Comprehensive study on central precocious puberty: molecular and clinical analyses in 90 patients.

Context: Defects in MKRN3, DLK1, KISS1, and KISS1R and some disorders, such as Temple syndrome (TS14), cause central precocious puberty (CPP). Recently, pathogenic variants (PVs) in MECP2 have been reported to be associated with CPP.

Objective: We aimed to clarify the contribution of (epi)genetic abnormalities to CPP and clinical and hormonal features in each etiology.

Caesarean section and childhood obesity at age 3 years derived from the Japan Environment and Children's Study.

Caesarean section (CS) birth is widely reported to be a risk factor for childhood obesity. Although susceptibility to childhood obesity is influenced by race and ethnicity, it is unclear whether this risk of childhood obesity with CS birth also applies in the Japanese population. We investigated the impact of CS birth on obesity at 3 years of age in Japanese children.

Glucokinase maturity-onset diabetes of the young as a mimicker of stress hyperglycemia: a case report.

Febrile seizures are frequently accompanied by stress-induced hyperglycemia. Herein, we report the case of a 1.5-yr-old girl with hyperglycemia during febrile seizures who was subsequently diagnosed with glucokinase (GCK) maturity-onset diabetes of the young (MODY), considering its distinction from stress hyperglycemia.

Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer.

Purpose: The effects of immune checkpoint inhibitors have been reported to be linked with immune-related adverse events (irAEs). In patients with advanced non-small-cell lung cancer, who tested positive for programmed death-ligand 1 (PD-L1), pembrolizumab, an immune checkpoint inhibitor can be used as a treatment, and it was found to improve overall survival. However, there are only a few reports on the relationship between the therapeutic effects of pembrolizumab in patients with lung cancer and the irAEs of pembrolizumab.

The causes of acute cough: a tertiary-care hospital study in Japan.

Objectives: Cough is the most frequent presenting complaint in general practice and has an adverse effect on an individual's well-being. Understanding the causes of cough is critical for appropriate patient management. According to its duration, cough is classified as acute, subacute, and chronic.

Visceral pleural biopsy under medical thoracoscopy for the diagnosis of lung adenocarcinoma.

Medical thoracoscopy is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surface and allows for diagnostic procedures. The diagnostic yield of medical thoracoscopy is high and is generally based on parietal pleural biopsy findings. Pleural biopsies are valuable for a diagnosis.

Intrapleural urokinase directly under medical thoracoscopy for the diagnosis of tuberculous pleurisy.

Medical thoracoscopy, also called "local anesthetic thoracoscopy" and "pleuroscopy," is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surfaces and channels to conduct diagnostic and therapeutic procedures. However, this technique is not helpful when substantial fibrous adhesions exist. We reported the first case of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of malignant pleural mesothelioma with severe multiloculated pleural effusions in 2019.

Osimertinib Administration as the Primary Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy for Brain Metastasis of De Novo T790M-positive Lung Cancer.

A 69-year-old woman underwent left upper lobectomy for left upper lobe lung adenocarcinoma. She later perceived a left visual field defect, and a brain metastasis was detected on head magnetic resonance imaging (MRI). Epidermal growth factor receptor (EGFR) testing identified two separate EGFR mutations: an L858R mutation in exon 21 and a de novo T790M mutation in exon 20.

Endobronchial Manifestation of Methotrexate-induced Lymphoproliferative Disorder.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD.

On-line sample preconcentration by polarity switching in floating electrode-integrated microchannel.

In this study, we found that the polarity switching was effective to enrich and separate fluorescent analytes which have weakly-dissociated groups in a floating platinum electrode (width, 50 µm; thickness, 2.5 µm)-integrated straight-channel in microchip electrophoresis (MCE). In the straight channel filled with an Alexa Flour 488 (AF488) solution, a sharp peak was observed after the polarity inversion with a 530-fold enhancement of the sensitivity relative to the conventional MCE analysis.

Sarcoid-Like Granulomatosis Induced by Nivolumab Treatment in a Lung Cancer Patient.

Nivolumab, an anti-PD-1 antibody, inhibits binding between PD-1 and PD-1 ligand and activates antigen-specific T cells that have become unresponsive to cancer cells. Although it is recommended as a second-line therapy in gene mutation-negative non-small-cell lung cancer, interstitial pneumonia is a well-known side effect of the drug; however, granulomatous lesions have rarely been reported. We describe the case of an 81-year-old male with cT1aN2M1b stage IV pleomorphic carcinoma of the left upper lobe of the lung.

Longitudinal study on the effectiveness of vitamin D supplements in exclusively breast-fed infants.

Vitamin D deficiency is a common health problem in infancy. Breast-fed infants are at a higher risk of rickets than formula-fed infants. We observed fluctuations in vitamin D levels in infancy (phase I, 2009-2010) and considered the benefits of vitamin D supplementation specifically in exclusively breast-fed infants in Japan (phase II, 2015).

Pleuritis Caused by Mycobacterium kyorinense without Pulmonary Involvement.

We herein describe the first known case of pleuritis caused by Mycobacterium kyorinense without pulmonary involvement. A 48-year-old man undergoing immunosuppressant therapy presented with cough and dyspnea. An accumulation of pleural fluid was noted; however, computed tomography revealed no pulmonary lesions.

Desmoplastic Small Round Cell Tumor of the Pleura Successfully Treated with a Lower Dose of Pazopanib.

Desmoplastic small round cell tumor (DSRCT) is an aggressive mesenchymal tumor which primarily affects the abdomen. Even a multimodal approach rarely achieves durable remission and the optimal therapy for extended disease is unknown. We herein describe a rare case of DSRCT arising from the pleura in a 32-year-old man.

Comparison of intestinal metabolism of CYP3A substrates between rats and humans: application of portal-systemic concentration difference method.

1. Rats are frequently used in pharmacokinetic studies during drug discovery. However, there is limited information regarding species differences in intestinal availability (Fg) between rats and humans.

Species differences in intestinal glucuronidation activities between humans, rats, dogs and monkeys.

1.  Glucuronidation via UDP-glucuronosyltransferase (UGT) in the intestine has been reported to influence the pharmacokinetics (PK) of drugs; however, information concerning the differences in activity between species is limited. Here, we investigated the in vitro and in vivo activities of intestinal glucuronidation for 17 UGT substrates in humans, rats, dogs and monkeys.

Novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals.

SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae (including β-lactamase-negative ampicillin-resistant strains), and Neisseria gonorrhoeae (including ciprofloxacin-resistant strains), with MIC(90)s of ≤ 1 μg/ml. Unlike tebipenem (MIC(50), 8 μg/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as Pseudomonas aeruginosa (MIC(50), ≥ 128 μg/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant S.

Quantitative prediction of human intestinal glucuronidation effects on intestinal availability of UDP-glucuronosyltransferase substrates using in vitro data.

We investigated whether the effects of intestinal glucuronidation on the first-pass effect can be predicted from in vitro data for UDP-glucuronosyltransferase (UGT) substrates. Human in vitro intrinsic glucuronidation clearance (CL(int, UGT)) for 11 UGT substrates was evaluated using pooled intestinal microsomes (4.00-4620 μl · min⁻¹ · mg⁻¹) and corrected by the free fraction in the microsomal mixture (CLu(int), (UGT) = 5.

Method for predicting human intestinal first-pass metabolism of UGT substrate compounds.

1. As intestinal glucuronidation has been suggested to generate the low oral bioavailability (F) of drugs, estimating its effects would be valuable for selecting drug candidates. Here, we investigated the absorption and intestinal availability (F(a)F(g)) in animals, and intrinsic clearance via UDP-glucuronosyltransferase (UGT) in intestinal microsomes (CL(int,UGT)) for three drug candidates possessing a carboxylic acid group, in an attempt to estimate the impact of intestinal glucuronidation on F and select potential drug candidates with high F in humans.

Prediction of human metabolism of FK3453 by aldehyde oxidase using chimeric mice transplanted with human or rat hepatocytes.

During drug development, it is important to predict the activities of multiple metabolic enzymes, not only cytochrome P450 (P450) but also non-P450 enzymes, such as conjugative enzymes and aldehyde oxidase (AO). In this study, we focused on prediction of AO-mediated human metabolism and pharmacokinetics (PK) of 6-(2-amino-4-phenylpyrimidine-5-yl)-2-isopropylpyridazin-3(2H)-one (FK3453) (Astellas Pharma Inc.), the development of which was suspended due to extremely low exposure in human, despite good oral bioavailability in rat and dog.

Quantitative prediction of intestinal glucuronidation of drugs in rats using in vitro metabolic clearance data.

UDP-glucuronosyltransferase (UGT) is highly expressed in the small intestine and catalyzes the glucuronidation of small molecules, which may affect the oral bioavailability of drugs. However, no method of predicting the in vivo observed fraction of absorbed drug (F(a)F(g)) affected by UGT has yet been established. Here, we investigated the relationship between F(a)F(g) and in vitro clearance of nine UGT substrates (ketoprofen, tolcapone, telmisartan, raloxifene, entacapone, resveratrol, buprenorphine, quercetin, and ezetimibe) via UGT in intestinal microsomes (CL(int, UGT)) in rats.

Correlation of intrinsic in vitro and in vivo clearance for drugs metabolized by hepatic UDP-glucuronosyltransferases in rats.

A method for quantitatively predicting the hepatic clearance of drugs by UDP-glucuronosyltransferases (UGTs) from in vitro data has not yet been established. We examined the relationship between in vitro and in vivo intrinsic clearance by rat hepatic UGTs using 10 drugs. For these 10 drugs, the in vitro intrinsic clearance by UGTs (CL(int, in vitro)) measured using alamethicin-activated rat liver microsomes was in the range 0.