A case of renal sarcoidosis complicated by parotid gland and uterine lesions.

BACKGROUND: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions. CASE PRESENTATION: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared. CONCLUSION: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.

Inactivation of SARS-CoV-2 variants by nitrogen-doped titanium dioxide loaded with metals as visible-light photocatalysts.

PURPOSE: We examined the inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a nitrogen-doped titanium dioxide (N-TiO2) visible-light photocatalyst that was activated via light irradiation in the natural environment and was safe for human use as a coating material. METHODS: The photocatalytic activity of glass slides coated with three types of N-TiO2 without metal or loaded with copper or silver and copper was investigated by measuring acetaldehyde degradation. The titer levels of infectious SARS-CoV-2 were measured using cell culture after exposing photocatalytically active coated glass slides to visible light for up to 60 min. RESULTS: N-TiO2 photoirradiation inactivated the SARS-CoV-2 Wuhan strain and this effect was enhanced by copper loading and further by the addition of silver. Hence, visible-light irradiation using silver and copper-loaded N-TiO2 inactivated the Delta, Omicron, and Wuhan strains. CONCLUSION: N-TiO2 could be used to inactivate SARS-CoV-2 variants, including emerging variants, in the environment.

Synthesis and activity of 3-oxo-α-ionone analogs as male attractants for the solanaceous fruit fly, Bactrocera latifrons (Diptera: Tephritidae).

A series of 3-oxygenated α-ionone analogs have been developed as highly specific male lures for the solanaceous fruit fly Bactrocera latifrons, a pest of solanaceous fruits. We compared the attractant and phagostimulant activities of analogs with or without (i) unsaturations at the 4,5- and/or 7,8-positions and (ii) oxygen moieties at the 3- and/or 9-positions of the ionone molecule. Since naturally occurring vomifoliol (V2) was found to induce a highly potent phagostimulant activity in B. latifrons males, related analogs including dehydrovomifoliol (V1), 6-hydroxy-α-ionone (U1), and 6-hydroxy-α-ionol (U2) were synthesized to evaluate their attractant and phagostimulant activities. Synthetic V1, V2, U1, and U2 exhibited low attractant activity, but their phagostimulant activity was relatively high. Optical isomers of 3-oxo-7,8-dihydro-α-ionone (P3) and V1 were prepared to examine the stereochemical specificity of attractants. (+)-(6R)-P3 and (+)-(6S)-V1 exhibited the corresponding activities, while their respective antipodal enantiomers were found entirely inactive.

Monoclonal immunoglobulin G1 κ-type atypical antiglomerular basement membrane disease accompanied by necrotizing glomerulonephritis
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INTRODUCTION: Patients without detectable serum antiglomerular basement membrane (GBM) antibodies but with GBM staining for immunoglobulins (Ig), absence of a crescentic phenotype, mild renal insufficiency, and absence of pulmonary hemorrhage have atypical anti-GBM diseases. We report the case of a 64-year-old man with slowly progressive glomerulonephritis. CASE HISTORY: A 64-year-old Peruvian man presented with persistent microscopic hematuria, proteinuria of 2.1 g/g creatinine (Cr), serum Cr 1.00 mg/dL, and C-reactive protein 0.80 mg/dL. Renal biopsy revealed necrotizing glomerulonephritis with 39% cellular crescent formation and diffuse segmental endocapillary proliferation. He had linear staining of monoclonal IgG1-κ in the capillary walls but no detectable serum anti-GBM antibodies. Because renal dysfunction was slowly progressing, steroid monotherapy was initiated, and serum Cr level decreased from 1.48 to 1.13 mg/dL. However, serum Cr increased again to 1.35 mg/dL owing to active glomerular damage with crescent formation and endocapillary proliferation, confirmed by the second renal biopsy at 9 months after therapy. Renal function improved after cyclophosphamide therapy. CONCLUSION: We described an atypical variant of anti-GBM disease due to monoclonal IgG1-κ. Unlike usual atypical anti-GBM disease cases, we observed crescent formation in our patient. Further investigations are needed to identify the cause of nondetectable serum anti-GBM antibodies and to describe the causal relationships between clinicopathological features and the pattern of IgG subclass and light chain in atypical anti-GBM disease.

Sodium-Glucose Cotransporter-2 Inhibitor Immediately Decreases Serum Uric Acid Levels in Type 2 Diabetic Patients.

BACKGROUND Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new antihyperglycemic drugs for type 2 diabetes. SGLT2 inhibitors ameliorate cardiovascular morbidity and mortality as well as kidney disease progression by reducing body weight (BW), blood pressure (BP), visceral adiposity, albuminuria, and serum uric acid and blood glucose levels. However, it is not clear which effects are pronounced, and what mechanisms are associated with these effects. MATERIAL AND METHODS This study recruited patients with type 2 diabetes who were prescribed an SGLT2 inhibitor for the first time in our outpatient department. Clinical parameters were measured before and 6 months after the administration of the SGLT2 inhibitor, without the addition of new drugs and dose changes for all prescribed drugs. RESULTS This study recruited 24 patients with type 2 diabetes. No significant differences in BP, glycated hemoglobin (HbA1c) levels, and low-density lipoprotein cholesterol levels were observed after SGLT2 inhibitor administration. In contrast, BW and serum uric acid levels decreased significantly, and the fractional excretion of uric acid (FEUA) increased significantly after administration. While no significant relationships were observed between serum uric acid and FEUA with respect to the percentage changes from baseline values, the percentage changes in serum uric acid levels from baseline were significantly and positively associated with those in serum creatinine levels. CONCLUSIONS Serum uric acid levels were immediately decreased owing to the administration of SGLT2 inhibitor, but BP, blood glucose, and serum lipid levels were unchanged. These changes in serum uric acid levels may be associated with changes in renal function.

Increased heart rate is associated with intrarenal renin-angiotensin system activation in chronic kidney disease patients.

BACKGROUND: A higher heart rate is one of the risk factors for heart failure and cardiovascular disease. Activation of the intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. However, the association between heart rate and intrarenal RAS activation is unclear. METHODS: We investigated the relationship between heart rate and urinary angiotensinogen (U-AGT) excretion, a surrogate marker for intrarenal RAS activity, in ten subjects without chronic kidney disease (CKD) and 72 CKD patients who were not taking medications that influence heart rate and RAS blockers (age 50.0 ± 17.4 years, 27 men and 45 women, serum creatinine (sCr) 1.85 ± 2.71 mg/dL, blood pressure 120.5 ± 15.8/72.9 ± 10.1 mmHg, heart rate 67.3 ± 8.9 /min, urinary protein excretion 1.27 ± 2.63 g/day, and U-AGT excretion 747.4 ± 2714.6 µg/day). RESULTS: As heart rate is influenced by behavior and emotion, we divided it into daytime and nighttime. Heart rate had a significant positive association with sCr levels during daytime and nighttime in CKD patients but not in non-CKD subjects. Moreover, although heart rate was not associated with U-AGT excretion levels in non-CKD subjects, it was associated with U-AGT excretion levels during daytime (r = 0.23 and p = 0.047) and nighttime (r = 0.45 and p < 0.01) in CKD patients. Multiple linear regression analysis revealed that heart rate had a significant positive association with the U-AGT excretion levels during nighttime, but not daytime, after adjustments for age, sex, body mass index, and sCr (ß = 0.31 and p = 0.034). CONCLUSION: Heart rate is associated with U-AGT excretion levels, especially during the nighttime, in CKD patients.

Melatonin ameliorates intrarenal renin-angiotensin system in a 5/6 nephrectomy rat model.

BACKGROUND: Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. It has been reported that reactive oxygen species (ROS) are important components of intrarenal RAS activation. Melatonin is recognized as a powerful antioxidant, and we recently reported that impaired nighttime melatonin secretion correlates negatively with urinary angiotensinogen excretion, the surrogate marker of intrarenal RAS activity in patients with CKD. However, whether melatonin supplementation ameliorates the augmentation of intrarenal RAS in CKD has remained unknown. We aimed to clarify whether exogenous melatonin ameliorates intrarenal RAS activation via the reduction of ROS production. METHODS: 5/6 Nephrectomized (Nx) rats were used as a chronic progressive CKD model and compared with sham-operated control rats. The Nx rats were divided into untreated Nx rats and melatonin-treated Nx rats. The levels of intrarenal RAS, ROS components, and renal injury were evaluated after 4 weeks of treatment. RESULTS: Compared with the control rats, the untreated Nx rats exhibited significant increases in intrarenal angiotensinogen, angiotensin II (AngII) type 1 receptors, and AngII, accompanied by elevated blood pressure, higher oxidative stress (8-hydroxy-2'-deoxyguanosine), lower antioxidant (superoxide dismutase) activity, and increased markers of interstitial fibrosis (α-smooth muscle actin, Snail, and type I collagen) in the remnant kidneys. Treatment with melatonin significantly reversed these abnormalities. CONCLUSION: Antioxidant treatment with melatonin was shown to ameliorate intrarenal RAS activation and renal injury in a 5/6 Nx rat model.

Apocrine hidrocystoma on the genitalia of a 9-year-old girl.

Apocrine hidrocystomas are mostly found on the cheeks and eyelids but also on the scalp and neck. The age distribution is from 30 to 70 years old. We report a case of an apocrine hidrocystoma on the genitalia of a 9-year-old girl.

Generic Learning-Based Ensemble Framework for Small Sample Size Face Recognition in Multi-Camera Networks.

Multi-camera networks have gained great interest in video-based surveillance systems for security monitoring, access control, etc. Person re-identification is an essential and challenging task in multi-camera networks, which aims to determine if a given individual has already appeared over the camera network. Individual recognition often uses faces as a trial and requires a large number of samples during the training phrase. This is difficult to fulfill due to the limitation of the camera hardware system and the unconstrained image capturing conditions. Conventional face recognition algorithms often encounter the "small sample size" (SSS) problem arising from the small number of training samples compared to the high dimensionality of the sample space. To overcome this problem, interest in the combination of multiple base classifiers has sparked research efforts in ensemble methods. However, existing ensemble methods still open two questions: (1) how to define diverse base classifiers from the small data; (2) how to avoid the diversity/accuracy dilemma occurring during ensemble. To address these problems, this paper proposes a novel generic learning-based ensemble framework, which augments the small data by generating new samples based on a generic distribution and introduces a tailored 0-1 knapsack algorithm to alleviate the diversity/accuracy dilemma. More diverse base classifiers can be generated from the expanded face space, and more appropriate base classifiers are selected for ensemble. Extensive experimental results on four benchmarks demonstrate the higher ability of our system to cope with the SSS problem compared to the state-of-the-art system.

Transformed Mycosis Fungoides with a Cytotoxic T-Cell Phenotype.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma and occasionally undergo large cell transformation (transformed MF, TMF), resulting in a poorer clinical outcome. We describe a case of TMF with an immunophenotypic shift. MF showed the CD4 + CD8- T-cell phenotype, while TMF exhibited the CD4-CD8 + T-cell phenotype. Moreover, TMF expressed cytotoxic markers of TIA1 and Granzyme B. A PCR analysis of T-cell receptor genes revealed peak sizes that were the same in both biopsies, indicating that these two lymphomas were derived from the same clone.

First case of successful eradication of the sweet potato weevil, Cylas formicarius (Fabricius), using the sterile insect technique.

This paper presents the first case of the successful eradication of a Coleoptera pest species over a wide area using a combination of male annihilation technique (MAT) and sterile insect technique (SIT) application. The sweet potato weevil, Cylas formicarius, is one of the most destructive and widely distributed pests of sweet potato, Ipomoea batatas. A project to eradicate it was launched in 1994 on Kume Island, Okinawa Prefecture, Japan. The MAT application was first used from November 1994 to January 1999 to reduce the density of wild populations. The distribution and densities of weevils were assessed by trapping them and surveying infestation rates in wild hosts and sweet potatoes in the field. The C. formicarius populations were suppressed by approximately 90% and plant infestations were reduced from 9.5% to less than 0.1% by using the MAT. Then, hundreds of thousands to millions of sterile weevils were released each week (ca. 460 million in total from 1999 to 2012). As a result, based on an analysis of 12748 stems and 48749 tubers, no weevil infections were detected in the stems or tubers of sweet potato since 1997. Since 2009, almost no wild weevils were captured in traps, and in wild host and sweet potato surveys no weevils have been found in any of the 580 locations and 8833 samples since October 2011. As of 28 December, 2012, C. formicarius is considered to have been eradicated from Kume Island. This paper describes the process of eradicating C. formicarius using SIT application integrated with MAT application for the first time and discusses some of the main challenges associated with the weevil eradication campaignl.

A Case of M-Type Phospholipase A2 Receptor-Associated Membranous Nephropathy With IgG4-Positive Cells Infiltration in the Interstitium.

A 70-year-old man was referred to our department for evaluation of nephrotic syndrome. Renal biopsy revealed membranous nephropathy (MN). Immunohistochemical analysis demonstrated IgG4-positive staining in the glomeruli and interstitial cells. The presence of serum anti-phospholipase A2 receptor (PLA2R) antibody and enhanced staining of PLA2R in the glomeruli was noted. Computed tomography unidentified the extrarenal lesions of IgG4-related disease. He was diagnosed with PLA2R-associated MN possibly complicated with IgG4 related kidney disease (IgG4-RKD). Storiform fibrosis, a typical manifestation of IgG4-RKD, was not apparent. We herein describe a case of serologically and histologically confirmed PLA2R-associated MN with IgG4+ cell infiltration into the interstitium without any signs of IgG4-RD.

Visualization of estimated prevalence of CES-D positivity accounting for background factors and AIS scores.

Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases.

A novel splicing variant of CADM2 as a protective transcript of psoriasis.

CADM2, a candidate gene for psoriasis, was identified by a genome-wide association study using microsatellites in the Japanese population (561 cases and 561 controls). Moreover, haplotype analysis included an additional 68 SNPs and indicated that a 110-kb haplotype block was detected for the protective risk haplotype of psoriasis. We also identified an initial exon of novel splicing variants in this haplotype block. A functional analysis by qRT-PCR using RNAs from the blood of 56 cases and 64 controls significantly demonstrated an inverse correlation between expression frequencies in a novel splicing variant and the number of alleles associated with psoriasis. To confirm these results, we must perform replication studies using other ethnic groups and more functional analysis particularly for skin tissues.

Enhancement of cellulolytic enzyme activity by clustering cellulose binding domains on nanoscaffolds.

Cellulose, one of the most abundant carbon resources, is degraded by cellulolytic enzymes called cellulases. Cellulases are generally modular proteins with independent catalytic and cellulose-binding domain (CBD) modules and, in some bacteria, catalytic modules are noncovalently assembled on a scaffold protein with CBD to form a giant protein complex called a cellulosome, which efficiently degrades water-insoluble hard materials. In this study, a catalytic module and CBD are independently prepared by recombinant means, and are heterogeneously clustered on streptavidin and on inorganic nanoparticles for the construction of artificial cellulosomes. Heteroclustering of the catalytic module with CBD results in significant improvements in the enzyme's degradation activity for water-insoluble substrates. In particular, the increase of CBD valency in the cluster structure critically enhances the catalytic activity by improving the affinity for substrates, and clustering with multiple CBDs on CdSe nanoparticles generates a 7.2-fold increase in the production of reducing sugars relative to that of the native free enzyme. The multivalent design of substrate-binding domain on clustered cellulases is important for the construction of the artificial cellulosome, and the nanoparticles are an effective scaffold for increasing the valence of CBD in clustered cellulases. A new design is proposed for artificial cellulosomes with multiple CBDs on noncellulosome-derived scaffold structures.

Involvement of angiotensin II type 1 receptors in interleukin-1ß-induced interleukin-6 production in human gingival fibroblasts.

The renin-angiotensin system is thought to be involved in inflammatory processes such as periodontitis. However, its precise role is still unclear. Therefore, in the present study the expression of the angiotensin II type 1 receptor (AT1R) was investigated in inflamed human gingival tissue, and the possible involvement of the AT1R in interleukin-1ß (IL-1ß)-induced interleukin-6 (IL-6) production by cultured human gingival fibroblasts (HGFs) was also studied. Immunohistochemical staining revealed that inflammatory cells and fibroblast-like cells were positive for the AT1R. However, in healthy gingival tissue, AT1R staining was very weak. The levels of AT1R mRNA and AT1R protein increased in HGFs after stimulation with IL-1ß. The levels of IL-1ß-induced IL6 mRNA and IL-6 protein were significantly reduced in AT1R gene-silenced HGFs compared with control HGFs. The data suggest that the AT1R may be involved in the regulation of gingival inflammation by modulating IL-1ß-induced IL-6 production in HGFs.

TPS1 terminator increases mRNA and protein yield in a Saccharomyces cerevisiae expression system.

Both terminators and promoters regulate gene expression. In Saccharomyces cerevisiae, the TPS1 terminator (TPS1t), coupled to a gene encoding a fluorescent protein, produced more transgenic mRNA and protein than did similar constructs containing other terminators, such as CYC1t, TDH3t, and PGK1t. This suggests that TPS1t can be used as a general terminator in the development of metabolically engineered yeast in high-yield systems.

Baseline Urinary Angiotensinogen Excretion Predicts Deterioration of the Kidney Function in Patients with Chronic Kidney Disease.

Objective The intrarenal renin-angiotensin system (RAS) is activated in patients with chronic kidney disease (CKD), and urinary angiotensinogen (AGT) levels, a surrogate marker of the intrarenal RAS activation, are associated with blood pressure (BP) and urinary albumin excretion. In addition, it has been shown that changes in urinary AGT levels correlate with annual changes in the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes and that elevated levels of urinary AGT in type 2 diabetic patients with albuminuria are a high-risk factor for worsening renal and cardiovascular complications. However, whether or not baseline urinary AGT levels predict deterioration of the kidney function in all patients with CKD is unclear. Methods We recruited 62 patients with CKD whose eGFR was >15 mL/min/1.73 m2. We performed 24-hour ambulatory BP monitoring at 30-min intervals and daily urinary collection to examine the urinary AGT levels and albumin excretion and measured the levels of plasma angiotensin II (Ang II), a surrogate marker of circulating RAS. In addition, annual changes in the eGFR were followed up for 3.4±1.5 years. Results Annual changes in the eGFR were significantly and negatively associated with urinary AGT levels (r=-0.31, p=0.015) as well as the age, systolic BP, and urinary albumin levels. In contrast, annual changes in the eGFR were not correlated with plasma Ang II levels. Furthermore, when dividing patients into quartiles according to urinary AGT levels, patients with the highest urinary AGT levels showed a progressive decline in the eGFR. Conclusion These results suggest that elevated baseline urinary AGT levels can predict renal dysfunction in patients with CKD.

Salt intake causes B-type natriuretic peptide elevation independently of blood pressure elevation in the general population without hypertension and heart disease.

ABSTRACT: Excessive salt intake causes hypertension and cardiovascular diseases (CVDs). B-type natriuretic peptide (BNP) is synthesized and released from the ventricle, and is a surrogate marker reflecting various CVDs. Moreover, when a slight BNP elevation is shown, it leads to a poor prognosis in the general population. However, the relationship between salt intake and BNP levels in the general population remains unclear, especially in those without hypertension and heart diseases.In this study, we recruited 1404 participants without hypertension and electrocardiogram abnormalities, who received regular annual health check-ups in Japan. Plasma BNP levels were measured, and daily salt intake levels were evaluated using urinary samples. In addition, some clinical parameters were obtained, and the data were cross-sectionally analyzed.The median of plasma BNP levels was 10.50 pg/mL, and daily salt intake was 8.50 ±â€Š1.85 g. When dividing participants into quartiles according to daily salt intake, those with the highest daily salt intake revealed the highest plasma BNP levels. Plasma BNP levels were significantly and positively associated with daily salt intake. Moreover, multiple linear regression analyses revealed that plasma BNP levels showed a significant positive association with daily salt intake levels after adjustments.Plasma BNP levels were significantly and positively associated with daily salt intake after adjustment in the general population. Plasma BNP levels may be a surrogate marker reflecting salt-induced heart diseases.

Circadian rhythm of the intrarenal renin-angiotensin system is caused by glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure in adriamycin nephropathy rats.

Circadian fluctuation disorder of the intrarenal renin-angiotensin system (RAS) causes that of blood pressure (BP) and renal damage. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen (AGT) filtered through damaged glomeruli regulates intrarenal RAS activity. Furthermore, glomerular permeability is more strongly affected by glomerular hypertension than by systemic hypertension. Thus, we aimed to clarify whether the circadian rhythm of intrarenal RAS activity is influenced by AGT filtered through damaged glomeruli due to glomerular capillary pressure. Rats with adriamycin nephropathy and an impaired glomerular filtration barrier were compared with control rats. In adriamycin nephropathy rats, olmesartan medoxomil (an angiotensin II type 1 receptor blocker) or hydralazine (a vasodilator) was administered, and the levels of intrarenal RAS components in the active and rest phases were evaluated. Moreover, the diameter ratio of afferent to efferent arterioles (A/E ratio), an indicator of glomerular capillary pressure, and the glomerular sieving coefficient (GSC) based on multiphoton microscopy in vivo imaging, which reflects glomerular permeability, were determined. Mild renal dysfunction was induced, and the systemic BP increased, resulting in increased A/E ratios in the adriamycin nephropathy rats compared with the control rats. Fluctuations in intrarenal RAS activity occurred in parallel with circadian fluctuations in glomerular capillary pressure, which disappeared with olmesartan treatment and were maintained with hydralazine treatment. Furthermore, the GSCs for AGT also showed similar changes. In conclusion, intrarenal RAS activity is influenced by the filtration of liver-derived AGT from damaged glomeruli due to circadian fluctuation disorder of the glomerular capillary pressure.