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Biomedical subjects

A Okamoto

Publications and source records attributed to A Okamoto.

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↗

Plasma protein S activity correlates with protein S genotype but is not sensitive to identify K196E mutant carriers.

BACKGROUND: Protein S (PS) is an anticoagulant protein that functions as a cofactor for activated protein C (APC), and congenital PS deficiency is a well-known risk factor for the development of deep vein thrombosis (DVT). Recently, we and others identified the K196E missense mutation in the second epidermal growth factor-like domain of PS as a genetic risk factor for DVT in the Japanese population. The incidence of this mutation is high in the Japanese population. OBJECTIVES: In the present study, we investigated the relationship between plasma PS activity and the presence of the K196E mutation. PATIENTS AND METHODS: We measured PS activity as a cofactor activity for APC in 1,862 Japanese individuals and determined the PS K196E genotype in this population. RESULTS: Individuals heterozygous for the mutant E-allele had lower plasma PS activity than wildtype subjects (mean +/- SD, 71.9 +/- 17.6%, n = 34 vs. 87.9 +/- 19.8%, n = 1,828, P < 0.0001). However, the PS activity of several heterozygous individuals (n = 8) was greater than the population average. In contrast, multiple wildtype subjects (n = 26) had PS activity less than 2 SD below the population mean, indicating that other genetic or environmental factors affect PS activity. CONCLUSIONS: Plasma PS activity itself is not suitable for identifying PS 196E carriers and other methods are required for carrier detection.

Adult↗

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↗

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↗

Identification of systemically expanded activated T cell clones in MRL/lpr and NZB/W F1 lupus model mice.

CD4(+) T lymphocytes play an important role in the pathogenesis of systemic lupus erythematosus (SLE). To characterize the clonal expansion of CD4(+) T cells in murine lupus models, we analysed the T cell clonality in various organs of young and nephritic MRL/lpr and NZB/W F1 mice using reverse transcription-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP) analysis. We demonstrated that some identical T cell clonotypes expanded and accumulated in different organs (the bilateral kidneys, brain, lung and intestine) in nephritic diseased mice, and that a number of these identical clonotypes were CD4(+) T cells. In contrast, young mice exhibited little accumulation of common clones in different organs. The T cell receptor (TCR) V beta usage of these identical clonotypes was limited to V beta 2, 6, 8.1, 10, 16 and 18 in MRL/lpr mice and to V beta 6 and 7 in NZB/W F1 mice. Furthermore, some conserved amino acid motifs such as I, D or E and G were observed in CDR3 loops of TCR beta chains from these identical CD4(+) clonotypes. The existence of systemically expanding CD4(+) T cell clones in the central nervous system (CNS) suggests the involvement of the systemic autoimmunity in CNS lesions of lupus. FACS-sorted CD4(+)CD69(+) cells from the kidney displayed expanded clonotypes identical to those obtained from the whole kidney and other organs from the same individual. These findings suggest that activated and clonally expanded CD4(+) T cells accumulate in different tissues of nephritic lupus mice, and these clonotypes might recognize restricted T cell epitopes on autoantigens involved in specific immune responses of SLE, thus playing a pathogenic role in these lupus mice.

Animals↗

Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study.

Reduced plasminogen activity with a normal level of antigen is commonly observed in Japanese individuals. The first reported patient with plasminogen deficiency was accompanied with deep vein thrombosis. The present study examines whether heterozygous or homozygous deficiency of plasminogen is a risk factor for thrombotic disease. This study measures the plasminogen activity of 4517 individuals in the general population, determines the cut-off to define plasminogen deficiency, and identifies plasminogen deficiencies in the control groups and thrombotic disease groups. In another study, we examined the phenotypes of consecutive patients with homozygous plasminogen deficiency detected in our hospital. We found 173 and two of 4517 individuals to have heterozygous and homozygous deficiency with normal plasminogen antigen level, respectively, and 19 to have heterozygous deficiency with reduced antigen levels. The incidence of plasminogen deficiency in an age- and sex-matched control group (13/324, 4.01% for deep vein thrombosis or 13/330, 3.94% for stroke) selected from the 4517 individuals was not significantly different from those in patients with deep vein thrombosis (3/108, 2.78%) or cardioembolic stroke (6/110, 5.55%). Among 19 patients with homozygous plasminogen deficiency showing about 10% plasminogen activity, none had deep vein thrombosis. These findings indicate that neither heterozygous nor homozygous plasminogen deficiency constitutes a significant risk factor for thrombotic disease.

Aged↗

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↗

Longitudinal observation of basic mandibular movements: report of a case.

Sound development of mandibular function during childhood is indispensable to establishing healthy function in adults. To examine this developmental process, longitudinal recordings of basic mandibular movements were done using an optoelectronic analysis. Mandibular movements were recorded on five separate occasions in one boy, from an age of six years and five months to 14 years and five months. The incisor pathways during protrusion and lateral excursion were initially shallow, with more anterior than inferior movement, but as he grew the amount of inferior movement and the amount of rotation both increased. Similarly, at his first recording there was very little hinge-like rotation during mouth closing, but rotation increased markedly after eruption of his permanent second molars. These findings suggest that mandibular movements change from being relatively simple with more translation in younger children to more complex movements with more rotation once the permanent dentition is established.

Adolescent↗

Analytical description of a neutral-induced tripole vortex in a plasma.

An analytical description of a stationary triple vortex, observed in a cylindrical plasma, is presented. The concentration of neutrals, which is rather high in the experiment, turns out to be of crucial importance due to a spatially dependent distribution. In the radial direction the neutral concentration is paraboliclike, yielding an effective radial force directed towards the axis of the system. This neutral force causes the rotation of the plasma in the direction which is opposite to the E-->xB--> drift. The stationary triple vortex develops for a starting Gaussian-density distribution and a rigid-body rotation of the plasma column.

Journal Article↗

Heat shock protein 27 was up-regulated in cisplatin resistant human ovarian tumor cell line and associated with the cisplatin resistance.

To understand the molecular basis for failure of cisplatin (CDDP) based chemotherapy, we compared gene expressions between CDDP sensitive and resistant ovarian tumor cell line, 2008 and 2008/C13*5.25, by mRNA differential display. We detected both up-regulated and down-regulated bands in the resistant cell and found some of them to be positive on Northern blotting. DNA sequencing revealed one to be mitochondrial heat shock protein 75. We found that HSP27 and HSP70 were also up-regulated in the resistant cell by Western blotting. Further, transient transfection with the HSP27 sense gene made the sensitive cell more resistant, while transient transfection with the antisense gene made it more sensitive.

Antineoplastic Agents↗

Synthesis and properties of peptide nucleic acids containing a psoralen unit.

We prepared the psoralen PNA unit from 8-methoxypsoralen and synthesized various PNAs containing psoralen by a typical (t)()Boc method. PNAs containing psoralen (P-PNA) at strand end formed a stable duplex with complementary DNA. The hybridization of P-PNA with complementary DNA resulted in a considerable decrease of the psoralen fluorescence.

Base Sequence↗

A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis.

In the screening for cisplatin (CDDP)-resistance related genes by a mRNA differential display method, we detected some increased bands in CDDP resistant ovarian tumor cell line 2008/C13*5.25. One of them, named DD9, was a positive fragment on Northern blot analysis. We cloned it as a full length cDNA by 5'RACE and found a novel gene, CRR9 (Cisplatin Resistance Related gene 9). The CRR9 gene was transcribed into a 2.0 kb mRNA, encoding 512 amino acids. The putative protein had transmembrane-like domains and well conserved on C terminus with human CLPTM1 and the homologs found in Drosophila and C. elegans. Transfection assay showed that the CDDP-sensitive strain 2008 with CRR9 was more sensitive to CDDP, indicating that CRR9 was not associated with the CDDP-resistance, but the CDDP-induced apoptosis.

Amino Acid Sequence↗

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↗