Somatic mosaicism for a SLC2A1 mutation: implications for genetic counseling for GLUT1 deficiency syndrome.

A heterozygous SLC2A1 mutation in the severely affected child was inherited from his less severely affected mother who was mosaic for the mutation.

Preemptive Living Donor Kidney Transplantation and Kidney Function at the Initial Hospital Visit: A Single-Center Case-Control Study.

BACKGROUND: Studies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. METHODS: A single-center, case-control study was conducted to determine the clinical factors that lead to referral for PKT. RESULTS: Between April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT-, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT-, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). CONCLUSIONS: Our results indicate that PKT should be performed within ∼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.

A parallel-group comparison study of celecoxib with loxoprofen sodium in third mandibular molar extraction patients.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used widely, but they may damage the upper gastrointestinal mucosa owing to their mechanism of action. Selective cyclooxygenase 2 (COX-2) inhibitors are known to have a reduced risk for such damage. In this comparative study, the efficacy and safety of the selective COX-2 inhibitor celecoxib for pain after third mandibular molar extraction were compared with those of loxoprofen sodium. This was a parallel-group comparison study; 107 patients who had undergone third mandibular molar extraction were given celecoxib and 102 were given loxoprofen. The level of pain on a visual analogue scale (VAS) 15 min and 30 min after taking the experimental drug decreased over time, with no significant difference between the two groups. The percentage of patients taking a second dose was 64.5% for celecoxib and 80.4% for loxoprofen. The time to second dose was significantly longer for celecoxib (533.5 min) than for loxoprofen (387.4 min). There was no significant difference in the patients' impression of efficacy between the two groups, with ratings of 'excellent' and 'good' for 77.4% in the loxoprofen group and 74.5% in the celecoxib group. These results demonstrate that celecoxib is of equal clinical value to loxoprofen for acute pain after third mandibular molar extraction.

Metal catalysts impregnated on porous media for aqueous phenol decomposition within three-phase fluidized-bed reactor.

Performance of metal catalysts to decompose aqueous phenol was experimentally investigated. Comparison of the phenol decomposition rates within three-phase fluidized-bed reactors utilizing only O(3), TiO(2) deposited on silica beads, metal catalyst (Ni or Co) impregnated on mesoporous carbon beads, or O(3) in combination with each catalyst was thoroughly examined. It was found that the use of Co catalyst with the presence of O(3) led to the best removal condition which aqueous phenol was completely decomposed within 10 min (k = 0.1944 min(-1)). In contrast, the use of TiO(2) without O(3) resulted in the worst decomposition of phenol (k = 0.0066 min(-1)). Some intermediate products, such as hydroquinone and catechol, were also detected but their final concentrations were negligibly low.

Surface melting and lamella rearrangement process in linear low density polyethylene.

The surface melting and lamella rearrangement process that happen in commercially available linear low-density polyethylene (LLDPE) were studied with special emphasis on conformational and crystal structural changes during the process. The thermal melting behavior of the specimens was examined by using differential scanning calorimetry and the occurrence of the surface melting was strongly suggested in low-crystallinity LLDPE (LLDPE-L) in the temperature range of 90-120 degrees C at the heating rate of 2 degrees C/min. The structural and conformational disordering process during heating was studied by IR spectroscopy combined with two-dimensional spectral correlation analysis. The formation of conformational defects has been determined to proceed prior to the overall disordering of orthorhombic crystalline structure in all the PE specimens except for LLDPE-L. During the heating process, conformational defects are preferably developed in side chains that are excluded from tightly packed orthorhombic crystal in PEs other than in LLDPE-L. The temperature dependency in the thickness of lamella layers of LLDPE-L examined by small-angle X-ray scattering indicates the occurrence of the lamella thickening in the temperature range where surface melting has been observed. In this way, the formation of new orthorhombic cells due to the lamella rearrangement dominates over the formation of conformational defects in LLDPE-L while other specimens indicate opposite. Wide-angle X-ray scattering shows significantly suppressed dilation of the unit cell in LLDPE-L, especially toward orthorhombic unit cell parameter a in the temperature range where lamella thickening process undergoes. It is implied that the lamella thickening happens not only by rearranging the chains originally exist in the interfacial region but also it incorporates those originally existing in the orthorhombic crystal phase in LLDPE-L. The heat-induced morphological changes are explored by means of polarized light microscope with liquid crystal universal compensator and circular polarizer (LC-PolScope). Unlike other PE specimen, high-crystallinity LLDPE (LLDPE-H) shows the retardance histogram with multiple peaks, indicating the presence of several types of higher order structure, such as aggregation within the specimen.

A step towards length control of titanate nanotubes using hydrothermal reaction with sonication pretreatment.

It was experimentally confirmed that the average length of titanate nanotubes (TNTs) can be increased and controlled to a certain degree by applying sonication pretreatment to their titania precursors prior to hydrothermal synthesis. Without sonication, the average length of the TNTs synthesized by the hydrothermal process was much shorter due to constricted diffusion of the hydroxyl ion (OH(-)) and the sodium ion (Na(+)) through the narrow interparticle space of agglomerated titania precursors, thereby retarding the TNT formation mechanism. On the other hand, much longer TNTs with an average hydrodynamic size of 490-1760 nm were produced when the sonication pretreatment was applied. Based on microscopic observations on the transformation of the present precursors and the reported nanotube formation phenomena during the hydrothermal process, a mechanism contributing to length control is proposed.

cDNA microarray analysis assists in diagnosis of malignant intrarenal pheochromocytoma originally masquerading as a renal cell carcinoma.

Intrarenal pheochromocytoma (paraganglioma) is a very rare tumour. Its diagnosis is often difficult to establish because of its rarity and its histological similarity to renal cell carcinoma (RCC). Recently, we examined the molecular signatures of different subtypes of kidney tumours by using cDNA microarray. The signature pattern for one tumour, which was originally diagnosed as granular cell RCC, was clearly distinct from that of any other subtype of kidney tumour, and led us to re-evaluate the case. Haematoxylin and eosin staining revealed histological features suggestive of pheochromocytoma, and immunohistochemical studies showed positive staining for neuroendocrine markers but not for keratin. A germline missense mutation, D119E, in the familial paraganglioma related gene succinate dehydrogenase subunit D (SDHD), was subsequently identified. The treatment modality was revised and radiotherapy was given, to which the patient responded, leading to a reduction in tumour size of 25% within the first month. To our knowledge, this is the first report of an intrarenal pheochromocytoma that was diagnosed with the assistance of cDNA microarray analysis.

Structure of carbon onions and nanotubes formed by arc in liquids.

Since carbon nanotubes and onions were discovered, many methods have been proposed for their production. For applications the main requirements are low capital cost, high purity of the produced material, simplicity of technique, and its potential for scale up. Recently a cathodic arc between two graphitic electrodes immersed in liquids has been demonstrated to be a simple method to produce carbon nanoparticles such as nanotubes and onions. In this paper high-resolution transmission electron microscopy is employed to examine the shape of the nanoparticles and the purity of the final material produced under various conditions. In this study we have used an arc discharge in two different liquids--liquid nitrogen and distilled water--and we have changed the grade of the carbon electrodes. The variety in structure, shape, and size of the produced particles is discussed in line with a model proposed to describe the physical process.

The expression of intestinal CYP3A4 in the piglet model.

PURPOSE: In our previous study, the blood levels of tacrolimus were higher in the short bowel and small bowel transplantation models than those in controls. Metabolism by intestinal cytochrome p450 3A4 (CYP3A4) has been reported to influence the blood level of orally administered tacrolimus. We performed immunohistochemistry to examine the localization of intestinal CYP3A4. MATERIALS AND METHODS: Twenty-four piglets were divided into three groups: group 1 were controls (n = 11); group 2, ileal resection of 2/3 proximal small intestine (n = 5); and group 3, total small intestinal resection followed by 1/3 allotransplantation of ileum (n = 8). Tacrolimus was orally administered from postoperative days 3 to 7. On day 7, blood samplings were performed for the trough level and the calculation of area under the concentration time curve (AUC). Intestinal specimens from the jejunum, ileum, colon, and ileal graft were obtained on days 0 and 10 for immunohistochemistry of CYP3A4. RESULTS: The trough and AUC values in group 2 were significantly higher than those in group 1. Furthermore those measurements in group 3 animals were higher than in group 2 (trough levels: 2.5 +/- 1.7, 11.2 +/- 2.1, 16.3 +/- 2.7 ng/mL and AUC values: 126 +/- 90, 319 +/- 155, 546 +/- 117 ng. h/mL). The expression levels of CYP3A4 were, jejunum > ileum > ileal graft > colon. CONCLUSIONS: The intensity and extent of CYP3A4 staining diminished in the ileal graft showing an inverse correlation to the blood concentrations.

The colon displays an absorptive capacity of tacrolimus.

PURPOSE: In our previous study, blood levels of orally administered tacrolimus were significantly higher in short bowel piglets than in control animals. It has been reported that the blood levels of tacrolimus are influenced by the metabolic activity of intestinal CYP3A4. If tacrolimus may be absorbed in the colon, direct administration of drug into this organ might be useful to augment bioavailability since the expression of CYP3A4 is low at this site. In the present study we evaluated the absorptive capacity of tacrolimus in the colon. MATERIALS AND METHODS: Piglets were divided into four groups: groups 1 and 2 were controls (n = 11 and 3, respectively); group 3 underwent resection of the entire small intestine (n = 8); and group 4 had a catheter placed in the cecum (n = 4). In groups 1 and 3, tacrolimus was administered orally; in group 2 it was given intravenously; and in group 4 it was injected into cecum through the catheter from postoperative days 3 to 7. On day 7, blood samples were obtained for drug measurements to calculate the area under the concentration time curve (AUC) values. RESULTS: The trough level and AUC values of tacrolimus in group 4 as well as in group 3 were significantly higher than those in group 1. In Group 4 animals showed a 60-minute time to peak concentration. CONCLUSIONS: Tacrolimus is absorbed by the colon. Since the blood levels were not influenced by the metabolic activity in the graft bowel, direct administration of tacrolimus into the colon might be useful in small intestinal transplantation.

Autoimmune hepatitis following allogeneic PBSCT from an HLA-matched sibling.

A 7-year-old boy with acute lymphoblastic leukemia (ALL) in second remission received an allogeneic PBSCT from his HLA-matched sister. Acute grade II graft-versus-host disease (GVHD) resolved with corticosteroids. Chronic GVHD in the skin and oral mucosa at around day 60 responded to corticosteroids and cyclosporin A. At 6 months after the transplant, he developed hepatic dysfunction with elevated serum transaminases and gamma-globulin. Liver biopsy revealed chronic inflammation with lymphocytes and plasma cells in portal areas without destruction of bile ducts, suggesting autoimmune hepatitis. While rare, autoimmune hepatitis should be considered a potential long-term complication in patients with hepatic dysfunction in the late post-transplant phase.

Carbon onions: carriers of the 217.5 nm interstellar absorption feature.

Ultraviolet-visible absorption measurements of high purity and well separated carbon onion samples are reported. The results show that, after purification, absorption features from carbon onions match well with the interstellar UV spectrum. The measurements show that the absorption peak position remains constant at 4.55+/-0.1 microm(-1), and the width varies from 1.2-1.6 microm(-1), a key feature of the interstellar spectrum. The similarities between the experimental and observed absorption spectra indicate that carbon onions are very strong candidates for the origin of the UV interstellar absorption peak at 4.6 microm(-1).

A case of lupus nephritis with alteration of the glomerular basement membrane associated with Takayasu's arteritis.

A 47-year-old Japanese woman with both Takayasu's arteritis (TA) and systemic lupus erythematosus (SLE) presented with unequal pulses in the upper extremities, diarrhea and proteinuria. In 1986, when she was 38 years old, angiography revealed stenosis of the left subclavian artery. In 1994, SLE was diagnosed on the basis of clinical and laboratory findings, including renal dysfunction, hematologic and immunologic abnormalities, a high titer of antinuclear antibody and a positive lupus band test on the skin. Renal biopsy showed lupus nephritis and glomerular lesions with a bubble-like appearance of the glomerular capillary wall with TA. Lupus nephritis coexisting with glomerulonephropathy associated with TA has rarely been reported.

Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma?

AIMS: Acinic cell-like breast carcinoma is a newly recognized entity, and few acinic cell-like breast carcinoma cases have been reported. All reported acinic cell-like breast carcinomas were counterparts of the solid type of acinic cell carcinoma of the salivary gland. We report here three cases of secretory breast carcinoma with acinic cell differentiation, and discuss the similarity between secretory breast carcinoma and acinic cell carcinoma of the salivary gland. METHODS AND RESULTS: The cases were histologically identical to acinic cell carcinoma of the salivary gland: papillary-cystic type in case 1, a mixture of papillary-cystic, microcystic and follicular type in case 2, and microfollicular type in case 3. Immunohistochemically, the tumour cells were positive for salivary-type amylase, lysozyme, S100 protein and alpha 1-antitrypsin, and negative or less reactive for gross cystic disease fluid protein-15 and oestrogen receptor. All three cases did not reveal metastasis or recurrence. CONCLUSIONS: These cases were typical of secretory breast carcinoma, and were clinically, histologically and immunohistochemically analogous to acinic cell carcinoma of the salivary gland. We emphasize that secretory breast carcinoma and acinic cell carcinoma of the salivary gland may be identical lesions.

High trough levels of oral FK506 induced by loss of small intestine.

To establish a safe and effective usage of oral tacrolimus (FK506) in small bowel transplantation (SBTx) recipients, trough levels and area under the curve (AUC) values of FK506 were assessed using swine models of SBTx and short bowel. Thirty-eight Landrace male piglets were divided into four groups as follows: Group 1, controls (n=13); Group 2, a one-third small bowel model (n=5); Group 3, a short bowel model (n=10); and Group 4, a one-third small bowel allograft model (n=10; five donors and five recipients). Piglets of Groups 1 and 3 were further divided into two sub-groups, according to the route of drug administration: Groups 1a (n=10) and 3a (n=7) received FK506 orally, and Groups 1b (n=3) and 3b (n=3) received FK506 intravenously. Oral or intravenous FK506 was started on post-operative day 3 and continued until day 7 in each group. On day 7, trough levels and AUC values were measured. In Groups 1a, 2, 3a and 4, trough levels of FK506 were 2.1+/-1.2 (p<0.01 vs. Group 2, 3a or 4), 11.2+/-2.1, 23.3+/-4.8 (p<0.05 vs. Group 2 or 4) and 14.6+/-3.0 ng/mL, and AUC values were 101+/-90 (p<0.01 vs. Group 3a or 4), 319&+/-155, 808+/-200, and 531+/-113 ng.h/mL, respectively. Both trough levels and AUC values were lowest in Group 1a and highest in Group 3a. Between Groups 1b and 3b, there was no significant difference in the blood levels of intravenous FK506. The shorter the functioning residual small intestine was, the higher the trough level of oral FK506 was, while the presence or absence of small intestine did not affect blood levels of intravenous FK506. These results suggest that oral FK506 is metabolized in the functioning small intestine during its absorption. Therefore, events which cause intestinal malfunction, such as graft rejection in SBTx, inflammation and loss of small intestine, may adversely raise the trough level of oral FK506.

Synthesis of carbon 'onions' in water.

The fabrication of carbon nanomaterials usually calls for expensive vacuum systems to generate plasmas and yields are disappointingly low. Here we describe a simple method for producing high-quality spherical carbon nano-'onions' in large quantities without the use of vacuum equipment. The nanoparticles, which have C60 cores surrounded by onion-like nested particles, are generated by an arc discharge between two graphite electrodes submerged in water. This technique is economical and environmentally benign, and produces uncontaminated nanoparticles which may be useful in many applications.

Localization and roles of CD44, hyaluronic acid and osteopontin in IgA nephropathy.

An important function of CD44 is to act as a cellular receptor for hyaluronic acid and osteopontin. Cell-matrix interactions mediated by the CD44/hyaluronic acid receptor-ligand pair are involved in the regulation of leukocyte migration and activation. Osteopontin is a molecule associated with cell adhesion and migration and functions through binding to CD44. This study examined whether CD44, hyaluronic acid and osteopontin participate in the progression of IgA nephropathy. CD44 was expressed in mesangial cells, crescents, tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. Hyaluronic acid was deposited in the capillary tuft of adhesion, crescents and the periglomerular area, and around damaged tubules. Osteopontin was expressed in tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. The glomerular and interstitial deposition of hyaluronic acid correlated with the glomerular and interstitial expression of CD44. The interstitial expression of CD44 correlated with the interstitial expression of osteopontin. The expression of both CD44 and osteopontin in the interstitium correlated with the extent of tubulointerstitial damage. The expression of CD44 in the interstitium correlated with the severity of chronic glomerular lesions. The glomerular and interstitial CD44 and hyaluronic acid expression correlated with proteinuria, and interstitial CD44 and hyaluronic acid expression correlated with creatinine clearance rate. In summary, this study suggests that CD44 participates in the progression of IgA nephropathy by binding hyaluronic acid and osteopontin.

Effect of distraction and coping style on in vivo exposure for specific phobia of spiders.

Recent studies have generated mixed findings regarding the effects of distraction on exposure-based treatments. Results have also been inconsistent regarding the effects of monitoring and blunting coping styles on outcome. The present study attempted to integrate these two areas of research. We hypothesized that the effect of distraction on treatment outcome might depend on coping style. Specifically, we predicted that for blunters (i.e.. individuals who tend to avoid threat-related information), distraction would interfere with the effects of exposure. However, we predicted that distraction might benefit monitors (i.e., individuals who tend to seek out threat-related information). Sixty individuals with a specific phobia of spiders underwent a single, two-hour session of exposure treatment. During the first hour, half of the participants were distracted by listening to an audiotape and the other half underwent exposure without distraction. In the second hour, all participants underwent focused exposure. Based on measures of heart rate, subjective fear, and behavioral testing, participants improved after one hour of treatment, and improved further during the second hour. However, neither distraction, coping style, nor their interaction had a significant effect on outcome. The present study provides support for the benefits of behavioral treatment for specific phobias. However, our hypotheses regarding distraction and coping style were not confirmed.