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A 47-year-old man was complaining of consciousness disorder. He had acute kidney injury, hypokalemia, and severe metabolic alkalosis. Initial treatment using intravenous infusion of 0.9% saline and potassium chloride improved his consciousness. It was clarified that he was a severe alcohol abuser who habitually self-vomited. We diagnosed him with volume depletion and pseudo-Bartter's syndrome due to loss of chloride by habitual vomiting. Gastrointestinal endoscopy demonstrated pyloric stenosis, which was ameliorated by Helicobacter pylori eradication therapy. We should consider volume depletion and pseudo-Bartter's syndrome as differential diagnoses when we encounter patients with acute kidney injury and severe metabolic alkalosis.

Supplementary Figure 1 from A New Melanoma Antigen Fatty Acid–Binding Protein 7, Involved in Proliferation and Invasion, Is a Potential Target for Immunotherapy and Molecular Target Therapy

The identification of molecules that are preferentially expressed in melanoma cells and involved in their malignant phenotypes is important for understanding melanoma biology and the development of new diagnostic and therapeutic methods. By comparing the expression profile of a melanoma cell line with those of various normal tissues using GeneChip and by confirming the actual expression of the selected genes by reverse transcription-PCR and Northern and Western blot analyses, fatty acid–binding protein 7 (FABP7), which is frequently expressed in melanomas, was identified. Immunohistochemical examination revealed that FABP7 was expressed in 11 of 15 melanoma tissues. By down-regulating the FABP7 expression with FABP7-specific small interfering RNAs, in vitro cell proliferation and Matrigel invasion were suppressed in two of six melanoma cell lines. Overexpression of FABP7 in a FABP7-negative embryonic kidney cell line 293T by transfecting with the FABP7 cDNA resulted in enhanced cell proliferation and Matrigel invasion, indicating that FABP7 plays a role in the malignant phenotype of some melanoma cell lines. IgG antibodies specific for the phage or bacterial recombinant FABP7 protein were detected in 14 of 25 (56%) or in 8 of 31 (26%) sera from melanoma patients, respectively, but not in sera from healthy individuals, indicating that FABP7 is an immunogenic antigen in melanoma patients. These results showed that FABP7 is frequently expressed in melanoma, may be involved in cell proliferation and invasion, and may be a potential target for development of diagnostic and therapeutic methods. (Cancer Res 2006; 66(8): 4443-9)

Supplementary Figure Legend from A New Melanoma Antigen Fatty Acid–Binding Protein 7, Involved in Proliferation and Invasion, Is a Potential Target for Immunotherapy and Molecular Target Therapy

Pituicytoma is a rare neoplasm, arising in the posterior pituitary or in the hypophyseal stalk, and its cytological findings have not yet been well-described. We have experienced a case of pituicytoma, which was difficult to diagnose intraoperatively, because of its cellular pleomorphism. A tumor measuring 18 mm in maximum diameter was found at the sella turcica in a Japanese woman in her forties. Both intraoperative crush cytology and histology of the resected tumor showed pleomorphic spindle or round cells, including multinucleated cells. Tumor cells were positive for TTF-1, S-100 protein, and vimentin, partially positive for glial fibrillary acidic protein and epithelial membrane antigen, and negative for synaptophysin, hormones of the anterior pituitary gland, CD34, Olig2, PAX8, and napsin A. Ki-67 labeling index was 2.0%. Tumors included in the differential diagnosis in general are pituitary adenoma, craniopharyngioma, germinoma, and metastatic tumor on the radiological standpoint, and pilocytic astrocytoma and meningioma on the cytological standpoint. However, our case was difficult to differentiate especially from high-grade glioma only by morphology, and immunohistochemistry including TTF-1 was helpful.

BackgroundCholesterol embolization syndrome (CES) is a disease associating with the systemic cholesterol crystal embolism and end-organ dysfunction due to the atherosclerotic plaque rupture, which is dominantly triggered by the intravascular intervention. There is no consensus for which types of anticoagulants we should use during the hemodialysis in patients with CES and end-stage renal disease.Case presentationWe had a 68-year-old man with CES due to intravascular intervention, who suffered the omental bleeding, instead of the embolism, immediately after the initiation of hemodialysis with heparinization. An emergent laparotomy found active bleeding from the omentum, which was surgically repaired. The histopathological analysis showed the embolization of cholesterol crystal clefts in the omentum artery and the injury of arterial wall structure accompanied by the infiltration of inflammatory cells. We preferred nafamostat mesylate during hemodialysis and he had no adverse events following the surgery.ConclusionsIt should be noticed that, in addition to the embolic events, bleeding events can develop in patients with CES, particularly following the initiation of hemodialysis with anticoagulation therapy.

He was a 92-year-old male patient with mild cognitive impairment while preserved activity of daily life. His renal dysfunction gradually increased due to the nephrosclerosis accompanied by systemic edema and water retention. We eventually decided to initiate peritoneal dialysis instead of standard hemodialysis for his end-stage renal dysfunction refractory to optimal medical therapy, given his preserved cognitive function and family support. He underwent an established therapeutic program for the peritoneal dialysis at home with an Information and Communication Technology (ICT).Given the increase in age of the patients with renal dysfunction, peritoneal dialysis has been receiving great attention as a home care strategy. The recent improvement in the device technology and ICT that enables us remote monitoring would reduce patients' effort in the management of peritoneal dialysis. Collaboration with home nursing and care workers would also be warranted for successful home care.

Here, we investigated the prevalence of Salmonella enterica, with and without resistance to 17 common antimicrobial agents, in 706 green anoles (Anolis carolinensis) that were collected in Naha and Tomigusuku Cities, Okinawa Main Island, Japan, between 2009 and 2014. Salmonella strains, including S. enterica Weltevreden and Enteritidis serovars, were identified in the large intestinal content samples extracted from 15 (2.1%) of the analyzed green anoles. No antimicrobial resistance was detected. Thus, the present study demonstrates that although the prevalence of Salmonella and the risk of its transmission from the green anoles to humans or other animals on Okinawa Main Island are relatively low, the green anole population nevertheless represents a potential source of Salmonella infection that could affect human health in this region.

Neuromedin U (NMU) mediates various physiological functions via NMUR1 and NMUR2 receptors. NMUR2 has been considered a promising treatment option for diabetes and obesity. Although NMU-8, a shorter peptide, has potent agonist activity for both receptors, it is metabolically unstable. Therefore, NMU-8 analogs modified with long-chain alkyl moieties via a linker were synthesized. An octadecanoyl analog (17) with amino acid substitutions [αMePhe19, Nle21, and Arg(Me)24] and a linker [Tra-γGlu-PEG(2)] dramatically increased NMUR2 selectivity, with retention of high agonist activity. Subcutaneous administration of 17 induced anorectic activity in C57BL/6J mice. Owing to its high metabolic stability, 17 would be useful in clarifying the physiological role and therapeutic application of NMU.

Variable-angle spectroscopic ellipsometry analysis is performed to study the impact of post-deposition annealing on the passivation performance of the heterocontacts consisting of titanium oxide and silicon oxide on crystalline silicon (c-Si) prepared by atomic layer deposition (ALD) for the development of high-performance ALD-TiO x /SiO y /c-Si heterocontacts. The highest lifetime of 1.8 ms is obtained for the TiO x /SiO y /c-Si heterocontacts grown at 175 °C after annealing at 275 °C for 3 min. With increasing annealing temperature, the TiO x layers of the TiO x /SiO y /c-Si heterocontacts become dominant. Furthermore, the amplitude of dielectric functions of the ALD-TiO x layer decreases as annealing temperature increases, which suggests that enhanced diffusion of Ti into SiO y interlayers at higher annealing temperature. The sufficient diffusion of Ti atoms into SiO y interlayers is caused by annealing at 275 °C for 3 min, yielding high-quality interface passivation.

The theoretical lateral current of the surface inversion layer in a crystalline silicon (cSi) surface for a p-aSi:H/i-aSi:H/cSi heterojunction (SHJ) solar cell was calculated using computer simulation and was compared with the experimental one to study defects/traps at the aSi:H/cSi interface and/or in the cSi surface and to detect the acceptor concentration (N a) in p-aSi:H. To experimentally extract the lateral surface inversion layer current, a field-effect transistor type test element group device was co-integrated with SHJ cells on the same wafer. From the correlation between the experimental and calculated lateral surface inversion layer current, the density of defects/traps (D it) at the aSi:H/cSi interface and/or in the cSi surface and the value of N a were extracted. The calculated lateral surface inversion layer current stayed unchanged for various minority carrier lifetimes in the substrate, suggesting that this method is not suffered from the variation in the material parameters in the substrate.

Background Evidence shows that computerized self-help interventions are effective for reducing symptoms of depression. One such intervention, SPARX, is a gamified mobile computerized cognitive behavioral therapy (cCBT) developed for adolescents in New Zealand, which was shown to be as effective as usual care for young people with mild-to-moderate symptoms of depression. However, gamified cCBT has not yet been tested in Japan. Objective This trial is designed to investigate whether a Japanese-adapted version of SPARX improves depressive symptoms in Japanese university students with mild-to-moderate depressive symptoms. Methods In this 7-week, multicenter, stratified, parallel-group, superiority randomized trial, participants will be allocated to either a treatment condition (SPARX) or a wait-list control condition. SPARX is a fully automated program, which will be delivered to the mobile phone or tablet device of the participants. SPARX is designed as an interactive fantasy game to guide the user through seven modules that teach key CBT strategies. All participants will be recruited from universities via advertisements on online bulletin boards, the campus newspaper, and posters. Participants in the treatment condition will use the SPARX program weekly. The primary outcome is the reduction of depressive symptoms (using Patient Health Questionnaires-9) measured at baseline and weekly: once after the 7-week intervention and once at a 1-month follow-up. Secondary outcomes include satisfaction with the program and satisfaction with life, measured by the Satisfaction With Life Scale; positive and negative moods, measured by the Profile of Mood States Second Edition; social functioning, measured by the EuroQol Instrument; rumination, measured by the Ruminative Responses Scale; and coping, measured by the Brief Coping Orientation to Problem Experienced Inventory. Results This study received funding from The Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido, and obtained institutional review board approval in September 2019. Data collection began in April 2019. Conclusions Results of this trial may provide further evidence for the efficacy of gamified cCBT for the treatment of depression and, specifically, provide support for using SPARX with Japanese university students. Trial Registration Japan Primary Registries Network UMIN000034354; https://tinyurl.com/uu7xd77 International Registered Report Identifier (IRRID) DERR1-10.2196/15164

In rare cases, differential diagnosis between bladder cancer (BC) and gynecological tract cancer (GTC) is difficult because of anatomical proximity and morphological similarity. We analyzed expression status of sex steroid hormone receptors in BC in this study. First, we investigated their usefulness as a histological marker for differential diagnosis. Second, we considered their roles in BC histogenesis.Estrogen receptor α (ERα) and progesterone receptor (PgR) expression was investigated by immunohistochemistry in 125 BCs obtained by transurethral resection or biopsy, then in nonneoplastic background mucosa (trigone, fundus, and dome) of 33 total cystectomy samples. They were evaluated as positive when ≥ 1% of 500 subject cells were immunoreactive with moderate or strong intensities.ERα and PgR were positive in 38.4% and 3.2% of BCs, respectively, suggesting that ERα status alone could not definitely differentiate between BC and GTC. ERα expression was not significantly associated with age and sex of BC patients and histopathology of BCs. Although not significant, ERα expression was more frequent in higher grade (G1/G2 vs. G3/G4; P = 0.143) and marginally associated with advanced stage of BCs (pTis/pTa/pT1 vs. pT2/pT3, P = 0.056). ERα expression was significantly more frequent in background mucosa with ERα-positive BC (In the epithelium and stroma; both P0.001). ERα expression was continuously observed from normal to malignant epithelium in some cases. Although not significant, Brunn's nest or cystitis glandularis was more frequent in background mucosa with ERα-positive BC (P = 0.218). Analyses of nonneoplastic mucosa in cystectomy revealed that ERα was more frequently positive in urothelium of trigone, a predilection site for cystitis glandularis, than those of fundus and dome, with a significant difference between trigone and dome (P = 0.034). These data suggest that chronic inflammation may up-regulate ERα in the background epithelium, especially in trigone, and ERα expression in BC might be the reflection of bladder epithelium from which BC arose.Usefulness of ERα was limited in differential diagnosis between BC and GTC. ERα up-regulation might not play a critical role in the development of BC because it was already noted in the background bladder mucosa.

We previously developed a chelating ligand, 1-(2-hydroxy-3-methoxybenzaldehyde)-4-aminosalicylhydrazone (HMB-ASH), which can chelate Fe(III) to form a complex. The HMB-ASH-Fe(III) complex exhibits a dose-dependent anti-proliferative effect in HepG2 cells, whereas the ligand, HMB-ASH, and Fe(III) alone had no considerable effect. The HMB-ASH-Fe(III) complex was composed of Fe(III):HMB-ASH (1:2), as determined by high-performance liquid chromatography with high-resolution mass spectrometry. The IC50 value was approximately 20 μM, which was comparable to those of the anti-cancer drugs oxaliplatin (OXP) and etoposide (ETP) under the same conditions. Similar to OXP and ETP, HMB-ASH-Fe(III) induced apoptosis in HepG2 cells, as revealed by terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling assay.

The natriuretic peptide (NP) system is a critical endocrine, autocrine, and paracrine system and has been investigated for potential use against cardiovascular and metabolic diseases. The clearance of NPs is regulated by the proteolysis of neutral endopeptidase (NEP) and by endocytosis via natriuretic peptide receptor-3 (NPR3). A linear NPR3-selective peptide, [Cha8]-ANP(7-16)-NH2 (1), showed potent binding affinity for NPR3 but poor predicted chemical stability due to its free thiol group. A 12-mer peptide (9) without a thiol group was designed by the hybridization of two NPR3-binding peptides: a linear ANP fragment peptide analog and musclin, a murine member of the bHLH family of transcription factors, possessed high binding affinity and strict selectivity for NPR3. To increase the proteolytic resistance of 9, amino acid substitutions at the cleavage sites led to hydroxyacetyl-[d-Phe5,d-Hyp7,Cha8,d-Ser9,Hyp11,Arg(Me)14]-ANP(5-15)-NHCH3 (23), showing high and selective binding affinity for NPR3 over NPR1 and excellent stability in mouse serum. Compound 23 increased intracellular cGMP concentrations in primary cultured adipocytes, and continuous administration induced substantial plasma cGMP elevation in mice, suggesting its potential to clarify the physiological role of NPR3 and its therapeutic application.

Summary Background Xeroderma pigmentosum (XP) is a photosensitive genodermatosis with increased susceptibility to skin cancers. Patients are typically diagnosed with XP when they consult a dermatologist for skin cancers. Case/Methods The genetic analysis and 2–8 years of follow-up for three school-age patients with XP-V is described. The patients were referred to us because of increased pigmented freckles; they had not experienced abnormal sunburn or developed skin cancer at their first visit. All patients harbored a genetic mutation in the POLH gene. XPV9KO was diagnosed at age 13 with a homozygous del1661A that creates a stop codon in the non-catalytic domain of POLH. The patient practiced sun protection, effectively preventing the development of skin cancer by age 21. XPV19KO was diagnosed at age 11 with a compound heterozygous mutation of G490T and C1066T, causing POLH truncation in the catalytic domain. This patient developed basal cell carcinoma at ages 12 and 13. XPV18KO was referred to us at age 11 and diagnosed with compound heterozygous variants of c.1246_1311del66 (exon 9 skipping), a novel mutation, and c.661_764 del104 (exon 6 skipping). Conclusion Freckle-like pigmentation on sun-exposed skin is sometimes the only sign of XP-V, and early diagnosis is extremely important for children.

Tropomyosin receptor kinase B (TrkB) is a known receptor of brain-derived neurotrophic factor (BDNF). Because it plays a critical role in the regulation of neuronal development, maturation, survival, etc., TrkB is a good target for drugs against central nervous system diseases. In this study, we aimed to generate peptidic TrkB agonists by applying random peptide phage display technology. After the phage panning against recombinant Fc-fused TrkB (TrkB-Fc), agonistic phages were directly screened against TrkB-expressing HEK293 cells. Through subsequent screening of the first-hit BM17 peptide-derived focus library, we successfully obtained the BM17d99 peptide, which had no sequence similarity with BDNF but had TrkB-binding capacity. We then synthesized a dimeric BM17d99 analog peptide that could phosphorylate or activate TrkB by facilitating receptor homodimerization. Treatment of TrkB-expressing HEK293 cells with the dimeric BM17d99 analog peptide significantly induced the phosphorylation of TrkB, suggesting that homodimerization of TrkB was enhanced by the dimeric peptide. This report demonstrates that our approach is useful for the generation of artificial peptidic agonists of cell surface receptors.

Objectives: In 2002, FDI (World Dental Federation) published a policy advocating that caries be treated by minimal intervention (MI). This MI policy has been accepted worldwide and is taught in universities. But acceptance in general dental practice has been slower, especially in Japan where healthcare payment and practice favour drilling and filling. To help disseminate this MI policy into general practice, the Japanese Society of Conservative Dentistry developed an evidence-based clinical guideline for restoring carious permanent teeth in adult patients. Methods: The guideline was developed by a committee of nine university clinicians and a librarian. The committee selected the most frequent clinical questions in treating caries and used electronic databases to search and assess the best scientific evidence for each. Members then added their clinical experience and discussed to reach consensus on each question on treating caries with MI policy. Graded recommendations and guidance were made for each clinical question. The provisional guideline was strengthened after review and discussion with university researchers and general practitioners. Results: The guideline addresses the 16 most frequent clinical questions in treating adult caries, including restorative methods and how to tackle root caries. Recommendations for treatment using MI policy were developed using the best scientific evidence and consensus of experienced clinicians. Clinical significance: The guideline offers a practical expert view of treating caries with the MI policy that incorporates the best scientific evidence, the latest techniques, the most preferable materials and the general consensus of expert clinicians., Journal of Dentistry, 40(2), pp.95-105; 2012

The mobility of people's activities, and cloud computing technologies are becoming advanced in the modern age of information and globalization. This study describes the capability of discussing townscape design while sharing a 3-dimensional virtual space with stakeholders in a distributed and synchronized environment. First of all, a townscape design support system based on a cloud computing type VR system is constructed. Next, an experiment of a distributed and synchronized discussion of townscape design is executed with examinees who are specialists in the townscape design field. The conclusions are as follows: 1. Users who use VR frequently and who use videoconferencing consider that the difference with face-to-face discussion is small. 2. The capability of distributed and synchronized discussions in the townscape design field is high.

This in vitro study investigated the relationship between assessments of dentin caries using a laser fluorescence device (DIAGNOdent) and a caries detector dye during caries removal. The dentin of eight extracted carious molars was removed at 300-microm interval points from the dentin surface toward the pulp chamber. Before and after each removal, images of the carious surfaces were taken in association with color-matching stickers (for color correction) and the surfaces were evaluated by DIAGNOdent based on fluorescence emission from the tooth surface. For the L* values (CIE 1976 L*a*b* color system), there was a strong negative correlation between DIAGNOdent results and the corrected L* values of the carious surfaces (Pearson's correlation coefficient: -0.853); additionally, there was a significant correlation between them (p0.05). However, there were no significant correlations between the DIAGNOdent results and the corrected a* and b* values of the carious surfaces (Pearson's correlation coefficients: 0.108 and 0.018 respectively). In conclusion, DIAGNOdent was shown to be applicable for caries diagnosis during caries removal.

Summary Objectives In some studies gap formation has been evaluated in just one section of the restorative. This in vitro study aimed to design a quantitative three-dimensional method for evaluation of the contraction gap in restoratives. Methods Cervical cavities were prepared on buccal, palatal or lingual surfaces in human extracted molars and were then filled with resin composites. Specimens were reduced every 100 μm in a direction parallel to the tooth axis, and perpendicular to the cavity floor from one proximal side to the other. The sequence of reducing the sections by 100 μm, image taking (250×) and observation of these images (maximal 2500×) were repeated. Three-dimensional images of the contraction gap were made using analytical software and the proportions of the interface with gap formation calculated. Results The mean proportions of the interface with gap formation of the self-etching system (Clearfil Liner Bond II Σ) was 41.7±6.3% and that of the self-priming system (Single Bond) was 38.2±3.9%; there was no significant difference. Conclusions Approximate three-dimensional images of the in vitro contraction gap could be drawn and the mean proportions of the interface with gap formation could be more precisely calculated than by previous methods.

Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.

Oncogenic mutations of molecules involved in the mitogen-activated protein kinase (MAPK) pathways provide signals mediating both tumor growth and invasion in various cancers including melanomas. BRAF somatic mutations, found in 66% of melanomas, have NIH3T3 transforming ability with the elevated kinase activity in vitro. We attempted to mediate RNA interference (RNAi) with HIV lentiviral vectors specific for either wild type or the most frequently mutated form of BRAF (V599E) in 10 melanoma cell lines, and found that RNAi inhibited the growth of most melanoma cell lines in vitro as well as in vivo, which was accompanied by decrease of both BRAF protein and ERK phosphorylation. Interestingly, the mutated BRAF (V599E)-specific siRNA inhibited the growth and MAPK activity of only melanoma cell lines with this mutation. Furthermore, BRAF RNAi inhibited matrigel invasion of melanoma cells accompanied with a decrease of matrix metalloproteinase activity and beta(1) integrin expression. These results clarify that the mutated BRAF (V599E) is essentially involved in malignant phenotype of melanoma cells through the MAPK activation and is an attractive molecular target for melanoma treatment. The lentivirus-mediated RNAi specific for oncogenic mutations may be a powerful technique for gene therapy of cancer.

The objective of this study was to investigate the feasibility of proximal surface caries detection using a laser fluorescence device, DIAGNOdent, through the sound dentin surrounding the cavity wall after removal of occlusal caries. Extracted sound human molars were ground to prepare horizontal and vertical dentin plates 1.4 mm thick. Extracted carious human molars were reduced in thickness horizontally from the occlusal surfaces until exposure of the dentin caries. The dentin plate was placed on the carious tooth. Before and after gradual thinning of the dentin plate from approximately 1.4 mm to 0.2 mm thick, the dentin caries was measured 10 times through the plate by the laser fluorescence device with a cone-shaped tip or a broad tip. When the dentin plate was reduced to less than 0.3 mm thick (using a combination of a horizontal plate and cone-shaped tip) or 0.2 mm thick (using the other combinations), the values measured with the laser fluorescence device were significantly larger than the values before reducing the thickness of the dentin. Based on these results, the device offers potential use as one of the screening tests for proximal surface caries detection through sound dentin when the sound dentin between tip and caries is thin.

Pallister-Hall syndrome was first described by Hall et al. in 1980. This syndrome is characterized by hypothalamic hamartoblastoma, hypopituitarism, polydactyly, imperforate anus and other anomalies. We report a case of a male infant with hypothalamic tumor, hypopituitarism, dysplastic metacarpals, micropenis and remarkable hypoglycemia. He has been treated with hydrocortisone, thyroid hormone, NaCl, fludrocortisone acetate and GH. He has grown well on this therapy.

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism.

Growth hormone (GH) secreted from the pituitary is essential for postnatal growth in animals. GH exerts its actions by a direct effect on target organs and by stimulating insulin-like growth factor I (IGF-I) production. In the human pituitary, there is a naturally occurring variant protein which has a molecular mass of 20 kDa (20K hGH) besides the major 22 kDa hGH (22K hGH), but the physiological actions of 20K hGH are still poorly understood. In this study we have examined its effects on the IGF-I mRNA expression in the pro B-cell line Ba/F3 cells stably expressing hGH receptor (Ba/F3-hGHR). Ba/F3-hGHR cells were incubated for 2 h with a series of various concentrations (10 pM to approximately 10 nM) of 20K or 22K hGH. The IGF-I mRNA expression in the Ba/F3-hGHR cells was detected by the RT-PCR method. IGF-I gene expression was increased by 20K and 22K hGH stimulation, but not by PRL or IL-3 in the Ba/F3-hGHR. And this effect was not observed in parental Ba/F3 cells. Lower concentrations of 20K hGH more strongly induced IGF-I gene expression than 22K-hGH. These results suggest that 20K and 22K hGH stimulate the IGF-I gene expression in the Ba/F3-hGHR through hGH receptors, and that the stronger effect of 20K hGH than that of 22K hGH in enhancing the IGF-I gene expression may be correlated with a 20K hGH specific receptor dimerization mechanism.

Branched-chain alpha-keto acid dehydrogenase kinase (BDK) phosphorylates and inactivates the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), which is the rate-limiting enzyme in the branched-chain amino acid catabolism. BDK has been believed to be bound to the BCKDC. However, recent our studies demonstrated that protein-protein interaction between BDK and BCKDC is one of the factors to regulate BDK activity. Furthermore, only the bound form of BDK appears to have its activity. In the present study, we examined effects of BDK inhibitors on the amount of BDK bound to the BCKDC using rat liver extracts. The bound form of BDK in the extracts of liver from low protein diet-fed rats was measured by an immunoprecipitation pull down assay with or without BDK inhibitors. Among the BDK inhibitors. alpha-ketoisocaproate, alpha-chloroisocaproate, and a-ketoisovalerate released the BDK from the complex. Furthermore, the releasing effect of these inhibitors on the BDK appeared to depend on their inhibition constants. On the other hand, clofibric acid and thiamine pyrophosphate had no effect on the protein-protein interaction between two enzymes. These results suggest that the dissociation of the BDK from the BCKDC is one of the mechanisms responsible for the action of some inhibitors to BDK.

Xeroderma pigmentosum (XP) is a photosensitive genodermatosis with increased susceptibility to skin cancers. Patients are typically diagnosed with XP when they consult a dermatologist for skin cancers.The genetic analysis and 2-8 years of follow-up for three school-age patients with XP-V is described. The patients were referred to us because of increased pigmented freckles; they had not experienced abnormal sunburn or developed skin cancer at their first visit. All patients harbored a genetic mutation in the POLH gene. XPV9KO was diagnosed at age 13 with a homozygous del1661A that creates a stop codon in the non-catalytic domain of POLH. The patient practiced sun protection, effectively preventing the development of skin cancer by age 21. XPV19KO was diagnosed at age 11 with a compound heterozygous mutation of G490T and C1066T, causing POLH truncation in the catalytic domain. This patient developed basal cell carcinoma at ages 12 and 13. XPV18KO was referred to us at age 11 and diagnosed with compound heterozygous variants of c.1246_1311del66 (exon 9 skipping), a novel mutation, and c.661_764 del104 (exon 6 skipping).Freckle-like pigmentation on sun-exposed skin is sometimes the only sign of XP-V, and early diagnosis is extremely important for children.

A 38-year-old Japanese woman with steroid-dependent ulcerative colitis developed generalized pustular psoriasis. Cyclosporine improved both her cutaneous lesions and bowel condition. Recent studies show that Th17 T cells are critically involved in the pathogenesis of both generalized pustular psoriasis and inflammatory bowel disease. Although molecular mechanisms seem similar, our case is the first report showing generalized pustular psoriasis associated with inflammatory bowel disease. We believe that our case may contribute to further understanding of both diseases and give us a chance to design a suitable therapy in the case of generalized pustular psoriasis complicating inflammatory bowel disease.

Polyvinylidene fluoride (PVDF) was crystallized as thin films on (001) cleavage planes of ionic crystals as well as one-axially oriented polymer surfaces by using vacuum-evaporation or solution-growth technique. The polymer surfaces regulated the molecular orientation of PVDF. The ionic crystals controled the molecular conformation and produced the highly ordered α-form (on NaCl and KCl) and β-form (on KBr) crystals of the polymer. Matching of the lattice spacings between the PVDF crystal and the substrates does not seem to be important in determining the crystalline form.

Background— The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a proinflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14 −/− mice that lack MRP-8/14 complexes. Methods and Results— We examined parenchymal rejection after major histocompatibility complex class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP-14 −/− recipients. Allograft survival averaged 5.9±2.9 weeks (n=10) in MRP-14 −/− recipients compared with >12 weeks (n=15; P −/− recipients had significantly higher parenchymal rejection scores (2.8±0.8; n=8) than did WT recipients (0.8±0.8; n=12; P −/− recipients had significantly increased T-cell and macrophage infiltration and increased mRNA levels of interferon-γ and interferon-γ–associated chemokines (CXCL9, CXCL10, and CXCL11), interleukin-6, and interleukin-17 with significantly higher levels of Th17 cells. MRP-14 −/− recipients also had significantly more lymphocytes in the adjacent para-aortic lymph nodes than did WT recipients (cells per lymph node: 23.7±0.7×10 5 for MRP-14 −/− versus 6.0±0.2×10 5 for WT; P −/− recipients of bm12 hearts expressed significantly higher levels of the costimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions with allo–endothelial cell–primed MRP-14 −/− DCs resulted in significantly higher antigen-presenting function than reactions using WT DCs. Ovalbumin-primed MRP-14 −/− DCs augmented proliferation of OT-II (ovalbumin-specific T cell receptor transgenic) CD4 + T cells with increased interleukin-2 and interferon-γ production. Cardiac allografts of B6 major histocompatibility complex class II −/− hosts and of B6 WT hosts receiving MRP-14 −/− DCs had significantly augmented inflammatory cell infiltration and accelerated allograft rejection compared with WT DCs from transferred recipient allografts. Bone marrow–derived MRP-14 −/− DCs infected with MRP-8 and MRP-14 retroviral vectors showed significantly decreased CD80 and CD86 expression compared with controls, indicating that MRP-8/14 regulates B7-costimulatory molecule expression. Conclusions— Our results indicate that MRP-14 regulates B7 molecule expression and reduces antigen presentation by DCs and subsequent T-cell priming. The absence of MRP-14 markedly increased T-cell activation and exacerbated allograft rejection, indicating a previously unrecognized role for MRP-14 in immune cell biology.

Volatile pyrolysates of a methyl methacrylate-butadiene-styrene copolymer (MBS) have been analyzed using a capillary gas chromatograph equipped with a Fourier transform infrared detector in tandem with a mass selective detector, and a gas chromatograph-atomic emission detector system. Among the volatile compounds observed were monomers used for synthesis of the polymer. Numerous oligomers of higher boiling point were also found; identification of these could be used to give structural information about the parent polymer. Combining information from these techniques was found to be extremely useful for the analysis of polymer pyrolysis products. In characterizing each compound it was found particularly helpful to juxtapose feature-specific chromatograms (e.g., single ion monitoring from the mass-selective detector and the selected wavelength chromatography from the infrared detector).

当教室10年間のBCE (Basal Cell Epithelioma) 35例36個につき検討した。男18例, 女17例で, 60歳代に多い。2年以内に半数以上が受診したが, 10年以上の経過も4例みられた。鼻, 眼囲, 頬, 頭に多く発生し, 大きさは径1cm以下が半数を占めた。主病変の組織型は, Solid type 25, Superficial type 5, Sclerosing type 4, Adenoid type 2の順であったが, 副病変として以上の他にCystic type 2, Keratotic type 1, Adamantinoid type 3がみられた。