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Biomedical subjects

A Harada

Publications and source records attributed to A Harada.

At least 163 records · Page 9Linked to original sources

Role of endogenous nitric oxide in ischemia-reperfusion injury in rat liver.

Evidence has accumulated that oxygen-derived free radicals contribute to the cellular damage induced by ischemia-reperfusion. It has been suggested that nitric oxide (NO) may act as a protective factor in ischemia-reperfusion injury since NO increases blood flow and may scavenge oxyradicals. Nevertheless, controversy exists as to the role of NO. This study was designed to clarify the role of endogenous NO in ischemia-reperfusion-induced liver injury in rats in vivo. Wistar rats weighing 250-300 g were divided into three groups: (1) untreated group (Control); (2) NG-nitro-L-arginine, a specific inhibitor of NO production (L-NNA); and (3) L-arginine-pretreated L-NNA group (AR+L-NNA). Occlusion of all vessels to the median and left hepatic lobes (60 min) was followed by reperfusion for 1 or 24 hr. L-NNA was administered before ischemia as a 10 mg/kg bolus. L-Arginine was given just before L-NNA administration as a 100 mg/kg bolus. Administration of L-NNA resulted in endothelial cell injury characterized by the elevation of serum hyaluronic acid as well as the reduction of hepatic tissue blood flow, and the recovery of hepatic adenosine triphosphate was depressed compared with the control after both 1 and 24 hr of reperfusion. Furthermore, the leakages of various liver enzymes and lipid peroxide were also increased, associated with histological damage. This effect of L-NNA was completely abolished by pretreatment with L-arginine. These results suggest that endogenous NO provides a protective effect against ischemia-reperfusion injury in rat liver.

Adenine Nucleotides↗

Molecular basis of inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1) polymorphism.

A genetic polymorphism of the inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1) was analyzed at the nucleic acid level. Three common alleles, ITIH1*1, ITIH1*2 and ITIH1*3, were characterized by mutations at codons 551 and 561 in exon 14. ITIH1*1 was characterized by GAG (Glu) at codon 551 and CAG (Gln) at codon 561, ITIH1*2, by GTG (Val) and CGG (Arg), and ITIH1*3, by GAG (Glu) and CGG (Arg).

Alpha-Globulins↗

Genetic polymorphism of the H1 subunit of inter-alpha-trypsin inhibitor.

Inter-alpha-trypsin inhibitor (ITI) consists of 3 subunits (H1, H2 and L) which are encoded by 3 distinct genes. We attempted to prepare the subunit-specific monoclonal antibodies to identify the subunit carrying ITI polymorphism. Three monoclonal antibodies which were specific against each of these 3 subunits (ITI H1, ITI H2 and ITI L) were selected. ITI types could be detected by anti ITI H1 antibody, but not by anti ITI H2 or anti ITI L antibodies. From the result, it was proved that ITI polymorphism originates from the ITI H1 gene products, therefore we propose to call this system ITI H1 polymorphism.

Alpha-Globulins↗

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↗

Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system.

Synapsin I is one of the major synaptic vesicle-associated proteins. Previous experiments implicated its crucial role in synaptogenesis and transmitter release. To better define the role of synapsin I in vivo, we used gene targeting to disrupt the murine synapsin I gene. Mutant mice lacking synapsin I appeared to develop normally and did not have gross anatomical abnormalities. However, when we examined the presynaptic structure of the hippocampal CA3 field in detail, we found that the sizes of mossy fiber giant terminals were significantly smaller, the number of synaptic vesicles became reduced, and the presynaptic structures altered, although the mossy fiber long-term potentiation remained intact. These results suggest significant contribution of synapsin I to the formation and maintenance of the presynaptic structure.

Animals↗

Prevention of endotoxin shock by an antibody against leukocyte integrin beta 2 through inhibiting production and action of TNF.

Septic shock remains a serious disorder associated with high mortality. Accumulating evidence indicates that TNF is a major and essential mediator of endotoxin shock. We report here that administration of an antibody against CD18 dramatically reduced endotoxin-induced shock in rabbits as revealed by prevention of severe hypotension, metabolic acidosis and a pathological change suggestive of disseminated intravascular coagulation with concomitant inhibition of elevation of plasma TNF activity. The anti-CD18 antibody also inhibited the hypotension induced by administering recombinant TNF. Furthermore, an antibody against a ligand for CD18 complexes, intercellular adhesion molecule-1, also prevented TNF-induced shock as well as endotoxin shock in rabbits. These observations suggest that adhesion of leukocytes to endothelium may be of primary importance in the action of TNF as well as in the production of TNF in vivo and that the antibody against adhesion molecules could be of therapeutic benefit in life-threatening septic shock in humans.

Acute-Phase Reaction↗

Intraportal endovascular ultrasonography in the diagnosis of portal vein invasion by pancreatobiliary carcinoma.

OBJECTIVE: The purpose of this study was to determine the value of intraportal endovascular ultrasonography (IPEUS) in the diagnosis of portal vein invasion by pancreatobiliary carcinoma. The authors reported their experiences with this new technique and compared it with conventional imaging technologies, such as portography and computed tomography (CT). SUMMARY BACKGROUND DATA: Pancreatobiliary carcinoma often invades the portal vein. Observation of the echogenic band of the portal vein wall by means of a high-frequency, high-resolution intravascular ultrasound catheter allows for the accurate diagnosis of the portal vein invasion. METHODS: A prospective study of 30 consecutive patients with pancreatobiliary carcinoma (16 pancreatic carcinomas, 8 bile duct carcinomas and 6 gallbladder carcinomas) was performed. In 23 cases IPEUS was performed intraoperatively from the superior mesenteric venous route with an 8 French, 20 MHz intravascular ultrasound catheter. In 7 cases IPEUS was performed before surgery from the percutaneous transhepatic route with a 6 French, 20 MHz intravascular ultrasound catheter. The finding of IPEUS was confirmed by pathologic examination of resected specimens and surgical exploration. The results of IPEUS were compared to those of portography and CT. RESULTS: Intraportal endovascular ultrasonography visualized the portal vein wall as an echogenic band with a thickness of 0.5 mm to 1.0 mm. The diagnostic criterion of portal vein invasion was destruction of this echogenic band. Portal vein invasion was found in 15 of 30 cases. Vascular invasion was confirmed by pathologic examination of resected specimens in 10 patients and operative findings in 5. The sensitivity, specificity, and overall accuracy of IPEUS for diagnosis of portal vein invasion was 100%, 93.3%, and 96.7%, respectively. The values were 80%, 67.7%, and 73.3% for portography and 53.3%, 80%, and 66.7%, respectively, for CT. CONCLUSIONS: Intraportal endovascular ultrasonography provided precise information about the relationship between the pancreatobiliary tumor and the portal vein wall. It was capable of accurately detecting or excluding early invasion of the portal vein wall by pancreatobiliary carcinoma.

Aged↗

Bacillus curdlanolyticus sp. nov. and Bacillus kobensis sp. nov., which hydrolyze resistant curdlan.

Taxonomic characteristics of seven bacterial strains which were isolated from soil and hydrolyze resistant curdlan were studied. These bacteria were aerobic, spore-forming rods, contained menaquinone 7 as a major quinone, contained anteiso-C15:0 and iso-C16:0 as major cellular fatty acids, had guanine-plus-cytosine contents of 50 to 52 mol%, and could be divided into two groups on the basis of physiological and chemotaxonomic characteristics and DNA-DNA hybridization data. We propose the following two new species: Bacillus curdlanolyticus for strains YK9, YK121, YK161, YK201, and YK203, with type strain YK9 (= IFO 15724); and Bacillus kobensis for strains YK205 and YK207, with type strain YK205 (= IFO 15729).

Aerobiosis↗

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↗

[A case of multiple sclerosis associated with lateralization of bone change].

We report a 63-year-old female, case of multiple sclerosis associated with lateralization of bone change. In 1969, at age 38 she lost sight in her right eye. After that, she had several episodes of remission and exacerbation. In 1992, left hemiparesis, sensory disturbance and vesicorectal disturbance appeared, and she was admitted to our hospital. Immediately, steroid pulse-therapy was initiated then steroids were tapered. Her muscle strength recovered to some degree. The left upper limb showed low skin temperature, edema and decreased circulation. In January and September of 1993, bone examinations were conducted using multiple scanning X-ray photodensitometry. Osteopenia was observed, especially in the left hand. The bone density in the right hand changed slightly during the 8-month course of the illness, but osteopenia in the left hand became more marked. The asymmetrical bone change suggested that osteopenia results from a disorder of the central nervous system, especially through autonomic disorder.

Bone Density↗

Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.

Acute Disease↗

Altered microtubule organization in small-calibre axons of mice lacking tau protein.

The tau gene encodes a protein (Tau) that is a major neuronal microtubule-associated protein localized mostly in axons. It has microtubule-binding and tubulin-polymerizing activity in vitro and is thought to make short crossbridges between axonal microtubules. Further, tau-transfected non-neuronal cells extend long axon-like processes in which microtubule bundles resembling those in axons are formed. In contrast, tau antisense oligonucleotides selectively suppress axonal elongation in cultured neurons. Thus tau is thought to be essential for neuronal cell morphogenesis, especially axonal elongation and maintenance. To test this hypothesis, we used gene targeting to produce mice lacking the tau gene. We show that the nervous system of tau-deficient mice appears to be normal immunohistologically. Furthermore, axonal elongation is not affected in cultured neurons. But in some small-calibre axons, microtubule stability is decreased and microtubule organization is significantly changed. We observed an increase in microtubule-associated protein 1A which may compensate for the functions of tau in large-calibre axons. Our results argue against the suggested role of tau in axonal elongation but confirm that it is crucial in the stabilization and organization of axonal microtubules in a certain type of axon.

Animals↗