Bowen disease on the foot associated with HPV

A 94 years old Japanese female was presented to our hospital with a skin lesion on her left foot. A physical examination found a markedly hyperkeratotic reddish-brown plaque, measuring 3 cm in diameter. A biopsy specimen showed prominent papillomatosis, hyperkeratosis, and atypical keratinocytes throughout the epidermis. Individual cell keratinization, multinucleated keratinocytes, and many keratinocytes with clear cytoplasm were seen. We excised the lesion, and the skin grafting was used for covering the skin defect. We investigated whether human papillomavirus (HPV) was present in the lesion, and HPV 16 DNA was detected using the polymerase chain reaction. Immunohistochemical analysis showed several HPV-positive cells in the upper epidermis. In addition, the tumor cells showed strong and diffuse expression of p16INK4a. Bowen disease (BD) is an intraepidermal squamous cell carcinoma. The precise pathogenesis of BD is unclear, but it involves various factors. HPV infection is one of these factors and is a well-known cause of BD of the genitalia and fingers. It has been shown that some BD lesions occurring at other locations are also associated with HPV. Dysregulation of the Rb / p16INK4a pathway is considered to play an important role in HPV-induced BD, but the precise mechanism remains to be elucidated

Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change

ADAMTS13によるvon Willebrand因子の切断増加は、本態性血小板血症患者における後天性von Willebrand症候群の発症に強く寄与する。

Background: Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased. Objective: We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET. Methods: Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF-related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight-categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C-terminal boundary, which is exposed following ADAMTS13-mediated cleavage of the Y1605-M1606 bond of the VWF A2 domain. Results: Patients with higher platelet counts had a significantly reduced high molecular weight (HMW)-VWFM index and an increased VWF-DP: VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF-DP/ VWF:Ag ratio was an independent predictor of the HMW-VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW-VWFM index and lower VWF-DP/ VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW-VWFM index and a decrease in the VWF-DP/ VWF:Ag ratio after cytoreductive therapy compared to pre-therapy values. Conclusion: In patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605-M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.博士（医学）・甲第881号・令和5年3月15

コウクウ ガク ガンメン アクセイ シュヨウ ノ エンカク テンイ ヒョウカ ニオケル クカンブ CT ケンサ ノ イチズケ

Abdominal CT examinations for the scouting of distant metastasis (DM) of orofacial malignant tumors were retrospectively evaluated, for the purpose of establishing the standard way of examination. Out of 159 patients with oral malignancies, 247 abdominal CT examinations were performed for the purpose of scouting DM. During the examination, intravenous contrast enhancement (CE) was performed in 166 examinations. DM were detected in 13 patients (8.2%). DM were found in 6 at administration, and 8 were late DM. Nine DM were detected out of 166 (5.4%) examinations with CE, and 5 were detected out of 81 (6.2%) examinations without CE. In detecting the DM, no improvement was found by CE. DM attacked lungs in 13, mediastinum in 3, liver in 2, paraaortic lymph nodes in 1, chest wall in 1, and vertebra in 1. Only 2 patients with DM were free from cervical metastasis, and the remainder was combined with cervical metastasis, regardless the status of the primary sites. Conclusions: Abdominal CT was useful for detecting DM. Intravenous CE was not necessary for scouting the DM. Patients with cervical metastasis had a high potential for developing DM

Construction of Cardiac Tissue Rings Using a Magnetic Tissue Fabrication Technique

Here we applied a magnetic force-based tissue engineering technique to cardiac tissue fabrication. A mixture of extracellular matrix precursor and cardiomyocytes labeled with magnetic nanoparticles was added into a well containing a central polycarbonate cylinder. With the use of a magnet, the cells were attracted to the bottom of the well and allowed to form a cell layer. During cultivation, the cell layer shrank towards the cylinder, leading to the formation of a ring-shaped tissue that possessed a multilayered cell structure and contractile properties. These results indicate that magnetic tissue fabrication is a promising approach for cardiac tissue engineering

Vasculature-driven stem cell population coordinates tissue scaling in dynamic organs

Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3⁺–basal cells (Tbx3⁺-BCs) and their neighboring cells where Adam8–extracellular signal–regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3⁺-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3⁺-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3⁺-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin

Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels : J-MICC Study

Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ) gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels

Interplay between crystal electric field and magnetic exchange anisotropies in the heavy-fermion antiferromagnet YbRhSb under pressure

We report the pressure effect on the magnetic ground state of the heavy-fermion (HF) canted antiferromagnet YbRhSb (orthorhombic ɛ-TiNiSi-type) by means of magnetization and resistivity measurements using a single crystal. At ambient pressure, this compound undergoes a transition at TM1=2.7 K into a canted antiferromagnetic (AF) state with a small spontaneous moment of 3×10-3 μB/Yb. With increasing pressure P above 1 GPa, another magnetic transition occurs at TM2 above TM1, and TM1(P) has a deep minimum of 2.5 K at 1.7 GPa. For P≥2 GPa, the canted AF structure changes to a ferromagnetic (FM) one, where a large moment 0.4 μB/Yb lies in the orthorhombic b-c plane and a metamagnetic transition occurs at B || a = 1.5 T. This unusual FM state below TM3≅4.3 K is ascribed to the balance between the single-ion crystalline electric field (CEF) anisotropy with easy direction || a and the intersite exchange interaction with easy b-c plane. Furthermore, we have investigated the pressure dependence of TM3 up to 20.4 GPa using electrical resistivity measurements. The structural stability under pressures up to 19 GPa was examined by x-ray diffraction. We find that TM3 above 2.5 GPa steeply increases up to about 7 K, showing a broad maximum and then slightly decreases with increasing pressure above 8 GPa, while the structure remains unchanged. We attribute the enhancement of TM3 above 2.5 GPa to an increase of the CEF anisotropy with respect to magnetic exchange anisotropy. Finally, we compare and discuss the volume dependence of magnetic phase diagram of YbRhSb with the isostructural HF ferromagnet YbNiSn

Polymorphisms and Body Mass Index Across Life Course

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways