Community pharmacists' measurement of health-related quality of life in outpatients taking high-risk drugs.

Patients experiencing severe side effects when taking high-risk drugs may have a significantly reduced health-related quality of life (QOL); therefore, it is important to identify changes in the health-related QOL in these patients. This study aimed to determine the health-related QOL in community pharmacy outpatients taking high-risk drugs. This prospective observational study was conducted in 29 community pharmacies with 71 pharmacists in 12 regions and cities in Japan from October to December 2020 and 760 patients were enrolled. Using descriptive questionnaires of EuroQOL-5-dimensions-5-levels (EQ-5D-5L), community pharmacists obtained health-related QOL data from outpatients taking high-risk drugs. The mean health-related QOL of all outpatients was 0.869. The health-related QOL decreased with increasing age. The outpatient health-related QOL was 0.700, 0.763, 0.785, and 0.817 when taking antiepileptic, antidepressant, digitalis, and antiarrhythmic drugs, respectively, which was lower than the average health-related QOL of all outpatients. Mobility and pain/ discomfort accounted for a large proportion of the decline in the health-related QOL with increasing age. There were no significant differences in personal care with increasing age; however, the number of outpatients with mobility, normal activity, and pain challenges decreased with age. In contrast, outpatients aged <65 years with anxiety/depression showed a lower than overall average health-related QOL. To the best of our knowledge, this is the first study in Japan to report an investigation by community pharmacists regarding health-related QOL assessment in outpatients taking high-risk drugs.

Panel of novel urine biomarkers for incident microalbuminuria in people with type 2 diabetes mellitus.

AIM: The need to identify novel biomarkers for early diagnosis and treatment of diabetic nephropathy is widely recognized. However, only a few studies have investigated the association between biomarkers and the onset of albuminuria. In this study, we aimed to investigate a panel of biomarkers suitable for predicting microalbuminuria. METHODS: Some 346 Japanese people with type 2 diabetes exhibiting normoalbuminuria were studied. The endpoint was defined as the onset of microalbuminuria. Thirty biomarkers were selected from among urinary biomarkers described in previous studies. A panel of biomarkers was selected using least absolute shrinkage and selection operator (LASSO). The prognostic performance of the developed panel was evaluated. RESULTS: During a mean follow-up of 6.2 years, 45 people progressed to microalbuminuria. A composite panel of six biomarkers (monocyte chemoattractant protein-1, osteopontin, soluble human tumour necrosis factor receptor-1, tenascin C, vascular endothelial growth factor-A and kidney injury molecule-1) was developed using LASSO. Compared with the basal model comprising estimated GFR and urinary albumin-to-creatinine ratio, addition of these six biomarkers significantly increased the overall C index from 0.773 to 0.824 (P = 0.019). Net reclassification improvement and integrated discrimination improvement were estimated to be 0.412 (P = 0.049) and 0.040 (P = 0.040), respectively. Decision curve analysis also showed that the model with the six novel biomarkers had a better prognostic value for predicting the onset of microalbuminuria. The optimism was moderate or negligible according to measures. CONCLUSIONS: The panel consisting of six novel urinary biomarkers effectively predicted incident microalbuminuria in people with type 2 diabetes.

Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes.

BACKGROUND AND OBJECTIVE: Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. MATERIAL AND METHODS: To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. RESULTS: Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. CONCLUSION: We identified TDP-43 as one of the novel TNF-α factors and found that it bound to the LPS-responsive element in the TNF-α promoter to increase TNF-α expression.

YKL-40 level in gingival crevicular fluid from patients with periodontitis and type 2 diabetes.

OBJECTIVE: YKL-40 is a chitin-binding glycoprotein, the level of which increases in inflammatory diseases, diabetes mellitus (DM), cardiovascular diseases, and tumors. Gingival crevicular fluid (GCF) contains many proteins and markers of periodontitis. The purpose of this study was to investigate YKL-40 level in GCF from patients with periodontitis and DM and the association between YKL-40 level and chronic periodontitis (CP) or DM. SUBJECTS AND METHODS: The subjects were 121 patients with DM, CP, DM and periodontitis (DM-P), and healthy subjects (H). GCF was collected using paper strips after the sites for GCF collection were clinically evaluated for probing depth (PD), gingival index (GI), and bleeding on probing (BOP). YKL-40 in GCF was identified by Western blotting, and its level was determined by ELISA. RESULTS: YKL-40 was contained in GCF samples from H, DM, CP, and DM-P sites, and its levels (amount and concentration) in CP and DM-P were significantly higher than those in H and DM. GCF YKL-40 level significantly correlated with PD and GI, and its level in BOP-positive sites was significantly higher than that in BOP-negative ones. CONCLUSIONS: GCF YKL-40 level was elevated in periodontitis, but not DM. YKL-40 in GCF may be an inflammatory marker for periodontitis.

Use of ultrasound-guided intercostal nerve block as a sole anaesthetic technique in a high-risk patient with Duchenne muscular dystrophy.

Duchenne muscular dystrophy is a progressive neuromuscular disease. Mortality is typically related to combined respiratory failure and dilated cardiomyopathy. Surgery under general anesthesia or deep sedation presents increased risks for pulmonary complications or ventilator dependency postoperatively. We describe the utility of ultrasound guided intercostal nerve blocks for surgery on the chest wall in a patient with Duchenne muscular dystrophy and severe respiratory compromise.

Resistin in gingival crevicular fluid and induction of resistin release by Porphyromonas gingivalis lipopolysaccharide in human neutrophils.

BACKGROUND AND OBJECTIVE: Resistin is an adipocytokine that induces insulin resistance and is predominantly expressed in adipocytes and peripheral blood mononuclear cells. Resistin expression increases in inflammatory diseases as well as diabetes mellitus, and is upregulated by bacterial pathogens and proinflammatory cytokines. The aim of this study was to identify resistin in human gingival crevicular fluid, to compare the resistin levels in gingival crevicular fluid between subjects with and without periodontitis and diabetes mellitus and to investigate the regulation of resistin release from human neutrophils by Porphyromonas gingivalis lipopolysaccharide (P-LPS). MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from patients with chronic periodontitis (n = 24), patients with diabetes mellitus-related periodontitis (n = 18) and healthy subjects (n = 21). Resistin in gingival crevicular fluid was determined using western blot analysis and an ELISA kit. The glycated hemoglobin (HbA(1c)) value was obtained from patients with diabetes mellitus-related periodontitis by a medical interview. Human neutrophils were cultured with P-LPS (0-1000 ng/mL), or incubated with inhibitors of actin or microtubule polymerization in the absence or presence of P-LPS. The medium and cellular fractions were used for determination of resistin by ELISA. RESULTS: The resistin level in gingival crevicular fluid from patients with periodontitis or diabetes mellitus-related periodontitis was significantly higher than that of healthy subjects. The resistin level in gingival crevicular fluid was correlated with gingival index score, but not blood HbA(1c) value. The P-LPS increased resistin release from human neutrophils, and its induction was decreased by actin polymerization inhibitors. CONCLUSION: We show, for the first time, the presence of resistin in gingival crevicular fluid. A high resistin level in gingival crevicular fluid samples from periodontitis patients may to some extent be related to P-LPS-induced resistin release from neutrophils.

Expression pattern of REIC/Dkk-3 in mouse squamous epithelia.

The REIC/Dkk (reduced expression in immortalized cells/Dickkopf-3) gene was originally identified as a tumour-suppressor gene with reduced expression in immortalized cells, cancer-cell lines and tumour tissues. Of the four members of the Dkk family, the REIC/Dkk-3 protein is unique in terms of DNA sequence, expression profiles and biological functions. In this study, we investigated and compared the expression patterns of the REIC/Dkk-3 protein in mouse squamous epithelia. Expression of REIC/Dkk-3 in the back skin was localized to the upper layer of the interfollicular epidermis, and the inner root sheath of hair follicles. Expression of REIC/Dkk-3 was detected in the ear skin, oral mucosa, tongue, oesophagus, uterine cervix, footpad and tail skin, but not in the cornea. Interestingly, expression was localized to the upper layers of these epithelial tissues. The physiological function of REIC/Dkk-3 is still unclear, but our detailed observation highlight its unique expression pattern in squamous epithelia.

Measurement of dynamic bite force during mastication.

Efficient mastication of different types and size of food depends on fast integration of sensory information from mechanoreceptors and central control mechanisms of jaw movements and applied bite force. The neural basis underlying mastication has been studied for decades but little progress in understanding the dynamics of bite force has been made mainly due to technical limitations of bite force recorders. The aims of this study were to develop a new intraoral bite force recorder which would allow the study of natural mastication without an increase in the occlusal vertical dimension and subsequently to analyze the relation between electromyographic (EMG) activity of jaw-closing muscles, jaw movements and bite force during mastication of five different types of food. Customized force recorders based on strain gauge sensors were fitted to the upper and lower molar teeth on the preferred chewing side in fourteen healthy and dentate subjects (21-39 years), and recordings were carried out during voluntary mastication of five different kinds of food. Intraoral force recordings were successively obtained from all subjects. anova showed that impulse of bite force as well as integrated EMG was significantly influenced by food (P<0·05), while time-related parameters were significantly affected by chewing cycles (P<0·001). This study demonstrates that intraoral force recordings are feasible and can provide new information on the dynamics of human mastication with direct implications for oral rehabilitation. We also propose that the control of bite force during mastication is achieved by anticipatory adjustment and encoding of bolus characteristics.

Si1-xGex anode synthesis on plastic films for flexible rechargeable batteries.

SiGe is a promising anode material for replacing graphite in next generation thin-film batteries owing to its high theoretical charge/discharge capacity. Metal-induced layer exchange (LE) is a unique technique used for the low-temperature synthesis of SiGe layers on arbitrary substrates. Here, we demonstrate the synthesis of Si1-xGex (x = 0-1) layers on plastic films using Al-induced LE. The resulting SiGe layers exhibited high electrical conductivity (up to 1200 S cm-1), reflecting the self-organized doping effect of LE. Moreover, the Si1-xGex layer synthesized by the same process was adopted as the anode for the lithium-ion battery. All Si1-xGex anodes showed clear charge/discharge operation and high coulombic efficiency (≥ 97%) after 100 cycles. While the discharge capacities almost reflected the theoretical values at each x at 0.1 C, the capacity degradation with increasing current rate strongly depended on x. Si-rich samples exhibited high initial capacity and low capacity retention, while Ge-rich samples showed contrasting characteristics. In particular, the Si1-xGex layers with x ≥ 0.8 showed excellent current rate performance owing to their high electrical conductivity and low volume expansion, maintaining a high capacity (> 500 mAh g-1) even at a high current rate (10 C). Thus, we revealed the relationship between SiGe composition and anode characteristics for the SiGe layers formed by LE at low temperatures. These results will pave the way for the next generation of flexible batteries based on SiGe anodes.

Research Note: Expression of IGF-1 and IGF-1 receptor proteins in skeletal muscle fiber types in chickens with hepatic fibrosis.

We investigated the expression of insulin-like growth factor 1 (IGF-1) and IGF-1 type 1 receptor (IGF-1R) in skeletal muscle fiber types in chickens with hepatic fibrosis induced by bile duct ligation (BDL). Eleven hens, approximately 104 weeks old, were randomly assigned to BDL (n = 4) and sham surgery (SHAM; n = 7) groups. In BDL hens, histopathology revealed marked bile duct proliferation and liver fibrosis. The cross-sectional area (CSA) of myofibers from both the pectoralis (PCT) muscles significantly decreased in the BDL group compared with the SHAM group (P < 0.01). In contrast, the CSA of myofibers from the femorotibialis lateralis (FTL) muscle did not decrease in the BDL group. Type I fibers were large, round, and hypertrophic. Elongated type IIA and IIB fibers were also present. For IGF-1 immunostaining, the immunoreaction intensity was higher in the PCT in the BDL group than the SHAM group. Within the BDL group, type I fibers from FTL had a stronger immunoreaction intensity than the type II fibers. For IGF-1R immunostaining, the intensity of the immunoreactions was similar within the PCT in the BDL group compared with the SHAM group. For FTL, type I fibers had stronger reactions to IGF-1R than type II fibers in the BDL group. These results suggest that type I fibers express both IGF-1 and IGF-1R and become hypertrophic in chickens with hepatic fibrosis.

Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression.

BACKGROUND: Oncogenic BRAF mutation had been considered to be a founder event in the formation of melanocytic tumours; however, we recently argued against this notion by showing marked polyclonality of BRAF mutations in acquired melanocytic nevi (Lin et al, J Natl Cancer Inst., 2009; 101:1423-7). Here, we tested whether similar heterogeneity of BRAF mutations exists in primary melanomas. METHODS: We isolated and sequenced single melanoma cells from five primary melanoma tissues using antibodies against human high-molecular-weight melanoma-associated antigen. We also examined 10 primary melanomas by the sensitive Mutector assay detecting the BRAF(V600E) mutation, as well as by cloning and sequencing of separated alleles. Furthermore, we estimated the frequency of BRAF mutant alleles in paired samples of primary tumour and recurrence or metastasis in three patients. RESULTS: Single-cell mutation analyses revealed that four of five primary melanomas contained both BRAF-wild-type and BRAF-mutant tumour cells. Tumour heterogeneity in terms of BRAF mutations was also shown in 8 of 10 primary melanomas. Selection of BRAF mutant alleles during progression was demonstrated in all the three patients. CONCLUSION: Acquisition of a BRAF mutation is not a founder event, but may be one of the multiple clonal events in melanoma development, which is selected for during the progression.

Fabrication of a submicron-channel organic field-effect transistor using a controllable electrospun single fibre as a shadow mask.

We demonstrate a simple and versatile method for the fabrication of a submicron channel for an organic field-effect transistor (OFET) using a single electrospun fibre as a shadow mask. A single electrospun fibre is produced by an alternative switching electrospinning method and is stretched 2.5-fold. The average diameter of the stretched fibres is 302 nm. The stretched fibre is placed on ultrathin dielectric layers of aluminium oxide and a self-assembled monolayer (SAM). During electrode deposition the fibre acts as a very small shadow mask. After removing the fibre, electrodes with very narrow gaps of around 350 nm and with high uniformity are easily obtained. We fabricate an OFET by depositing pentacene as an active layer onto the electrodes. The OFET is operable at low voltages, with a threshold voltage of - 1.1 V and a subthreshold swing of 0.27 V decade(-1), values which are one order of magnitude lower than those obtained with a channel length of 75 µm.

Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis.

A novel subset of T cells characterized by the expression of an invariant T cell antigen receptor (TCR) encoded by V alpha 24J alpha Q gene segments was investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction analysis demonstrated that the V alpha 24 TCR repertoire was selectively used in CD4-CD8- double-negative T cells both in patients and in healthy individuals, while almost all families of TCR V alpha were expressed in single-positive T cell fractions. The V alpha 24+ double-negative T cells were increased by approximately fivefold in patients. However, sequence analysis clearly showed significant differences in the V alpha 24 TCR repertoire dominating in patients and healthy donors. In healthy individuals, the invariant V alpha 24J alpha Q was expanded and comprised 20-50% of the total TCR-alpha, while their selective reduction was observed in SSc patients who also showed expansion of invariant V alpha 24 TCR other than V alpha 24J alpha Q. Analogous to murine invariant V alpha 14J alpha 281 TCR, these results suggest that T cells with invariant V alpha 24J alpha Q TCR would function as regulatory T cells, whereas T cells bearing other invariant V alpha 24 TCR in SSc patients could be autoaggressive T cells in nature.

Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis.

To determine the cytokine balance in patients with lupus nephritis (LN), we analysed kidney-infiltrating T cells. Renal biopsy samples from 15 systemic lupus erythematosus (SLE) patients were used. In accordance with the classification of International Society of Nephrology/Renal Pathology Society, they were categorized into Class III, Class III+V (Class III-predominant group, n = 4), Class IV, Class IV+V (Class IV-predominant group, n = 7) and Class V (n = 4) groups. The single-cell samples of both the glomelular and interstitial infiltrating cells were captured by laser-microdissection. The glomerular and interstitial infiltrating T cells produced interleukin (IL)-2, IL-4, IL-10, IL-13 and IL-17 cytokines in the Class III-predominant, Class IV-predominant and Class V groups. Interferon-gamma was detected only in the glomeruli of the Class III-predominant and Class V group samples. The expression level of IL-17 was correlated closely with clinical parameters such as haematuria, blood urea nitrogen level, SLE Disease Activity Index scores in both glomeruli and interstitium, urine protein level in glomeruli and serum creatinine and creatinine clearance levels in interstitium. This suggests that the glomerular infiltrating T cells might act as T helper type 1 (Th1), Th2 and Th17 cells while the interstitial infiltrating T cells, act as Th2 and Th17 cells in the Class III-predominant and Class V groups. In contrast, both the glomerular and interstitial infiltrating T cells might act as Th2 and Th17 cells in the Class IV-predominant group. The cytokine balances may be dependent upon the classification of renal pathology, and IL-17 might play a critical role in SLE development.

Subjective Evaluation of Denture Adhesives: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Healing of ungrafted bone defects of the talus after benign tumour removal.

BACKGROUND: Curettage of benign tumours commonly results in significant bone defects that are reconstructed with autologous grafts, allografts, bone cement or bone substitute. We have treated such defects in the talus without reconstruction with bone or any other material. We now report the healing of these ungrafted defects in eight patients treated with curettage for benign talar tumours. METHODS: Eight consecutive patients were reviewed retrospectively at a mean follow-up of 82 months (range: 28-180 months). Mean age was 21.7 years (range: 12.3-31.3 years) and mean defect size was 16.5 cm(3) (range: 3.5-48 cm(3)). Outcome measures included time to radiological consolidation, ankle pain and stiffness, talar collapse, and tibiotalar joint osteoarthritis. RESULTS: Full consolidation of the defect occurred within 6-12 months in all patients. One patient had minor discomfort over the scar, but there was no ankle joint pain. Two patients had some ankle stiffness, although one had established ankle osteoarthritis prior to surgery. No talar collapse, fracture or new significant osteoarthritis of the ankle was observed. CONCLUSIONS: We conclude that bone grafting is not a necessary adjunct to the curettage of talar lesions.

Enhanced collagen synthesis and transcription by peak E, a contaminant of L-tryptophan preparations associated with the eosinophilia myalgia syndrome epidemic.

The pathogenesis of the eosinophilia myalgia syndrome (EMS) remains unclear. Several abnormal constituents have been found in the L-tryptophan lots responsible for the illness, particularly, 1,1-ethylidenebis[L-tryptophan], also called peak E or EBT, and 3-phenylamino-alanine or peak 5. However, the role of these contaminants in the pathogenesis of EMS and in the development of fibrosis is unknown. We now report that peak E, a dimer of L-tryptophan, is a potent stimulus for human dermal fibroblast DNA and collagen synthesis. Peak E (0.1-1.0 microM) increased DNA synthesis up to four-fold (P = 0.0001) in a dose-dependent manner (r = 0.987). When added to monolayer cultures for 2 to 24 h, peak E (0.5 to 100 microM) caused a progressive, more than threefold increase in alpha 1(I) procollagen mRNA levels and collagenous protein. No increase in procollagen mRNA levels was found after the addition of another major L-tryptophan contaminant, peak 5, or with L-tryptophan itself. Transient transfection with a 2.5-kb alpha 1(I) procollagen promoter-luciferase construct showed that peak E causes a twofold upregulation of promoter activity (P = 0.022). Contraction of collagen gels, consisting of human dermal fibroblasts incorporated into a type I collagen lattice, was enhanced two-fold by exposure to peak E (P = 0.001). We conclude that a major constituent of contaminated batches of L-tryptophan, peak E, is a potent stimulus for fibroblast activation and collagen synthesis. This stimulatory action of peak E may provide a direct mechanism for the development of fibrosis in EMS.

Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS.

[Effects of intra-coronary and intra-graft administration of nicorandil for coronary spasm after coronary artery bypass grafting].

Coronary artery spasm after coronary artery bypass grafting (CABG) is relatively rare, but when it occurs, it is fatal. In cases of circulatory collapse just after surgery, coronary spasm should be suspected, and immediate diagnosis by coronary angiography is necessary. We conducted a study to assess the clinical characteristics of coronary spasm after CABG and the usefulness of intra-coronary and intra-graft administration of nicorandil. Study subjects were 7 patients (6 men and 1 woman, mean age 60.4 years) in whom coronary spasm after CABG was diagnosed angiographically from January 1992 to December 2003. Off-pump CABG (OPCAB) had been performed in 2 patients. Despite continuous administration of nitroglycerin and diltiazem hydrochloride during surgery, sudden circulatory collapse occurred during surgery or within 24 hours after CABG in all 7 patients. All required mechanical circulatory support, and emergency coronary angiography revealed severe graft and native coronary spasms. Intracoronary and/or intra-graft administration of diltiazem hydrochloride or nitroglycerin was not very effective, however, administration of nicorandil was effective for vasodilatation. One patient suffered brain damage and died, but the other 6 patients recovered and were discharged without complication. In conclusion, intra-coronary and/or intra-graft administration of nicorandil appears to be useful for the treatment of coronary spasm after CABG.

Development of a microwave ion source for ion implantations.

A microwave ion source is expected to have a long lifetime, as it has fewer consumables. Thus, we are in the process of developing a microwave ion source for ion implantation applications. In this paper, we report on a newly developed plasma chamber and the extracted P(+) beam currents. The volume of the plasma chamber is optimized by varying the length of a boron nitride block installed within the chamber. The extracted P(+) beam current is more than 30 mA, at a 25 kV acceleration voltage, using PH3 gas.