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Biomedical subjects

K Tsuruta

Publications and source records attributed to K Tsuruta.

At least 19 recordsLinked to original sources

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.

Acute Disease↗

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.

Aged↗

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.

Bile Ducts, Extrahepatic↗

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.

Autoimmune Diseases↗

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.

Journal Article↗

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.

Autoimmune Diseases↗

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.

Adult↗

Regression of an unresectable pancreatic tumor following nonmyeloablative allogeneic peripheral-blood stem-cell transplantation.

A 59-year-old female with an unresectable, large pancreatic tumor (10.0 x 8.0 cm(2) on CT scan) underwent nonmyeloablative allogeneic peripheral-blood stem-cell transplantation from her HLA-identical sibling. Pronounced tumor regression and relief from pain without acute graft-versus-host disease (GVHD) were observed following transplantation. The patient is surviving (more than 300 days) after transplantation, with extensive chronic GVHD, and has tumor regression with an 80% reduction in tumor size. The observed clinical course may suggest a graft-versus-tumor effect on the pancreatic tumor following allogeneic stem-cell transplantation.

Adenocarcinoma↗

Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.

BACKGROUND: Autoimmune pancreatitis is a unique clinical entity proposed recently, and is sometimes associated with inflammation of other organs. AIMS: To examine the pathophysiology of the pancreas and other organs in patients with autoimmune pancreatitis. PATIENTS AND METHODS: We evaluated clinicopathological findings in six resected and one autopsied patient with autoimmune pancreatitis. The pancreas, peripancreatic tissue, bile duct, and gall bladder were examined histologically and immunohistochemically. Biopsied salivary gland and cervical lymph node of one patient were also examined. We also performed similar immunohistochemical examinations in pancreatectomy specimens from 10 patients with alcoholic chronic pancreatitis and biopsied salivary glands from five patients with Sjögren's syndrome. RESULTS: Stenosis of the extrahepatic bile duct was detected in all patients. Histological findings were characterised by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Immunohistochemically, diffusely infiltrating cells consisted predominantly of CD4 or CD8 positive T lymphocytes and IgG4 positive plasma cells. Similar inflammatory processes also involved the peripancreatic tissue, extrahepatic bile duct, gall bladder, and salivary gland. Lymph nodes were swollen with infiltration of IgG4 positive plasma cells. None of these findings was seen in alcoholic chronic pancreatitis or Sjögren's syndrome. CONCLUSIONS: The development of the specific inflammations in extensive organs as well as the pancreas in patients with autoimmune pancreatitis strongly suggests a close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.

Aged↗

Structure of finite two-dimensional Yukawa lattices: dust crystals.

Dust particles in plasmas are often confined near the boundary between the plasma bulk and the sheath where the gravitation is balanced by electrostatic force. To keep dust particles from running away horizontally, an electrostatic potential is usually applied to the electrode surrounding these dusty plasmas and, under appropriate conditions, we have finite two-dimensional lattices of dust particles. Modeling the interaction between dust particles as the isotropic Yukawa interaction, structures of finite two-dimensional Yukawa systems at low temperatures have been analyzed both by numerical simulations and variational methods. The effect of the correlation energy between dust particles is shown to play an important role in the formation of the one-body distribution in these systems.

Journal Article↗

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer.

BACKGROUND AND OBJECTIVES: The combination of 5-fluorouracil and radiotherapy is thought to be the most effective treatment for locally unresectable pancreatic carcinoma. The outcomes, however, are far from acceptable from the viewpoint of long-term survival. We assessed the survival benefits of oral adjuvant chemotherapy with doxifluridine (5'-DFUR) following radiotherapy for patients with the disease. METHODS: Thirty-five consecutive patients who underwent bypass surgery and radiotherapy for localized advanced unresectable adenocarcinoma of the pancreas head were retrospectively reviewed in regard to disease progression and survival. Ten of the 35 patients underwent adjuvant chemotherapy with 5'-DFUR after radiotherapy in an outpatient setting. RESULTS: The 1-year survival for patients treated with radiotherapy alone was 29%. The 1-, 2-, and 3-year survivals for patients treated with the adjuvant chemotherapy after radiotherapy were 50, 40, and 30%, respectively (P = 0.0069, log-rank test). The elevation of tumor markers was delayed (P = 0.0346) and local control rate was improved (P = 0.0475) in patients with chemotherapy. Multivariate analysis demonstrated that the adjuvant chemotherapy with 5'-DFUR was a significant independent prognostic factor as well as tumor size. CONCLUSIONS: The adjuvant chemotherapy with 5'-DFUR following radiotherapy led to a significant prolongation of the survival for patients with unresectable localized pancreatic cancer.

Administration, Oral↗

[Clinicopathologic study on chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct].

We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases.

Adult↗

Fistulation method: simple and safe pancreaticojejunostomy after pancreatoduodenectomy.

BACKGROUND: A pancreatic leak from the pancreaticojejunostomy after pancreatoduodenectomy has a potential risk of serious complications. We devised a simplified fistulation method for pancreaticojejunostomy. METHODS: The fistulation method, which uses a pancreatic drainage tube as a stent without pancreatic duct-to-jejunal mucosa anastomosis, was applied to 162 consecutive patients. They were divided into 3 groups according to the state of the pancreatic remnant: group 1, soft and normal parenchyma (n = 71); group 2, firm and thickened parenchyma (n = 40); group 3, hard and atrophic parenchyma (n = 51). The consistency in relation to the incidence of pancreatic leak and mortality were analyzed. Morphologic changes of the pancreatic remnant in long-term survivors of group 1 were assessed with computed tomography. RESULTS: A pancreatic leak occurred in 3 patients from group 1, in 2 patients from group 2, and in no patients from group 3 (leak rate, 3%). No operative mortality and 5 hospital deaths (3%) unrelated to a pancreatic leak were observed. The parenchyma of the pancreatic remnant was well preserved in 52% of the long-term survivors and the pancreatic duct was not dilated in 63%. CONCLUSIONS: The fistulation method can be performed safely and easily regardless of the state of the pancreatic remnant, and it provides every surgeon with a low incidence of pancreatic leak among patients.

Chi-Square Distribution↗

Immunohistochemical localization of pancreatic secretory trypsin inhibitor in malignant pancreatic endocrine tumors.

Differentiation of benign from malignant pancreatic endocrine tumors by existing clinical, biochemical, histologic, and cytologic criteria is difficult. We immunohistochemically localized pancreatic secretory trypsin inhibitor (PSTI) in 28 pancreatic endocrine tumors (13 benign, 15 malignant). PSTI-immunoreactive cells were detected in nine endocrine tumors. Immunoreactivity in these tumors was detected in nearly all tumor cells in five cases, scattered cells in two cases, and a few cells in two cases. All positive cases were malignant, and eight were equal to or larger than 10 cm. Serum concentrations of PSTI were markedly elevated in the two patients so tested. PSTI may be a specific immunohistochemical marker for malignant pancreatic endocrine tumors.

Adult↗

Interleukin-15 (IL-15) can replace the IL-2 signal in IL-2-dependent adult T-cell leukemia (ATL) cell lines: expression of IL-15 receptor alpha on ATL cells.

Interleukin-15 receptor (IL-15R) and IL-2R have the same beta and gamma chains, but IL-15R has a specific alpha chain distinct from that of IL-2Ralpha, which is indispensable for the high affinity binding of IL-15. In the present study, we examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL-15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold excess amount of IL-2, proliferated in response to IL-15 to the same degree as to the stimulation with IL-2, and were maintained without IL-2. The responses to 1L-15 were inhibited by the antibodies against IL-2R beta or gamma chains but was not by the IL-2R alpha chain antibody. [125I]-IL-15 exhibited a single high-affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription-coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the mRNA of IL-15R alpha. The cell lines also had IL-15 mRNA. Despite the presence of IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of fresh ATL cells and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also responded to IL-15. These results suggest that ATL cells have the complete form of IL-15R and respond to IL-15. Such an IL-15-dependent cell proliferation mechanism might be used in the development of ATL and for the invasion and proliferation of ATL cells in the visceral organs.

Adult↗

Pharmacokinetics and safety of a novel recombinant soluble human thrombomodulin, ART-123, in healthy male volunteers.

The safety and pharmacokinetics of a novel recombinant soluble human thrombomodulin, ART-123 were evaluated in single- and multiple-dose studies involving 16 healthy male volunteers. ART-123 was administered by intravenous infusion over 2 hours. The single-dose study indicated that plasma ART-123 levels at doses of 0.03, 0.1, and 0.3 mg declined biexponentially and those half-lives were approximately 4 hours (t1/2 alpha) and 20 hours (t1/2 beta), respectively. The mean plasma peak concentration and area under the plasma concentration-time curves increased in proportion to the given doses. Mean urinary recovery within the first 48 hours was between 54.3% and 59.8% of dose. In the multiple-dose study, ART-123 was administered at a dose of 0.2 mg once daily for 3 days. ART-123 did not accumulate as judged from plasma concentrations and urinary recovery. There were no abnormal findings in objective symptoms and laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, bleeding time, coagulation and hemostatic parameters, blood chemistry, and urinalysis. There were no significant adverse reactions or abnormalities in physical and laboratory examinations that could definitely be attributed to the drug at a dose of 0.3 mg as a single administration and at a dose of 0.2 mg once daily for 3 days. These results indicate that ART-123 is safe at doses up to 0.2 mg once daily for 3 days and may have clinical application. Further studies are needed, however, to evaluate the safety and pharmacokinetics of ART-123 in the targeted population.

Adult↗

A novel recombinant soluble human thrombomodulin, ART-123, activates the protein C pathway in healthy male volunteers.

The effect of a novel recombinant soluble human thrombomodulin, ART-123, on protein C activation was investigated by measuring plasma prothrombinase activity in four healthy male volunteers. ART-123 at a dose of 0.3 mg was administered as a bolus intravenous injection for 1 minute. Plasma ART-123 concentration and prothrombinase activity were determined before and immediately, 24, and 48 hours after injection, and thromboelastography was recorded before and immediately and 24 hours after injection. The mean elimination half-life was 19.82 +/- 2.10 hours. Compared with pretreatment levels, ART-123 reduced prothrombinase activity by 44.2 +/- 11.7%, 52.1 +/- 10.8%, and 61.0 +/- 14.7%, respectively, immediately, 24, and 48 hours after injection, suggesting that ART-123 activated the protein C pathway. ART-123 did not affect thromboelastography values. There were no abnormal findings for objective signs or laboratory tests, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, coagulation and hemostatic parameters, blood chemistry, and urinalysis. Based on these observations, ART-123 at a dose of 0.3 mg can activate the protein C pathway in healthy volunteers.

Adult↗