Localization of increased hepatic vascular resistance in liver cirrhosis

To determine the localization of increased vascular resistance in cirrhotic liver, blood pressures were measured by a direct cannulation method at several key points in the hepatic vascular pathway in normal and cirrhotic rats. Cirrhosis was produced by feeding a choline-deficient diet. Blood pressures in normal rats were 110 mm H2O in the portal vein, 68 mm H2O in the terminal portal venule, 28 mm H2O in the terminal hepatic venule and 20 mm H2O in the inferior vena cava. In cirrhotic rats, blood pressures in the portal vein and the terminal portal venule were 173 and 100 mm H2O, respectively, while those in the terminal hepatic venule and the inferior vena cava were elevated only slightly above normal. These hemodynamic data suggest that an increase in vascular resistance in cirrhotic liver is present in the intrahepatic portal vein and sinusoids, but not in intrahepatic hepatic vein. In cirrhotic liver, stenosis and distortion were found in peripheral branches of the portal vein, and sinusoidal stenoses and a decrease in sinusoidal space were recognized. Accordingly, it is suggested that the increase in vascular resistance in the intrahepatic portal vein and sinusoids correlate with these structural changes. Although severe stenoses and distortion were found in hepatic vein branches, it was thought that they do not contribute to portal hypertension because of lack of increase in vascular resistance in the intrahepatic hepatic vein.     

Impaired exercise-related myocardial uptake of technetium-99m-tetrofosmin in relation to coronary narrowing and diabetic state: assessment with quantitative single photon emission computed tomography

Despite the diagnostic efficacy of stress myocardial perfusion imaging, the correlation between the actual perfusion tracer activity and diseased state of a coronary artery has not been studied in detail. We estimated exercise-related perfusion augmentation in relation to disease states of a coronary artery in diabetic and non-diabetic patients by a newly developed quantitative technetium (Tc)-99m-tetrofosmin myocardial imaging technique. Tc-99m-tetrofosmin tomographic imaging with an exercise-rest protocol was performed in 26 stable coronary patients and in 8 age-matched controls. Percent increase (%IR) in myocardial count during symptom-limited submaximal exercise-stress was calculated in 16 non-infarcted polar map segments and in each coronary territory by a subtraction technique with corrections for physical decay and injected tracer doses, and the results were compared with those of angiographically quantified coronary diameter stenosis (%DS). Percent IR and peak heart rate during exercise showed a positive linear correlation both in coronary territories with significant stenosis (%DS > or = 75%) and in control or nonstenotic (%DS < 75%) territories. The regression line in stenotic regions was, however. significantly (p < 0.01) shifted downward compared to that in non-stenotic regions. Percent IR in stenotic regions showed a significant inverse correlation with %DS. Coronary stenosis of 75% or more was identified by a %IR cutoff value of 40% with 77% sensitivity, 70% specificity, and an accuracy of 72%. In coronary territories with a %DS of less than 75%, %IR in diabetic patients was significantly lower (46+/-15%) than that in nondiabetic patients (61+/-25%). Thus, blunted exercise-related augmentation of myocardial uptake of Tc-99m-tetrofosmin correlates with the severity of coronary narrowing and diabetic state.     

Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves

The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but negative for keratinocyte marker keratin 15, suggesting their relatively undifferentiated state. These cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In vivo studies show the nestin-driven GFP hair follicle stem cells can differentiate into blood vessels and neural tissue after transplantation to the subcutis of nude mice. Equivalent hair follicle stem cells derived from transgenic mice with beta-actin-driven GFP implanted into the gap region of a severed sciatic nerve greatly enhance the rate of nerve regeneration and the restoration of nerve function. The follicle cells transdifferentiate largely into Schwann cells, which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair follicle stem cells, walking print length and intermediate toe spread significantly recovered, indicating that the transplanted mice recovered the ability to walk normally. These results suggest that hair follicle stem cells provide an important, accessible, autologous source of adult stem cells for regenerative medicine.     

Long-term follow-up study of three patients with the long QT syndrome.

We studied three women with the long QT syndrome. They were aged 42, 52 and 25 years and had experienced recurrent syncopal attacks. We followed case 1 for 17, case 2 for 18, and case 3 for over 6 y. The attacks tended to occur during the premenstrual stage in case 1 and case 2; case 3 often experienced attacks after exercise. The QT(U)c intervals on admission were 0.68, 0.62, and 0.50 in case 1, 2, and 3, respectively. Torsade de pointes followed by ventricular fibrillation was documented in case 1 and case 2. Although each was treated with a beta-blocker, none was fully compliant with the regimen. In case 1, estrogen therapy administered to maintain the hormonal balance premenstrually effectively prevented attacks. Despite the inconsistent use of beta-blockers, the attacks in case 1 and case 2 tended to decrease with age. Case 2 experienced no attacks after menopause. Cause 3 took medication consistently and remained free of attacks for over 6 y. Although she discontinued beta-blocker therapy because of pregnancy, she has experienced no attacks to date. These case studies suggest that hormonal status may be important in the development of syncopal attacks in female patients with the long QT syndrome.     

A case of pulmonary coccidioidomycosis presented with bilateral infiltrative opacities and eosinophilia

A 53-year-old male was admitted to our hospital complaining of high fever with chillness, cough and dyspnea after traveling to Arizona in the United States. The chest X-ray films taken on admission showed consolidation in the right middle lung field and bilateral nodular shadows. The laboratory data revealed an increase in white blood cell counts with eosinophilia, and a rise in erythrocyte sediment rate and serum C-reactive protein. The biopsied lung specimen by video-assisted thoracoscopic surgery showed granulomatous inflammation consisting of eosinophils and giant cells. In addition, typical spherules filled with endopores were detected in the specimen. The diagnosis of primary pulmonary coccidioidomycosis was made. After the treatment of a three months' regimen with itraconazole at the daily dosage of 200 mg, the patient's symptoms, laboratory data and radiological findings markedly improved.     

Modulation of corticospinal excitability dependent upon imagined force level

Motor imagery is defined as the mental execution of a movement without any muscle activity. In the present study, corticospinal excitability was assessed by motor evoked potentials (MEPs) when the subjects imagined isometric elbow flexion at various force levels. Electromyography was recorded from the right brachioradialis, the biceps brachii and the triceps brachii muscles. First, the maximum voluntary contraction (MVC) of elbow flexion was recorded in each subject. Subjects practiced performing 10, 30 and 60 % MVC using visual feedback. After the practice, MEPs were recorded during the imagery of elbow flexion with the forces of 10, 30 and 60 % MVC without any feedback. After the MEPs recording, we assigned subjects to reproduce the actual elbow flexion force at 10, 30 and 60 % MVC. The MEPs amplitudes in the brachioradialis and biceps brachii in the 60 % MVC condition were significantly greater than those in the 10 % MVC condition (p < 0.05). These findings suggest that the enhancement of corticospinal excitability during motor imagery is associated with an increase in imagined force level.     

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 rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site

Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion. Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since type 5–7 fusions were reported recently, they are classified as type 1–7. We examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion were completely identical to the recent report, but the case had the same fusion patterns in both primary and metastatic sites. In our case, increased splicing activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There is another possibility that metastasis might develop through the increased splicing activity in the fusion.     

Evaluation of an artificial intelligence system for detecting vertical root fracture on panoramic radiography

Objectives

The aim of this study was to evaluate the use of a convolutional neural network (CNN) system for detecting vertical root fracture (VRF) on panoramic radiography.

Methods

Three hundred panoramic images containing a total of 330 VRF teeth with clearly visible fracture lines were selected from our hospital imaging database. Confirmation of VRF lines was performed by two radiologists and one endodontist. Eighty percent (240 images) of the 300 images were assigned to a training set and 20% (60 images) to a test set. A CNN-based deep learning model for the detection of VRFs was built using DetectNet with DIGITS version 5.0. To defend test data selection bias and increase reliability, fivefold cross-validation was performed. Diagnostic performance was evaluated using recall, precision, and F measure.

Results

Of the 330 VRFs, 267 were detected. Twenty teeth without fractures were falsely detected. Recall was 0.75, precision 0.93, and F measure 0.83.

Conclusions

The CNN learning model has shown promise as a tool to detect VRFs on panoramic images and to function as a CAD tool.