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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 847 records · Page 47Linked to original sources

[Anti-nuclear antibodies (ANA) in sera of aged subjects, with special reference to two cases with high titers of anti-centromere antibody (ACA)].

Recently, tissue cultured cells including HEp-2 cell have widely been used as the substrates for detecting autoantibody to nuclear antigen (ANA) by indirect immunofluorescence method. In this study, sera from aged subjects ranging from 70 to 92 years of age were examined for the presence of anti-nuclear antibodies by the indirect immunofluorescence method. Positive reactions were obtained in 51 of 269(23.3%) aged subjects and positive fluorescent staining patterns of ANA were speckled in 40, homogeneous in one, speckled + homogeneous in 4, nucleolar in one and discrete speckled in two sera respectively. The titers of ANA were low ranging between 1:20 and 1:320, however two cases showed discrete speckled staining with high titers at 1:2,560. Antibody to extractable nuclear antigen (ENA) was not detected by precipitation test in aged subjects. The aged individuals with low ANA titers did not show any symptoms suggestive of collagen diseases. In two patients whose sera contained high titers of anti-centromere antibody (ACA), one was suspected to be accompanied by primary biliary cirrhosis (PBC), however the other showed neither any other abnormal symptoms nor abnormal laboratory data. Our results indicated that low titer ANA other than ACA might not be clinically significant in aged subjects.

Adult↗

[Clinical evaluation of lung scintigraphy with 99mTc-technegas].

The aim of this study is to evaluate the safety and clinical usefulness of lung scintigraphy using 99mTc-technegas produced by the evaporation of pertechnetate elution at 2500 degrees C. Lung images were recorded by the gamma camera-computer system after a few deep inspirations of 99mTc-technegas. One healthy volunteer and 32 patients including 10 with lung cancer, 8 with chronic obstructive lung disease, 5 with pulmonary embolism, 2 with interstitial pneumonia, 2 with bronchiectasis and 12 with other various disease were studied. Delayed images were taken at more than 1 hour later in one healthy and 13 patients to investigate the interval changes of the intrapulmonary distribution of 99mTc-technegas. Obvious differences of radioactive distribution between early and delayed image were observed in only 2/14 cases. Penetration index (P.I.) averaged 0.81 +/- 0.11 for early images and 0.85 +/- 0.12 for delayed image. There was no significant difference between P.I. for early and delayed images. More than 97 MBq of 99mTc-macroaggregated albumin (99mTc-MAA) were required to obtain the adequate perfusion images after the acquisition of lung images with about 37 MBq of 99mTc-technegas. Bronchial deposits of 99mTc-technegas were shown in 12/33 cases and pathological defects in 26/32 patients (81.3%). Twenty three of 33 cases also had a perfusion scintigraphy with 99mTc-MAA. Ventilation perfusion mismatches were presented in 5/5 patients with pulmonary embolism and 1/10 patients with lung cancer. The safety was confirmed in all cases and clinical usefulness in 30/32 patients (94%). In conclusion, the safety and clinical usefulness of lung scintigraphy with 99mTc-technegas were proven in this study.

Adolescent↗

Suppressive effects of intracellular glutathione on hydroxyl radical production induced by tumor necrosis factor.

Protective effects of intracellular glutathione (GSH) against the cytotoxicity of human recombinant tumor necrosis factor (TNF) were investigated. Three tumor cell lines (L-M, B-16, HeLa) were used as target cells. Exposure of these cells to buthionine sulfoximine (BSO) or diethyl maleate (DEM) resulted in the depletion of intracellular GSH content to 5.2-43.0% of control values and enhancement of their susceptibility to TNF cytotoxicity. The hydroxyl radical production in L-M cells stimulated by TNF was increased by treatment with BSO or DEM. These results are consistent with the suggestion that intracellular GSH exerts its protective function against the cytocidal effect of TNF by inhibiting the hydroxyl radical production stimulated by TNF.

Animals↗

Synthesis and release of acetylcholine by cultured bovine arterial endothelial cells.

Using cultured endothelial cells prepared from bovine carotid artery, and a specific radioimmunoassay for acetylcholine (ACh), the synthesis and release of ACh by vascular endothelial cells were investigated directly. ACh content in the culture medium after 24 h of incubation in the presence of isoflurophate, a nonspecific cholinesterase inhibitor, was about 16 times higher than that in endothelial cells, indicating that ACh synthesized inside the cells was released rapidly. The presence of ACh in the culture medium was further confirmed qualitatively using high-performance liquid chromatography with an electrocapture detection. These results represent the first direct evidence that endothelial cells can synthesize and release ACh, suggesting the possibility that ACh acts not only as a neurotransmitter but also as an autacoid under certain conditions.

Acetylcholine↗

Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect.

Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration of neutrophils under agarose and enhanced their migration in the multiwell chemotaxis chamber. To assess the physiological significance of these differing in vitro TNF effects, ex vivo and in vivo investigations were performed using animal models. Neutrophils from the peripheral blood of rabbits preadministered systemic TNF showed impaired ability to migrate toward chemoattractants in vitro. In addition, systemic TNF administration suppressed zymosan-activated plasma-induced local accumulation of leukocytes in mouse skin. The results indicate that circulating TNF may act as a suppressor for local inflammatory reaction.

Animals↗

Inhibition of oxygen toxicity by targeting superoxide dismutase to endothelial cell surface.

Since enzymes that degrade reactive oxygens, such as superoxide dismutase (SOD), are significantly lower in plasma than in intracellular compartments, cell surface membranes should be protected against hazardous oxygens particularly when animals are challenged with oxidative stress. To minimize oxygen toxicity on endothelial cell surface, a fusion gene consisting of cDNA coding human Cu2+/Zn2(+)-SOD and heparin-binding peptide was constructed and expressed in yeast. The resulting enzyme (HB-SOD) bound to a heparin-Sepharose column and cultured endothelial cells; binding was inhibited either by high NaCl concentrations or heparin. When injected intravenously, HB-SOD predominantly bound to vascular endothelial cell surface. Carrageenin-induced paw edema and cold-induced brain edema of the rat were markedly inhibited by a single dose of HB-SOD. These results suggest that superoxide radical and/or its metabolite(s) occurring at or near the outer surface of vascular endothelial cells might play a critical role in the pathogenesis of vasogenic edema.

Animals↗

Expression of endogenous tumor necrosis factor as a protective protein against the cytotoxicity of exogenous tumor necrosis factor.

Based on the finding that expression of endogenous tumor necrosis factor (TNF) which is not detected in TNF-susceptible cells was observed in TNF-resistant cells, the assumption was made that endogenous TNF may be a protective protein against the cytotoxic activity of TNF. In order to confirm this possibility, we investigated the relationship between expression of endogenous TNF and TNF susceptibility by using the gene transfection method. When L-M, TNF-highly sensitive murine fibrosarcoma cells were transfected with a human TNF gene, the stable transfectants expressed endogenous TNF and acquired resistance to TNF. Conversely, when endogenous TNF synthesis was inhibited by introducing an antisense TNF gene into HeLa, TNF-less sensitive human cervical cancer cells, the sensitivity was enhanced. These findings indicate that endogenous TNF is one of the protective factors against the cytotoxic activity of TNF.

Animals↗

The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis.

Acute myelofibrosis is often associated with acute megakaryoblastic leukemia (AMKBL). Although the exact mechanism for the progression of myelofibrosis in AMKBL is unclear, certain humoral factors from megakaryoblastic cells, the precursors of platelets, may be involved in the enhancement of collagen synthesis by bone marrow fibroblasts. The present study, therefore, is an investigation of the possible pathogenic role of transforming growth factor-beta (TGF-beta), known to be a very potent collagen-stimulating factor found in platelets in the myelofibrosis of AMKBL. The results obtained were as follows: (1) Conditioned media from peripheral megakaryoblasts taken from an AMKBL patient and from established megakaryoblast cell lines (MEG-01) had much greater stimulatory effects on collagen synthesis in bone marrow fibroblasts than conditioned media from other leukemic cell types. (2) Based on an assessment of soft agar colony formation, there was greater TGF-beta activity in media that had been conditioned from megakaryoblasts than in media from other leukemic cell types. (3) When compared with other leukemic-cell types, megakaryoblasts showed substantially greater expression of TGF-beta mRNA that was hybridized at 2.5 kb with a TGF-beta cDNA probe, and TGF-beta polypeptides were detected at 13 Kd with anti-TGF-beta antibodies. (4) The addition of the anti-TGF-beta antibody inhibited the stimulatory effects of the megakaryoblast conditioned medium on collagen synthesis in bone marrow fibroblasts. These results clearly suggest that megakaryoblasts produce and secrete an active form of TGF-beta and stimulate collagen synthesis in bone marrow fibroblasts in a paracrine manner.

Animals↗

Necessity of IgE antibodies and mast cells for manifestation of resistance against larval Haemaphysalis longicornis ticks in mice.

Genetically mast cell-deficient WBB6F1-W/Wv mice showed an apparent defect in manifestation of the resistance against larval Haemaphysalis longicornis ticks, but their serum IgE levels increased more than 100-fold after the second tick infestation. Immune sera obtained from the WBB6F1-W/Wv mice were adoptively transferred to the other WBB6F1-W/Wv mice which had received intracutaneous injections of WBB6F1-+/+ mouse-derived cultured mast cells. Because the resistance against ticks was detectable only when both mast cells and IgE antibodies were available, immediate hypersensitivity reaction appeared to have a physiologic role in the manifestation of the resistance against H. longicornis ticks.

Animals↗

Env-derived gp55 gene of Friend spleen focus-forming virus specifically induces neoplastic proliferation of erythroid progenitor cells.

A group of retroviruses carrying truncated viral genes has recently been suggested as the cause of new patterns of diseases. One such virus is the replication defective component of the Friend murine leukemia virus (F-MuLV) complex, called Friend spleen focus forming virus (F-SFFV). This virus induces erythroblastosis, and a virion envelope-related glycoprotein, gp55, encoded by F-SFFV has been suggested as the pathogenic gene. The role of the gp55 gene is, however, yet unclear in the apparently multistep erythroleukemogenesis. By separately producing transgenic mice harboring the whole F-SFFV DNA, the gp55 gene alone under the control of the retroviral long terminal repeat (LTR) and the gp55 gene under the control of cytoplasmic beta actin transcriptional regulatory unit, we show here that the gp55 gene is capable of inducing neoplastic proliferation of erythroid progenitor cells specifically in the absence of helper virus and other F-SFFV sequences. Under the control of the viral LTR the gp55 expression was detected only in leukemic tissues, but under the control of cytoplasmic beta-actin regulatory sequences, the gp55 was also expressed in a variety of normal tissues including preleukemic normal spleens. The development of erythroleukemia was suppressed under the genetic background of C57B1/6 mouse (resistant to F-MuLV; Fv-2rr), and required additional events even under the background of DDD mouse (susceptible to F-MuLV; Fv-2ss). The p53 and Spi-1 genes were frequently aberrant in transplanted tumors and cell lines derived from them, but were not in primary leukemic spleens.

Animals↗

Effect of tumour necrosis factor in the mouse-tail model of psoriasis.

The effects of local and systemic administration of tumour necrosis factor (TNF) on the mouse-tail model of psoriasis were examined histologically at 4 days after administration. Subcutaneous injection of TNF at 1 x 10(1) to 1 x 10(4) units/mouse resulted in dose-dependent formation of a granular layer in the tail scales, which was quantified as the percentage of tail scales having granular layer formations extending over half or more of their surface and was larger than that occurring in untreated mice and in mice receiving injections of vehicle solution alone. Daily intraperitoneal injection of TNF at 1 x 10(3) or 1 x 10(4) units/mouse for 28 days resulted in similar granular layer formation and in a significantly reduced mitotic index of the tail keratinocytes, indicating an antiproliferative effect of TNF. The lowered mitotic index and the induction of granular layers, apparently attributable to a modulation of keratinocyte proliferation and differentiation by TNF, suggest that TNF may be effective as a drug for treatment of psoriasis.

Animals↗

Demonstration of both beta 1- and beta 2-adrenoceptors mediating negative chronotropic effects on spontaneous activity in isolated bovine mesenteric lymphatics.

The pharmacological classification of beta-adrenoceptor subtypes in isolated bovine mesenteric lymphatics was studied by using various beta-adrenoceptor agonists and antagonists. Isoproterenol (ISP) (10(-10)-10(-8) M) produced dose-dependent negative chronotropic effects on the rhythm of spontaneous contractions in the lymphatic preparation. The ISP-induced effects were dose-dependently blocked by pretreatment with 10(-8)-10(-7) M metoprolol (a selective beta 1 antagonist) as well as 10(-8)-10(-7) M propranolol (a beta 1 and beta 2 antagonist). Dobutamine (a selective beta 1 agonist) caused a dose-dependent negative chronotropic effect, which was significantly blocked by pretreatment with 10(-8) M metoprolol. Salbutamol and procaterol (selective beta 2 agonists) also produced dose-dependent negative chronotropic effects, which were dose-dependently inhibited by pretreatment with 10(-8)-10(-7) M propranolol, but not by 10(-7) M metoprolol. The decreasing order of the relative potency was as follows: ISP greater than procaterol greater than salbutamol greater than dobutamine. These results suggest that bovine mesenteric lymphatics contain both beta 1- and beta 2-adrenoceptors and that both subtypes can produce a negative chronotropic effect on the rhythm of spontaneous contractions, when stimulated.

Adrenergic beta-Agonists↗

Oligomerization of Friend spleen focus-forming virus (SFFV) env glycoproteins.

The glycoprotein gp55 and its processed form gp65, which are encoded by the env gene of Friend spleen focus-forming virus (SFFV), have been implicated in the initiation of the murine acute erythroleukemia induced by Friend virus (FV). Analyses of these glycoproteins by chemical crosslinking and nonreducing/reducing two-dimensional electrophoresis showed that both gp55 and gp65 exist as monomer and disulfide-bonded dimer and trimer. These oligomers could be detected in various FV-infected erythroleukemia cell lines, as well as in the spleen cells of FV-induced erythroleukemic mice, suggesting that oligomerization is an intrinsic feature of SFFV env glycoproteins.

Animals↗

Livebirth prevalence and follow-up of malformation syndromes in 27,472 newborns.

The results of a survey of the birth prevalence of congenital anomalies among 27,472 consecutive newborn babies at a large maternity hospital in Tokyo are reported. There were 29 cases with trisomy-21; 5 cases with trisomy-13 syndrome; 5 with trisomy-18 syndrome; 2 with cri-du-chat syndrome; and one each with partial monosomy 4p, partial trisomy 5p, partial trisomy 6p, partial trisomy 9p, partial trisomy 9q, partial monosomy 10p, and partial monosomy 13q. Single cases of the following were observed: the Hallermann-Streiff syndrome, the Treacher-Collins syndrome, achondroplasia, arthrogryposis, the Beckwith-Wiedemann syndrome, the asplenia syndrome, the Klippel-Trenaunay-Weber syndrome, the Marfan syndrome, the Carpenter syndrome, the Goldenhar syndrome, and the Pierre Robin syndrome. The results of follow-ups to determine the life-prognosis of each patient with an autosomal aberration are reported.

Chromosome Aberrations↗

A novel N6-substituted adenosine isolated from mi huan jun (Armillaria mellea) as a cerebral-protecting compound.

Successive purification of a crude extract of cultured Mi Huan Jun mycelia, followed by an assay of the effect on complete ischemia in mice, led to the isolation of a new compound with cerebral protecting activity, hereafter designated as AMG-1. The structure of AMG-1 was proposed as being 6-(5-hydroxy-2-pyridyl-methylamino)-9-beta-ribofuranosylpurine (1) on the basis of its UV, mass, 1H-NMR, and 13C-NMR spectra.

Adenosine↗

Armillaric acid, a new antibiotic produced by Armillaria mellea.

A new antibiotic armillaric acid (2), has been isolated from the cultured mycelia of Armillaria mella (Vahl. ex Fr.) Quel (Trichlometaceae). Its structure was elucidated on the basis of the spectral data. Compound 2 exhibits inhibitory activity against gram-positive bacteria and yeast.

Agaricales↗

Efficacy of closed-system drainage in treating chronic subdural hematoma: a prospective comparative study.

The authors conducted a prospective comparative study on the recurrence rate of chronic subdural hematoma after the use of two different treatment modalities: burr-hole irrigation of the hematoma cavity with (Group A) and without closed-system drainage (Group B). Thirty-eight patients were studied. Patients were assigned to groups sequentially upon admission. There were no significant differences between the two groups for age, sex, preoperative hematoma volume, and density on computed tomographic scan. One patient in Group A (5%) suffered a recurrence as opposed to 6 in Group B (33%). The difference in recurrence rate between the two groups was statistically significant (P less than 0.05). The authors conclude that closed-system drainage after burr-hole irrigation reduces the recurrence rate of chronic subdural hematoma.

Aged↗