Adrenaline increases the rate of cross-bridge cycling in rat cardiac muscle

To characterize the myocardial cross-bridge dynamics in catecholamine-induced positive inotropic state, we studied the effects of adrenaline (6 X 10(-6) M) on the transient central segment length (SL) response to step decrease in tension in rat right ventricular papillary muscle in barium contracture. The time course of this response is thought to reflect the kinetics of actin-myosin interaction. The muscle was released stepwise from the steady contracture tension (Tc) to new steady tension levels (Tr) of varying magnitudes at 22 degrees C. When the tension decrease was less than 0.7 Tc, the SL transient responses comprised, in most cases, four phases. The first phase was a rapid and minute shortening during tension reduction; the second was a slow further shortening; the third, a slow lengthening; and the fourth, an extremely slow shortening toward a new steady length under the new tension. Adrenaline showed almost no effect on Tc and the amplitude of SL transients, but markedly reduced the duration of the second (D2) and third (D3) phases of SL transient regardless of the amplitude of tension reduction. The reduction of duration was 14 +/- 3% in D2 and 26 +/- 5% in D3 at Tr/Tc of 0.84 +/- 0.03 on the average (mean +/- S.D.) in nine preparations. The velocity measured from the quasi-steady SL shortening in the second phase increased with the addition of adrenaline, regardless of the amplitude of tension reduction. The increase in the shortening velocity was 16 +/- 6% (mean +/- S.D., n = 9) at Tr/Tc of 0.18 +/- 0.04. These results suggest that adrenaline increases the rate of cross-bridge cycling in cardiac muscle independent of activation level.     

Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.     

17β-Estradiol Enhances Contact Hypersensitivity in a Hair Cycle-Dependent Manner and Retards Thymic Atrophy with Age

The effect of 17β-estradiol (E2) on murine contact hypersensitivity (CHS), thymic atrophy, and hair-cycle change related to growth was investigated. Female mice were ovariectomized. E2 (3.2 μg) was injected subcutaneously along with the sensitizer 4‐ethoxymethylene-2-phenyl-2-oxazolin-5-one (OXA), and a hypersensitive reaction was elicited with OXA on the ear in mice of various ages. E2 enhanced allergy only in 3- and 7-week-old mice, just prior to hair regrowth. Age-related thymus atrophy was repressed in the E2-treated mice compared with the control mice. E2 alone did not cause thymus involution, but it did inhibit thymus involution and regeneration after CHS.     

Using a High-Speed Movie Camera to Evaluate Slice Dropping in Clinical Image Interpretation with Stack Mode Viewers

The purpose of this study is to verify objectively the rate of slice omission during paging on picture archiving and communication system (PACS) viewers by recording the images shown on the computer displays of these viewers with a high-speed movie camera. This study was approved by the institutional review board. A sequential number from 1 to 250 was superimposed on each slice of a series of clinical Digital Imaging and Communication in Medicine (DICOM) data. The slices were displayed using several DICOM viewers, including in-house developed freeware and clinical PACS viewers. The freeware viewer and one of the clinical PACS viewers included functions to prevent slice dropping. The series was displayed in stack mode and paged in both automatic and manual paging modes. The display was recorded with a high-speed movie camera and played back at a slow speed to check whether slices were dropped. The paging speeds were also measured. With a paging speed faster than half the refresh rate of the display, some viewers dropped up to 52.4 % of the slices, while other well-designed viewers did not, if used with the correct settings. Slice dropping during paging was objectively confirmed using a high-speed movie camera. To prevent slice dropping, the viewer must be specially designed for the purpose and must be used with the correct settings, or the paging speed must be slower than half of the display refresh rate.     

Induction of Mutant Sik3Sleepy Allele in Neurons in Late Infancy Increases Sleep Need

Sleep is regulated in a homeostatic manner. Sleep deprivation increases sleep need, which is compensated mainly by increased EEG δ power during non-rapid eye movement sleep (NREMS) and, to a lesser extent, by increased sleep amount. Although genetic factors determine the constitutive level of sleep need and sleep amount in mice and humans, the molecular entity behind sleep need remains unknown. Recently, we found that a gain-of-function Sleepy (Slp) mutation in the salt-inducible kinase 3 (Sik3) gene, which produces the mutant SIK3(SLP) protein, leads to an increase in NREMS EEG δ power and sleep amount. Since Sik3^Slp mice express SIK3(SLP) in various types of cells in the brain as well as multiple peripheral tissues from the embryonic stage, the cell type and developmental stage responsible for the sleep phenotype in Sik3^Slp mice remain to be elucidated. Here, we generated two mouse lines, synapsin1^CreERT2 and Sik3^ex13flox mice, which enable inducible Cre-mediated, conditional expression of SIK3(SLP) in neurons on tamoxifen administration. Administration of tamoxifen to synapsin1^CreERT2 mice during late infancy resulted in higher recombination efficiency than administration during adolescence. SIK3(SLP) expression after late infancy increased NREMS and NREMS δ power in male synapsin1^CreERT2; Sik3^ex13flox/+ mice. The expression of SIK3(SLP) after adolescence led to a higher NREMS δ power without a significant change in NREMS amounts. Thus, neuron-specific expression of SIK3(SLP) after late infancy is sufficient to increase sleep.SIGNIFICANCE STATEMENT The propensity to accumulate sleep need during wakefulness and to dissipate it during sleep underlies the homeostatic regulation of sleep. However, little is known about the developmental stage and cell types involved in determining the homeostatic regulation of sleep. Here, we show that Sik3^Slp allele induction in mature neurons in late infancy is sufficient to increase non-rapid eye movement sleep amount and non-rapid eye movement sleep δ power. SIK3 signaling in neurons constitutes an intracellular mechanism to increase sleep.     

A case of allergic fungal rhinosinusitis caused by Schizophyllum commune identified in both patient's nasal sputum and veranda's soil samples

This is a case report of allergic fungal rhinosinusitis caused by Schizophyllum commune (S. commune) identified in a patient's nasal mucus and environmental soil sample using (r)DNA sequencing. Although filamentous basidiomycetes, including S. commune, are known as environmental pathogens causing allergic respiratory diseases worldwide, many patients with infections caused by S. commune have not been correctly diagnosed. Repeated exposures to environmental floating fungi supposedly make an easy sensitization and colonization of fungi in the nasal passages, resulting in the onset of allergic fungal rhinosinusitis due to S. commune in our living environments. This report indicates the importance of reconsidering allergic respiratory diseases associated with our living environments.     

Evaluation of Surveyor nuclease for rapid identification of FKS genes mutations in Candida glabrata

IntroductionInfections with Candida glabrata have recently gained worldwide attention owing to its association with long hospitalizations and high mortality rates. This problem is highlighted when the infection is associated with echinocandin resistance, which is used for first-line therapy. Echinocandin resistance is exclusively attributed to functional mutations in FKS genes, and especially in hot spot (HS) regions. Unfortunately, few studies have focused on the rapid identification of FKS mutations associated with echinocandin resistance in C. glabrata. This study was intended to evaluate and validate the use of Surveyor nuclease assay (SN) for detection of FKS gene mutations.MethodsSN was evaluated against three segments of FKS1 and FKS2 genes including whole gene, regions including all HSs, and the region including only HS1.ResultsOur results showed that SN results are basically dependent on the type of gene as well as the segment type. Interestingly, SN can detect mutations in the region containing HS1 in both FKS1 and FKS2 genes. Furthermore, SN can detect mutations in the segment containing all HS regions for FKS1 but not FKS2. SN was unable to detect mutations in the whole FKS1 and FKS2 genes.ConclusionsAs far as we know, this is the first study to validate SN for rapid identification of FKS gene mutations. This assay could be used as a sample for rapid identification of mutations associated with HS1 region in FKS genes, which have a predominant role for echinocandin resistance induction in C. glabrata.     

Pancreatic Follicular Lymphoma Presenting as Acute Pancreatitis: Report of a Case

Pancreatic B-cell lymphoma is rare; it accounts for 0.2% to 2.0% of extranodal non-Hodgkin lymphoma, and constitutes less than 0.5% of all pancreatic malignancies. Most histologic types of the pancreatic lymphoma are diffuse large B-cell lymphoma, and follicular lymphoma is quite rare. We report here a case of pancreatic follicular lymphoma that was initially detected by acute pancreatitis. This is the first reported case of pancreatic follicular lymphoma presenting with acute pancreatitis. A 71-year-old woman had epigastric and left upper quadrant abdominal pain. Computed tomography (CT) revealed features of acute pancreatitis. After standard therapy for pancreatitis, enhanced CT showed a pancreatic tumor (50 × 35 mm) in the body of the pancreas with gradual enhancement. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed a complete interruption of the pancreatic duct in the body, with mild dilation of the duct in the tail of the pancreas. Endoscopic ultrasonography revealed hypervascularity of the pancreatic tumor. The patient underwent distal pancreatectomy to remove the cause of pancreatitis and to disclose the diagnosis. Histologic examination revealed follicular lymphoma of pancreas. Despite recent improvement in clinical strategies, differential diagnosis between pancreatic lymphoma and pancreatic cancer is still difficult without histologic information. Pancreatic lymphoma should be considered as a differential diagnosis in a patient who initially presents with acute pancreatitis.Key words: Pancreatic lymphoma, Acute pancreatitis, Follicular lymphomaPancreatic B-cell lymphoma is rare; it accounts for 0.2% to 2.0% of extranodal non-Hodgkin lymphoma¹ and constitutes less than 0.5% of all pancreatic malignancies.^2,3 Most histologic types of pancreatic lymphoma are diffuse large B-cell lymphoma, and follicular lymphoma is quite rare. In addition, acute pancreatitis caused by pancreatic lymphoma is also rare.Despite recent improvements in clinical strategies, differential diagnosis of pancreatic lymphoma with pancreatic cancer or autoimmune pancreatitis (AIP) is still difficult without histologic examination.We report here a rare case of a 71-year-old female with pancreatic follicular lymphoma that initially presented as acute pancreatitis.     

Conditional Deletion of Indian Hedgehog in Limb Mesenchyme Results in Complete Loss of Growth Plate Formation but Allows Mature Osteoblast Differentiation

Indian hedgehog (Ihh) is widely recognized as an essential factor for proper skeletal development. Previous in vivo studies using mutant Ihh mouse models were limited by perinatal lethality or carried out after a growth plate formed. Thus the important role of Ihh in mesenchymal cell differentiation has not been investigated. In this study, we established Prx1‐Cre;Ihh^fl/fl mice to ablate Ihh specifically in limb mesenchyme to allow us to observe the phenotype continuously from prenatal development to 3 weeks of age. Mutant mice displayed severe limb abnormalities characterized by complete lack of secondary ossification center and growth plate, indicating an essential role for Ihh in the development of these structures. Interestingly, we discovered that osteoblast differentiation and bone formation could occur in conditions of deficient Ihh. This is a novel finding that has not been observed because of the early lethality of previous Ihh mutants. Mature osteoblasts expressing osteocalcin could be detected in the center of mutant bones at postnatal day 10 (P10). Osteoclasts and blood vessel formation were also present, suggesting active bone remodeling. Histomorphometric analyses show a significant increase in osteoclast number with no major changes in bone formation rate at 3 weeks of age. Mutant long bones in the limbs were deformed, with cortices comprised of irregular woven bone. Also, there was a marked decrease in gene expression of osteoblastic and osteocytic markers. Moreover, mutant long bones displayed bone dysplasia in which we observed increased osteoclast activity and partially reduced osteoblastic and osteocytic differentiation that lead ultimately to loss of bone structures at 3 weeks of age. In summary, our data show for the first time, the presence of mature osteoblasts in long bones of the limbs despite the complete loss of growth plate formation due to Ihh deficiency. These data indicate an important function for Ihh in regulating limb mesenchymal cell differentiation. © 2015 American Society for Bone and Mineral Research.