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Biomedical subjects

A Nakao

Publications and source records attributed to A Nakao.

At least 19 recordsLinked to original sources

Anti-neutrophil antibody attenuates the severity of acute lung injury in rats with experimental acute pancreatitis.

OBJECTIVE: To examine the role of activated neutrophils in microvascular injury after severe acute pancreatitis. We used the polyclonal anti-rat neutrophil antibody (PoAb) to deplete peripheral neutrophil counts and the anti-rat monoclonal antibody (MoAb) CD18 to block neutrophil adherence functions. DESIGN: Prospective, controlled trial. SETTING: Laboratory. PARTICIPANTS: Anesthetized male Wistar breeder rats, in which necrotizing pancreatitis was induced by injecting necrotizing agents into the pancreatic duct. INTERVENTIONS: Treatment groups received an infusion of PoAb, 8 mL/kg, before induction of pancreatitis or MoAb CD18, 2 mg/kg, after induction of pancreatitis. Control animals received 2 mL of rabbit serum or 1 mL of saline solution. MAIN OUTCOME MEASURES: Survival rate, white blood cell count, levels of serum amylase and lipase, myeloperoxidase activity in the lung, lipid peroxide levels in the pancreas, and results of histological studies. RESULTS: The survival rate of rats treated either with PoAb before or MoAb CD18 after induction of sepsis improved significantly (P < .01). Histologically and according to the levels of neutrophil myeloperoxidase in their lungs, rats treated with the antibodies 24 hours after inducing pancreatitis improved significantly (P < .05). Moreover, the serum lipase concentrations and lipid peroxide levels in the pancreas of these rats decreased significantly (P < .05). CONCLUSIONS: Both the depletion of peripheral neutrophils by PoAb and blocking of neutrophil adherence functions by MoAb CD18 may help to prevent acute lung injury caused by severe acute pancreatitis in this model.

Acute Disease

Dopamine compensates for deterioration of hepatic hemodynamics and metabolism during occlusion and reperfusion of the hepatic artery.

OBJECTIVE: To investigate the effects of temporary hepatic arterial occlusion and dopamine on hepatic hemodynamics and metabolism. DESIGN: Experimental animal study in a dog model. The proper hepatic artery was occluded for 60 minutes; then, it was reperfused for 60 minutes. Hepatic hemodynamic and oxygen metabolic values, lactate uptake ratios, and blood glucose levels were determined repeatedly throughout the experiment. Data are given as mean +/- SE. INTERVENTION: In another group, dopamine hydrochloride, 10 micrograms/kg per minute, was infused intravenously throughout the experiment, and the same variables were recorded. RESULTS: Portal vein blood flow continuously decreased during occlusion, and it decreased even further after declamping of the hepatic artery; this led to a disturbance of oxygen and lactate metabolism in the control group. Dopamine increased the portal vein blood flow from 84.9% +/- 3.9% to 100.9% +/- 3.6% of the preocclusion levels after 60-minute occlusion and from 79.0% +/- 3.6% to 93.6% +/- 5.1% of the preocclusion levels after 60-minute reperfusion (P < .05, respectively). Dopamine also enhanced the hepatic oxygen uptake ratio from 112.8% +/- 12.0% to 150.7% +/- 11.6% of the preocclusion levels after 60-minute reperfusion (P < .05, respectively). These factors contributed to acceleration of the hepatic oxygen consumption and lactate uptake ratio in the group of dogs that were infused with dopamine. CONCLUSIONS: Temporary occlusion of the hepatic artery causes deterioration of hepatic hemodynamics and metabolism. Administration of dopamine is an effective way to support hepatic function during occlusion of the hepatic artery.

Analysis of Variance

Lymph node metastases in carcinoma of the head of the pancreas region.

Histopathological examination of lymph node metastatic involvement in 139 specimens obtained from patients who underwent pancreatoduodenectomy or total pancreatectomy combined with wide resection of lymph nodes was performed, to clarify the critical areas of lymph node dissection in patients with carcinoma of the head of the pancreas region. Perigastric lymph node involvement in patients with carcinoma of the head of the pancreas was 14 per cent, in those with carcinoma of the distal bile duct 0 per cent and in those with carcinoma of the papilla of Vater 4 per cent. Para-aortic lymph node involvement in patients with carcinoma of the head of the pancreas, the distal bile duct and the papilla of Vater was 26, 9 and 0 per cent, respectively. On the basis of these results, pylorus-preserving pancreatoduodenectomy is indicated in almost all patients with carcinoma of the distal bile duct and the papilla of Vater. In patients with carcinoma of the head of the pancreas, however, wide dissection of lymph nodes, including para-aortic lymph nodes, should be carried out because of the relatively high incidence of para-aortic lymph node involvement.

Carcinoma, Ductal, Breast

Intraoperative peritoneal washing cytology with the rapid immunoperoxidase method using microwave irradiation.

The rapid immunocytochemical staining of gastrointestinal cancer-associated antigens, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), for intraoperative peritoneal washing cytology of pancreatic or biliary carcinoma can be completed in only 25 minutes by using microwave irradiation to accelerate incubation of the primary antibody. Only 3-second irradiation at 500 W for fresh smears produced specific antigen staining of malignant cells similar to that obtained with longer incubation, and the sensitivity of intraoperative cytology was greater than by the conventional staining method. The rapid immunocytochemical staining method of peritoneal washings at laparotomy can provide sensitive information for determining more aggressive therapy for intraperitoneal spread of malignant cells before closing the abdominal wall.

Aged

Clinical significance of portal invasion by pancreatic head carcinoma.

BACKGROUND: The purpose of the present study was to clarify the indication of aggressive surgery for pancreatic head carcinoma. METHODS: Laparatomy was performed in 153 patients with carcinoma, 101 of whom underwent resection of the carcinoma. With histologic examination the degree of carcinoma invasion into the portal vein was classified into grades 0, I, or II according to the depth of invasion by the carcinoma. Macroscopic carcinoma invasion into portal vein was classified into types A, B, C, or D according to preoperative findings on the portal phase of superior mesenteric angiography or intraoperative portography. RESULTS: Macroscopic findings correlated with the histologic invasion grades. The 1-year survival rate was 39.6% in grade 0, 11.3% in grade I, and 5.5% in grade II cases. The survival rates of patients with type A (p < 0.01), B (p < 0.05), and C invasion (p < 0.01) were higher than those of patients who did not undergo resection; however, no significant difference in the survival rates between patients who did not undergo resection and patients with type D invasion was observed. CONCLUSIONS: For locally advanced carcinoma of the pancreatic head or entire pancreas, patients with type D invasion have no indication of aggressive surgery.

Adult

Role of intravascular ultrasonography in detecting intravascular tumor thrombi: a preliminary report.

BACKGROUND: We evaluated the role of intravascular ultrasonography in the diagnosis of intravascular tumor thrombi. METHODS: During the past 2 years intracaval endovascular ultrasonography was performed in 26 selected patients to diagnose inferior vena cava invasion. Results of positive intracaval endovascular ultrasonogram were correlated with the pathologic findings of resected specimens and autopsy and with other imaging technologies such as computed tomography and angiography. RESULTS: Six patients had positive studies of intracaval tumor thrombus. In all cases detailed horizontal images perpendicular to the inferior vena cava axis were studied. Five of the six patients underwent resection. Intravascular ultrasonography correctly predicted the extent of the tumor thrombus, the degree of tumor adherence to the vessel wall, and the intraluminal movement of the tumor thrombus. Floating thrombi were visualized as an intraluminal to-and-fro movement. Thrombus adhesion to the vessel wall appeared as an absence of space between the tumor and the wall, with no respiratory movement of the thrombus. CONCLUSIONS: Intravascular ultrasonography was useful for the accurate diagnosis of intravascular tumor thrombi and aided in formulating the operative strategy.

Adult

Detection of O2- generation and neutrophil accumulation in rat lungs after acute necrotizing pancreatitis.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) and PMN-derived superoxide anions (O2-) have been found to mediate acute respiratory distress syndrome (ARDS). But the evidence has been obtained only indirectly, (for example, by treatment with free radical scavengers or by measuring lipid peroxides). METHODS: We used chemiluminescence technique to measure O2- generation directly from the surface of rat lungs with necrotizing pancreatitis. Myeloperoxidase activity in the lung tissue was measured by a new chemiluminescence method to quantitate pulmonary neutrophil sequestration. RESULTS: Transient bursts of chemiluminescence that reflected O2- generation were observed at the lung surface 3 to 5 hours after necrotizing pancreatitis was induced. No O2- dependent chemiluminescence was detected at the lung surfaces of the neutropenic rat made by pretreatment with polyclonal antineutrophil antibody. Myeloperoxidase activity was significantly high (mean, 1690 cell numbers/mg wet tissue) in the necrotizing pancreatitis rat lung (p < 0.005). CONCLUSIONS: These data confirmed that activated neutrophils and neutrophil-derived superoxide anions were implicated in lung injury after acute severe pancreatitis.

Acute Disease

Detection of superoxide free radicals in rats with acute pancreatitis.

To study the importance of oxygen-derived free radicals in acute pancreatitis, an experimental study of in vivo detection of superoxide free radicals (O2-) was performed using rats. Using a new chemiluminescence probe (2-methyl-6-[p-methoxyphenyl]-3,7-dihydro-imidazol[1,2-1]pyrazin- 3-one; MCLA; a Cypridina luciferin analogue) and a highly sensitive photon counting system, O2- from the pancreatic surface of rats with experimental acute pancreatitis induced by 180 micrograms cerulein/kg was detected. The time course of MCLA-dependent luminescence suggested that O2- production began 2-3 h after cerulein injection and then decreased gradually. Superoxide free radical production in the pancreas of rats with cerulein-induced acute pancreatitis was confirmed using MCLA-dependent chemiluminescence. This new method allows direct observation of the behavior of oxygen-derived free radicals.

Acute Disease

Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two-stage polymerase chain reaction/restriction fragment length polymorphism analysis.

Hepatic metastasis and retroperitoneal recurrence generally are considered to be the two primary modes of recurrence in pancreatic cancer. The goal of this study was to determine if patients with pancreatic adenocarcinoma have hepatic and peritoneal micrometastasis at operation. Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutations. Liver tissue specimens were obtained from 30 patients (17 with pancreatic adenocarcinoma and 13 with other diseases) with a biopsy needle at operation. Peritoneal washings were obtained during operation from 20 patients with pancreatic adenocarcinoma. Two-stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K-ras oncogene mutation at codon 12. Thirteen of 17 pancreatic adenocarcinoma patients had K-ras gene mutations in the liver, whereas all 13 patients with other diseases did not. However, only two of 20 pancreatic adenocarcinoma patients revealed K-ras gene mutation in peritoneal lavage fluids. These results indicate the feasibility of detecting hepatic micrometastasis in patients with pancreatic adenocarcinoma, and imply that PCR/RFLP analysis may be of value in the diagnosis, treatment and follow-up of hepatic metastasis of pancreatic adenocarcinoma.

Adenocarcinoma

Heparin effects on superoxide production by neutrophils.

Heparin is widely used in the treatment of various diseases, but the mechanisms of its biologic actions remain largely obscure. Recently, oxygen radicals, which are produced in a variety of conditions and cause tissue damage, have been implicated in the pathophysiology of various diseases. To investigate the relationship between heparin and oxygen radical production by neutrophils, we compared the effects of standard heparin (heparin sodium), which has been widely used, and a recently developed low molecular weight heparin (LMWH) which has potent anti-Xa activity, on neutrophil oxygen radical production in vitro. Standard heparin increased neutrophil oxygen radical production slightly at the low concentrations used clinically but reduced it at high concentrations, so that the effect of heparin on neutrophil oxygen radical production was biphasic. The effects of LMWH on neutrophil oxygen radical production were slight at both low and high concentrations. In disseminated intravascular coagulation (DIC) locally activated neutrophils produce oxygen radicals and have toxic effects in vivo. Thus we concluded that LMWH should be indicated for the treatment of DIC.

Free Radicals

Immunohistochemical staining for endotoxin using horseshoe crab factor C in fecal peritonitis.

The object of the present study was to apply a new immunohistochemical staining method to the in vivo determination of endotoxin localization. The immunohistochemical staining method requires factor C (an initiation factor in the Limulus clotting system which is mediated by endotoxin) as a specific ligand of endotoxin, and a newly developed murine monoclonal antibody to factor C. The blood endotoxin level and endotoxin localization in the rat were determined before and at 6, 12 and 24 h after intraperitoneal injection of 0.25 g/kg of fresh rat feces. The greatest blood endotoxin level was achieved at 12 h after the injection, and uptake of endotoxin was evident in Kupffer cells in the liver at 24 h after the injection. There has been no report on determining endotoxin localization in cases of endotoxemia attributed to fecal peritonitis. This new immunohistochemical staining method for determining endotoxin localization will contribute to the histopathological diagnosis of endotoxemia in humans.

Animals

Expression of tumor necrosis factor receptors in human lung cancer cells and normal lung tissues.

The purpose of this study was to investigate the expression of tumor necrosis factor (TNF) receptors for the control of the biologic action of TNF-alpha in lung cancer cells and normal lung tissues. Lung cancer specimens and normal lung tissues were freshly obtained in pairs from 15 patients who underwent surgery for lung cancer. Thirteen lung cancer specimens expressed the 55 kDa TNF receptor messenger RNA (mRNA), whereas only six lung cancer specimens expressed the 75 kDa TNF receptor mRNA by Northern blot analysis. The 55 kDa and 75 kDa TNF receptors mRNA were detected in all and 11 normal lung tissues, respectively. All four lung carcinoma cell lines examined expressed the 55 kDa TNF receptor mRNA, but only RERF-LC-MS (MS) expressed both the 55 kDa and 75 kDa TNF receptors mRNA. Immunohistochemical examination revealed that lung cancer cells expressed the 55 kDa TNF receptor, but not the 75 kDa TNF receptor at the protein level. In normal lung tissues, the 55 kDa TNF receptor was detected in alveolar macrophages, bronchioles, and some small vessels. The 75 kDa TNF receptor was detected in alveolar macrophages. All four lung carcinoma cell lines examined exhibited the only 55 kDa TNF receptor. TNF-mediated tumor cell lysis was observed in all lung carcinoma cell lines that exhibited the 55 kDa TNF receptor except A549, which is a TNF-insensitive cell line. In surface binding assays, specific surface binding of TNF-alpha to TNF-insensitive cell line A549 was observed to be about half that of TNF-sensitive cell lines. We demonstrated the expression of two distinct TNF receptors in human lung cancer and normal lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Expression of cell adhesion molecules in the lungs of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory disorder restricted to the lungs. Leukocyte entry into the area of inflammation is regulated, at least partly, by endothelial expression of leukocyte-selective cell adhesion molecules (CAMs). To investigate the relevance of these CAMs to the accumulation of leukocytes in IPF, we examined the expression of E-selectin (endothelial leukocyte adhesion molecule-1; ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by immunohistochemistry in lung tissue from nine patients with IPF and five nonsmoking normal subjects. The results demonstrated that in normal lungs, ICAM-1 was weakly expressed on endothelial cells, but neither E-selectin nor VCAM-1 was detected. In the lungs of patients with IPF, E-selectin expression on endothelial cells was restricted to honeycombing regions. Endothelial expression of ICAM-1 was increased throughout the tissue, but VCAM-1 was not detected in IPF. The distribution of leukocytes in lungs with IPF consisted of mostly lymphocyte accumulation in the interstitium and neutrophil accumulation within the airspaces of honeycomb regions. These results suggest that E-selectin may play a role in the recruitment of neutrophils in regions of honeycombing and that ICAM-1 may play a role in lymphocyte recruitment into the interstitium in addition to contributing to neutrophil recruitment in regions of honeycombing in patients with IPF.

Aged

[Efficacy of treatment with frequent and low-dose epirubicin in two cases of pulmonary metastases after surgery of liver cancer].

Case 1 was a 55-year-old male with multiple pulmonary metastases after two operations to excise hepatocellular carcinoma. Treatment consisted of initial administration of 5'-DFUR (po), followed by frequent administration of low-dose epirubicin (20 mg/body once every 2 weeks iv). This resulted in disappearance of the pulmonary metastases and a striking decrease in the AFP level. Case 2 was a 68-year-old male with multiple pulmonary metastases after surgery for hepatocellular carcinoma. Treatment with 5-FU (iv; once a week) and epirubicin (20 mg/body once every 2 weeks iv) resulted in disappearance of the pulmonary metastases and a marked decrease in the AFP level. It was concluded that administration of epirubicin in frequent, low doses is a useful method for the treatment of pulmonary metastasis after surgery for liver cancer, and it can be safely performed even on an outpatient basis.

Aged

Detection and quantitation of EP3 prostaglandin E2 receptor mRNA along mouse nephron segments by RT-PCR.

mRNA of the EP3 prostaglandin E2 (PGE2) receptor was detected and quantitated in microdissected mouse nephron segments by a modified protocol of reverse transcription-polymerase chain reaction (RT-PCR). At the step of RT, a point mutation was introduced in cDNA, which made a new restriction site for the Mbo I enzyme. PCR was performed using a set of primers on the same exon, and genomic DNA was coamplified with cDNA by these primers. PCR products were treated with Mbo I, and signals from genomic DNA and mRNA were separately detected on gel electrophoresis. The relative amount of mRNA per cell was expressed as a ratio of amount of product from mRNA to that from genomic DNA. EP3 PGE2 receptor mRNA expression was abundant in thick ascending limb of Henle, present to a lesser extent in distal convoluted tubules and collecting ducts, and undetectable in glomeruli, proximal tubules, and descending thin limb. The results support the notion that PGE2 modulates water and solute transport through the EP3 receptor in specific structures of the kidney.

Animals

Clinical significance of abnormal prothrombin (DCP) in relation to postoperative survival and prognosis in patients with hepatocellular carcinoma.

OBJECTIVES: In this study we correlate plasma des-gamma-carboxy prothrombin (DCP) levels with prognosis in patients with hepatocellular carcinoma (HCC) in combination with serum alpha-fetoprotein levels (AFP). METHODS: Levels of DCP were measured in 165 patients with HCC by an enzyme immunoassay (EIA, E-1023) with an anti-DCP monoclonal antibody. RESULTS: There was no correlation between the plasma DCP levels and the serum AFP levels. The positive rate obtained from the combination assay was 72.1%. The survival rates of the patients with elevated levels of both DCP and AFP were significantly lower than those of the groups with normal DCP and AFP levels (p < 0.05). The disease-free survival rates of patients with elevated DCP and AFP levels were also significantly lower than those of patients with normal DCP and AFP levels (p < 0.05). The recurrence rate within a postoperative period of 2 yr was higher in the patients with elevated DCP and AFP levels than in those with normal levels. CONCLUSIONS: The determination of plasma DCP levels combined with AFP levels appears to be useful for the diagnosis and prognosis of HCC, and is useful also in postoperative monitoring for recurrence.

Antibodies, Monoclonal

Expression of the CD15 antigen in hepatocellular carcinoma.

Expression of the CD15 antigen, which is one of the adhesion molecules, was studied immunohistochemically to investigate the mechanism of intrahepatic metastasis in 56 hepatocellular carcinomas (HCC). Twenty-nine percent (16 of 56) of the HCC expressed CD15. No noncancerous hepatocytes expressed CD15. CD15-positive HCC had histologic intrahepatic metastasis more often than did CD15-negative HCC; the difference was statistically significant (P < 0.02). The survival rate of patients with CD15-negative HCC was better than that of patients with CD15-positive HCC, although the difference was not statistically significant. The authors speculate that there is a relationship between the expression of CD15 and intrahepatic metastasis in HCC.

Antigens, CD