X-ray absorption near edge structure and first-principles spectral investigations of cationic disorder in MgAl2O4 induced by swift heavy ions.

Cationic disorder in the MgAl2O4 spinel induced by swift heavy ions was investigated using the X-ray absorption near edge structure. With changes in the irradiation fluences of 200 MeV Xe ions, the Mg K-edge and Al K-edge spectra were synchronously changed. The calculated spectra based on density function theory indicate that the change in the experimental spectra was due to cationic disorder between Mg in tetrahedral sites and Al in octahedral sites. These results suggest a high inversion degree to an extent that the completely random configuration is achieved in MgAl2O4 induced by the high density electronic excitation under swift heavy ion irradiation.

Evaluation of immunomodulatory effect of recombinant human granulocyte-macrophage colony-stimulating factor on polymorphonuclear cell from dogs with cancer in vitro.

The objective of this in vitro study was to evaluate the immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on polymorphonuclear cell (PMN) function in dogs with cancer. PMNs were harvested from dogs with naturally developing cancer as a pre-clinical model to evaluate the immunomodulatory effects of rhGM-CSF on PMN phagocytic and cytotoxic functions, cytokine production and receptor expression. Some aspects of cancer-related PMN dysfunction in dogs with cancer were restored following incubation with rhGM-CSF including PMN phagocytosis, respiratory burst and LPS-induced TNF-α production. In addition, rhGM-CSF increased surface HLA-DR expression on the PMNs of dogs with cancer. These data suggests that dysfunction of innate immune response in dogs with cancer may be improved by rhGM-CSF. The results of this study provided a pathophysiologic rationale for the initiation of clinical trials to continue evaluating rhGM-CSF as an immunomodulatory therapy in dogs with cancer.

Contactless electrical conductivity measurement of metallic submicron-grain material: Application to the study of aluminum with severe plastic deformation.

We measured the electrical conductivity σ of aluminum specimen consisting of submicron-grains by observing the AC magnetic susceptibility resulting from the eddy current. By using a commercial platform for magnetic measurement, contactless measurement of the relative electrical conductivity σn of a nonmagnetic metal is possible over a wide temperature (T) range. By referring to σ at room temperature, obtained by the four-terminal method, σn(T) was transformed into σ(T). This approach is useful for cylinder specimens, in which the estimation of the radius and/or volume is difficult. An experiment in which aluminum underwent accumulative roll bonding, which is a severe plastic deformation process, validated this method of evaluating σ as a function of the fraction of high-angle grain boundaries.

Chemotherapy and remission status do not alter pre-existing innate immune dysfunction in dogs with lymphoma.

Dogs with lymphoma have altered innate immunity and little is known about the effects of chemotherapy on innate immune function in dogs. Lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) - induced leukocyte cytokine production capacity, and phagocytosis and respiratory burst were evaluated in dogs prior to and following 6 weeks of chemotherapy. Dogs had decreased TNF production following LPS stimulation and increased IL-10 production following PG stimulation, which did not improve following remission of lymphoma. Dogs also had reduced E. coli-induced respiratory burst function after chemotherapy induced complete or partial remission. Dogs with lymphoma have an imbalance in pro-and anti-inflammatory cytokine production which did not improve with remission, and, following treatment, a decrease in respiratory burst function. Altered immune responses following exposure to bacterial pathogen associated molecular pattern motifs and bacteria may have many implications in the management of canine lymphoma.

Correlation between urine and serum BK virus levels after renal transplantation.

BACKGROUND: Quantification of the serum level of BK virus is used as a surrogate marker for the early onset of BK virus nephropathy. However, little is known about the diagnostic value of the urine level of BK virus for nephropathy or the relationship between the serum and urine viral load. We investigated the correlation between urine and serum BK virus levels after renal transplantation. METHODS: From November 2008 to August 2013, a total of 270 renal transplant patients who were followed at our institution were included in this study. Urine and serum were collected simultaneously. BK virus levels were quantified in 894 urine and serum samples using a real-time polymerase chain reaction assay. RESULTS: BK virus was detected in 178 urine samples and 36 serum samples. Among the BK virus-positive urine subjects, the positive predictive value for viral detection in the serum was 9% (13/147) when the urinary virus level was <10(7) copies/mL and 74% (23/31) when the urinary virus was ≥ 10(7) copies/mL. Serum BK viral levels were ∼2-3 log units lower than those in urine. CONCLUSIONS: BK virus was detected more frequently in serum when present in urine at ≥ 10(7) copies/mL after renal transplantation.

Malignant bladder pheochromocytoma with SDHB genetic mutation.

A 30-year-old man presented with micturition pain and was diagnosed with a submucosal tumor in the right wall of the bladder with metastasis to the right obturator lymph node. Transurethral resection led to a diagnosis of invasive malignant pheochromocytoma. Radical cystectomy, neobladder reconstruction and bilateral iliac lymph node dissection were performed. Genetic analysis revealed succinate dehydrogenase B-associated hereditary pheochromocytoma/paraganglioma syndrome. 10 months after the operation, he had no evidence of recurrence.

Ecological niche and potential geographic distribution of the invasive fruit fly Bactrocera invadens (Diptera, Tephritidae).

Two correlative approaches to the challenge of ecological niche modeling (genetic algorithm, maximum entropy) were used to estimate the potential global distribution of the invasive fruit fly, Bactrocera invadens, based on associations between known occurrence records and a set of environmental predictor variables. The two models yielded similar estimates, largely corresponding to Equatorial climate classes with high levels of precipitation. The maximum entropy approach was somewhat more conservative in its evaluation of suitability, depending on thresholds for presence/absence that are selected, largely excluding areas with distinct dry seasons; the genetic algorithm models, in contrast, indicate that climate class as partly suitable. Predictive tests based on independent distributional data indicate that model predictions are quite robust. Field observations in Benin and Tanzania confirm relationships between seasonal occurrences of this species and humidity and temperature.

Development of boron nanocapsules for neutron capture therapy.

High accumulation and selective delivery of boron into tumor tissues are the most important requirements to achieve efficient neutron capture therapy of cancers. We focused on liposomal boron delivery system in order to achieve a large amount of boron delivery to tumor. We synthesized the double-tailed boron cluster lipid 4c according to our reported procedure with modification. Size distribution of liposomes prepared from the boron cluster lipid 4c, DMPC, PEG-DSPE, and cholesterol was determined as 100 nm in diameter by an electrophoretic light scattering spectrophotometer. A high level of (10)B concentration (22 ppm) was observed in tumor tissue at 24 h after the administration of boron liposomes.

Pharmacokinetics of recombinant human soluble thrombomodulin, thrombomodulin alfa in the rat.

1. The study aimed to investigate the pharmacokinetics of thrombomodulin alpha (TM-alpha), human-soluble thrombomodulin in rats. 2. Intravenously administered TM-alpha was eliminated in two phases (T(1/2 alpha) = 0.2-0.3 h and T(1/2 beta) = 6-8 h), and the elimination curve was linear in a dose range of 10-250 microg kg(-1). Based on the results of tissue concentration studies after reaching the steady-state, the highest concentration of TM-alpha was seen in the plasma, suggesting the low levels of transfer to tissues (< or = 22% of plasma levels). 3. In vivo metabolism of TM-alpha was also analysed using high-performance liquid chromatography. The main peak observed in the plasma was TM-alpha, and even 72 h after the last dose of repeated administrations, 80% or more was unchanged form. Approximately half of the radioactivity excreted in the urine was recovered as a peak corresponding to TM-alpha. 4. The results reveal that although plasma clearance was lower in the renally impaired rats, the decrease was not large, with a difference of only about 20%. As a result, although the cause remains unclear, it is considered unlikely that the plasma concentrations of TM-alpha will vary considerably in patients with renal impairment.

Can MRCP replace ERCP for the diagnosis of autoimmune pancreatitis?

BACKGROUND: It is of utmost importance that autoimmune pancreatitis (AIP) be differentiated from pancreatic cancer. Irregular narrowing of the main pancreatic duct is a characteristic finding in AIP; it is useful for differentiating AIP from pancreatic cancer stenosis. This study evaluated the usefulness of magnetic resonance cholangiopancreatography (MRCP) for the diagnosis of AIP and assessed whether MRCP could replace endoscopic retrograde cholangiopancreatography (ERCP) for diagnosing AIP. METHODS: The MRCP and ERCP findings of 20 AIP patients were compared. RESULTS: On MRCP, the narrowed portion of the main pancreatic duct was not visualized, while the noninvolved segments of the pancreatic duct were visualized. The degree of upstream dilatation of the proximal main pancreatic duct was milder in AIP than in pancreatic cancer patients. In the skipped type, only skipped narrowed lesions were not visualized. After steroid therapy for AIP, the nonvisualized main pancreatic duct became visualized. CONCLUSIONS: MRCP cannot replace ERCP for the diagnosis of AIP, since narrowing of the main pancreatic duct in AIP was not visualized on MRCP. MRCP findings of segmental or skipped nonvisualized main pancreatic duct accompanied by a less dilated upstream main pancreatic duct may suggest the presence of AIP. MRCP is useful for following AIP patients.

Barrier distributions derived from quasielastic backscattering of 48Ti, 54Cr, 56Fe, 64Ni, and 70Zn projectiles on a 208Pb target.

In order to study the nucleus-nucleus interaction in Pb-based cold fusion, we have measured excitation functions for quasielastic scattering of 48Ti, 54Cr, 56Fe, 64Ni, and 70Zn projectiles on a 208Pb target at backward angles. The barrier distributions were derived from the first derivative of measured quasielastic scattering cross sections relative to the Rutherford scattering cross section. The centroids of the barrier distributions show a deviation from several predicted barrier heights toward the low energy side. The shape of the barrier distributions is well reproduced by the results of a coupled-channel calculation taking account of the coupling effects of two phonon excitations of the quadrupole vibration for the projectiles and of the octupole vibration for the 208Pb target.

Pancreatographic investigation of the pancreatic duct system.

BACKGROUND: Embryologically, the pancreatic duct system develops by the fusion between the dorsal and ventral pancreatic bud ducts. It has been suggested that the proximal part of the main dorsal pancreatic duct partially regresses to form the accessory pancreatic duct (APD). Aim of this study was to clarify the anatomy of the pancreatic duct system of the head of the pancreas and investigate the embryology of the normal pancreatic duct system. METHODS: We reviewed endoscopic retrograde pancreatography of normal pancreatic heads (n = 256) and pancreas divisum (n = 36), focusing on long inferior branches arising from the APD and the main pancreatic duct (MPD). The accessory pancreatograms were divided into two patterns of course and shape, the long type (171 cases) and the short type (85 cases) according to the length of the MPD from the orifice to the junction with the APD. The long-type APD formed a straight line and joined the MPD at the neck portion of the pancreas. The short-type APD joined the MPD near its first inferior branch. RESULTS: The shape of the long-type APD was quite similar to that of the dorsal pancreatic duct of pancreas divisum. The short-type APD was less likely to have a long inferior branch arising from the APD. The length of the APD from the orifice to the first long inferior branch was similar in the long-type APD (19.4 +/- 4.0 mm) and in the short-type APD (18.8 +/- 4.2 mm). The first long inferior branch from the long-type APD passed though the MPD near the origin of the inferior branch from the MPD, whereas the short-type APD joined the MPD near its inferior branch. CONCLUSIONS: There are two types of APD. The long-type APD was quite similar to the shape of the dorsal pancreatic duct of pancreas divisum, and seems to represent a continuation of the main duct of the dorsal pancreatic bud. The short-type APD was less likely to have a long inferior branch, and seems to be formed by the most proximal part of the main duct of the dorsal pancreatic bud and its long inferior branch.

MRCP of congenital pancreaticobiliary malformation.

BACKGROUND: Congenital pancreaticobiliary malformations are sometimes associated with acute or chronic pancreatitis and biliary carcinoma. Currently, magnetic resonance cholangiopancreatography (MRCP) is one of the first choices for investigating and diagnosing pancreaticobiliary diseases noninvasively. We compared the accuracy of conventional MRCP and endoscopic retrograde cholangiopancreatography (ERCP) in making the diagnosis of congenital pancreaticobiliary malformations. METHODS: In patients with pancreas divisum (n = 17), pancreaticobiliary maljunction (n = 12), choledochocele (n = 2), and annular pancreas (n = 1) who underwent ERCP and MRCP, the diagnostic accuracy and findings on MRCP were compared with those on ERCP. RESULTS: Of the 32 patients with congenital pancreaticobiliary malformations diagnosed on ERCP, 23 (72%) presented the same diagnosis on MRCP. Complete pancreas divisum was diagnosed in 73% on MRCP based on the finding of a dominant dorsal pancreatic duct crossing the lower bile duct and emptying into the duodenum without communicating with the ventral pancreatic duct. Pancreaticobiliary maljunction was diagnosed in 75% on MRCP based on the finding of an anomalous union between the common bile duct and the pancreatic duct and the existence of a long common channel. CONCLUSIONS: Conventional MRCP is a useful, noninvasive tool for diagnosing congenital pancreaticobiliary malformations; and the diagnostic accuracy can be increased with three-dimensional MRCP or dynamic MRCP with secretin stimulation.

The presence of a common channel and associated pancreaticobiliary diseases: a prospective ERCP study.

BACKGROUND: There are few endoscopic retrograde cholangiographic studies dealing with the relationship between the presence of a common channel and associated pancreaticobiliary diseases. AIMS: To endoscopically determine the incidence of common channels and assess whether the anatomy of the pancreaticobiliary ductal drainage into the duodenum has any bearing on pancreaticobiliary diseases. PATIENTS AND METHODS: We prospectively examined a common channel formation in 354 endoscopic retrograde cholangiographic cases. Cases with a common channel were divided into three groups: pancreaticobiliary maljunction, high confluence of pancreaticobiliary ducts with a common channel > or =6 mm in which the communication was occluded with the sphincter contraction, and common channel < or =5 mm in length. RESULTS: A common channel was observed in 131 cases (37.0%) including 11 with pancreaticobiliary maljunction and 13 with high confluence of pancreaticobiliary ducts. In cases with a common channel, the incidences of associated gallbladder carcinoma and acute pancreatitis were both 11.5%, which were significantly higher than 1.8% and 4.9% seen in cases without a common channel. In pancreaticobiliary maljunction cases, incidence of associated gallbladder carcinoma was 72.7%. CONCLUSION: The presence of an obvious common channel was observed in 37.0%. A close relationship is suggested between the presence of a common channel and development of gallbladder carcinoma and acute pancreatitis.

IgG4-related sclerosing disease incorporating sclerosing pancreatitis, cholangitis, sialadenitis and retroperitoneal fibrosis with lymphadenopathy.

BACKGROUND AND AIMS: Autoimmune pancreatitis is usually associated with elevated serum IgG4 concentrations, and sometimes with sclerosing cholangitis and Sjögren's syndrome. This study aimed to elucidate the proposed entity of IgG4-related sclerosing disease. METHODS: Subjects were patients with autoimmune pancreatitis (n = 26), sclerosing sialadenitis (n = 5), chronic alcoholic pancreatitis (n = 20), sialolithiasis (n = 34), Sjögren's syndrome (n = 50), and primary sclerosing cholangitis (n = 3). Sections of various organs and tissues of these patients were examined immunohistochemically using antibodies to CD4-T, CD8-T, and CD20-B cell subsets and IgG4, and serum IgG4 concentrations were measured. RESULTS: Patients with autoimmune pancreatitis were associated with sclerosing cholangitis (n = 23), sclerosing sialadenitis (n = 2), retroperitoneal fibrosis (n = 2), and abdominal (n = 5) and cervical (n = 4) lymphadenopathy. They demonstrated infiltrations of more abundant IgG4-positive plasma cells in the pancreas, peripancreatic retroperitoneal tissues, extrahepatic bile duct, gallbladder, stomach, minor salivary gland, and abdominal lymph nodes compared with those of other diseases (p < 0.01). Such infiltrations were also observed in the minor salivary gland and submandibular gland of patients with sclerosing sialadenitis (p < 0.01). Serum IgG4 concentrations were significantly elevated in patients with autoimmune pancreatitis and sclerosing sialadenitis (p < 0.01). CONCLUSION: We propose a new clinicopathological entity of IgG4-related sclerosing disease incorporating sclerosing pancreatitis, cholangitis, sialadenitis and retroperitoneal fibrosis with lymphadenopathy.

Gastrointestinal findings in patients with autoimmune pancreatitis.

BACKGROUND AND STUDY AIMS: Autoimmune pancreatitis (AIP) is a condition that has been proposed as a clinical entity only fairly recently. Its pathogenesis involves autoimmune mechanisms. Although the radiological findings in patients with AIP have been well evaluated, few studies have focused on the gastrointestinal findings in these patients. The aim of this study was to explore the endoscopic and histological findings in the gastrointestinal tract in patients with autoimmune pancreatitis. PATIENTS AND METHODS: The endoscopic findings in the stomach (n = 10), the duodenum (n = 18), the major duodenal papilla (n = 18), and the colon (n = 5) in 24 patients with AIP were reviewed. These were compared with the results of histological examination of gastric mucosa (n = 13), duodenal mucosa (n = 9), the major duodenal papilla (n = 3), and colonic mucosa (n = 3) in these patients. All these specimens were subjected to immunohistochemical study using anti-IgG4 antibody. RESULTS: Foci of slightly pale, thickened mucosa with loss of visible vascular pattern were observed in the stomach in four patients and in the colon in two patients on endoscopy. Slight or moderate swelling of the major duodenal papilla was detected in five patients. Slight to moderate lymphoplasmacytic infiltration was observed in the lamina propria of the gastric and colonic mucosa, and of the major duodenal papilla. Heavy infiltration with IgG4-positive plasma cells (>10 cells per high-power field) was observed in the lamina propria of the stomach in seven patients, of the colon in two patients, and of the major duodenal papilla in three patients; this was not observed in the control patients, who had other diseases. CONCLUSIONS: Although there were no specific endoscopic findings in the stomach or colon in patients with autoimmune pancreatitis, foci of slightly pale, thickened mucosa with loss of visible vascular pattern were observed in some cases. This indistinct change seen on endoscopy appears to be due to heavy infiltration with IgG4-positive plasma cells, associated with CD4- or CD8-positive T lymphocytes, in the lamina propria of the gastric or colonic mucosa.

Origin of the long common channel based on pancreatographic findings in pancreaticobiliary maljunction.

BACKGROUND AND AIMS: The origin of a long common channel in pancreaticobiliary maljunction was suggested to be the ventral pancreatic duct. Pathogenesis of long common channels was investigated by anatomically analysing the arrangement of pancreatic ducts in pancreaticobiliary maljunction. MATERIALS AND METHODS: Cholangiopancreatography was performed for 66 cases of pancreaticobiliary maljunction and 200 controls. The accessory pancreatic duct was classified according to course and shape. In cases with long- or short-type accessory pancreatic duct, lengths of the main pancreatic duct from orifice to first inferior branch and junction with the accessory pancreatic duct, and the common channel were measured. RESULTS: Lengths of the main pancreatic duct from orifice to first inferior branch or junction with the accessory pancreatic duct were significantly longer in cases of pancreaticobiliary maljunction cases with the long- or short-type accessory pancreatic duct than in controls (p<0.01). Lengths of the main pancreatic duct from first inferior branch to junction with the accessory pancreatic duct were roughly equivalent in pancreaticobiliary maljunction and controls. CONCLUSIONS: Long common channels in pancreaticobiliary maljunction might be formed embryologically with adhesion of the right ventral pancreatic duct and the terminal portion of the bile duct.

Evidence of complete fusion in the sub-barrier 16O+238U reaction.

Evaporation residue cross sections in the 16O+238U reaction were measured for the energy range from above- to extreme sub-barrier. The cross sections are reproduced by a statistical model calculation, for which partial cross sections are calculated by a coupled-channel model taking into account the prolate deformation of 238U. Complete fusion was observed in the collision of the projectile with the tips of the 238U target, in the same way as the side collision.

Morphological changes after steroid therapy in autoimmune pancreatitis.

BACKGROUND: Although many patients with autoimmune pancreatitis undergo steroid therapy, detailed evaluation of morphological changes in the pancreas and bile duct following therapy has not been performed in this disease. In this study serological and morphological changes occurring during steroid treatment of autoimmune pancreatitis are comparatively examined. METHODS: Ten patients with autoimmune pancreatitis were treated with corticosteroids. Morphological findings were: pancreatic enlargement (n = 9), irregular narrowing of the main pancreatic duct (n = 10), and biliary stenosis (n = 9). An initial dose of prednisolone was 40-30 mg/day, and this was tapered by 5 mg every 1-2 weeks. All patients underwent ultrasound and serological testing 1-2 weeks after commencing medication, followed by weekly serological testing and by CT and endoscopic retrograde cholangiopancreatography after 1-2 months. Radiological and serological changes were compared. RESULTS: All 10 patients were responsive to steroid therapy. Pancreatic size normalized within 1 month; however, irregularity of the pancreatic duct remained in 6 patients. Rigidity or lateral deformity of the bile duct remained in 3 patients and biliary stenosis persisted in 5. Four patients in whom elevated serum IgG4 failed to normalize also showed incomplete morphological improvement. Three patients with complete improvement of the pancreatic duct stopped medication, but recurrence of pancreatitis did not occur. CONCLUSIONS: Although steroid therapy was morphologically and serologically effective in patients with autoimmune pancreatitis, cholangiopancreatographic abnormalities remained in many patients. Morphological improvement on cholangiopancreatography and normalization of serum IgG4 after steroid therapy appeared to be good indicators for discontinuing medication in patients with autoimmune pancreatitis.

Phase I study of a novel recombinant human soluble thrombomodulin, ART-123.

BACKGROUND: Anticoagulants are often given for extended periods of time to patients at high risk for venous thromboembolism, such as after orthopedic surgery. Daily subcutaneous (sc) injections can be inconvenient to the patient. A long-acting anticoagulant requiring less frequent dosing could make treatment more acceptable. Thrombomodulin is a natural anticoagulant that activates protein C, which leads to inactivation of factor (F)Va and FVIIIa and decreased thrombin formation. Recombinant human thrombomodulin is a novel anticoagulant with a long half-life in animal models. METHODS AND RESULTS: This phase I study examined pharmacokinetics, pharmacodynamics, and safety of recombinant human soluble thrombomodulin (ART-123) after administration of doses between 0.02 and 0.06 mg kg(-1) body weight intravenously (iv), and between 0.02 and 0.45 mg kg(-1) sc in 55 healthy volunteers. The plasma half-life was 2-3 days after sc injection of various single doses. Plasma ART-123 levels estimated to be needed for prevention of thrombus formation in humans were maintained for at least 6 days after single sc injection of 0.30 and 0.45 mg kg(-1) ART-123. Antithrombotic activity with these doses was demonstrated by achieving prothrombinase inhibition of more than 80% for more than 6 days after administration. No major bleeding occurred. Pharmacodynamic modeling revealed that adequate antithrombotic ART-123 levels can be achieved for 6 days with one dose of 0.45 mg kg(-1) ART-123, and for 12 days with 2 doses of 0.30 mg kg(-1), given 5 days apart. CONCLUSIONS: Recombinant human soluble thrombomodulin (ART-123) has a long half-life after sc injection and is well tolerated, making it a suitable agent to be tested in clinical thromboprophylaxis trials.