PubMed Health⌕ Search

Biomedical subjects

Hitoshi Nakajima

Publications and source records attributed to Hitoshi Nakajima.

33 records · Page 2Linked to original sources
PubMed2003

A new clinicopathological entity of IgG4-related autoimmune disease.

BACKGROUND: Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases. METHODS: To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies. RESULTS: In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls. CONCLUSIONS: These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved. Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.

Aged↗
PubMed2003

Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a newly described entity with characteristic clinical, histologic, and morphologic changes, in which autoimmune mechanisms are involved in pathogenesis. However, difficulties can arise in the differentiation of AIP from pancreatic carcinoma. The aims of this study were to clarify clinical and radiologic features of AIP to elucidate areas of diagnostic confusion. METHODS: Clinical, serologic, and radiologic findings were evaluated in 17 patients with AIP. RESULTS: All 17 patients were initially suspected to have pancreatic carcinoma. The patients were predominantly elderly men who frequently presented with jaundice but without features of acute pancreatitis. Elevation of serum gamma-globulin and IgG along with the presence of autoantibodies were usually evident, whereas serum tumor markers were elevated in 54% of cases. Stenosis of the bile duct was detected in 94% of cases. Diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct were radiologically characteristic; however, segmental swelling and narrowing were detected in seven and two patients, respectively. In segmental cases, neither atrophy of the distal pancreas nor marked upstream dilation of the distal main pancreatic duct was observed. Angiographic abnormalities occurred in 54% of cases. Serologic and radiologic abnormalities showed considerable improvement with steroid therapy. CONCLUSIONS: Frequent stenosis of the bile duct, elevation of serum tumor markers, segmental pancreatic enlargement or narrowing of the main pancreatic duct, and angiographic abnormalities can cause confusion in the differential diagnosis of AIP and pancreatic carcinoma.

Adult↗
PubMed2003

Enhanced expression of the apoptosis inducing ligand TRAIL in mononuclear cells after myocardial infarction.

Tumor necrosis factor (TNF) family proteins including TNF-alpha and Fas (CD95)-ligand have been implicated in the development of acute myocardial infarction (AMI). We studied whether AMI patients displayed up-regulation of another TNF family member, TNF-related-apoptosis-inducing ligand (TRAIL), on peripheral blood mononuclear cells (PBMCs). We compared expression of TRAIL on PBMCs from 26 patients in the acute phase of AMI with that on PBMCs from 16 healthy control subjects using flow cytometry and RT-PCR. In addition, expression of TRAIL protein on PBMCs from patients in the acute phase of AMI was also compared with that from the same patients 7 days later. Furthermore, we compared the expression of TRAIL protein on CD4+, CD8+, CD14+, and CD19+ cells from patients in the acute phase of AMI with that from control subjects using flow cytometry. Finally, expression of the TRAIL receptors (TRAILR)-1 and TRAILR-2 in human cardiomyocytes was examined immunohistochemically. Expression of TRAIL protein was significantly higher in the acute phase of AMI than in control subjects. Expression of TRAIL protein was significantly higher in the acute phase of AMI than 7 days later. TRAIL mRNA expression in the acute phase of AMI was higher than in control subjects. Expression of TRAIL protein on CD4+ and CD14+ cells from AMI patients was significantly higher than that from control subjects. Expression of TRAILR-1 and TRAILR-2 in human cardiomyocytes was confirmed immunohistochemically. TRAIL on infiltrating CD4 and CD146 cells may be involved in the induction of cardiomyocyte apoptosis after AMI.

Apoptosis↗
PubMed2003

[Usefulness of rapid quantitative cardiac troponin T and myoglobin assays for the diagnosis of acute myocardial infarction].

BACKGROUND AND OBJECTIVES: The rapid cardiac troponin T (cTnT) test is widely used to detect myocardial necrosis in the emergency setting. This assay system is rapid and myocardial-specific, but the plasma cTnT concentration is difficult to determine quantitatively. A recently developed bedside cTnT and myoglobin (Mb) analyzer (CARDIAC system) was evaluated. METHODS: The new CARDIAC system was used to measure plasma cTnT and Mb levels, and serum levels of creatine kinase MB isoenzyme (CK-MB), cTnT and Mb were measured by conventional assays in 160 consecutive emergency patients with suspected acute myocardial infarction. RESULTS: The sensitivity of cTnT for identifying acute myocardial infarction was 76%, significantly higher than that of Mb (67%, p < 0.01) and CK-MB (54%, p < 0.05). The diagnostic sensitivities in patients admitted < or = 3 hr and 3-6 hr after onset were 52% and 65% for cTnT, 60% and 90% for Mb, and 36% and 50% for CK-MB, respectively. These sensitivities of Mb were significantly higher than those of CK-MB but not cTnT. However, the sensitivity of cTnT (100%) was significantly higher than that of Mb (58%, p < 0.01) and CK-MB (70%, p < 0.001) in patients admitted > 6 hr after onset. The specificities of cTnT, Mb and CK-MB were 96%, 76% (p < 0.001 vs cTnT and CK-MB) and 95%, respectively. Therefore, cTnT (86%) had significantly (p < 0.001) higher diagnostic accuracy compared with Mb (71%) and CK-MB (75%). Combination diagnosis using cTnT and Mb showed the highest sensitivity (86%) compared with cTnT (p < 0.05) and Mb (p < 0.001). The correlation coefficients between the levels measured by CARDIAC system and those by ordinary assays were 0.98 in cTnT and 0.97 in Mb. CONCLUSIONS: Bedside rapid quantitative assays of cTnT and Mb are useful as a point of care test for the diagnosis of acute myocardial infarction.

Aged↗
PubMed2002

Effectiveness of a novel serotonin blocker, sarpogrelate, for patients with angina pectoris.

BACKGROUND: We have recently demonstrated that a single oral administration of sarpogrelate, a 5-HT(2A) receptor antagonist, may improve exercise capacity in anginal patients with well-developed collaterals. The aim of the current study was to investigate the effectiveness of 2-week treatment with sarpogrelate on anginal symptoms and exercise capacity in anginal patients. METHODS: A treadmill exercise test was repeated after a 2-week period with or without sarpogrelate (100 mg 3 times a day) in 20 patients with angiographically proven stable angina. Anginal symptoms and daily physical activity by the specific activity scale (SAS) were also evaluated. RESULTS: Treatment with sarpogrelate significantly increased the SAS score and prolonged exercise time to the onset of 0.1-mV ST depression. When data were analyzed in a subgroup of patients (n = 8) with well-developed collaterals, the treatment with sarpogrelate decreased the number of anginal attacks (control vs sarpogrelate, 3.0 +/- 2.8 vs 0.9 +/- 1.1/2 weeks, P <.05), increased the SAS score (5.2 +/- 1.6 vs 6.2 +/- 1.3 METS, P <.05), and increased the time to the onset of 0.1-mV ST depression (235 +/- 84 vs 295 +/- 127 seconds, P <.05). In addition, the double product at the onset of 0.1-mV ST depression increased by 15% (P <.05) after sarpogrelate. In contrast, all parameters were not significantly changed after sarpogrelate treatment in patients (n = 12) without well-developed collaterals. CONCLUSIONS: These findings indicate the therapeutic effectiveness of sarpogrelate for anginal patients, especially for patients with well-developed collaterals.

Aged↗
PubMed2002

Anti-atherosclerotic effects of tamoxifen in cholesterol-fed ovariectomized rabbits.

It has been indicated that the anti-estrogen agent, tamoxifen, developed for the treatment of breast cancer, may act on the vascular system as an estrogen agonist. However, to our knowledge few reports suggest that tamoxifen exerts anti-atherogenic actions. In the present study, we evaluated the anti-atherosclerotic effects of tamoxifen in ovariectomized cholesterol-fed rabbits. Ovariectomized rabbits were fed a 1% cholesterol diet and divided into 4 groups: control group (C, n=5); estrogen treatment (E, n=6); low-dose tamoxifen treatment (0.5 mg/kg) (LT, n=6); and high-dose tamoxifen (1.0 mg/kg) (HT, n=7). After 6 weeks, both Oil red O-positive areas on the intimal surfaces of aortae and the ratios of intimal to medial areas (I/M ratios) measured from cross-sections of aortae were significantly lower in groups E, LT and HT compared with group C. Although there were no significant differences in serum NOx (NO2 and NO3) levels among the 4 groups, NOx levels were slightly higher in groups E, LT and HT than group C. Acetylcholine (ACh) was administered to all animals, and the responses of ear arteriole diameters were compared among the 4 groups. While ear arteriole diameters were significantly decreased in group C, no significant changes were observed in groups E, LT or HT following ACh administration. Ratios of ear arteriole diameters after to before ACh administration were significantly greater in groups E, LT and HT compared to group C. These findings suggest that tamoxifen exerts anti-atherosclerotic effects, and that these effects are attributed to the maintenance of vascular endothelial function.

Animals↗
PubMedDate not supplied

Acute pancreatitis and a long common channel.

BACKGROUND: As sphincter action does not functionally affect the union in pancreaticobiliary maljunction (PBM), two-way regurgitation occurs. We investigated the features of acute pancreatitis associated with patients displaying a long common channel. METHODS: We reviewed 3210 endoscopic retrograde cholangiopancreatograms. PBM was diagnosed in 107 patients with a long common channel in which communication between the pancreatic and bile duct was maintained even during sphincter contraction. High confluence of pancreaticobiliary ducts (HCPBD) was diagnosed in 60 patients with a common channel >or=6 mm long in which communication between the two ducts was occluded with sphincter contraction. RESULTS: Of patients with PBM, four had acute pancreatitis. Etiology of acute pancreatitis in the two patients was suspected to involve impaction in a long common channel. Of patients with HCPBD, 17 displayed acute pancreatitis. Three patients had a history of excessive alcohol intake and 10 patients were associated with choledocholithiasis or cholecystitis. The remaining four patients had no history of them. CONCLUSIONS: Acute pancreatitis occurs in 13% of patients with a long common channel. Obstruction of a long common channel by stones easily induces bile flow into the pancreas. Even if no obstruction is present, biliopancreatic reflux induces acute pancreatitis in some patients.

Acute Disease↗
PubMedDate not supplied

Cerivastatin-induced apoptosis of human aortic smooth muscle cells through partial inhibition of basal activation of extracellular signal-regulated kinases.

BACKGROUND: The beneficial effects of cerivastatin including hypolipidemic properties have been demonstrated to involve nonlipid as well as lipid mechanisms. In the present study, we examined the mechanisms underlying cerivastatin-induced growth inhibition of human aortic smooth muscle (ASM) cells. METHODS: Human ASM cells were cultured in 96-well plates with or without cerivastatin in the presence or absence of mitogen-activated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase MEK1/MEK 2 inhibitor PD98059. Cell growth was assessed by colorimetric quantitation of NADH, and cell viability was determined by trypan blue dye exclusion method. The induction of apoptosis was determined by propidium iodide (PI) staining method using flow cytometer. The activation of ERKs or c-Jun N-terminal kinases (JNKs) was determined by Western blotting using antibodies (Abs) specific for phospho-ERKs or phospho-JNKs. RESULTS: Treatment of the ASM cells with cerivastatin prevented cell growth in a concentration-dependent manner through at least induction of apoptosis. The cerivastatin-induced apoptosis was reversed by coincubation with isoprenoid [mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP)] suggesting a role for isoprenoid in the cerivastatin-induced apoptosis. The cerivastatin cooperated with a MEK1/MEK2 inhibitor PD98059 to induce apoptosis, which appeared to correlate with down-regulation of ERK activation (phospho-ERKs expression) induced by the combination. CONCLUSION: Cerivastatin-induced blockade of ERK activation in ASM cells might result in growth inhibition including apoptosis, which might explain some aspects of the beneficial effects of cerivastatin on coronary artery disease.

Aorta↗
PubMedDate not supplied

Extrapancreatic lesions in autoimmune pancreatitis.

GOALS: To examine extrapancreatic lesions associated with autoimmune pancreatitis. BACKGROUND: Autoimmune pancreatitis is a unique clinical entity proposed recently, and is reported to occasionally be associated with other autoimmune diseases. STUDY: Extrapancreatic lesions were examined clinically, radiologically, and histologically in 25 patients with autoimmune pancreatitis. RESULTS: Stenosis of the bile duct was observed in 22 patients (lower bile duct [n = 19], upper bile duct [n = 1], intrahepatic bile duct [n = 2]). Marked extrapancreatic bile duct wall thickening not associated with obvious cholangiographic abnormality was seen on ultrasound in 3 patients. Enlargement of the salivary glands and cervical lymph nodes was detected in 4 patients. Abdominal lymphadenopathy was observed in 5 of 8 patients at laparotomy. Retroperitoneal fibrosis was noted in 2 patients. Obliterative phlebitis of the pancreatic and peripancreatic veins was observed histologically in all 6 resected specimens. Marked stenosis of the portal vein and encasement of the peripancreatic arteries was observed in 4 and 8 of 14 patients who underwent abdominal angiography, respectively. Diabetes mellitus was diagnosed in 13 patients. All associated extrapancreatic lesions except diabetes mellitus improved after steroid therapy. CONCLUSIONS: Extrapancreatic lesions found to be occasionally associated with autoimmune pancreatitis were stenosis of the bile duct, enlargement of the salivary glands, abdominal or cervical lymphadenopathy, retroperitoneal fibrosis, stenosis of the peripancreatic arteries or portal vein, and diabetes mellitus. It is possible that these lesions are induced by the same inflammatory mechanisms as autoimmune pancreatitis.

Autoimmune Diseases↗
PubMedDate not supplied

Clinical significance of the accessory pancreatic duct.

BACKGROUND/AIMS: The accessory pancreatic duct is the smaller and less constant pancreatic duct in comparison with the main pancreatic duct. We investigated the patency of the accessory pancreatic duct and its role in pancreatic pathophysiology. METHODOLOGY: Dye-injection endoscopic retrograde pancreatography was performed in 411 patients. In patients in whom the main pancreatic duct could be selectively cannulated, contrast medium with indigo carmine was injected through the catheter. Excretion of the dye from the minor duodenal papilla was observed endoscopically. RESULTS: Patency of the accessory pancreatic duct was 43% of the 291 control cases. In the 46 patients with acute pancreatitis, 8 (17%) had a patent accessory pancreatic duct. The difference in patency between this group and the normal group was significant (p < 0.01). Especially, patency of the accessory pancreatic duct was only 8% of the 13 patients with acute biliary pancreatitis. In the patients with pancreaticobiliary maljunction, biliary carcinoma occurred in 72% of patients with a nonpatent accessory pancreatic duct, but in contrast, it occurred only in 30% of those with a patent accessory pancreatic duct. This difference was significant (p < 0.05). Lower amylase level in the bile of patients with pancreaticobiliary maljunction with a patent accessory pancreatic duct was frequently observed than those with a nonpatent accessory pancreatic duct. CONCLUSIONS: A patent accessory pancreatic duct may prevent acute pancreatitis by lowering the pressure in the main pancreatic duct. In cases of pancreaticobiliary maljunction with a patent accessory pancreatic duct, the incidence of carcinogenesis of the bile duct might be lower, as the reflux of the pancreatic juice to the bile duct might be reduced by the flow of the pancreatic juice into the duodenum through the accessory pancreatic duct.

Acute Disease↗
PubMedDate not supplied

Chronic pancreatitis progressing from segmental lesions.

BACKGROUND/AIMS: Chronic pancreatitis is histologically and functionally a progressive disease. To examine the natural history of chronic pancreatitis, we evaluated serial pancreatography in cases of chronic pancreatitis, focusing on the progression of diffuse-type chronic pancreatitis from the segmental type. METHODOLOGY: We reviewed 57 patients with chronic pancreatitis who had undergone endoscopic retrograde pancreatography on more than 2 occasions at intervals of at least 1 year. Cases of chronic pancreatitis were categorized as diffuse (n=37) and segmental (n=20) on the findings of initial endoscopic retrograde pancreatography. RESULTS: Twenty-three cases of diffuse-type chronic pancreatitis showed progression of pancreatic duct abnormalities. Segmental abnormalities of the main pancreatic duct at the body or tail of the pancreas spread to the head of the pancreas in 8 cases. Etiologies of these cases of chronic pancreatitis were alcoholic, in which patients continued drinking after initial endoscopic retrograde pancreatography. In 2 patients who underwent distal pancreatectomy, although segmental lesions showed typical histological findings of alcoholic chronic pancreatitis, appearances near the margin of these lesions were almost normal or indicated slight interlobular fibrosis. CONCLUSIONS: The pancreatic tail might represent the site of the initial lesion in some cases of alcoholic pancreatitis.

Adult↗
PubMedDate not supplied

Digestion and absorption of patients with autoimmune pancreatitis.

BACKGROUND/AIMS: In patients with autoimmune pancreatitis, radiological, serological and pancreatic functional abnormalities usually improve with steroid therapy. However, no studies have specifically focused on digestion and absorption in such patients. This study aims to investigate digestion and absorption, in addition to pancreatic endocrine and exocrine function, and their responses to steroid therapy in patients with autoimmune pancreatitis. METHODOLOGY: Ideal body weight index, levels of serum albumin, total cholesterol and glucose, or glycosylated hemoglobin values were investigated in 22 patients with autoimmune pancreatitis. N-benzoyl-L-tyrosyl-paraminobenzoic acid excretion test was performed in 9 patients. In 10 patients treated with steroids, these factors were examined again about 2 months after medication. RESULTS: Levels of serum albumin decreased, while ideal body weight index and levels of serum albumin and cholesterol significantly increased after steroid therapy. Eleven (50%) patients showed evidence of diabetes mellitus, but this improved in 6 of 8 patients treated with steroids. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 7 patients treated. CONCLUSIONS: Mild malnutrition as well as impaired pancreatic endocrine and exocrine function were frequently detected in patients with autoimmune pancreatitis. Steroid therapy was occasionally effective for these conditions.

Adult↗
PubMedDate not supplied

Biliary carcinoma risk in patients with pancreaticobiliary maljunction and the degree of extrahepatic bile duct dilatation.

BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) carries a high risk of biliary carcinoma. This study aimed to examine the biliary complications of patients with PBM in relation to the degree of extra-hepatic bile duct dilatation. METHODOLOGY: Ninety-eight cases of PBM could be divided into 5 groups according to the maximum diameter of the extrahepatic bile duct: < or = 10mm, 11-15mm, 16-20mm, 21-30mm, > or = 31mm. The clinicopathological findings of biliary carcinomas associated with PBM were compared with 232 cases of gallbladder carcinoma and 159 cases of bile duct carcinoma that were not associated with PBM. RESULTS: Gallbladder carcinoma occurred in 36 of 65 patients (55%) with PBM whose maximum diameter of the extrahepatic bile duct was < or = 30mm, but no gallbladder carcinoma occurred in patients with PBM whose diameter was > or = 31mm. Bile duct carcinoma occurred in 6 of 52 patients (12%) with PBM whose diameter was > or = 21mm, but no bile duct carcinoma occurred in patients with PBM whose diameter was < or = 20mm. The age at diagnosis of the patients with gallbladder or bile duct carcinoma associated with PBM was significantly younger than those without PBM (p<0.01). CONCLUSIONS: PBM with an extrahepatic bile duct diameter < or = 30mm is associated with a high risk of gallbladder carcinoma. PBM with an extrahepatic bile duct diameter > or = 21mm is associated with a high risk of bile duct carcinoma. Prophylactic cholecystectomy is recommended for patients with PBM without biliary dilatation.

Adolescent↗
PubMedDate not supplied

Comparison of radiological and histological findings in autoimmune pancreatitis.

BACKGROUND/AIMS: Autoimmune pancreatitis displays radiological findings that are sometimes difficult to differentiate from pancreatic carcinoma. To understand the essential radiological features of autoimmune pancreatitis (AIP), we compared imaging and histological findings in resected AIP specimens. METHODOLOGY: Findings of ultrasonography, computed tomography, endoscopic retrograde cholangiopancreatography and angiography were examined retrospectively for 6 patients who underwent pancreatoduodenectomy on suspicion of pancreatic carcinoma, and compared with histological findings of the resected specimens. RESULTS: Ultrasonography showed an enlarged hypoechoic pancreas with sausage-like appearance and no lobulation in the contour of the pancreas. On computed tomography imaging, delayed enhancement of the swollen pancreatic parenchyma became evident. Dense lymphoplasmacytic infiltration with fibrosis involving peripancreatic tissue was observed throughout almost the entire pancreas. Periductal non-occlusive fibrosis with lymphoplasmacytic infiltration induced narrowing of the pancreatic duct. Stenosis of the common bile duct is frequently associated with autoimmune pancreatitis and is induced by diffuse thickening of the duct wall by the same inflammatory process as that of the pancreas. The fibroinflammatory process also involves blood vessels. CONCLUSIONS: Characteristic radiological findings of autoimmune pancreatitis are induced with systemic histological changes of lymphoplasmacytic infiltration with fibrosis, and differ from schirrous invasion of pancreatic carcinoma.

Aged↗