Publications by authors named "Ohuchi N"

Article Synopsis
  • The study investigates two cases of extremely low HDL cholesterol levels linked to mutations in the ABCA1 gene, which is important for cholesterol transport, particularly in Tangier disease.
  • In the first case, a 20-year-old woman with multiple health issues showed mutations leading to decreased cholesterol efflux and ABCA1 protein levels, while also having another condition called Krabbe disease.
  • The second case involved a 51-year-old woman with similar low HDL levels and different mutations confirming Tangier disease, highlighting the complexity of mutations and their pathogenic mechanisms.
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Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced male subfertility have been reported, the entire mechanism of obesity-induced male infertility still remains unclear. Here, we show that sperm count, sperm motility and sperm fertilizing ability were decreased in male mice fed a high-fat diet and that the expression of the AdipoR1 gene and protein was decreased, and the expression of pro-apoptotic genes and protein increased, in the testis from mice fed a high-fat diet.

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Article Synopsis
  • - This study involves a 47-year-old Japanese woman with inherited non-alcoholic steatohepatitis (NASH) and severe dyslipidemia, who showed improvement with SGLT2 inhibitor treatment.
  • - Whole-exome sequencing revealed several mutations, including the known PNPLA3 I148M mutation, along with additional mutations in LGALS3, PEMT, and a novel mutation in MUL1 that may affect mitochondrial function.
  • - The findings suggest that multiple genetic factors contribute to NASH and dyslipidemia, and that the efficacy of SGLT2 inhibitors may vary based on individual genetic backgrounds.
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Summary: A paired homeodomain transcription factor, PAX6 (paired-box 6), is essential for the development and differentiation of pancreatic endocrine cells as well as ocular cells. Despite the impairment of insulin secretion observed in PAX6-deficient mice, evidence implicating causal association between PAX6 gene mutations and monogenic forms of human diabetes is limited. We herein describe a 33-year-old Japanese woman with congenital aniridia who was referred to our hospital because of her uncontrolled diabetes with elevated hemoglobin A1c (13.

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Importance: Mammography has limited accuracy in breast cancer screening. Ultrasonography, when used in conjunction with mammography screening, is helpful to detect early-stage and invasive cancers for asymptomatic women with dense and nondense breasts.

Objective: To evaluate the performance of adjunctive ultrasonography with mammography for breast cancer screening, according to differences in breast density.

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Article Synopsis
  • TP53 status, identified through a gene expression profile, serves as an important independent prognostic factor for breast cancer, guiding treatment strategies.
  • A new multiplex reverse transcription-polymerase chain reaction system was created to accurately classify 189 breast cancer patients as having either a TP53 mutant or wild-type signature.
  • Results showed that patients with the TP53 mutant signature had significantly shorter recurrence-free survival compared to those with the wild-type signature, highlighting the diagnostic system's potential for better prognostic assessments and treatment plans.
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Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice.

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Clinical application of accumulated medical big data is a hot topic in medical informatics. Not only for suggesting possible diagnoses in each individual, large medical database can be possibly used for detecting undiagnosed patients in the general population. In this study, we tried to develop a computerized system of detecting overlooked undiagnosed patients with rare chronic diseases in the community population by utilizing the uniformed national medical insurance record database.

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Although cyclin-dependent kinase (CDK) 4/6 inhibitors have exhibited remarkable results for patients with estrogen receptor (ER)-positive breast cancer in clinical trials, the mechanism of CDK4/6 inhibitor resistance remains unclear. Thus, this study aimed to investigate the mechanism of CDK4/6 inhibitor resistance using two CDK4/6 inhibitor resistant breast cancer cell lines. We established CDK6 overexpressed cell lines (MCF7-C6) from MCF-7 cells using the stably transfected CDK6 expression vector.

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Purpose: Inflammation-based markers predict the long-term outcomes of various malignancies. We investigated the relationship between the modified Glasgow prognostic score (mGPS) and the long-term outcomes of obstructive colorectal cancer in patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery.

Methods: We retrospectively analyzed 63 consecutive patients with pathological stage II and III obstructive colorectal cancer from 2013 to 2018.

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In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance.

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Article Synopsis
  • The study investigates molecules related to drug resistance and tumor progression in triple-negative breast cancer (TNBC) patients who have residual disease after neoadjuvant chemotherapy (NAC).
  • It involved 148 Japanese TNBC patients, analyzing factors like KI67, Topoisomerase IIα, and PTEN before and after NAC treatment.
  • The findings indicate that certain molecular markers (e.g., p53, ABCC1/MRP1, and PTEN) could predict treatment response and tumor relapse, providing insights into the mechanisms behind resistance in TNBC patients.
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Positron emission mammography (PEM) has higher detection sensitivity for breast cancer compared with whole-body positron emission tomography (PET) due to higher spatial resolution. We have developed a new PEM device with high resolution over a wide field of view. This PEM device comprises novel scintillation crystals, praseodymium-doped lutetium aluminum garnet (Pr:LuAG).

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BRCA-related breast carcinoma can be prevented through prophylactic surgery and an intensive follow-up regimen. However, BRCA genetic tests cannot be routinely performed, and some BRCA mutations could not be defined as deleterious mutations or normal variants. Therefore, an easy functional assay of BRCA will be useful to evaluate BRCA status.

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Purpose: signature has a robust predictive performance for prognosis in early-stage breast cancer, but the experiment that reported this relied on public microarray data and fresh-frozen samples. Before signature can be used in a clinical setting, a simple and low-cost diagnostic system using formalin-fixed paraffin-embedded (FFPE) samples is needed. New treatments based on the biological characteristics of signature are expected to follow.

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Background: Elf5 is a transcription factor previously shown to be involved in regulating cell differentiation in both normal and pathological breast tissues. Pertinently, Elf5 was reported to interact with the FOXA1 transcription factor, a pivotal regulatory factor in a subset of AR overexpressing triple negative cancer (TNBC) cases.

Methods: We examined the correlation among AR, FOXA1, and Elf5 expression in a series of TNBC cases.

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Alcohol consumption is a risk factor for breast cancer in Western countries, but few studies have evaluated the risk for Japanese women, who have a relatively low alcohol intake. This case-control study investigated the association of alcohol consumption with breast cancer risk according to estrogen-receptor and progesterone-receptor (ER/PgR) status in Japanese women. From female patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2011, 1,256 breast cancer cases (669 ER+/PgR+, 162 ER+/PgR-, 21 ER-/PgR+, 305 ER-/PgR-, and 99 missing) and 2,933 controls were selected.

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Objectives: We aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose (F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff.

Methods: Sixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining F-FDG accumulation were scanned by high-resolution PEM.

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Background: Subcutaneous islet transplantation is associated with minimal invasiveness, but poor vascularization. Thus, the optimization of the prevascularization procedures is crucial for improving the outcomes. Although the effectiveness of basic fibroblast growth factor (bFGF) was reported, the optimal procedures remain unclear.

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Purpose: The tumor microenvironment plays pivotal roles in promotion of many malignancies. Cancer-associated fibroblasts (CAFs) have been well-known to promote proliferation, angiogenesis, and metastasis but mechanistic understanding of tumor-stroma interactions is not yet complete. Recently, estrogen synthetic enzymes were reported to be upregulated by co-culture with stromal cells in ER positive breast carcinoma (BC) but effects of co-culture on androgen metabolism have not been extensively examined.

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The quantitative sensitivity and dynamic range of conventional immunohistochemistry (IHC) with 3,3'-diaminobenzidine (IHC-DAB) used in pathological diagnosis in hospitals are poor, because enzyme activity can affect the IHC-DAB chromogenic reaction. Although fluorescent IHC can effectively increase the quantitative sensitivity of conventional IHC, tissue autofluorescence interferes with the sensitivity. Here, we created new fluorescent nanoparticles called phosphor-integrated dots (PIDs).

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Background: No optimal methods for short-term hepatocyte preservation have been established. We have recently developed a prominent oxygen-permeable bag (Tohoku Device [TD]) for pancreatic islet culture and transplantation. In this study, we investigated whether TD is also effective for hepatocyte preservation and tried to optimize other conditions.

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Background: The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.

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Background: Breast adipocytes play important roles in both the development and function of mammary epithelial cells. Therefore, carcinoma-adipose stromal cell (ASC) interactions have been considered pivotal in supporting tumor growth in breast cancer. In addition, it has been demonstrated that the biological features of cancer-associated adipocytes differ from those of normal ASCs.

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