection and restoration are critical in optical transport mesh networks. This paper discusses the problem of quality-of-service (QoS)-based protection in terms of the protection-switching time and availability for end-to-end lightpaths in a WDM mesh network. We analyze the backup lightpath-sharing problem in such networks and study the correlation of the working lightpaths and the impact of the correlation on the sharing of the backup lightpaths. We present a multi-protocol-label-switching (MPLS) control-based fully distributed algorithm to solve the protection problem. The proposed algorithm includes intelligent and automatic procedures to set up, take down, activate, restore, and manage backup lightpaths. It greatly reduces the required resources for protection by allowing the sharing of network resources by multiple backup lightpaths. At the same time, it guarantees, if possible, to satisfy the availability requirement even with resource sharing by taking the correlation of working lightpaths into consideration. A simple analysis of the proposed algorithm in terms of computation time and message complexity indicates that the implementation of the algorithm is practical. The illustrative studies that compare the performance of 1:1, unlimited sharing, and QoS-based backup sharing algorithms indicate that QoS-based sharing achieves comparable performance as unlimited sharing, which is much better than the 1:1 backup scheme in terms of connection blocking probability, average number of connections in the network for a given offered load, and network resource utilization.     

Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions

We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.     

Chronic effects of glucose on insulin signaling in A-10 vascular smooth muscle cells

To examine the effects of hyperglycemia on insulin signaling in A-10 vascular smooth muscle cells, cells were treated with extracellular D-glucose and effects of insulin were studied on the diacylglycerol-protein kinase C signaling system. A-10 cells specifically bound 125I-insulin, and insulin-like growth factor-I did not displace the label. 125I-insulin binding was unaltered under hyperglycemic conditions. To determine if insulin receptors were coupled to other insulin-regulated processes, diacylglycerol, protein kinase C, and glucose transport were evaluated. Insulin increased cellular diacylglycerol (DAG) levels which were also increased following glucose treatment and not further stimulated by insulin. The uptake of 2-[3H]deoxy-D-glucose (2-DOG) was stimulated by insulin and 12-O-tetradecanoyl phorbol 13-acetate (TPA). Insulin- and TPA-stimulated 2-[3H]DOG uptake was inhibited by a protein kinase inhibitor, staurosporine. Preincubation of cells with 500 nM TPA overnight resulted in the inhibition of insulin- and TPA-stimulated 2-[3H]DOG uptake. Protein kinase C activity was translocated from cytosolic to membrane fractions following insulin treatment. Overnight glucose (25 mM) treatment resulted in a 50% decrease in protein kinase C enzyme activity and > 90% decrease in protein kinase C beta immunoreactive levels. Protein kinase C activity and levels were not affected by osmotic control media containing mannitol. A-10 cells express GLUT4-type glucose transporters. Neither insulin-regulatable glucose transporter (GLUT4) mRNA nor GLUT4 protein levels were diminished by glucose. Significant decreases in insulin- and TPA-stimulated 2-[3H]DOG uptake occurred, however, with glucose. The down-regulation of protein kinase C beta and resultant inhibition of 2-[3H]DOG uptake by chronic glucose suggests a biochemical link between hyperglycemia and DAG-protein kinase C signaling in vascular smooth muscle cells.     

Kinetic trapping of oxygen in cell respiration

Cell respiration in eukaryotes is catalysed by mitochondrial enzyme cytochrome c oxidase. In bacteria there are many variants of this enzyme, all of which have a binuclear haem iron-copper centre at which O2 reduction occurs, and a low-spin haem, which serves as the immediate electron donor to this centre. It is essential that the components of the cell respiratory system have a high affinity for oxygen because of the low concentration of dissolved O2 in the tissues; however, the binding of O2 to the respiratory haem-copper oxidases is very weak. This paradox has been attributed to kinetic trapping during fast reaction of O2 bound within the enzyme's binuclear haem iron-copper centre. Our earlier work indicated that electron transfer from the low-spin haem to the oxygen-bound nuclear centre may be necessary for such kinetic oxygen trapping. Here we show that specific decrease of the haem-haem electron transfer rate in the respiratory haem-copper oxidase from Escherichia coli leads to a corresponding decrease in the enzyme's operational steady-state affinity for O2. This demonstrates directly that fast electron transfer between the haem groups is a key process in achieving the high affinity for oxygen in cell respiration.     

Clinical applications of fundus reflection densitometry

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.