[A Case of Drug-Induced Pneumomediastinum Preceding Interstitial Pneumonitis Onset during Treatment with a First-Line Regimen of GnP in a Patient with Unresectable Pancreatic Cancer].

Background: The highest prevalence of drug-induced interstitial pneumonitis(IP)occurs in patients receiving antineoplastic agents, such as cytotoxic chemotherapeutic drugs, molecular targeted drugs, and immune checkpoint inhibitors. A certain period of the treatment for IP requires discontinuation of the anticancer therapy, resulting in progression of the malignant status.

Case: A 70-year-old man was incidentally diagnosed with locally advanced unresectable pancreatic cancer in the course of his treatment for ventricular dysrhythmia.

[A Case of Advanced Late Recurrence of Hormone Receptor Positive Breast Cancer Successfully Treated with Abemaciclib and Anastrozole].

Background: In step with the aging of the Japanese population, late recurrence of hormone receptor positive (HR+) breast cancer occurring especially beyond 20 years after the initial diagnosis has been recognized as not rare anymore, as it has been occurring at a constant rate lately. The administration of an aromatase inhibitor with a CDK4/6 inhibitor has become the gold standard in Japan for cases of recurring HR+ breast cancer without severe visceral metastasis.

Case: A 73- year-old woman was diagnosed by chance with late recurrence of HR+ breast cancer 21 years after undergoing radical resection followed by adjuvant anastrozole for 5 years for stage Ⅲb right breast cancer.

Long-term remission of bilateral Wilms tumors that developed from premature separation of chromatids/mosaic variegated aneuploidy syndrome due to bilateral nephrectomy and peritoneal dialysis.

We report a 38-month-old Japanese male with premature chromatid separation/mosaic variegated aneuploidy syndrome bearing biallelic BUB1B germline mutations who suffered from bilateral Wilms tumor. After right nephrectomy, dactinomycin monotherapy was administered for the left Wilms tumor; however, severe adverse reaction prevented the patient from receiving further chemotherapy. Left nephrectomy was then performed without postoperative chemotherapy.

A Case of Portal Venous Stenting for Metastatic Hilar Stricture After the Radical Resection of Colon Cancer.

Like standard stenting in an unresectable malignant stricture of the biliary or digestive tract, minimally invasive modality for portal stenosis is indispensable for palliation. We describe here a safe and practical procedure of portal stenting in a case of metastatic hilar strictures developed nine years after the radical resection of sigmoid colon cancer. After urgent delivery of the biliary tract stenting for the relief of jaundice, the patient received palliative stenting for the stricture of the portal trunk.

TBCD may be a causal gene in progressive neurodegenerative encephalopathy with atypical infantile spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by survival motor neuron gene mutations. Variant forms of SMA accompanied by additional clinical presentations have been classified as atypical SMA and are thought to be caused by variants in as yet unidentified causative genes. Here, we presented the clinical findings of two siblings with an SMA variant followed by progressive cerebral atrophy, and the results of whole-exome sequencing analyses of the family quartet that was performed to identify potential causative variants.

Genotype-phenotype correlations in alternating hemiplegia of childhood.

Objective: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype-phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC.

Methods: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study.

Amygdala kindling induces nestin expression in the leptomeninges of the neocortex.

Nestin is an intermediate filament found in neurogenic progenitors and non-neuronal cells. Nestin-immunoreactivity (IR) in the brain often increases after brain damage. Here we show that amygdala kindling, which mimics the epileptic seizures, also induces nestin expression in the brain.

[A case of S-1-resistant resected advanced gastric cancer with para-aortic lymph node recurrence responding to bi-weekly CPT-11 and CDDP].

A 64-year-old man with advanced gastric cancer who underwent a curative total gastrectomy(LM, Less, Type 3, 70×55 mm, por1>tub2>sig, pT3(ss), med, INF b, ly3, v3, pN3b(41/61), pPM0, pDM0, pT3N3bM0, Stage III B)followed by adjuvant chemotherapy(paclitaxel+S-1)a year ago, revealed an increasing level of serum CEA and para-aortic lymphnode (#16b1)recurrence on abdominal CT. He was given chemotherapy with low-dose weekday CDDP+S-1 for the recurrence, after which he failed to respond. Thereafter, he received 2nd-line chemotherapy with bi-weekly CPT-11+CDDP as a S-1- refractory regimen.

ERK2 contributes to the control of social behaviors in mice.

Signaling through extracellular signal-regulated kinase (ERK) is important in multiple signal transduction networks in the CNS. However, the specific role of ERK2 in in vivo brain functions is not fully understood. Here we show that ERK2 play a critical role in regulating social behaviors as well as cognitive and emotional behaviors in mice.

Role of mouse hepatitis virus (MHV) receptor murine CEACAM1 in the resistance of mice to MHV infection: studies of mice with chimeric mCEACAM1a and mCEACAM1b.

Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele.

[A case of advanced breast cancer with multiple bone metastases responding to docetaxel and high-dose toremifene as fourth-line chemo-endocrine therapy].

A 55-year old woman, who underwent left mastectomy (Bt+Ax), was revealed to have sternum metastasis by postoperative 99mTc bone scanning(T1bN1M1). She received daily aromatase inhibitor (anastrozole), as a primary systemic endocrine therapy, and biweekly pamidronate for metastatic breast cancer. However, she depended on folk medicine a year later, at which time the primary treatment was discontinued.

Cytomegalovirus infection mimicking juvenile myelomonocytic leukemia showing hypersensitivity to granulocyte-macrophage colony stimulating factor.

We describe an infant with cytomegalovirus (CMV) infection presenting as transient myeloproliferation resembling juvenile myelomonocytic leukemia (JMML). The patient fulfilled the international diagnostic criteria of JMML, including hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). Viral studies using serologic assays and polymerase chain reaction (PCR) were positive for CMV.

Dual involvement of G-substrate in motor learning revealed by gene deletion.

In this study, we generated mice lacking the gene for G-substrate, a specific substrate for cGMP-dependent protein kinase uniquely located in cerebellar Purkinje cells, and explored their specific functional deficits. G-substrate-deficient Purkinje cells in slices obtained at postnatal weeks (PWs) 10-15 maintained electrophysiological properties essentially similar to those from WT littermates. Conjunction of parallel fiber stimulation and depolarizing pulses induced long-term depression (LTD) normally.

A novel form of memory for auditory fear conditioning at a low-intensity unconditioned stimulus.

Fear is one of the most potent emotional experiences and is an adaptive component of response to potentially threatening stimuli. On the other hand, too much or inappropriate fear accounts for many common psychiatric problems. Cumulative evidence suggests that the amygdala plays a central role in the acquisition, storage and expression of fear memory.

Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain.

Neurogenesis occurs continuously in the forebrain of adult mammals, but the functional importance of adult neurogenesis is still unclear. Here, using a genetic labeling method in adult mice, we found that continuous neurogenesis results in the replacement of the majority of granule neurons in the olfactory bulb and a substantial addition of granule neurons to the hippocampal dentate gyrus. Genetic ablation of newly formed neurons in adult mice led to a gradual decrease in the number of granule cells in the olfactory bulb, inhibition of increases in the granule cell number in the dentate gyrus and impairment of behaviors in contextual and spatial memory, which are known to depend on hippocampus.

Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory.

Long-lasting neuronal plasticity as well as long-term memory (LTM) requires de novo synthesis of proteins through dynamic regulation of gene expression. cAMP-responsive element (CRE)-mediated gene transcription occurs in an activity-dependent manner and plays a pivotal role in neuronal plasticity and LTM in a variety of species. To study the physiological role of inducible cAMP early repressor (ICER), a CRE-mediated gene transcription repressor, in neuronal plasticity and LTM, we generated two types of ICER mutant mice: ICER-overexpressing (OE) mice and ICER-specific knock-out (KO) mice.

Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy.

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy.

Morning rise of blood pressure assessed by home blood pressure monitoring is associated with left ventricular hypertrophy in hypertensive patients receiving long-term antihypertensive medication.

To assess the influence of morning rise of systolic blood pressure (SBP) as assessed by home blood pressure monitoring on the left ventricular mass index (LVMI) in relation to the blood pressure control status, we evaluated M-mode cardiac echocardiography in 626 hypertensive subjects (412 men and 214 women; mean age, 61.3+/-10.1 years) who were receiving antihypertensive medication.

Innate versus learned odour processing in the mouse olfactory bulb.

The mammalian olfactory system mediates various responses, including aversive behaviours to spoiled foods and fear responses to predator odours. In the olfactory bulb, each glomerulus represents a single species of odorant receptor. Because a single odorant can interact with several different receptor species, the odour information received in the olfactory epithelium is converted to a topographical map of multiple glomeruli activated in distinct areas in the olfactory bulb.

Extracellular signal-regulated kinase 2 (ERK2) knockdown mice show deficits in long-term memory; ERK2 has a specific function in learning and memory.

The extracellular signal-regulated kinase (ERK) 1 and 2 are important signaling components implicated in learning and memory. These isoforms display a high degree of sequence homology and share a similar substrate profile. However, recent findings suggest that these isoforms may have distinct roles: whereas ERK1 seems to be not so important for associative learning, ERK2 might be critically involved in learning and memory.

Pael receptor is involved in dopamine metabolism in the nigrostriatal system.

Pael receptor (Pael-R) has been identified as one of the substrates of Parkin, a ubiquitin ligase responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When Parkin is inactivated, unfolded Pael-R accumulates in the endoplasmic reticulum and results in neuronal death by unfolded protein stress, suggesting that Pael-R has an important role in the pathogenesis of AR-JP. Here we report the analyses on Pael-R-deficient (KO) and Pael-R-transgenic (Tg) mice.

Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation.

Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulation of Pael-R in the substantia nigra pars compacta of mice by retrograde infection induced endoplasmic reticulum (ER) stress leads to death of dopaminergic neurons.

R-spondin3 is required for mouse placental development.

Mouse R-spondin3 (Rspo3) is a member of the R-spondin protein family, which is characterized by furin-like cysteine-rich domains and a thrombospondin type 1 repeat. Rspo3 has been proposed to function as a secretory molecule that promotes the Wnt/beta-catenin signaling pathway. We generated mice bearing a mutant Rspo3 allele in which a lacZ-coding region replaced the coding region of the first exon.

Morning rise in blood pressure is a predictor of left ventricular hypertrophy in treated hypertensive patients.

To assess the relationship between home blood pressure and left ventricular mass, we evaluated cardiac echocardiography in 297 hypertensive subjects (188 men and 109 women; mean age, 62.8+/-10.3 years) who were treated with amlodipine monotherapy over 1 year (mean dose, 5.

Insulin resistance in patients with chronic kidney disease.

Background: It has been reported that insulin resistance appears at an earlier stage of chronic kidney disease (CKD). However, few data are available concerning what factors of metabolic abnormalities, such as apolipoprotein (Apo) profile or acidosis, might be associated with insulin resistance in patients with CKD.

Methods: We used the hyperinsulinemic euglycemic glucose clamp technique to examine insulin sensitivity in patients without diabetes (n = 29) with different stages of renal function.