[Epstein-Barr virus-associated gastritis with perigastric lymphadenopathy accompanied by infectious mononucleosis:a case report].

A 28-year-old female patient with no particular medical history had a sore throat seven days before admission. Subsequently, she developed malaise, right abdominal pain, and a fever of 38°C and visited our hospital. A blood test revealed a mild inflammatory response and elevated liver enzymes, and she was admitted to the hospital for detailed examination and acute liver injury treatment. Various viral tests and autoantibody measurements revealed elevated Epstein-Barr virus (EBV) immunoglobulin M and negative EB nuclear antigen antibodies. Therefore, she was diagnosed with primary infectious mononucleosis-associated EB viral hepatitis. Abdominal computed tomography upon admission revealed swollen lymph nodes around the stomach;thus, esophagogastroduodenoscopy (EGD) was performed. A histopathological examination revealed severe lymphocytic infiltration, and EB encoding region in situ hybridization demonstrated that 10-20% of the lymphocytes were EBV-infected. Drip and rest treatment improved the patient's liver enzymes, and her symptoms resolved. Repeat EGD after two months revealed improved gastric erosions. Here, we report a case of EBV-associated gastritis that was discovered due to perigastric lymphadenopathy accompanied by infectious mononucleosis. This report includes a review of the literature because a few studies reported EBV-associated gastritis.

Sensitization pattern to environmental allergens in a Japanese population.

Background: We previously described the prevalence of allergen-specific IgE in a general population of Japanese adults. Objective: We sought to elucidate allergen sensitization patterns in this population. Methods: Serum samples had been obtained from 800 blood donors aged 20 to 59 years and living in Tokyo, Japan, in 2005 and stored in the Japanese Red Cross Society. These samples were examined for IgE levels, total and specific for 23 allergens or allergen sources correlated with allergic airway diseases using the ImmunoCAP method. Exploratory and confirmatory factor analyses were performed to uncover the relationship among allergen-specific IgE based on their titers. Hierarchical cluster analysis was executed using Ward's method based on standardized factor scores identified through factor analysis. Results: Exploratory factor analysis revealed 6 categories of allergen-specific IgE: specific to 2 types of animals (insects and Dermatophagoides pteronyssinus/animal dander), 2 types of pollens (group 1 [Japanese cedar and cypress] and group 2 [alder, grass, and weeds]), and 2 types of microorganisms (fungi and commensal microorganisms on the skin). The Japanese population was categorized into 3 clusters: (A) nonatopic type, (B) house dust mite-dominant sensitization type, and (C) panatopic type. The panatopic group could be further classified into 2 subclusters positive and negative for fungal sensitization. Conclusions: This study demonstrated that a Japanese population could be divided into 3 clusters according to the sensitization pattern to 6 types of allergens.

Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

Immune and allergenic effects of the microalga Coccomyxa sp. strain KJ in healthy humans: A pilot study.

BACKGROUND: The Coccomyxa sp. strain KJ (Coccomyxa KJ), a microalga found in Japan, has a potential function in controlling viral infections. Recently, its dry powder has been marketed as a health food product. OBJECTIVES: This pilot study investigated the effects of Coccomyxa KJ powder tablet intake on allergic reactions and immune functions in healthy participants. MATERIAL AND METHODS: Nine healthy volunteers (4 males and 5 females) who expressed interest in foods containing Coccomyxa KJ, and were willing to undergo blood tests, were recruited. Each individual was asked to take 2 Coccomyxa KJ powder tablets (0.3 g) before breakfast once a day for 4 weeks. The salivary immunoglobulin A (IgA) level and blood parameters (white blood cell (WBC) count, eosinophil and lymphocyte counts and percentages, natural killer (NK) cell activity, interleukin (IL)-6 level, and T helper (Th)1/Th2 cell ratio) were evaluated at baseline and weeks 2 and 4. RESULTS: The 4-week intake of Coccomyxa KJ did not affect salivary IgA levels, WBC count, eosinophil and lymphocyte counts and percentages, or the Th1/Th2 ratio. There were significant differences in the NK cell activity after 4 weeks, with an average increase of 11.78 (95% confidence interval (95% CI): 6.80-16.76). None of the patients experienced adverse reactions during or after the study. CONCLUSIONS: Long-term Coccomyxa KJ intake improved NK cell activity without causing adverse effects on the indicators of local immunity, systemic inflammation and immune response balance. This study suggests that Coccomyxa KJ powder tablets can induce beneficial immune modifications without causing any adverse effects.

Structural aging of human neurons is opposite of the changes in schizophrenia.

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 × 10-4). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 × 10-4), indicating that neurite structure is relevant to brain function. This report is based on our 3D analysis of human brain tissues over a decade and is unprecedented in terms of the number of cases. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia.

Structural diverseness of neurons between brain areas and between cases.

The cerebral cortex is composed of multiple cortical areas that exert a wide variety of brain functions. Although human brain neurons are genetically and areally mosaic, the three-dimensional structural differences between neurons in different brain areas or between the neurons of different individuals have not been delineated. Here we report a nanometer-scale geometric analysis of brain tissues of the superior temporal gyrus of schizophrenia and control cases. The results of the analysis and a comparison with results for the anterior cingulate cortex indicated that (1) neuron structures are significantly dissimilar between brain areas and that (2) the dissimilarity varies from case to case. The structural diverseness was mainly observed in terms of the neurite curvature that inversely correlates with the diameters of the neurites and spines. The analysis also revealed the geometric differences between the neurons of the schizophrenia and control cases. The schizophrenia cases showed a thin and tortuous neuronal network compared with the controls, suggesting that the neuron structure is associated with the disorder. The area dependency of the neuron structure and its diverseness between individuals should represent the individuality of brain functions.

The Implementation of a Hospital-wide Practice for the Selective Use of Carbapenems Based on the Monitoring of Susceptibility of Pseudomonas aeruginosa Isolates.

OBJECTIVES: To control carbapenem-resistant Pseudomonas aeruginosa, we implemented a hospital-wide policy concerning the selective use of carbapenems based on the monitoring of P. aeruginosa isolates for susceptibility to five carbapenems using a customized dry plate method. In this study, we retrospectively investigated the outcome of our measures to control carbapenem-resistant P. aeruginosa. METHODS: To select effective carbapenems, 100 clinical isolates were collected, and the minimum inhibitory concentration (MIC) to 5 carbapenems (IPM/CS, MEPM, DRPM, BIPM and PAPM/BP) was monitored using a customized dry plate method from 2006 to 2013. Carbapenems, which were associated with a high rate of drug resistance in P. aeruginosa, were restricted from use during our intervention study. The antimicrobial use density per 100 bed-days (AUD100) of carbapenems and the detection rates of carbapenem (IPM/CS and MEPM)-resistant P. aeruginosa were determined during the period of the intervention. RESULTS: The isolates consistently showed higher rates of drug-resistant P. aeruginosa in IPM/CS and PAPM/BP. Thus, DRPM, MEPM and BIPM were adopted for hospital-wide use. The detection rates of all IPM/Cs and MEPM-resistant P. aeruginosa significantly decreased. Meanwhile, the consumption of carbapenems showed an increasing trend. CONCLUSIONS: The outcome of the hospital-wide implementation of the selective use of carbapenems based on periodic monitoring of the susceptibility of P. aeruginosa isolates was retrospectively studied. Implementation of this measure might have contributed in part to the control of carbapenem-resistant P. aeruginosa in our hospital.

Comparison between the location and the histomorphological/immunohistochemical characteristics of noninvasive neoplasms of the ampulla of Vater.

To determine useful factors when selecting an appropriate procedure for noninvasive ampullary neoplasia, we investigated the relationship between the location and the histomorphological/immunohistochemical characteristics of 56 noninvasive ampullary neoplasms obtained by endoscopic papillectomy (EP). All subjects were classified according to histomorphology and location of neoplasms, and we evaluated the characteristics of each classified group using complementary immunohistochemical procedures. The CK20-positive rates of each location type were also evaluated. Subjects presented with 52 intestinal-type adenomas (low/high grade, 32:20) and 4 noninvasive pancreatobiliary papillary neoplasms (low/high grade, 1:3). Twenty-seven periampullary (peri-AMP)-type tumors and 23 extended-type tumors comprised the intestinal type, and the intra-ampullary (intra-AMP) type was composed of 4 pancreatobiliary and 2 intestinal histomorphological types. The CK20-positive rates of these 3 location types differed significantly (peri-AMP type, 50.6% ± 21.0%; extended type, 35.4% ± 18.6%; intra-AMP type, 6.9% ± 6.3%). The CK20-positive rate for intestinal-type tumors of the intra-AMP location type was lower than that of the peri-AMP location type. Intestinal-type tumors without CDX2 expression included extended and intra-AMP types, which are tumors that may show positive vertical margins when EP is performed. In this study, we found that an understanding of pancreatobiliary-type histology is an important aspect for the investigation of tumors involving the common channel of the ampulla. Furthermore, immunostaining of CDX2 and CK20 provides beneficial information if considering whether to perform an EP.

Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases.

BACKGROUND: Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. METHODS: Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. RESULTS: A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. CONCLUSION: One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial pressure, because our study revealed a significant positive association between the rate of pulmonary arterial stenosis and right ventricular thickness. In addition, diffuse type gastric carcinoma may be apt to cause the remodeling of the pulmonary artery.

Histopathological study of murine pulmonary cryptococcosis induced by Cryptococcus gattii and Cryptococcus neoformans.

Although Cryptococcus gattii can cause life-threatening complications, putative virulence factors of C. gattii remain controversial. Therefore, we conducted the present study to elucidate the virulence factors of the yeast and found that the mortality rate of mice infected with C. gattii R265 was significantly higher than that of those infected with C. gattii 5815; however, no difference was found in the mortality rates between mice infected with C. gattii R265 and Cryptococcus neoformans H99. In contrast, we found a significant difference in histopathological findings of the lungs between mice infected with C. gattii R265 and C. neoformans H99. The former showed alveolar expansion due to yeast proliferation with much lesser macrophage response, whereas the latter showed numerous nodules in the alveolar space consisting of macrophages and multinucleated giant cells. Furthermore, alveolar expansion was more enhanced in mice infected with C. gattii R265 than in those infected with C. gattii 5815. Our study confirmed that there is a different pathophysiology leading to death during C. gattii and C. neoformans infections. The result can provide two characteristics of C. gattii: one includes some mechanisms to escape from host recognition via macrophage and another includes a high performance of pulmonary structural alteration. These characteristics may be associated with the high virulence of C. gattii.

Multivariate one-sided multiple comparison procedure with a control based on the approximate likelihood ratio test.

In this study, we discuss a multiple comparison procedure with a control for multivariate one-sided test in each pairwise comparison. For pairwise comparisons, we use the approximate likelihood ratio test statistics derived by Tang et al. (An approximate likelihood ratio test for a normal mean vector with nonnegative components with application to clinical trials. Biometrika 1989, 76, 577-583). We derive a formula to determine the critical value for pairwise comparisons satisfying a specified significance level. Furthermore, we formulate the power of the test for our multiple comparison procedure. Finally, we give some numerical examples regarding the critical values and the power of the test.

A new transcutaneous energy transmission system with hybrid energy coils for driving an implantable biventricular assist device.

We have developed a new transcutaneous energy transmission (TET) system for a totally implantable biventricular assist device (BVAD) system in the New Energy and Industrial Development Organization (NEDO) artificial heart project. The TET system mainly consists of an energy transmitter, a hybrid energy coil unit, an energy receiver, an internal battery system, and an optical telemetry system. The hybrid energy coil unit consists of an air-core energy transmission coil and an energy-receiving coil having a ferrite core. Internal units of the TET system are encapsulated in a titanium alloy casing, which has a size of 111 mm in width, 73 mm in length, and 25 mm in height. In in vitro experiments, the TET system can transmit a maximum electric energy of 60 Watts, and it has a maximum transmission efficiency of 87.3%. A maximum surface temperature of 46.1 degrees C was measured at the ferrite core of the energy-receiving coil during an energy transmission of 20 Watts in air. The long-term performance test shows that the TET system has been able to operate stably for over 4 years with a decrease of energy-transmission efficiency from 85% to 80%. In conclusion, the TET system with the hybrid energy coil can overcome the drawback of previously reported TET systems, and it promises to be the highest performance TET system in the world.

Ten-year NEDO BVAD development program: moving forward to the clinical arena.

Since 1995, the Baylor Group has been developing a totally implantable NEDO BVAD system. This 10-year program was completed in March 2005, and preparation for clinical trials is underway. This article summarizes the entire 10-year NEDO program and describes the strategy for clinical trials. The project aimed to achieve: (1) dual centrifugal pumps with the ability of full biventricular support, (2) a compact system implantable into small adults, (3) a totally implantable system with transcutaneous energy transmission system (TETS), (4) a durable system with a lifetime of over 5 years, and (5) a system free of thrombus and with minimal hemolysis. The final goals are to complete preclinical system evaluations and commence the clinical trials in the near future. In vitro studies have demonstrated a pump capacity of over 8.5 l/min and an Index of Hemolysis of <0.004 g/100 l. The pump-bearing life expectancy was over 5 years. To date, eight pumps endured in vivo studies of over 3 months without complications, including thromboembolic events. The in vitro endurance studies of eight pumps are longer than 1 year. There were no mechanical malfunctions or pump failure. A stepwise clinical trial is being planned: Step1, a wearable BVAD/VAD will be clinically studied; Step 2, the BVAD/VAD will be implanted intracorporeally without TETS; and, Step 3, a totally implantable system will be clinically evaluated. The NEDO BVAD system has completed preclinical testing. Clinical trial preparation is underway.

The pivot wash in two impeller modes for the Baylor/Miwatec centrifugal blood pump.

A centrifugal blood pump with a double pivot impeller and an eccentric inlet port is being developed as an implantable artificial heart by the Baylor College of Medicine and Miwatec Co. Ltd. Flow visualization measurements were conducted to compare the flow around the pivot for two impeller operational modes: the top and the bottom contact modes. In the top contact mode, one-way flow in the pivot gap due to the eccentric vortex was observed, and sufficient wall shear rate to prevent thrombus formation was attained around the bottom pivot for over 1,400 rpm. Computational fluid dynamic analyses confirmed that the causes of the eccentric vortex were the inlet eccentricity and the pressure imbalance in the volute.

Development of a bidirectional transcutaneous optical data transmission system for artificial hearts allowing long-distance data communication with low electric power consumption.

We have developed a wavelength division bidirectional transcutaneous optical data transmission system using amplitude shift keying (ASK) modulation. The bidirectional optical data transmission system consists of two kinds of light emitting diodes (LEDs) having different wavelengths and an ASK modulator and demodulator. Two narrow directional visible LEDs with a peak output wavelength of 590 nm were used to transmit data from inside the body to outside the body, and a narrow directional near-infrared LED with a peak output wavelength of 940 nm was used for transmission from outside the body to inside the body. The ASK modulator employs a carrier pulse signal (50 kHz) to support a maximum data transmission rate of 9600 bps. An in vitro experiment showed that the maximum tissue thickness of near-infrared optical data transmission without error was 45 mm; the figure was 20 mm for visible optical data transmission. There was no interference between the signals under full-duplex data transmission. Electric power consumption for the data transmission links was 122 mW for near-infrared light and 162 mW (81 mW x 2) for visible light. From the above results, a bidirectional transcutaneous optical data transmission system promises adequate performance for monitoring and control of an artificial heart.

Flow visualization in a centrifugal blood pump with an eccentric inlet port.

Flow visualization analysis was applied to the Baylor/Miwatec centrifugal artificial heart to evaluate its fluid dynamic characteristics regarding antithrombogenicity. An eccentric vortex was found both in the upper and the lower gaps of the impeller, which is supposed to be caused by the eccentric inlet port. Therefore, one-way flow toward the outlet is formed and washes the pivot. The combination of an eccentric vortex and a pivot bearing that is washed is unique to the Baylor/Miwatec pump. For the male pivots exposed to periodic wash, the minimum shear rate around the bottom pivot was estimated to be 650/s, which is higher than the threshold for thrombus formation shown by other studies. The wall shear rate at the impeller bottom surface was found to be larger in the top contact mode than in the bottom contact mode.