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Biomedical subjects

K Asanuma

Publications and source records attributed to K Asanuma.

At least 19 recordsLinked to original sources

Diffusion of cytotoxic concentrations of nitric oxide generated luminally at the gastro-oesophageal junction of rats.

BACKGROUND: In humans, high concentrations of nitric oxide are generated luminally at the gastro-oesophageal junction through enterosalivary recirculation of dietary nitrate. AIM: To investigate whether luminal nitric oxide can diffuse into the adjacent digestive tissue and alter tissue integrity. METHODS: We designed an animal model using Wistar rats in which physiological concentrations of nitrite and acidified ascorbic acid were administered separately so that the two reactants first meet to form nitric oxide at the gastro-oesophageal junction. Luminal and tissue concentrations of nitric oxide were measured with an electrode and an electron paramagnetic resonance spectrometer, respectively. Concentrations of glutathione in the tissue were measured as a marker of nitrosative stress. RESULTS: High concentrations of luminal nitric oxide were generated locally at the gastro-oesophageal junction of nitrite administered rats, reproducing a phenomenon observed in humans. High levels of nitric oxide were also detected largely in the superficial epithelium of the gastro-oesophageal junction. The concentration of tissue glutathione at the gastro-oesophageal junction was significantly lower in nitrite administered rats compared with control rats, whereas that in the distal stomach was similar in the two rat groups. CONCLUSIONS: Using an animal model, this study demonstrated that nitric oxide generated in the lumen diffuses into the adjacent gastric tissue to a substantial degree, leading to localised consumption of glutathione in the tissue. Nitrosative stress induced by this mechanism may be involved in the high prevalence of inflammation and metaplasia, and subsequent development of neoplastic disease at this site.

Animals↗

CD16+CD57- natural killer cells in multifocal motor neuropathy.

We analyzed the CD16+CD57- lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57- NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57- NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.

Adult↗

Decreased striatal D2 receptor binding in non-manifesting carriers of the DYT1 dystonia mutation.

To determine whether reduced striatal D2 receptor binding reported in patients with idiopathic torsion dystonia is associated with the genotype, the authors used PET and [11C]-raclopride to assess non-manifesting carriers of the DYT1 mutation. D2 receptor binding was reduced by approximately 15% in caudate and putamen (p < 0.005). These results suggest that striatal D2 binding reductions are a trait feature of the DYT1 genotype.

Adult↗

Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions.

In humans, protein C inhibitor (PCI) is expressed in various tissues and present in many body fluids including plasma and seminal fluid. In rodents, PCI is expressed in reproductive organs only and is absent in plasma. In this study, we characterized the tissue expression and physiological role of PCI in novel human PCI gene transgenic (TG) mice. Northern blot and immunohistochemical analyses demonstrated that human PCI is expressed in liver hepatocytes, renal epithelial cells as well as heart, brain and reproductive organs of the TG mice. This PCI tissue distribution is similar to that found in humans. PCI in plasma of TG mice showed the same immunological and functional properties as human plasma PCI. Next, we evaluated the effect of PCI on coagulation, inflammation and tissue damage in lipopolysaccharide-treated TG mice. The results suggested that PCI efficiently inhibits not only the anticoagulant and anti-inflammatory activities of exogenously injected human activated protein C (APC) but also that of endogenously produced APC in mice with endotoxemia. These findings suggest that PCI exerts a procoagulant and proinflammatory effect by inhibiting APC. We believe our results also show how useful these TG mice may be for assessing the therapeutic effect of human APC in vivo and for evaluating the role of PCI in human physiological and pathological conditions.

Animals↗

A malignant peripheral nerve-sheath tumour responding to chemotherapy.

A malignant peripheral nerve-sheath tumour developed in the right S1 nerve root in a man aged 30 causing back pain and sciatica. CT and MRI revealed a destructive tumour of the sacrum invading the retroperitoneal space. The tumour was not resectable with an adequate margin. Chemotherapy, consisting of high-dose ifosfamide followed by a combination of vincristine, doxorubicin and cyclophosphamide, was given with success. Malignant peripheral nerve-sheath tumours are thought to respond weakly to chemotherapy, but the response in our patient was complete.

Adult↗

Modulation of the onset age in primary dystonia by APOE genotype.

APOE polymorphisms were studied in 200 unrelated patients with primary dystonia as well as 300 age-matched control subjects. Although no difference was found in APOE genotype between the patients with dystonia and the controls, APOE-epsilon4 carriers developed the disease on average approximately 10 years earlier than APOE-epsilon4 noncarriers (p = 0.0012). This suggests that APOE-epsilon4 genotype affects the clinical presentation of primary dystonia.

Adolescent↗

Morphological analysis of leucocyte transmigration in the pleural cavity.

The role that pleural mesothelial cells play in leucocyte transmigration into the pleural cavity was investigated in lipopolysaccharide-stimulated mice. Changes in mesothelial cell morphology and changes in expression of adhesion molecules on mesothelial cells and leucocytes were analysed by light microscopy, immunohistochemistry, transmission electron microscopy (TEM) and immuno-scanning electron microscopy (immuno-SEM). After stimulation, the mesothelial cells separated completely from one another before leucocyte penetration across the mesothelial layer occurred. These changes occurred primarily in the immediate vicinity of ribs, where a large number of leucocytes accumulated. Immuno-SEM showed that the expression of intercellular adhesion molecule-1 (ICAM-1) on the parietal pleural mesothelial cells was significantly up-regulated by lipopolysaccharide stimulation, and that of vascular cell adhesion molecule-1 (VCAM-1) was induced. Both were restricted to the microvilli of the mesothelial cells. By contrast, expression of intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), peripheral node addressin (PNAd) and fibronectin were not detected. Lymphocyte function associated antigen-1 (LFA-1), macrophage-1 molecule (Mac-1) and very late appearing antigen-4 (VLA-4), all ligands of ICAM-1 and VCAM-1, were present on the transmigrated neutrophils and macrophages. These findings demonstrate that the immediate vicinity of ribs is a source of leucocyte migration into the pleural space.

Animals↗

Chondroblastoma: a study of 11 cases.

AIM: Chondroblastoma is an infrequent and unique neoplasm that is histologically characterized by chondroblastoma cells, osteoclast-like giant cells and sometimes reactive osteoid. Although it is generally regarded as benign, it may recur and sporadically metastasize to the lung. Many important questions concerning the prognostic factors and adequate surgical treatment of chondroblastoma have not been fully answered and remain controversial. The purpose of this study was to determine clinicopathological features useful in prediction of the tumour behaviours. METHODS: Eleven chondroblastoma cases were reviwed clinicopathologically. According to Enneking's radiographic grading system, seven cases were classified as stage I, three cases as stage II and one case was classified as stage III. RESULTS: Nine cases had initially been treated with simple curettage, one had aggressive curettage applied as a primary surgery and one underwent amputation. Among the nine simple curettage cases, one recurred and was reoperated with aggressive curettage. Adjuvant treatment (alcohol and/or cement) was applied in the two aggressive curettage cases; none demonstrated further tumour recurrence. All lesions were curettaged, and one case recurred. The rate of proliferating-cell nuclear antigen expression was significantly higher in the recurrent case. CONCLUSION: The recurrent case seemed to have a high growth activity. Simple curettage was effective for local control during the initial treatment in most cases, but aggressive curettage and adjuvant treatment with alcohol and/or cement was useful for local control in recurrent chondroblastoma and chondroblastoma presenting with an aggressive behaviour.

Adolescent↗

Macroscopic extranodal invasion is a risk factor for tumor recurrence in papillary thyroid cancer.

Papillary thyroid cancer patients, upon whom curative operation was performed, were investigated to clarify whether or not macroscopic extranodal invasion is a risk factor for recurrence. They were divided into three groups: group A, patients whose primary tumor showed extrathyroidal invasion (n=31); group B, those whose metastatic lymph nodes showed extranodal invasion (n=6); group C, those who showed both extrathyroidal and extranodal invasion (n=9). Recurrence was significantly higher in groups B and C than in group A (P<0.05). It was concluded that macroscopic extranodal invasion to the adjacent structures was a risk factor for recurrence in patients with papillary thyroid cancer.

Adult↗

Three-dimensional morphological analysis of antigen-antibody reaction in hepatic sinusoids preserved in hypothermic UW solution.

ICAM-1 antigen-antibody reaction was visualized by three-dimensional immunoscanning electron microscopy of hepatic sinusoids in rat liver treated with hypothermic University of Wisconsin (UW) organ preservation solution. The results were compared with similar antigen-antibody reactions carried out with immunoliposomes injected in vivo. Morphologically, the hepatic sinusoids were preserved well during the hypothermic procedure. Endothelial cells had a large number of fenestrations, which partly aggregated and formed sieve plates. ICAM-1 expression was induced by injection of LPS and detected by monoclonal antibody in the UW solution followed by gold-labeled secondary antibody. ICAM-1 was restricted mostly to the unique areas of sieve plates with immature, small fenestrations. A similar distribution of ICAM-1 was present when detected by in vivo injection of immunoliposomes containing the monoclonal ICAM-1 antibody. The results showed that antigen-antibody reactions can take place in livers preserved in hypothermic UW solution. Further, the reaction is similar to that which could occur in vivo during transplantation. This suggests that it may be possible to block potentially harmful antigen-antibody reactions by addition of appropriate antibodies to hypothermic UW solution prior to transplantation.

Adenosine↗

The rate of tumour growth does not distinguish between malignant and benign thyroid nodules.

OBJECTIVE: To clarify whether or not the rate of tumour growth is a useful measure for distinguishing papillary thyroid cancer from benign nodules. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: Fourteen patients with 27 nodules (<20 mm) followed up for 20 months or more. INTERVENTIONS: High resolution ultrasonography (US). MAIN OUTCOME MEASURE: Growth rate. RESULTS: There were 15 papillary thyroid cancers and 12 benign nodules. The median tumour diameters at the first and the last US examination were 9.0 mm (range 6-19) and 9.0 mm (range 5-21) in papillary thyroid cancers followed up for 37 months (range 21-85), and 11.5 mm (range 4-19) and 11.5 mm (range 5-23) in benign nodules followed up for 38 months (range 20-84), respectively. CONCLUSION: The rate of growth of thyroid nodules as documented by ultrasound did not prove to be useful in distinguishing between malignancy and benign disease of small thyroid nodules (<20 mm).

Adult↗

Induction of micronuclei in mice exposed to static magnetic fields.

The aim of this experiment was to investigate whether static magnetic fields (SMFs) have cytogenetic effects in mouse bone marrow cells. The frequency of micronuclei was significantly increased by exposure of mice to 3.0 T for 48 and 72 h and 4.7 T for 24, 48 and 72 h. The increase in micronucleus frequency was dose dependent at all times. Micronucleus frequency at 4.7 T was higher than at 3.0 T. We consider that the increased numbers of micronuclei may be attributable to a stress reaction caused by SMFs or a direct clastogenic/spindle disturbance effect of SMFs.

Animals↗

An intron 4 gene polymorphism in endothelial cell nitric oxide synthase might modulate lipid metabolism in nondiabetic patients on hemodialysis.

We investigated the relationship between endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and lipid metabolism in patients with nondiabetic chronic renal failure on hemodialysis. Serum from 181 nondiabetic patients on hemodialysis were examined. A genomic DNA fragment was amplified by polymerase chain reaction (PCR) for determining the ecNOS genotype. The PCR products were designated as a and b alleles by electrophoresis. In hemodialysis patients, the frequency of the ecNOS4 for b/b, b/a and a/a genotype was 76.6, 22.8 and 0.6%, respectively. There was not significant difference in the levels of total cholesterol (TC), triglyceride (TG) and calculated low-density lipoprotein cholesterol (LDL-c) in sera between patients (aa and ba) with the a allele and patients (bb) without the a allele. On the other hand, the levels of serum high-density lipoprotein cholesterol (HDL-c) in patients with the a allele (51.9 +/- 3.33 mg/dl) were significantly higher than those in patients without the a allele (43.05 +/- 1.40 mg/dl) (p = 0.005). The frequency of patients with the a allele and low levels of serum HDL-c among patients with a long duration of dialysis (> or =10 years) was significantly lower than that in patients with short duration of dialysis (<10 years) (p = 0.05). It appears that an intron 4 gene polymorphism in ecNOS may modulate lipid metabolism in nondiabetic patients on hemodialysis and the a allele of ecNOS gene polymorphism may affect the prognosis of hemodialysis patients with low levels of serum HDL-c.

Alleles↗