Search PubMedSearch

Biomedical subjects

N Matsuura

Publications and source records attributed to N Matsuura.

At least 19 recordsLinked to original sources

Malignant schwannoma of the liver.

Malignant schwannoma is the most common soft tissue sarcoma in adults, but primary schwannoma of the liver is extremely rare. We report an autopsy case of malignant schwannoma of the liver in a 63-year-old man. The tumor involved almost the entire right lobe of the liver. Microscopically, it was composed of moderately pleomorphic spindle cells with hyperchromatic nuclei with mitotic figures. The spindle cells were stained positively with antibodies to both S-100 protein and vimentin. Necrosis was found in the primary tumor. Only four other cases of malignant schwannoma of the liver were found in a review of the literature. Pertinent features of these tumors are discussed.

Fatal Outcome

Down-regulation of Th2 cell-mediated murine peritoneal eosinophilia by antiallergic agents.

Local eosinophilia has been linked to the pathogenesis of the inflammatory aspect of allergic diseases. The present study found that co-injection of D10G4.1 (D10) cells, a murine Th2 clone, with conalbumin (CA) into the peritoneal cavity of AKR/J mice increased the number of peritoneal eosinophils. The accumulation of eosinophils reached a maximum level at 24 to 48 hr and was accompanied by a marked increase in the number of neutrophils and a minor increase in the number of mononuclear cells. D10-induced peritoneal eosinophilia was suppressed by administration of either anti-IL-4 and anti-IL-5 monoclonal antibodies in an additive manner or by cyclosporin A (CsA). Interestingly, suplatast tosilate (IPD-1151T), known to be antiallergic agent capable of suppressing IgE synthesis and chemical mediator release, but not disodium cromoglycate, selectively suppressed eosinophil accumulation. Taken together with the observation that CsA and IPD-1151T suppressed IL-4 and IL-5 production by CA-stimulated D10 cells in vitro, the present results strongly suggest that agents capable of down-regulating Th2 cell cytokine production may attenuate allergic inflammation by impairing the recruitment of eosinophils that is mediated by Th2 cells.

Animals

Interleukin-1 receptor antagonist modifies the changes in vital organs induced by acute necrotizing pancreatitis in a rat experimental model.

OBJECTIVE: Interleukin-1 (IL-1) is a mediator in some critical conditions such as septic shock and multiple organ failure. Acute pancreatitis is one of the noted causes of multiple organ failure but the mechanism by which local inflammation progresses to systemic disease is unknown. In this study, we used an IL-1 receptor antagonist (IL-1ra) to investigate whether multiple organ failure due to acute pancreatitis is mediated by IL-1, as in other causes such as severe infection, trauma, and major surgery. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory of a university medical school. SUBJECTS: Specific pathogen-free male Wistar rats weighing 200 to 250 g. INTERVENTIONS: Necrotizing pancreatitis was induced by retrograde injection of deoxycholate solution into the biliopancreatic duct. IL-1ra was injected intravenously at a dose of 10 mg/kg 15 mins before induction of acute pancreatitis and then infused continuously at a rate of 5 mg/kg/hr for the following 24 hrs. MEASUREMENTS AND MAIN RESULTS: Although treatment with recombinant human IL-1ra did not affect the degree of local pancreatic insult, it significantly reduced mortality, improved urine output as an indicator of the state of shock, and ameliorated the accumulation of neutrophils into the lung in a rat experimental pancreatitis model. CONCLUSIONS: We concluded that multiple organ failure in severe pancreatitis is mediated, at least in part, by IL-1 through the activation of neutrophils. Furthermore, we concluded that circulatory collapse may also be important in the mechanism of the lethal effect of pancreatitis.

Acute Disease

Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production.

IL-4 is shown to up-regulate its own receptor (IL-4R) on human lymphocytes, but the functional significance of up-regulated IL-4R is not clear regarding IgE production. This study investigated the possible role of IL-4-induced up-regulation of IL-4R on B cells in the induction of human IgE synthesis by means of antisense strategy. Among three antisense oligodeoxynucleotides designed against the downstream of translation initiation site of IL-4R cDNA, S-oligo 1, complementary to nucleotide 1-24, showed the strongest inhibition of the constitutive expression of IL-4R on Daudi cells. Addition of S-oligo 1 together with IL-4 also decreased the up-regulated but not constitutive levels of IL-4R on peripheral blood B cells without affecting the concomitant enhancement of CD23, CD40, HLA-DR and surface IgM expression, indicating that its effect is specific for IL-4R up-regulation. When S-oligo 1 was added to B cells costimulated with IL-4 and anti-CD40 MoAb, it induced a dose-dependent inhibition of IgE production. This inhibition was accompanied by a decrease in the expression of mature C epsilon transcripts, whereas the accumulation of germ-line C epsilon transcripts was not affected by S-oligo 1. These data suggest that the signal transduction mediated by the up-regulated IL-4R on B cells may be intimately associated with the induction of isotype switching to IgE that leads to mature C epsilon transcription and IgE production.

Antigens, CD

Interleukin 10 reduces mortality from severe peritonitis in mice.

Interleukin 10 (IL-10) is known to suppress the induction of proinflammatory cytokines such as tumor necrosis factor (TNF) and IL-1 and is itself induced by monocytes and macrophages during sepsis. We studied the therapeutic efficacy of IL-10 by testing its effect on the survival rate in the murine cecal ligation-and-puncture (CLP) model. Administration of 1 microgram or more of recombinant murine IL-10 6 h after induction of sepsis decreased lethality in septic mice significantly and also suppressed the elevation of circulating TNF after sepsis. However, treatment with the same dose of IL-10 simultaneously or 6 h before induction of CLP had no effect on survival, and treatment with anti-TNF antibody after induction of CLP had no effect on the survival rate. These data suggest that cytokine modulation with IL-10 is a potential candidate for the treatment of sepsis and sepsis-related multiple organ failure.

Animals

Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischemic brain areas after focal ischemia in rats.

BACKGROUND AND PURPOSE: We have indicated that neutrophils play an important role in cerebral ischemia-reperfusion injury. Neutrophils are also known to adhere to the endothelial wall through adhesion molecules and to infiltrate into the tissue, and this neutrophilic invasion correlates with the concentration gradient of chemotactic factors. The aim of the present study was to evaluate the role of cytokine-induced neutrophil chemoattractant (CINC) on brain damage in rats from transient ischemia. METHODS: The brain water content was measured to evaluate postischemic brain injury in rats with 60 minutes of middle cerebral artery occlusion with perfusion. An enzyme-linked immunosorbent assay was used to evaluate the blood and brain concentrations of CINC, and enzymatic and histological techniques were used to measure the neutrophilic infiltration into the brain. RESULTS: The increase of water content was first observed at 6 hours after reperfusion, after which this increase was gradual, with brain edema peaking from 24 to 48 hours after reperfusion. Neutrophilic infiltration into the parenchyma and myeloperoxidase activity were first noted 12 hours after reperfusion, after which a marked increase occurred from 24 to 48 hours after reperfusion. In the ischemic brain areas, CINC was first detected at 3 hours after reperfusion. The CINC level peaked at 12 hours after reperfusion (9.15 +/- 0.45 ng/g wet wt, n = 5 and then gradually reduced from 24 to 48 hours after reperfusion (5.35 +/- 0.95 ng/g wet wt, n = 5, and 1.25 +/- 0.10 ng/g wet wt, n = 5, respectively). Interestingly, the serum CINC concentration was transiently elevated from 3 to 6 hours after reperfusion. No CINC production was detected in the brain of rats subjected to 60 minutes of ischemia without reperfusion. CONCLUSIONS: A marked increase in CINC concentration was detected in brain and serum during early reperfusion. This suggests that the time course of CINC production precedes brain edema formation and neutrophilic infiltration. It thus appears that CINC may play an important role in neutrophilic infiltration in ischemic lesion and in brain edema formation after ischemia-reperfusion injury.

Animals

Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats.

BACKGROUND AND PURPOSE: It has been suggested that interleukin-1 (IL-1) is a potent inflammatory mediator and that it is synthesized and secreted into the brain parenchyma. The aim of the present study is to evaluate the contribution of IL-1 to brain edema formation after focal brain ischemia. METHODS: The brain water content was measured to evaluate postischemic brain injury in rats after 60 minutes of middle cerebral artery occlusion and reperfusion. The effects of exogenous application of recombinant human interleukin-1 beta (rhIL-1 beta), anti-interleukin-1 beta neutralizing antibodies (anti-IL-1 beta), and the IL-1 blocker zinc protoporphyrin (ZnPP) on brain water content were observed, and histological technique was used to measure the infarction size and number of inflammatory cells infiltrated into the brain. RESULTS: Transient ischemia induced marked increase of brain water content, necrosis, and neutrophilic infiltration in the cortex perfused by the middle cerebral artery and the dorsal and ventral areas of the caudate putamen. Injection of rhIL-1 beta into the left lateral ventricle immediately after reperfusion markedly enhanced ischemic brain edema formation in these three areas in a dose-dependent manner (88.4 +/- 0.7% and 86.6 +/- 0.4% in the dorsal and ventral parts of the caudate putamen, respectively, in rats treated with 10 ng rhIL-1 beta; P < .01). rhIL-1 beta also increased the size of the brain infarction, and it tended to increase the number of infiltrating neutrophils in ischemic areas and the number of neutrophils adherent to the endothelium. In contrast, administration of anti-IL-1 beta and ZnPP into the left cerebral ventricle attenuated the postischemic increase of brain water content and decreased the size of brain infarction (83.5 +/- 2.0% and 79.9 +/- 2.0% in the dorsal and ventral parts of the caudate putamen, respectively, in rats treated with 10 micrograms anti-IL-1 beta; P < .01). The number of neutrophils that infiltrated into ischemic areas also tended to decrease with anti-IL-1 beta or ZnPP treatment. CONCLUSIONS: Application of rhIL-1 beta augmented the increase of brain water content, and application of anti-IL-1 beta depressed the increase of water content. These results tended to correlate with the neutrophilic infiltration into the parenchyma. It thus appears that IL-1 beta may play an important role in ischemic brain damage after reperfusion.

Animals

Intraorbital malignant lymphoma presenting with tumor stain on angiography--case report.

A 58-year-old male presented with a 1 month history of left retro-orbital pain and diplopia. Computed tomography demonstrated an isodense intraorbital tumor with slight homogeneous enhancement. Magnetic resonance imaging showed the tumor was isointensity on T1-weighted imaging, slightly high intensity on T2-weighted imaging, and slightly enhanced by gadolinium-diethylenetriaminepenta-acetic acid. Left external carotid angiography showed a tumor stain fed from the branches of the left internal maxillary artery. The tumor was partially removed. The histological diagnosis was malignant lymphoma. Tumor staining is rare in intraorbital malignant lymphoma and is not adequate for differential diagnosis of intraorbital tumors, so biopsy is essential.

Carotid Artery, External

Changes in serum granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) after surgical intervention.

To evaluate the physiological role of G-CSF following surgery, we measured the serum levels of immunoreactive IL-6 and G-CSF sequentially in nine patients after major elective thoracoabdominal surgery for esophageal carcinoma. Both G-CSF and IL-6 levels reached their maxima at the first postoperative day and decreased thereafter. There was a significant correlation between serum G-CSF (y) and IL-6 (x) levels (y = 3.273x + 3.991; r = 0.787, n = 78, p < 0.001). In the case that developed aspiration pneumonia and ARDS at the second postoperative day, the measured G-CSF level was less than half the predicted value. The relationship between serum G-CSF and IL-6 levels supports the central role of G-CSF as the host defense response modifier and, thus, low G-CSF levels in the circulation is one reason for the immunodeficient state after major surgery.

Aged

Different migration patterns of antigen-presenting cells correlate with Th1/Th2-type responses in mice.

Antibodies are produced when antigen-presenting cells (APC) pulsed with an antigen are injected intravenously (i.v.) into BALB/c mice, but subcutaneous (s.c.) injection of such APC causes delayed-type hypersensitivity (DTH). To identify the anatomic sites where T and B cells are activated, we labelled splenic dendritic cells (DC) with a fluorochrome, PKH 26, injected them i.v. or s.c., and used the label to locate them. When the DC were injected i.v., germinal centres in the spleen were hyperplastic on day 1. Most DC moved to T-dependent areas of the white and red pulp on day 1 and remained there at least until day 5, but no DC migrated into the lymph nodes. When the DC were injected s.c., they were in the sinus on day 1 and had entered T-dependent area of draining lymph nodes only by day 3; hyperplasia of germinal centres in the spleen and migration of DC into the spleen were not found. We used the polymerase chain reaction (PCR) to study which mice had spleen cells and lymph node cells that produced the cytokines interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma). In the sensitization phase, day 1 after DC injection i.v., almost all IL-10 transcript was found in spleen cells, but after DC injection s.c., IL-2 message was most abundant in lymph node cells. The expression of mRNA for IL-4 and IFN-gamma in mice that received DC i.v. was not different from that in mice that received DC s.c. in this phase. Immunohistochemical staining showed that cells stained for IL-10 were in the T-dependent area of the spleen from mice that received DC i.v. 1 day after the injection. Three days after the injection of DC i.v., cells stained for IL-10 were in the germinal centres as well. The number of such cells in the spleen of mice that received DC i.v. was significantly more than that in mice that received DC s.c. IL-10 may be important in development of TH2 response.

Animals

[Subclassification, molecular structure, function and ligand in integrin superfamily].

Integrins are the major family of cell surface receptors that mediate adhesion to the extracellular matrix and sometimes cell-cell adhesive interactions. These integrin-mediated adhesive interactions are involved in the regulation of many cellular functions, including embryonic development, tumor cell growth and metastasis, programmed cell death, hemostasis, inflammation, immune reaction, bone reabsorption, etc. Integrins are composed of alpha and beta transmembrane subunits selected from among 16 alpha and 8 beta subunits that heterodimerize to produce more than 20 different receptors which bind specific ligands. Ligand binding sites have been clarified by chimera integrin protein in some integrins. Integrins link to intracellular cytoskeletal complexes and bundles of actin filaments. There have been many reports about intracellular signaling pathways activated by integrin-ligand interactions.

Humans

[Analysis of the mechanism of tumor metastasis by the transfection of integrin cDNA].

Integrin plays an important role in tumor metastasis through its interaction with extracellular matrix and endothelial cell. We have examined the role of each integrin in tumor metastasis by using transfection of integrin cDNA into various cells. Transfection of integrin alpha 2 subunit into RD cells, human rhabdomyosarcoma cells which do not express integrin alpha 2 beta 1, potentiated the frequency of metastases in various organs; lung, bone, adrenal gland, lymph node. alpha 4-transfectant of Chinese hamster ovary (CHO) cells, which do not have alpha 4 beta 1 on the cell surface, metastasized to bone through its interaction with VCAM-1 in the bone marrow stroma cells. On the other hand, alpha 5-transfectant of CHO cells was much less tumorgenic than parent CHO cells. These data suggest integrin influence tumor metastasis sometimes favorably and sometimes unfavorably according to the activity and the balance of various integrins.

Animals

[Studies concerning the pathogenesis of trigeminal neuralgia caused by cerebellopontine angle tumors].

It has been well recognized that neurovascular compression can elicit trigeminal neuralgia (TN) and microvascular decompression surgery has become popular as a radical treatment of this clinical symptom. Cerebellopontine (C-P) angle tumors, however, as well known, can also cause TN. Four hundred fifty six patients with TN underwent posterior fossa exploration between 1984 and 1992 in our clinic, and among them, 45 (9.9%) patients harbored C-P angle tumors which were causative of TN. They included 22 epidermoids, 18 meningiomas and 5 neurinomas. The patient population consisted of 35 women and 10 men, ranging in age from 28 to 73 years, with a mean age of 51.7 years. The mean age of the patients of TN with tumors is considerably lower than that of neurovascular compression patients (61.0 years), particularly in cases of neurinomas (44.4 years) and epidermoids (48.0 years) (p < 0.01). Such difference in ages at the onset of symptom may be explained by the fact that the tumor growth in the C-P angle develops earlier than changes of the vasculature of the vertebrobasilar artery system by aging. Anatomical relationships between the 5th cranial nerve and offending arteries or tumors verified at surgery are as follows; Type A: The nerve is totally encased by the tumor. Type B: The axis of the nerve is distorted by the tumor. Type C: The nerve is shifted by the tumor and is compressed by the artery contralaterally. Type D: The nerve is compressed by the artery which was displaced by the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Monozygotic twins of different apparent sex.

We report on twins of unlike sex who shared a 45,X/46,X,+mar karyotype. The mar chromosome was found to be Yq- by DNA analysis. Marker studies, including 8 VNTR loci, yielded a probability of monozygosity of 0.99999996.

Adolescent

Effect of granulocyte-macrophage colony-stimulating factor on sepsis-induced organ injury in rats.

The administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with severe active infections has been questioned because activation of neutrophils may cause tissue injury. To identify the effect of GM-CSF administration on severe sepsis, we examined the survival rate and pathologic changes in vital organs using the rat lethal sepsis model. Rats received 20 micrograms of recombinant murine GM-CSF (rmGM-CSF) 3 hours after the onset of peritonitis induced by cecal ligation and puncture. After 48 hours, the survival rate did not improve, and earlier deaths than in the control group were observed. In addition, the inhibition of early leuko-sequestration in the peritoneal cavity was seen in animals treated with GM-CSF. These results suggested that the administration of rmGM-CSF after the onset of sepsis was not beneficial; thus, we concluded that care should be taken in the clinical use of GM-CSF in severe infection.

Animals

Overexpression of pancreatic secretory trypsin inhibitor in pancreatic cancer. Evaluation of its biological function as a growth factor.

Four clones of pancreatic secretory trypsin inhibitor (PSTI)-overexpressing cells (TF-PANC clones 1, 6, 8, and 36) were established to evaluate the physiological function of PSTI secreted by cancer cells, by means of introducing a PSTI-expression vector (pRSV-PSTI) into the human pancreatic adenocarcinoma cell line (PANC-1). No obvious changes were observed in the histological features of these transplanted tumors in nude mice, in the growth of TF-PANC and PANC-1, or that of 3T3 fibroblasts when cocultured with them. Addition of recombinant human PSTI to the cultured media resulted in no increase in proliferation of fibroblasts (3T3 and WI-38) or of four pancreatic cancer cell lines (PANC-1, CAPAN-I, MIAPaCa-2, and Hs766T). These results suggest that the estimation of tumor-bearing PSTI as a paracrine or autocrine growth factor in recent studies should be given careful consideration.

3T3 Cells

Development of proliferative retinopathy in Japanese patients with IDDM: Tokyo Women's Medical College Epidemiologic Study.

We studied the development of proliferative diabetic retinopathy (PDR) in Japanese insulin-dependent diabetes mellitus (IDDM). Subjects were 373 patients who were diagnosed as IDDM between 1951 and 1984, before the age of 30 years, and had no PDR at the first visit to the Diabetes Center. Development of PDR was analyzed by Kaplan-Meier's life-table method in relation to the duration of IDDM. The cumulative incidence of PDR was 20% at 15 years of duration of IDDM, 40% at 19 years, and 70% at 29 years. Female patients (n = 233) developed PDR significantly faster than males (n = 140) (P < 0.002). In both sexes, patients with onset of IDDM at 0-8 years showed significantly slower development than patients with the onset at 9-17 (P < 0.0001) and 18-29 years (P < 0.001). Impact of femaleness on the development was the greatest in patients with age at onset of IDDM at 9-17 years (P < 0.005). Analysis according to the calendar year at onset of IDDM and diabetes duration at the first visit to the Diabetes Center did not show any significant influence on the development of PDR. In conclusion, sex and age at onset of IDDM may be associated with increased risk for the development of PDR in relation to the duration of diabetes in Japanese IDDM.

Adolescent