A5028170044- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Heart Failure Treatment and Management
- Thyroid Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Hormonal Regulation and Hypertension
- Connective tissue disorders research
- Renal and related cancers
- Osteoarthritis Treatment and Mechanisms
- Pulmonary Hypertension Research and Treatments
- Trauma Management and Diagnosis
- interferon and immune responses
- Adrenal Hormones and Disorders
- Child Nutrition and Feeding Issues
- Blood Coagulation and Thrombosis Mechanisms
- Sinusitis and nasal conditions
- Adrenal and Paraganglionic Tumors
- Restraint-Related Deaths
- Mesenchymal stem cell research
- Pleural and Pulmonary Diseases
- Neurogenetic and Muscular Disorders Research
- Cleft Lip and Palate Research
- Proteoglycans and glycosaminoglycans research
- Neuroendocrine Tumor Research Advances
- Neonatal Respiratory Health Research
Kyoto University
1994-2024
Diabetes Australia
2017
Kyoto Medical Center
2012
Background: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, death-ligand 1 (PD-L1) 2 (PD-L2). Nivolumab an anti-PD-1 monoclonal antibody approved malignant melanoma, advanced non–small lung cancer, renal carcinoma Japan. Thyrotoxicosis hypothyroidism have both been reported international Phase 3 studies national post-marketing surveillance nivolumab Methods: This study...
Although peptides are safe and useful as therapeutics, they often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy increasing efficacy of therapies. Natriuretic receptor B (NPR-B) its naturally occurring ligand, C-type natriuretic (CNP), potent stimulators endochondral bone growth, activating CNP/NPR-B expected to be powerful treating impaired skeletal growth. CNP cleared by (NPR-C); therefore, we investigated effect reducing rate on...
Abstract Growth impairment in mucopolysaccharidoses (MPSs) is an unresolved issue as it resistant to enzyme replacement therapy (ERT) and growth hormone therapy. C-type natriuretic peptide (CNP) a promising agent that has growth-promoting effects. Here we investigate the effects of CNP on MPSs using Gusbmps-2J mice, model for MPS type VII, with combination ERT by hydrodynamic gene delivery. Although monotherapies were not sufficient restore short statures treated resulted successful...
A delayed diagnosis of insulinoma remains a clinical issue. Hypoglycemic symptoms can mimic neuropsychiatric disorders such as epilepsy. 27-year-old woman with history epilepsy and anti-epileptic drugs (AEDs) developed repeated seizures after 9-year asymptomatic interval. She had received transient treatment AEDs before the possibility hypoglycemia was considered. Following insulinoma, distal pancreatectomy performed; her didn't occur again. The early requires vigilance not only for in...
We have previously investigated the physiological role of C-type natriuretic peptide (CNP) on endochondral bone growth, mainly with mutant mouse models deficient in CNP, and reported that CNP is indispensable for growth mice. However, survival rate knockout (KO) mice fell to as low about 70% until 10 weeks after birth, we could not sufficiently analyze phenotype at adult stage. Herein, generated KO rats by using zinc-finger nuclease-mediated genome editing technology. established two lines...
Signaling by C-type natriuretic peptide (CNP) and its receptor, receptor-B, is a pivotal stimulator of endochondral bone growth. We recently developed CNP knockout (KO) rats that exhibit impaired skeletal growth with early plate closure. In the current study, we further characterized phenotype morphology in CNP-KO rats, effects exogenous rats. used CNP-53, an endogenous form consisting 53 amino acids, administered it for four weeks continuous subcutaneous infusion at 0.15 or 0.5 mg/kg/day to...
Regulatory mechanisms of iodothyronine deiodinases (DIOs) require further elucidation, and conventional methods for evaluating DIOs are unsuitable high-throughput screening (HTS). Here we explored factors transcriptional regulation 3 types (DIO1, DIO2, DIO3) from a chemical library using our designed HTS. We constructed HTS based on promoter assay performed screen 2480 bioactive compounds. For compounds that were clinically approved, validated hit through retrospective cohort study in...
A 52-year-old woman with overlap syndrome and interstitial pneumonia underwent immunosuppressive therapy she was suspected to suffer from pulmonary aspergillosis. Oral voriconazole initiated, a rapid elevation of alkaline phosphatase (ALP) occurred after 4 weeks. After 2 months, the patient presented diffuse pain in bilateral skeletal regions, bone scintigraphy revealed multiple areas increased radiotracer uptake. We involvement as voriconazole-induced periostitis. Actually, plasma fluoride...
Programmed cell death-1 (PD-1) blockade therapy frequently results in immune-related adverse events involving the thyroid gland (thyroid irAEs). Although clinical features of irAEs are known, mechanisms remain unclear. Here, we conducted a pilot study to investigate irAE development from perspective autoantibodies. We performed immunoprecipitation-based assays using sera 3 patients who developed with PD-1 by nivolumab and HEK293T lysates, including overexpressed proteins interest (NKX2-1,...
Abstract Growth retardation is an important side effect of glucocorticoid (GC)-based drugs, which are widely used in various preparations to treat many pediatric diseases. We investigated the therapeutic exogenous CNP-53, a stable molecular form intrinsic CNP, on mouse model GC-induced growth retardation. found that CNP-53 successfully restored when both dexamethasone (DEX) and were injected from 4 8 weeks old. Notably, was not effective during first week. From 5 old, neither advance DEX,...
Abstract Longitudinal bone growth is achieved by a tightly controlled process termed endochondral formation. C-type natriuretic peptide (CNP) stimulates formation through binding to its specific receptor, guanylyl cyclase (GC)-B. However, CNP/GC-B signaling dynamics in different stages of have not been fully clarified, especially terms the interaction between cyclic guanine monophosphate (cGMP) and adenosine (cAMP) pathways. Here, we demonstrated that CNP activates cAMP/protein kinase A...
Rationale: Unilateral adrenalectomy as part of surgical resection renal cell carcinoma (RCC) is not thought to increase the risk chronic adrenal insufficiency, contralateral gland assumed be capable compensating for lost function resected gland. However, recent studies have indicated that might cause irreversible impairment adrenocortical reserve. We describe a case primary insufficiency in 68-year-old man who previously underwent unilateral adrenonephrectomy, which was complicated by severe...
Skeletal growth in mammals, which owes the of an individual, occurs at plate and to observe analyze its dynamic is high interest. Here we performed live imaging analysis a fetal murine long bone organ culture using two-photon excitation microscopy. We could explanted ulna, as well resultant linear elongation explants. As for factors contributing plate, displacement length each chondrocyte was larger prehypertrophic or hypertrophic zone than proliferative zone. The segmented area...
C-type natriuretic peptide (CNP) is a pivotal enhancer of endochondral bone growth and expected to be therapeutic reagent for impaired skeletal growth. Although we showed that CNP stimulates as local regulator in the plate via autocrine/paracrine system, abundantly produced other various tissues its blood concentration reported correlate positively with velocity. Therefore investigated systemic regulation levels using rodent models. In order examine whether undergoes feedback regulation,...
A unique clinical course was observed in a patient with resistance to thyroid hormone β (RTHβ) caused by variant of the THRB gene leading replacement glycine arginine codon 347 (p.G347R). He presented syndrome inappropriate secretion thyrotropin (TSH) (free T4 [fT4]: 32.43 pmol/L, TSH: 4.67 mIU/L), but slowly developed progressive hypothyroidism (fT4: 8.37 100.90 mIU/L) that resolved after suspending bezafibrate (BZ) treatment 32.18 7.14 mIU/L). This study clinically and experimentally...
In peripheral tissues, triiodothyronine (T3) production and consequent thyroid hormone actions are mainly regulated by iodothyronine deiodinases (DIOs) classified into 3 types: D1, D2, D3. We aimed to investigate the effects of DIOs on economy independent hypothalamus-pituitary-thyroid axis. cloned coding sequences human with FLAG-tag HiBiT-tag a pcDNA3.1 vector. To obtain full-length proteins, we modified these vectors cloning selenocysteine insertion sequence each DIO (SECIS vectors)....
C-type natriuretic peptide (CNP)-knockout (KO) rats exhibit impaired skeletal growth, with long bones shorter than those in wild-type (WT) rats. This study compared craniofacial morphology the CNP-KO rat that Spontaneous Dwarf Rat (SDR), a growth hormone (GH)-deficient model. The effects of subcutaneous administration human CNP 53 amino acids (CNP-53) from 5 weeks age for 4 on were also investigated. Skulls at 9 longitudinally and foramen magnum was smaller WT There no differences stenosis...
Acute ipsilateral pulmonary oedema is a well documented complication of the treatment lung collapse secondary to pneumothorax, pleural effusion and atelectasis. We present case bilateral re–expansion following removal an intrathoracic haematoma. High protein concentration fluid suggests increased vascular permeability as cause this oedema.
Abstract Aims Programmed cell death-1 (PD-1) blockade therapy frequently results in immune-related adverse events involving the thyroid gland (thyroid irAEs). Although clinical features of irAEs are known, mechanisms remain unclear. Here, we conducted a pilot study to investigate irAE development from perspective autoantibodies. Methods We performed immunoprecipitation-based assays using sera 3 patients who developed with PD-1 by nivolumab and HEK293T lysates, including overexpressed...
Abstract Background In peripheral tissues, triiodothyronine (T3) production and consequent thyroid hormone actions are mainly regulated by iodothyronine deiodinases (DIOs) classified into 3 types: D1, D2, D3. Although economy in the DIO-deficient mice patients carrying genetic variants of DIOs was well clarified, a condition upregulation not enough elucidated. We aimed to investigate effects on action using novel DIO-overexpressing that were yet generated. Methods cloned coding sequences...