Search Results (14)

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients’ quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine’s impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ. Full article

Background: Primary bladder lymphoma is generally regarded as having a favorable prognosis due to the predominance of low-grade lymphomas confined to the bladder. However, our investigation reveals that cases with extravesical extension, predominantly involving diffuse large B-cell lymphoma (DLBCL), exhibit a distinct clinical course with varied prognostic outcomes. Methods: In this report, we present and analyzed the clinical features and outcomes of 47 patients with primary bladder lymphoma with extravesical extension, including the case that we experienced. Results: An 77-year-old man who experienced fever, anorexia, and general malaise was referred to our hospital. Initial laboratory tests indicated severe renal failure, pyuria, and Escherichia coli bacteremia, accompanied by diffuse thickening of the bladder walls and increased attenuation in the surrounding adipose tissues. Initially misdiagnosed with a severe urinary tract infection leading to sepsis, the patient was treated with antibiotics and hemodialysis. Upon readmission due to abdominal pressure, imaging identified an intra-abdominal mass connected to the bladder wall. A bladder biopsy was performed, resulting in the diagnosis of primary bladder DLBCL with perivesical extension, classified as germinal center B-cell type. Taking inspiration from this case, the review of 46 patients was implemented. As a result, we resolved that primary bladder lymphoma often includes indolent types like Mucosa-associated lymphoid tissue lymphoma, but cases with extravesical expansion are predominantly DLBCL. Conclusions: This case emphasizes the diagnostic complexities of distinguishing primary bladder lymphoma from urinary tract infections and underscores the prognostic implications of extravesical extension. Our comprehensive review of the literature on primary bladder lymphomas with extravesical involvement highlights the clinical characteristics, therapeutic challenges, and need for heightened diagnostic vigilance and tailored treatment strategies for this subset of patients. Full article

We propose a new concept image sensor suitable for viewing and sensing applications. This is a report of a CMOS image sensor with a pixel architecture consisting of a 1.5 μm pixel with four-floating-diffusions-shared pixel structures and a 3.0 μm pixel with an in-pixel capacitor. These pixels are four small quadrate pixels and one big square pixel, also called quadrate–square pixels. They are arranged in a staggered pitch array. The 1.5 μm pixel pitch allows for a resolution high enough to recognize distant road signs. The 3 μm pixel with intra-pixel capacitance provides two types of signal outputs: a low-noise signal with high conversion efficiency and a highly saturated signal output, resulting in a high dynamic range (HDR). Two types of signals with long exposure times are read out from the vertical pixel, and four types of signals are read out from the horizontal pixel. In addition, two signals with short exposure times are read out again from the square pixel. A total of eight different signals are read out. This allows two rows to be read out simultaneously while reducing motion blur. This architecture achieves both an HDR of 106 dB and LED flicker mitigation (LFM), as well as being motion-artifact-free and motion-blur-less. As a result, moving subjects can be accurately recognized and detected with good color reproducibility in any lighting environment. This allows a single sensor to deliver the performance required for viewing and sensing applications. Full article

Intense itching significantly reduces the quality of life, and atopic dermatitis is associated with psychiatric conditions, such as anxiety and depression. Psoriasis, another inflammatory skin disease, is often complicated by psychiatric symptoms, including depression; however, the pathogenesis of these mediating factors is poorly understood. This study used a spontaneous dermatitis mouse model (KCASP1Tg) and evaluated the psychiatric symptoms. We also used Janus kinase (JAK) inhibitors to manage the behaviors. Gene expression analysis and RT-PCR of the cerebral cortex of KCASP1Tg and wild-type (WT) mice were performed to examine differences in mRNA expression. KCASP1Tg mice had lower activity, higher anxiety-like behavior, and abnormal behavior. The mRNA expression of S100a8 and Lipocalin 2 (Lcn2) in the brain regions was higher in KCASP1Tg mice. Furthermore, IL-1β stimulation increased Lcn2 mRNA expression in astrocyte cultures. KCASP1Tg mice had predominantly elevated plasma Lcn2 compared to WT mice, which improved with JAK inhibition, but behavioral abnormalities in KCASP1Tg mice did not improve, despite JAK inhibition. In summary, our data revealed that Lcn2 is closely associated with anxiety symptoms, but the anxiety and depression symptoms caused by chronic skin inflammation may be irreversible. This study demonstrated that active control of skin inflammation is essential for preventing anxiety. Full article

The glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide has been shown to improve body weight and glycemic control and reduce major cardiovascular (CV) events. In Japan, dulaglutide is used at a fixed dose of 0.75 mg, which is lower than that in Europe and North America. However, the reports of real-world efficacy on metabolic parameters in Japanese patients with type 2 diabetes (T2DM) are limited. This study aimed to examine the real-world efficacy of GLP-1RA dulaglutide on metabolic parameters in Japanese patients with T2DM. We retrospectively selected patients with T2DM who had been prescribed dulaglutide continuously for 12 months or longer between September 2015 and December 2020 and compared metabolic parameters at baseline with the data at 12 months after the start of dulaglutide. One hundred twenty-one patients were enrolled in this study. The 12-month dulaglutide treatment reduced body weight by 1.7 kg and hemoglobin A1c by 1.1%. Significant improvements were also observed in serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and non-HDL-C. The change in HbA1c during dulaglutide treatment was significantly correlated with the changes in HDL-C (R = −0.236, p = 0.013), LDL-C (R = 0.377, p = 0.005) and non-HDL-C (R = 0.415, p < 0.001). The improvements in HbA1c, HDL-C, TG and non-HDL-C were greater in patients concurrently treated with SGLT2 inhibitors (SGLT2is) at baseline. In conclusion, the treatment with dulaglutide has beneficial effects on multiple CV risk factors in Japanese patients with T2DM. Full article

The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis. Full article

A 91-year-old woman visited our department with scattered small nodule lesions and multiple pules or plaques with a stuck-on appearance. The lesions were intractable and resistant to several treatments. Immunodeficiency was excluded by examinations including a CT scan, white blood cell (WBC) counts, natural killer and neutrophil function assays, and IgG titers against human papillomavirus (HPV) 20. HPV20 was identified using the PCR method. The finding of the skin biopsy showed an irritated type of feature of seborrheic keratosis. Additionally, immunohistochemical staining of the lesion revealed that both TNF-α and IFN-ɤ were produced at the skin lesions. The patient‘s serum zinc level was slightly low. We noticed that zinc deficiency has been reported to decrease the cytotoxic activity of natural killer cells, which play an important role in eliminating virus-infected cells and tumor cells. Finally, zinc oxide ointment was found to improve the lesions dramatically. HPV20 causes tumors only in immunodeficient patients or in patients with epidermodysplasia verruciformis (EV). In EV, EVER1- or EVER2-encoding membrane proteins, of which are related to zinc transport protein-1 expressed on the membrane of the endoplasmic reticulum, were mutated, leading to increased susceptibility to various viral and bacterial infections due to the decreased intracellular zinc concentration. We speculated that the reduction in local zinc concentration was ameliorated by using zinc oxide ointment, resulting in the recovery from HPV20 infection. Full article

Atopic dermatitis (AD) is classified as a type 2 disease owing to the majority of type 2 lymphocytes that constitute the skin-infiltrating leukocytes. However, all of the type 1–3 lymphocytes intermingle in inflamed skin lesions. Here, using an AD mouse model where caspase-1 was specifically amplified under keratin-14 induction, we analyzed the sequential changes in type 1–3 inflammatory cytokines in lymphocytes purified from the cervical lymph nodes. Cells were cultured and stained for CD4, CD8, and γδTCR, followed by intracellular cytokines. Cytokine production in innate lymphocyte cells (ILCs) and the protein expression of type 2 cytokine IL-17E (IL-25) were investigated. We observed that, as inflammation progresses, the cytokine-producing T cells increased and abundant IL-13 but low levels of IL-4 are produced in CD4-positive T cells and ILCs. TNF-α and IFN-γ levels increased continuously. The total number of T cells and ILCs peaked at 4 months and decreased in the chronic phase. In addition, IL-25 may be simultaneously produced by IL-17F-producing cells. IL-25-producing cells increased in a time-dependent manner during the chronic phase and may work specifically for the prolongation of type 2 inflammation. Altogether, these findings suggest that inhibition of IL-25 may be a potential target in the treatment of inflammation. Full article

Rickettsia and Coxiella spp. are pathogens transmitted by ticks to humans. However, the developmental stage of the tick carrying the greatest risk of infection is unknown. Detection of pathogen-specific genes proves that ticks carrying Rickettsia or Coxiella spp. constitute a reservoir of infection. However, conventional PCR methods are unable to quantitate the pathogens within ticks. In the present study, we collected ticks in the endemic area of Japanese spotted fever, caused by Rickettsia japonica, and determined the rate of tick-borne pathogens carried by the ticks. As a method of evaluation, next-generation sequencing was used to estimate the proportion of pathogens in 10 adult and 10 larval ticks. Ticks were identified Haemaphysalis longicornis (H.L) from the results of the sequencing of PCR products amplified using tick identification-specific primers. The gene detection rates were 10/10 for Rickettsia sp. and 10/10 for Coxiella sp. among the adult ticks. For the larval ticks, the ratios were 7/10 and 5/10 for Rickettsia sp. and Coxiella sp., respectively. The largest proportion of Coxiella sp.-specific DNA reached 96% in one adult tick. The proportion of Rickettsia sp. genes ranged from 1.76% to 41.81% (mean, 15.56%) in the adult ticks. The proportions of Coxiella and Rickettsia spp. genes in the larvae ranged from 0% to 27.4% (mean 5.86%) and from 0% to 14.6% (mean 3.38%), respectively. When the percentage of Rickettsia sp., out of all pathogens detected via next-generation sequencing, was analyzed between the adult and larval stages of the ticks, a significant difference was observed at p = 0.0254. For Coxiella sp., a highly significant difference (p < 0.0001) was found between the adult and larval stages of the ticks. In conclusion, the detection rates and proportions of Rickettsia and Coxiella spp. genes were highest in adult H.L ticks. The risk of contracting tick-borne infections may increase with bites from adult ticks, especially those harboring Coxiella sp. Full article

Ten years ago, a 56-year-old woman with a history of IgA nephropathy who received a living-donor kidney transplant across ABO barriers was managed with immunosuppressive drugs. The kidney transplant donor was her father who had poor kidney function. The patient’s renal function was stable for 10 years. The patient visited our department with a complaint of skin rash, occurring 2 days after an onset of fever. Although a skin rash is atypical for Japanese spotted fever (JSF), we suspected JSF and started treatment with minocycline because we found a scar suggestive of an eschar. Furthermore, the blood test results were similar to those associated with JSF, and the patient lived in a JSF-endemic area. The patient’s symptoms improved after 1 week. She was diagnosed with JSF by serological tests against Rickettsia japonica. JSF usually does not cause any complications after recovery. However, the patient’s renal function did not completely recover. JSF can cause an atypical rash in patients taking excessive immunosuppressive drugs. Early treatment is required for patients with suspected JSF to prevent complications of renal dysfunction after receiving a living-donor kidney transplant. Full article

Systemic amyloidosis is recognized as a serious complication of rheumatoid arthritis or inflammatory bowel disease, but also of inflammatory skin disease. However, the detailed molecular mechanism of amyloidosis associated with cutaneous inflammation remains unclear, and therapeutic approaches are limited. Here, we investigated the pathophysiology of amyloidosis secondary to cutaneous inflammation and the therapeutic effects of Janus kinase (JAK) inhibitors by examining a mouse model of spontaneous dermatitis (KCASP1Tg mice). Moreover, KCASP1Tg mice were crossed with interleukin-17A (IL-17A) knockout mice to generate IL-17A-/KCASP1Tg and examine the role of IL-17A in amyloidosis under cutaneous inflammation. KCASP1Tg mice showed severe amyloid deposition in the liver and spleen. Increased serum-neutral fat levels and decreased lymphocyte production were observed in the spleen. Overproduction of amyloidosis was partially ameliorated by the administration of JAK inhibitors and was further improved in IL-17A-/KCASP1Tg mice. IL-17A-producing cells included CD4, gamma delta, and CD8 T cells. In summary, our results from the analysis of a mouse model of dermatitis revealed that skin-derived inflammatory cytokines can induce amyloid deposition in the liver and spleen, and that the administration of JAK inhibitors and, even more, IL-17A ablation, reduced amyloidosis. This study demonstrates that active control of skin inflammation is essential to prevent internal organ amyloidosis. Full article

Malnutrition is not only regarded as a complication of rheumatoid arthritis and inflammatory bowel disease but also that of inflammatory skin disease; however, the mechanisms and efficacy of its treatment have not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of malnutrition in inflammatory skin conditions and efficacy of its treatment. We employed spontaneous skin inflammation mice models overexpressing human caspase-1 in the epidermal keratinocytes. Body weight, nutrition level, and α1-antitrypsin fecal concentration were measured. The gastrointestinal tract was histologically and functionally investigated. Fluorescein isothiocyanate (FITC)-dextran was forcibly fed on an empty stomach, and plasma FITC-dextran was measured. The treatment efficacy of antibodies against tumor necrosis factor-α (TNF-α) and interleukin (IL)-α/β as well as Janus kinase (JAK) inhibitors was investigated. Compared with wild-type littermates, the inflammatory skin mice models showed a lowered body weight, reduction of serum albumin level, amyloid deposition in the stomach, small intestine, and large intestine, and increased α1-antitrypsin fecal concentration. However, the plasma FITC-dextran was unchanged between the dermatitis models and wild-type littermates. The over-produced serum amyloid A1 in the liver was detected in the plasma in the dermatitis model. Antibodies against TNF-α and IL-α/β showed partial effects on amyloid deposition; however, JAK inhibitors improved gastrointestinal amyloidosis with the improvement of skin symptoms. Chronic dermatitis is closely related to secondary amyloidosis in the gastrointestinal tract, resulting in hypoalbuminemia. Therefore, active control of skin inflammation is essential for preventing gastrointestinal complications. Full article

(1) Background. Rickettsia japonica (R. japonica) infection induces severe inflammation, and the disappearance of eosinophil in the acute stage is one of the phenomena. (2) Materials and Methods. In the current study, we measured the serum concentrations of Th1, Th2, and Th17 cytokines in the acute and recovery stages. (3) Results. In the acute phase, IL-6 and IFN-γ levels were elevated and we speculated that they played a role as a defense mechanism against R. japonica. The high concentration of IFN-γ suppressed the differentiation of eosinophil and induced apoptosis of eosinophil, leading to the disappearance of eosinophil. On day 7, IL-6 and IFN-γ concentrations were decreased, and Th2 cytokines such as IL-5 and IL-9 were slightly increased. On day 14, eosinophil count recovered to the normal level. The transition of serum cytokine concentration in R. japonica infection was presented. (4) Conclusions. IL-6 and IFN-γ seem to be critical cytokines as defense mechanism against R. japonica in the acute phase, and this may deeply connect to the decrease of eosinophil. Full article

Secondary osteoporosis can also be caused by chronic inflammatory skin disease as well as rheumatoid arthritis or inflammatory bowel disease. However, the exact role of osteoporosis in inflammatory skin conditions has not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of osteoporosis in inflammatory skin conditions and the therapeutic impact of osteoporosis medication on inflammatory skin disease. We employed model mice of spontaneous skin inflammation, specifically overexpressing human caspase-1 in the epidermis. Bone density and the expression of various mRNAs in the femur were examined by micro CT and RT-PCR. The effects of minodronate and anti-RANKL antibody on bone structure, histology, and femur blood flow were studied. The mouse model of skin inflammation showed a marked decrease in bone density compared to wild-type littermates with abnormalities in both bone resorption and formation. Minodronate improved bone density by decreasing osteoclasts, but anti-RANKL antibody did not improve. In the dermatitis model, the blood flow in the bone marrow was decreased, and minodronate restored this parameter. A model of persistent dermatitis exhibited marked osteoporosis, but the impact of chronic dermatitis on osteoporosis has not been thoroughly investigated. We should explore the pathogenesis of osteoporosis in skin inflammatory diseases. Full article