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Biomedical subjects

R Saito

Publications and source records attributed to R Saito.

At least 181 records · Page 10Linked to original sources

Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction.

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN-gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL-3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.

Aged↗

Studies on the synthesis of nucleotidyl-peptides. II. The preparation of a nucleotidyl-peptide having a 5'-nucleotidyl-(P-O)-serine phosphodiester bond.

The preparation of a nucleotidyl-peptide having a thymidine-5'-yl-(P-O)-serine phosphodiester bond, [H-Ala-Ser(pTpT)-Phe-OH](24) is described. After condensation between the phosphorylated peptide component and an oligonucleotide component, all protecting groups could be removed under neutral conditions without beta-elimination of the pTpT from the serine moiety.

Nucleotides↗

Central administration of senktide, a tachykinin NK-3 agonist, has an antidiuretic action by stimulating AVP release in water-loaded rats.

Intracerebroventricular (i.c.v.) injections of senktide (0.01-10 nmol), a tachykinin NK-3 agonist, had an antidiuretic action in water-loaded rats (4.5% body wt.). Pretreatment with OPC-31260 (1 mg/kg, i.v.), a non-peptide vasopressin V2 antagonist, inhibited the antidiuretic action induced by exogenous arginine vasopressin (AVP, 0.1 micrograms/kg, i.v.) and senktide (0.1 nmol, i.c.v.). In addition, senktide (11.8 nmol, i.c.v.) caused a marked increase of the plasma AVP level in conscious rats. These results suggest that the central NKB analogue senktide has an antidiuretic effect by stimulating AVP secretion from the pituitary gland through the NK-3 receptor in the hypothalamus.

Animals↗

Propentofylline (HWA285) inhibits the release of dopamine during transient ischemia and modulates its metabolism in rat striatum.

Propentofylline (HWA285) has been reported to protect neuronal cells through the inhibition of glutamate release during transient ischemia. We studied whether HWA285 inhibits dopamine (DA) release, and how HWA285 modulates DA metabolism in the rat model. HWA285 was perfused through a microdialysis probe placed in the rat striatum during 20 min transient ischemia. In rats perfused by HWA285, ischemic DA release was significantly inhibited, and DA metabolism showed better recovery in contrast with unperfused rats.

3,4-Dihydroxyphenylacetic Acid↗

Receptor-mediated specific biological activity of a beta-amyloid protein fragment for NK-1 substance P receptors.

A beta-amyloid protein fragment AP21-35 (tetradeapeptide with amino acid residues 21-35) was found to be a highly selective agonist of substance P receptors (NK-1) among three tachykinin receptor subtypes. This peptide fragment contracted the smooth muscle preparations of guinea pig ileum in a dose dependent manner (EC50 = 22 microM). This activity was completely reversed by CP-96,345-1, a specific antagonist of NK-1 receptors, whereas atropine for NK-3 had no effect. The peptide was inactive in rat vas deferens which contains predominantly NK-2 receptors. These results indicated that AP21-35 is a highly selective agonist for NK-1 receptors. In the radio-ligand receptor binding assay using [125I]-Bolton-Hunter substance P to membranes from guinea pig ileum, the fragment exhibited a distinct dose-response curve (IC50 = 11 microM). All the present data strongly suggest that beta-amyloid protein function as a peptide ligand of substance P receptors with some pathophysiologic activities.

Amino Acid Sequence↗

Immunocytologic analysis of cells obtained from bronchoalveolar lavage in a model of rat lung allograft rejection.

Left lung transplantation (n = 30) between BN rat (RT1n) and LEW rat (RT1(1)) was performed to examine serial changes in the inflammatory cell profile and T-cell subsets occurring in bronchoalveolar lavage (BAL) obtained after transplantation. Transplanted animals were sacrificed on Days 1 to 7 post-transplantation. Previous studies show that lung allografts between these rat strains were strongly rejected within 7 days. The serial change in the cell profile of BAL showed a marked initial predominance of polymorphonuclear leukocytes, a decrease in macrophages, and a temporary increase in number of eosinophils on Day 2 post-transplantation. A gradual increase in lymphocytes coincident with progression of rejection was also noted. Immunocytologic studies using monoclonal antibodies specific for rat T-cell subsets and interleukin-2 receptor (IL-2R) showed significant increase in pan-T-cells on Days 3, 4, and 5 and T-suppressor/cytotoxic (CD8 positive) fraction on Days 4 and 5, whereas the T-helper (CD4 positive) fraction peaked on Day 2. The frequency of T-cells expressing IL-2R (55 kDa), indicating activated T-cells, significantly increased as early as Day 2 and maintained its high value thereafter. mRNA levels for IL-2R were detectable in the allografts on Day 2 and peaked on Day 5 post-transplantation. The value of CD4/CD8 T-cell ratios rose initially and then dropped below 1.0 on Days 4 and 5. These values differed markedly from those of syngeneic transplants (Lew-->Lew) examined on Day 5 post-transplantation. First, no significant changes in BAL cytology were seen when syngeneic transplants were compared with normal (Lew) lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of magnetic resonance imaging in the diagnosis of Takayasu's arteritis during pregnancy: a case report.

We report a case of Takayasu's arteritis in a 29-year-old primigravid woman. The diagnosis of Takayasu's arteritis is usually made on the basis of clinical findings, with definitive diagnosis being made by angiography. To avoid the large amount of radiation needed for angiography, we used magnetic resonance imaging to establish a presumptive diagnosis. The diagnosis was confirmed two weeks postpartum by angiography.

Adult↗

The participation of tumor necrosis factor in the pathogenesis of lung allograft rejection in the rat.

Tumor necrosis factor alpha and beta are polypeptide cytokines with a wide range of metabolic, immunologic, and inflammatory activities. TNF is known to participate in immune mediated injury of native lungs, but a role for TNF in mediating lung allograft rejection (AR) has not been established. In experiments reported here, we assessed the role of TNF in mediating lung AR in a rat model of lung transplantation (BN-->Lew) (RT1n-->RT1l). This model shows florid AR with all grafts completely destroyed by day 6 posttransplant. Graft pathology is characterized by massive lymphocytic infiltrates and hemorrhagic necrosis. Initially, 5 lung allograft recipients in each group were sacrificed on days 1 to 6 posttransplant. Allografts were removed, mRNA isolated, and Northern blotting or RT-PCR performed with blots probed with cDNAs or oligos specific for rat TNF-alpha cyclophylin and gamma-actin. Data were compared with syngeneic transplants (Lew-->Lew) and with normal controls. In addition, frozen lung allograft tissue was examined by indirect immunofluorescence, using antibodies specific for TNF. TNF-alpha mRNA levels were detectable on day 2 posttransplant, and peaked on days 6-7 posttransplant. IF studies showed TNF protein expression in mononuclear cells of rejecting allografts on day 3, peaking on day 6. Both TNF-alpha mRNA and protein levels correlated with maximal AR and hemorrhagic necrosis of grafts. Minimal TNF-alpha mRNA or protein was detected in syngeneic grafts or in contralateral native lungs. We then examined the ability of a rabbit polyclonal anti-TNF-alpha (7000 U/day) and anti-TNF-beta (5000 U/day) with 30% crossreactivity with rat TNF to modify the AR response. For each group, 4-5 left lung transplants were performed as described, and animals treated with anti-TNF-alpha, anti-TNF-beta, (anti-TNF-alpha+anti-TNF-beta) or with preimmune rabbit sera. All animals were sacrificed on day 6 posttransplant. Several pathological categories of inflammation were examined and scored (0-4), with a score of 0 = 0% involvement; 1 = 1-25% involvement; 2 = 26-50% involvement; 3 = 51-75% involvement; and 4 = 76-100% involvement. The mean and SD scores were obtained for all animals in the treatment categories mentioned above, and compared with preimmune-treated controls. Briefly, no differences in perivascular, peribronchial, or peribronchiolar cell infiltrates or edema were seen in treatment groups compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Child traffic accident injuries in Japan.

This study analyzes the characteristics of traffic accidents involving children. It discusses why children with certain attributes and in specific situations are exposed to a higher traffic accident risk, in light of their ability to deal with traffic and their body characteristics. Finally, based on these results, it offers some conclusions and recommendations on ways of improving child safety in road traffic.

Accident Prevention↗

Cytotoxicity of platinum(IV) and platinum(II) complexes containing 1R,2R-cyclohexanediamine as a ligand.

Several Pt(IV) and Pt(II) complexes containing 1R,2R-cyclohexanediamine (1R,2R-dach) as a carrier ligand were synthesized. The cytotoxicities and the uptake of the platinum complexes by leukemia L1210 cells were compared in order to study the correlation between their structures and cytotoxicities. [Pt(II)Cl2(1R,2R-dach)], [(Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)], which have excellent anticancer properties, exhibited very high cytotoxicities and were easily taken up by leukemia L1210 cells. [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)] also had high cytotoxicities. After a short incubation time, the uptake of [Pt(II)Cl2(1R,2R-dach)], [Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)] by leukemia L1210 cells were respectively very similar to those of [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)]. In addition, trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] (Y2: oxalato or malonato) did not exhibit cytotoxicity towards leukemia L1210 cells, whereas trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)] (Y2: oxalato or malonato) were highly cytotoxic. The accumulation of trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] in leukemia L1210 cells was much lower than that of trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)]. Platinum(IV) complexes, in which leaving groups are replaced by hydroxide groups, have decreased cytotoxic activity, because the hydroxide groups of the platinum(IV) complex reduce the uptake of platinum by the cells. trans(OH),cis(Cl)-[Pt(IV)(OH)2Cl2(1R,2R-dach)], which has hydroxide and chloride groups, was easily incorporated into the cells and exhibited the high cytotoxic activity. This behavior indicates that the chloride group apparently overcomes the ameliorating effect of the hydroxide group.

Animals↗

Otoconia in young and elderly persons: a temporal bone study.

Using serially sectioned human temporal bones, the volumes of otoconia masses were compared between young children and elderly people. The latter group had significantly less otoconia volume than the former group, both in the macula utriculi and macula sacculi. The ratio between macula utriculi and macula sacculi was 100:70 in the young group, whereas it was 100:35 in the elderly group. Thus, the macula sacculi in the elderly group showed the severest otoconia reduction.

Aged↗

[Smoking restrictions in medical schools in Japan].

The theme of the 6th WHO World Non-Smoking Day in 1993 was "Health services: our window to a tobacco-free world". A survey of the public health departments of all medical schools and universities was conducted in April, 1992 in order to investigate the state of smoking restrictions in those departments responsible for training in health services. Responses were received from 76 schools out of 80. The results were as follows: 1) In school cafeteria: Smoking prohibited (17.8%), Separate smoking/non-smoking areas (21.9%), Unrestricted smoking (60.3%), In student lounges: Smoking prohibited (2.9%), Separate Smoking/non-smoking areas (7.1%), Unrestricted smoking (90.0%), 2) The number of schools with tobacco vending machines: 59 schools (77.6%), 3) In medical faculty meetings: Smoking prohibited--32 schools (42.1%), Unrestricted smoking--22 schools (28.9%), No rules but no smokers--22 schools (28.9%), A total of 54 schools (71.0%) have established non-smoking meetings. 4) The number of school that give no attention to raking students aware of smoking risks: 6 schools As a result of this investigation, one national and one private medical school initiated prohibition of smoking at medical faculty meetings. In order to stimulate consciousness of the health hazards of smoking in future medical professionals, freshmen orientation should be utilized for teaching about the risks of both tobacco and "chug-a-lugging" of alcoholic beverages. In addition, the elimination of tobacco vending machines from all medical department area is strongly indicated.

Humans↗

[Surgical treatment of stage IVa thymoma].

The relationship between prognosis of the disease and the type of surgery were reviewed in 110 cases of thymoma. Surgical procedures were classified into four types: total resection (TR), subtotal resection (SR), partial resection (PR) and exploratory thoracotomy (ET), and the extent of the disease was expressed as stage I through IV based on Masaoka's classification. Ten-year survival rates for stage III and IVa diseases were 5 6.2% in TR, 37.9% in SR and 30.3% in PR. None of the patients in ET survived more than 28 months. Tumor death after surgery was not observed in TR. Two of three patients with stage IVa disease who underwent TR are alive without recurrence of the tumor at 37 months and 6 months after surgery. The pleuropneumonectomy was performed in the former case. One of four patients who underwent SR and one of three patients who underwent PR both with stage IVa disease are alive at 71 and 150 months after surgical intervention, respectively, in spite of the presence of the tumor relapse. In these patients, repeated chemotherapy and radiotherapy were administered following the resection of the primary lesion. In conclusion, it was indicated that the improvement of the survival rate could be obtained by resection the tumor as completely as possible in stage III and IVa thymoma, as long-term survival has been proved to be possible by macroscopically complete removal of the primary site and pleural disseminations followed by combined adjuvant therapy in patient with stage IVa disease.

Adolescent↗

Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus.

The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland.

Animals↗