Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD.

The interactions between chemokines and their receptors may have an important role in initiating GVHD after allogeneic hematopoietic SCT (allo-HSCT). CCL25 and CCR9 are unique because they are exclusively expressed in epithelial cells and in Peyer's patches of the small intestine. We focused on rs12721497 (G926A), one of the non-synonymous single nucleotide polymorphisms (SNPs) in the CCR9 gene, and analyzed the SNP of donors in 167 consecutive patients who received allo-HSCT from an HLA-identical sibling donor. Genotypes were tested for associations with acute and chronic GVHD in each organ and transplant outcome. Multivariate analyses showed that the genotype 926AG was significantly associated with the incidence of acute stage > or =2 skin GVHD (hazard ratio: 3.2; 95% confidence interval (95% CI): 1.1-9.1; P=0.032) and chronic skin GVHD (hazard ratio: 4.1; 95% CI: 1.1-15; P=0.036), but not with GVHD in other organs or with relapse, non-relapse mortality or OS. To clarify the functional differences between genotypes, each SNP in retroviral vectors was transfected into Jurkat cells. In chemotaxis assays, the 926G transfectant showed greater response to CCL25 than the 926A transfectant. In conclusion, more active homing of CCR9-926AG T cells to Peyer's patches may produce changes in Ag presentation and result in increased incidence of skin GVHD.

Bending strength and depth of cure of light-cured composite resins irradiated using filters that simulate enamel.

This study evaluates the light-attenuating effects of enamel on the properties of light-cured restorative resins using simple experimental filters. Three filters were designed to replicate the light transmittance characteristics of 0.5, 1.0 and 1.5 mm thick human enamel. The bending strength, depth of cure, and levels of residual monomer for 12 shades of three commercial light-cured composite resins were examined. These resins were cured either using direct irradiation from a light source or irradiation through one of the filters. For all materials, the bending strength and depth of cure of specimens irradiated through a filter were lower and the levels of residual monomer were higher than those found in specimens irradiated directly. The results indicate that the light-attenuating effect of enamel reduces the polymerization efficiency, resulting in poorer mechanical properties of light-cured composite resins.

Intestinal thrombotic microangiopathy after allogeneic bone marrow transplantation: a clinical imitator of acute enteric graft-versus-host disease.

Thrombotic microangiopathy after bone marrow transplantation (post-BMT TMA) is a serious transplant-related complication. We identified 16 patients with TMA after allogeneic BMT who showed histopathological evidence of intestinal TMA in their gut specimens (six autopsies, 10 biopsies). In all, 14 patients had grade II-IV acute graft-versus-host disease (GVHD). The first seven patients were retrospectively diagnosed with TMA. Since six of them were diagnosed with progressive GVHD at that time because there was no awareness of the existence of intestinal TMA, they received more intensive treatment for GVHD, but all died between days +49 and +253. In contrast, the remaining nine patients were recently diagnosed with intestinal TMA on the basis of colonoscopic biopsies. For eight of these patients, the immunosuppressants were reduced, and the patients' intestinal symptoms improved gradually. Six of the nine patients were still alive 12 months after the diagnosis of TMA. Our findings suggest that the gut may be a site involved in post-BMT TMA, presenting as ischemic enterocolitis. Differentiating intestinal TMA from acute GVHD is important in patients suffering from severe and refractory diarrhea after BMT.

Physical and mechanical properties of PMMA resins containing gamma-methacryloxypropyltrimethoxysilane.

The polymethylmethacrylate (PMMA) resins containing gamma-methacryloxypropyltrimethoxysilane (gamma -MPS) of 0, 2, 4, 6, 10, 15, 20 and 30 mo1%, added to methylmethacrylate, were prepared using a monomer-polymer technique and stored in air or water at 37 +/- 0.5 degrees C for 28 days. The flexural strength and flexural modulus of the PMMA resins containing gamma -MPS of 20 and 30 mo1% were significantly smaller than those containing 2-6 mo1% and the same statements were true for the adhesive strength to porcelain tooth. However, its value of adhesive strength to Co-Cr alloy was remarkably less than to porcelain tooth. By contrast, there was no significant difference among the Knoop hardness of the PMMA resins examined. On the other hand, the thermal expansion had an increasing tendency with an increase of a gamma -MPS content. The dynamic shear modulus within a temperature measured (20-140 degrees C) decreased s1ightly as the gamma -MPS content of the PMMA resins increased, and the peak temperature of mechanical loss tangent also tended to decrease. These results indicated that the PMMA resin containing gamma -MPS of 6 mol% was the best composition from the standpoint of an excellent adhesive strength against porcelain, although its water absorption was 1.9 times that of PMMA.

TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways.

We previously reported the fusion of the TEL gene to the Syk gene in myelodysplastic syndrome with t(9;12)(q22;p12). TEL-Syk fusion transformed interleukin-3 (IL-3)-dependent murine hematopoietic cell line BaF3 to growth factor independence. Here, we investigate the intracellular signal transduction of the stable transfectants. TEL-Syk fusion protein was associated with the p85 subunit of phosphatidyl inositol 3 kinase (PI3-K) followed by the activation of Akt in the absence of IL-3. Vav, phospholipase C-gamma2 and mitogen-activated protein kinase (MAPK) were also constitutively activated. TEL-Syk also activated the signal transducer and activator of transcription 5 (STAT5) in the absence of Janus kinase 2 activation. None of these kinases were phosphorylated in the BaF3 cells transfected with TELDeltaPNT-Syk in which the oligomerization domain of TEL was deleted. Inhibitor analysis showed that the MAPK pathway was important in TEL-Syk-mediated cell proliferation. The immunofluorescence technique revealed that the TEL-Syk fusion protein was located in the cytoplasm. These data suggest that TEL-Syk fusion protein in the cytoplasm leads to the constitutive activation of PI3-K/Akt, MAPK and STAT5 signal pathways, which are closely involved in IL-3-independent cell proliferation of BaF3 cells.

Dynamic viscoelastic properties of commercial glass-fibre reinforced resin used for crowns and bridges.

In order to investigate the thermal stability, the physical and mechanical, and dynamic viscoelastic properties of glass-fibre reinforced composite materials were measured. The G' of the seven materials examined was within 5;20 +/- 14; 55 and 4;50-14; 35 GPa for dry and wet specimens in air at 37 degrees C, respectively, and decreased with increasing temperature. The G' values of dry specimens decreased by 7;74-15;4% when heated to 60 degrees C. The value of tan delta ranged from 0;0102 to 0;0295 and from 0.0181 to 0.0406 for dry and wet specimens in air at 37 degrees C, respectively. The coefficient of linear thermal expansion between 30 and 60 degrees C ranged from 0;557 to 3; 95 x 10-5/ degrees C. Moreover, the filler content ranged from 56; 36 to 88; 87 wt%. These results showed that the magnitudes of G', tan delta, and the coefficient of linear thermal expansion and water absorption depend on the inorganic filler or glass-fibre content; i.e. the amount of resin matrix. Moreover, for all the materials examined, the G' values were thermostable in the temperature range encountered in the oral cavity.

Effect of photo-irradiation on hardness of soft lining materials for denture base.

Nine photo-activated acrylic-type (EPL) soft lining materials were produced experimentally to examine their durability. The purpose of this study was to investigate the effect of photo-irradiation on the hardness of experimental soft lining materials. The hardness (Hex) of the nine EPLs was increased 4.3-170.1% by exposing them to light. The effect of irradiation on the Hex of the EPLs was remarkable when the material contained much ethylmethacrylate, together with smaller amounts of di-n-butyl phthalate. Moreover, the Hex tended to increase for EPLs in which the liquid portion contained less di-n-butyl phthalate or more ethanol (Et). The weight change ratio (Wc) was greater for EPL specimens containing less Et. The Wcs ranged from 0.118 to 0.661% after 8 weeks. These results showed that the Hexs of six of the EPLs were approximately equal to those of four commercially available soft lining materials, and these six EPLs may have properties favouring their use in clinical dentistry.

Effect of ethanol on the hardness and relaxation modulus of experimental photo-activated soft lining materials stored in aqueous solutions.

We studied changes in the hardness, relaxation modulus [Er(t)], and weight change ratio (Wc) of experimental photo-activated acrylic soft lining materials (EPLs) stored in three aqueous solutions [distilled water (DW), physiological saline solution (PS), and artificial saliva (AS)] at 37 degrees C for 8 weeks. The hardness of the EPLs increased markedly during the first 4 days of storage, and subsequently changed little. The greatest hardness occurred in the EPL specimen containing the largest amount of ethanol (Et). The relaxation modulus [Er(8)] of the EPLs ranged from 1.35 to 1.66 MPa immediately before storage, and from 1.43 to 2.21 MPa after an 8-week immersion. Like hardness, the increase in [Er(t)] was greatest when the EPL contained large amounts of Et. The Wc ranged from 0.118 to 0.661% after storage for 8 weeks, and increased most for the EPL specimen containing the smallest amount of Et. Furthermore, 3-7 days after the start of immersion many hollows were observed in the surface of specimens with a high Et content. The results indicate that Wc and hollow formation are sensitive to the Et content of the EPL, and that Et content is closely tied to the change in hardness and relaxation modulus with time.

Acute renal failure after a sea anemone sting.

A 27-year-old man suffering from severe swelling and pain in his right arm was referred to our hospital. He showed signs of acute renal failure (ARF) with severe dermatitis of his right arm. Three days before being admitted, he accidentally touched some kind of marine organism with his right hand while snorkeling in the Sulu Sea around Cebu Island. Within a few minutes, he was experiencing severe pain in his right hand. Then his right hand gradually became swollen. The marine creature responsible for this injury was thought to have been a sea anemone, which is a type of coelenterate. Histologic findings of a renal biopsy indicated that acute tubular necrosis (ATN) had caused ARF in this patient's case. Supportive therapies improved renal function of this patient, and steroid pulse therapy attenuated the severe skin discoloration. The ATN was thought to have been caused by the poison from a sea anemone because there were no other conceivable reasons for the patient's condition. This is the first time that a marine envenomation case has been reported in which the sting of a sea anemone has caused ATN without the failure of any other organs.

Quality of life in adult patients after stem cell transplantation.

Many articles pertaining to quality of life (QOL) following stem cell transplantation have been published in the US and western Europe. However, since the actions of health insurance systems and overall cultural aspects are strongly associated with QOL, investigations into QOL should be carried out within all countries. Therefore, we have investigated the QOL of adult patients following stem cell transplantation at 31 hospitals in Japan. The survivors, who were surveyed by mail questionnaire, were 20 years or older at the time of this study. The underlying diseases were acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, myelodysplastic syndrome, and multiple myeloma. Median age at the time of the study was 36 years, and median interval after transplantation was 35.3 months. Of 383 patients surveyed, 282 (73.6%) responded to the questionnaire. One hundred and ninety-two patients were treated with an allogeneic-related transplantation, 52 with allogeneic-unrelated, and 38 with an autologous transplantation. Our data revealed that the length of time since transplantation and the diagnosis of chronic GVHD were associated with QOL. When unrelated and related transplantation recipients were compared, ratings on relief from pain, stability in weight, and confidence in dealing with daily life were lower among unrelated transplantation patients.

Successful ribavirin therapy for severe adenovirus hemorrhagic cystitis after allogeneic marrow transplant from close HLA donors rather than distant donors.

Intravenous ribavirin was given to nine patients who had developed severe adenovirus-induced hemorrhagic cystitis (AD-HC) which was resistant to conventional therapy or where there was involvement of other organs after allogeneic BMT. Three patients recovered completely from AD-HC, two of whom had been resistant to vidarabine. All three had received sibling BMTs (2 HLA matched, 1 HLA mismatched). Five patients who received BMTs from related (2 HLA mismatched) or unrelated (1 HLA matched, 2 HLA mismatched) showed an improvement in symptoms but had recurrent AD-HC after discontinuation of ribavirin. Improvement in clinical symptoms and termination of virus excretion were well correlated. The last patient who received a mismatched unrelated BMT died during ribavirin therapy. Ribavirin was notably more effective among patients receiving BMTs from siblings in contrast to patients receiving BMTs from alternative donors (<0.05). One patient experienced severe pancytopenia during the second treatment with ribavirin after HC recurrence and recovered after ceasing ribavirin. Thus, ribavirin seems to be very effective for severe AD-HC for some recipients who receive transplants from a genetically close donor. Bone Marrow Transplantation (2000) 25, 545-548.

Dynamic viscoelastic properties of photo-activated composite resins containing short glass fibres.

The dynamic shear modulus in torsion (G'), water absorption, thermal expansion and residual monomer of the reinforced materials produced by adding four short glass fibres (19 microm in mean diameter and 86.1--763 microm in mean length) and one spherical E glass (11.1 microm in mean diameter) were examined and discussed in comparison with those of the materials without filler. G' of short fibre reinforced composites increased with fibre length and reached a maximum value near 382 microm for a dry specimen and near 156 microm for a wet one. In addition, the coefficient of thermal expansion of the fibre reinforced composites and the amount of residual monomer decreased considerably compared with those of composites containing spherical glass. There was no significant difference in water absorption between the fibre reinforced composites and the composites containing spherical glass. Therefore, it was concluded that the reinforcement method of adding short glass fibres is favourable for improving the viscoelastic properties of the materials.

Flexural properties and impact strength of denture base polymer reinforced with woven glass fibers.

OBJECTIVES: The present investigation was undertaken to determine the reinforcing effect of woven glass fibers on deflection, flexural strength, flexural modulus and impact strength of acrylic denture base polymer. METHODS: Three silanized or unsilanized woven glass fibers were used. Specimens were made by heating the denture cure resin dough containing glass fibers, which were sheathed in the dough. Specimens with four different thicknesses and of five different types were made, incorporating the glass fiber. Three-point flexural test and flywheel type impact test were employed to determine the flexural properties and impact strength. RESULTS: When specimens contained unsilanized glass fiber, the flexural strength in specimens of 1 and 2 mm thickness and the impact strength in specimens of 2 mm thickness were higher than those of specimens without glass fiber (p < 0.01). On the contrary, the flexural strength and deflection in specimens reinforced with silanized glass fiber of 1 mm thickness were significantly higher (p < 0.01, p < 0.05) than those of unreinforced specimens. Further, the impact strength in specimens reinforced with silanized glass fiber of 2 mm thickness was significantly higher (p < 0.01) than that of unreinforced specimens. Statistically significant differences were found in the flexural strength (p < 0.05) and in the impact strength (p < 0.01) when specimens of 4 mm thickness were reinforced with two or three unsilanized glass fibers. SIGNIFICANCE: The reinforcement with glass fiber was effective in thin specimens, and the reinforcing effect increased with the increase of the number of glass fibers in the case of thick specimens.

Adding silanes to MMA: the effects on the water absorption, adhesive strength and mechanical properties of acrylic denture base resins.

The adhesive strength of porcelain artificial teeth and polymethylmethacrylates (PMMAs), which contained silanes with various number of vinyl or ethoxy groups, and the mechanical and physical properties of the PMMAs were measured. Four types of PMMAs with silanes showed high adhesive shear strength and caused fractures in the porcelain. Water absorption of the PMMAs increased with the addition of silane, but that of one type with silane was almost the same as the PMMA only type. The flexural strengths of the PMMAs with silane, except for one type, showed no significant differences compared with that of PMMA (p < 0.05). The Tg levels of all PMMAs with silane fell less than that of PMMA. From these results, it was found that PMMA with silane from three vinyl groups and one ethoxy group showed excellent chemical bonding to porcelain and low water absorption.

A method for evaluating color stability of light-cured composite resins using an experimental filter.

The purpose of this study was to investigate a method for evaluating color stability of light-cured composite resins using an experimental filter that simulates human enamel. The light transmission coefficients and their spectral distributions from 400 to 600 nm of twelve enamel specimens were measured. The experimental filter was designed so that its light transmittance characteristics were similar to those of enamel. Color stability tests for ten shades of two light-cured composite resins, which were irradiated directly and indirectly through the experimental filter with a light source, were performed. Despite different irradiation procedures, most materials exhibited significant color changes in the color stability test. Although the differences were small, the group of specimens irradiated indirectly through the filter showed significantly higher color differences in comparison with those irradiated directly. Our results indicate that the light attenuating effect of enamel affects the color stability of light-cured composite resins.

An evaluation of acrylic complete dentures using the discrimination of elastic bodies or viscous fluids.

The discrimination test on elastic bodies and viscous fluids was carried out for 16 young dentists and 13 denture patients, because it is considered that dentures affect the ability to discriminate food. The materials used in this test were six thermoplastic polyurethane elastomers with compressive elastic moduli from 11.8 to 62.0 MPa and six silicone impression pastes with coefficients of viscosity from 1.77 x 10(-2) to 23.0 x 10(-2) MPa x s. The subjects (dentists and patients) discriminated the materials based on differences in elastic moduli or coefficients of viscosity by chewing the materials for 10 s. From these experiments, it became clear that the ability to discriminate between elastic bodies or viscous fluids upon chewing, of subjects who use complete-dentures in combination with their own teeth and either an upper or lower complete-denture (S/D) or who have a set of complete-dentures in both jaws (D/D) decreased considerably, compared with that of subjects who have their own teeth in upper and lower jaws (S/S). The ratios of S/D and D/D against S/S were 0.5 and 0.3, respectively. This indicates that with an increase in the area occupied by dentures in the oral cavity, the value of the differential threshold increased markedly and made food discrimination more difficult. In addition, discriminating viscous fluids was 2.4 to 3.1 times more difficult compared with the discrimination of elastic bodies, independent of denture placement.

A new preconditioning regimen with melphalan, busulphan and total body irradiation followed by low-dose immunosuppressant in allogeneic haemopoietic stem cell transplantation.

Twenty adult patients with high-risk leukaemia underwent allogeneic haemopoietic stem cell transplantation after melphalan, busulphan and total body irradiation followed by short-term methotrexate and low-dose cyclosporine or tacrolimus. Three patients developed veno-occlusive disease and no patient developed renal dysfunction. Seven patients experienced grade II-IV acute graft-versus-host disease (aGVHD) and five patients experienced grade III-IV. The 3-year probabilities of relapse and leukaemia-free survival were 22 +/- 11% (95% confidence interval) and 50 +/- 11%, respectively. These data suggest that this preconditioning regimen followed by a low-dose immunosuppressant provided a more anti-leukaemic effect without increased regimen-related toxicity and aGVHD.

Consistency of alginate impression materials and their evaluation.

The apparent viscosity of 17 commercially available alginate impression materials was examined using a rheometer. Each material was mixed for 15 s at a temperature of 23 +/- 0.5 degrees C, using a specially designed alginate mixing instrument. The water powder ratio was determined according to the manufacturer's instruction. The mixed alginate paste was immediately transferred to the sample stage of the rheometer or to a commercial perforated metal tray. Over the same time scale adjusted according to the rheometer test, a discrimination test (subjective test) was performed by 16 young dentists (each with more than 4 years experience). The apparent viscosity of all materials rose as a function of time after mixing and most of the material had properties similar to pseudoplastic fluids. The relationship between the results of the subjective test and the experimental values (objective test) with the rheometer was expressed in a quadratic equation. The maximum value of the apparent viscosity derived from this result was 1.52 x 10(3) Pa.s.

Effects of thermal cycling on dynamic viscoelastic properties of four commercial resins for crown and bridge.

To elucidate the effects of thermal cycling on the viscoelastic properties of four commercial resins for crown and bridge, dynamic shear modulus (G'), mechanical loss tangent (tan delta), Knoop hardness, water sorption and appearance of specimen surfaces before and after thermal cycling test were determined. The changes of G' and tan delta for two materials were insignificant with increased repetitions of thermal cycling. Those of the other two materials were statistically significant: in particular, G' at temperatures above 60 degrees C was inclined to increase slightly and tan delta decreased considerably. While the Knoop hardness of the materials was a little decreased over a number of 75,000 thermal cycles, the water sorption almost attained an equilibrium in uptake after 14,000 thermal cycles. Furthermore, cracks on the specimen surface were observed after 37,500 to 75,000 thermal cycles. From these results, the deterioration of materials was observed as damage to the specimen surface. Moreover, it could be presumed that the materials would be further polymerized during the period of thermal cycling.

[FK506 for the prophylaxis of graft-versus-host-disease after bone marrow transplantation from HLA-genotypically mismatched unrelated donor].

Eleven leukemia patients who had undergone bone marrow transplants from HLA-A, B, DR genotypically mismatched unrelated donors received FK506 and short-term methotrexate as prophylaxis for graft-versus-host disease (GVHD). Grade III-IV acute GVHD developed in 2 of the patients, and chronic GVHD developed in 4 of the other patients. Adverse drug reaction included reversible nephrotoxicity, hyperglycemia (all patients) and hypertension (9 patients). Hyperglycemia and hypertension of grade 3 or higher occurred mostly in the patients who were on supplemental steroids. However, severe nephrotoxicity was not observed. Complications included cystitis (4 patients), cytomegalovirus colitis (3 patients), Interstitial Pneumonitis (IP) (3 patients), tuberculosis (1 patient), and thrombotic microangiopathy (1 patient). None of patients relapsed. Although close monitoring of FK506 blood concentration and patient clinical signs are required, we concluded that FK506 is effective for GVHD prophylaxis after bone marrow transplantation from HLA-A, B, DR genotypically mismatched unrelated donors, and that adverse reactions due to FK506 are controllable. To determine the long-term effectiveness of this drug, it will be necessary to conduct prospective randomized studies that compare it wiht cycloporin A as a preventive treatment against GVHD in patients who receive bone marrow transplants from HLA genotypically mismatched unrelated donors.