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1.
An acromegalic patient with galactorrhea was treated with an ergot alkaloid, 2-Br-alpha-ergocryptine (CB-154). Serum prolactin decreased rapidly to normal level by CB-154 and the complete cessation of galactorrhea was noted. The inhibitory effect of CB-154 On growth hormone (GH) release was also noted, but slight. The mechanism of inhibitory action of CB-154 on both prolactin and GH secretion was discussed in connection with the experimental model of pituitary tumors, in which both hormones were produced by a single type of tumor cells. The discontinuation of CB-154 treatment was associated with the return of both prolactin and GH levels to the initial high values with resumption of galactorrhea. 相似文献
2.
Yuan Z Kishimoto C Sano H Shioji K Xu Y Yokode M 《American journal of physiology. Heart and circulatory physiology》2003,285(2):H899-H906
Atherosclerosis is associated with immune activation. Immunoglobulin is used for the treatment of immune-mediated diseases. The mechanisms and importance of the Fc portion of immunoglobulin upon experimental atherosclerosis in apolipoprotein E-deficient mice were examined. Experimental atherosclerosis was induced in mice fed a high-fat diet containing 0.3% cholesterol. Over 8, 12, and 16 wk, on alternate days, mice were treated with an intraperitoneal injection of either 1 g.kg-1.day-1 of human intact immunoglobulin or F(ab')2 fragments of human immunoglobulin. Fatty streak formation and fibrofatty plaques were markedly suppressed in mice that received intact immunoglobulin for 8, 12, and 16 wk. In contrast, atherosclerotic lesions were not ameliorated in mice that received F(ab')2 fragments. Immunohistochemical analysis revealed that macrophage accumulation in the fatty streak lesions was suppressed in mice received intact immunoglobulin but not in those that received F(ab')2 fragments. In addition, the cytotoxic activities of splenocytes from immunoglobulin-treated mice, but not from F(ab')2 fragment-treated mice, were significantly suppressed compared with those from human serum albumin-treated mice. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. Immunoglobulin therapy markedly suppressed atherosclerosis due to Fc receptor-mediated anti-inflammatory and immunomodulating actions. The antiatherosclerotic effects of immunoglobulin may be related to the suppression of cytotoxic activity of atherogenic T cells and the reduction of macrophage accumulation in the lesions. 相似文献
3.
Yuan Z Nimata M Okabe TA Shioji K Hasegawa K Kita T Kishimoto C 《American journal of physiology. Heart and circulatory physiology》2005,289(3):H1147-H1152
Some ANG II receptor type 1 (AT(1)) antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. However, the effects of the drugs on autoimmune diseases are unknown. We tested the hypothesis that olmesartan, a novel AT(1) antagonist, ameliorated experimental autoimmune myocarditis (EAM) in rats attributed to the suppression of inflammatory cytokines as well as to the immunomodulatory action of the heart. We administered olmesartan orally at does of 1, 3, and 10 mg.kg(-1).day(-1) to rats with EAM for 3 wk. The results showed that olmesartan decreased blood pressure significantly compared with the untreated group and markedly reduced the severity of myocarditis associated with the decrease of myocardial macrophage, CD4(+), and CD8(+) T-cell expression by comparison of heart wt-to-body wt ratios, pericardial effusion scores, and macroscopic and microscopic scores. Numbers of myocardial interleukin-1beta (IL-1beta)-positive-staining cells (obtained by immunohistochemistry) and quantities of IL-1beta expression (obtained by Western blotting) were significantly lower in rats with EAM given olmesartan treatment compared with rats given vehicle. Cardiac myosin-specific, delayed-type hypersensitivity was significantly lower in olmesartan-treated rats than in control rats. The cytotoxic activities of lymphocytes in rats with EAM treated with olmesartan were reduced compared with untreated control rats. In vitro study showed that both olmesartan and its active metabolite RNH-6270 suppressed IL-1beta production in U-937 cells and cultured myocytes. Olmesartan ameliorates acute EAM in rats. The cardioprotection of olmesartan may be due to suppression of inflammatory cytokines as well as to suppressive effects of cytotoxic myocardial injury in addition to hemodynamic modifications. 相似文献
4.
We report the clinical response and adverse events of a female patient treated for recurrent malignant pheochromocytoma using the tyrosine kinase inhibitor sunitinib. A 41-year-old woman underwent adrenectomy and nephrectomy forpotentially malignant adrenal pheochromocytoma. Fifty-four months after surgery, abdominal computed tomography (CT) and Iodine-131 metaiodobenzylguanidine((131)I-MIBG) scintigraphy revealed multiple tumors in the liver. Two chemotherapy protocols were administered in succession (first line: cyclophosphamide/vinblastine/dacarbazine; second line: cisplatin/docetaxel/ifomide). Despite these treatments, however, the tumors continued to progress. Treatment with sunitinib was initiated, but the patient quickly developed critical hypertension caused by tumor lysis syndrome. The sunitinib dose was reduced, and a partial response, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), was observed after 6 treatment cycles. Moreover, no severe adverse events occurred during this lower-dose sunitinib treatment. Unfortunately, sunitinib treatment became unaffordable for the patient, who eventually resorted to palliative care and died 37 months later. This case study is consistent with previous reports indicating that appropriate doses of sunitinib can induce a partial antitumor response in patients with refractory pheochromocytoma. 相似文献
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Yuan Z Kishimoto C Shioji K Nakamura H Yodoi J Sasayama S 《Molecular and cellular biochemistry》2003,248(1-2):185-192
Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was increased by the preconditioning treatment. In rats with experimental autoimmune myocarditis (EAM), the protein carbonyl content, a marker of cellular protein oxidation, was increased accompanied with enhanced TRX expression. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes. The severity of the myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21 in which TRX was up regulated when the inflammation started, but not in temocapril treatment from day 15–21 in which TRX was not up-regulated when the inflammation started. The results suggest that TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis associated with inducing TRX increase in a preconditioning manner, although the mechanism of TRX induction by temocapril remains to be elucidated. 相似文献
7.
K. Ishizeki Shintaro Nomura Masaharu Takigawa Hiroya Shioji Tokio Nawa 《Histochemistry and cell biology》1998,110(5):457-466
The localization of osteopontin (OP) was examined in Meckel’s cartilage cells that bipotentially expressed cartilage and
bone phenotypes during cellular transformation in vitro. Cultured cells were analyzed by in situ hybridization, immunostaining
followed by light and electron microscopy, electron microscopy, and electron probe microanalysis. The combination of ultrastructural
analysis and immunoperoxidase staining indicated that OP-synthesizing cells were cells that were autonomously undergoing a
change from chondrocytes to bone-forming cells at the top of nodules. Double immunofluorescence staining of 2-week-old cultures
revealed that OP was first synthesized by chondrocytic cells at the top of nodules. After further time in culture, the distribution
of OP expanded from the central toward the peripheral regions of the nodules. Electron probe microanalysis revealed that the
localization of OP was associated with matrices of calcified cartilage and osteoid nodules that contained calcium and phosphorus.
Immunoperoxidase electron microscopy revealed that, in addition to the intracellular immunoreactivity in chondrocytes and
small round cells that were undergoing transformation, matrix foci of calcospherites and matrix vesicles, in particular, included
growing crystals that were immunopositive for OP. An intense signal due to mRNA for OP in 3-week-old cultures was detected
in nodule-forming round cells, while fibroblastic cells, spreading in a monolayer over the periphery of nodules, were only
weakly labeled. These findings indicate that OP might be expressed sequentially by chondrocytes and by cells that are transdifferentiating
further and exhibit an osteocytic phenotype, and moreover, that expression of OP is closely associated with calcifying foci
in the extracellular matrix.
Accepted: 26 May 1998 相似文献
8.
Influence of Sulfate-Reducing Bacteria on Outdoor Hydrogen Production by Photosynthetic Bacterium with Seawater 总被引:1,自引:0,他引:1
The application of seawater for bacterial fermentative production is a cost-effective technology. Hydrogen production by
marine photosynthetic bacterium with seawater failed to continue after more than 10 days, and was accompanied by the formation
of hydrogen sulfide and a change in culture color from red to black. However, substrate consumption in the blackish culture
was comparable to that in a hydrogen-producing culture. A decrease in hydrogen production occurred upon the addition of sodium
sulfide at concentrations of 1.5 mM or higher. PCR analysis targeted at the 16S rDNA sequence selective for sulfate-reducing
bacteria revealed the existence of sulfate-reducing bacteria in inoculation cultures of the phototrophic bacterium and medium
for hydrogen production. Hence, the high sulfate concentration of seawater, the low oxidation-reduction potential under hydrogen-producing
conditions, and the presence of electron donors such as acetate might promote the metabolic activities of sulfate-reducing
bacteria, resulting in the deterioration of hydrogen production with seawater.
Received: 15 September 1999 / Accepted: 14 October 1999 相似文献
9.
Yamaguchi T Shioji I Sugimoto A Yamaoka M 《Biochemical and biophysical research communications》2002,293(1):517-520
Some authors have suggested that psychological stress induces the production of reactive oxygen species (ROS). Some studies have supported that bilirubin exerts anti-oxidative effects in vivo. However, it is not known whether ROS induced by psychological stress provoke bilirubin oxidation in vivo. We investigated if the concentration of bilirubin oxidative metabolite (BOM), a bilirubin oxidative metabolite, increased in urine from subjects exposed to psychological stress. Sixty healthy male volunteers working in a pharmaceutical company were divided into a Group I which did not attend a conference, a Group II which attended a conference but did not deliver a speech, and a Group III which attended a conference and delivered speeches in the presence of the company executives. Subjective stress was scored (self-rating score) after subjects in Group III delivered their speeches at the conference. Urine was collected on the next day. The BOM concentrations, as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. The concentration of BOM in Group III was significantly higher compared to that in Groups I and II (p<0.01 and p<0.05, respectively). Furthermore, in Group III, the concentration of BOM correlated with the self-rating stress score (r=0.53, p<0.01). These findings suggest that emotional stimuli are associated with an increase in the oxidative metabolites of bilirubin in human urine, and that BOMs could be useful markers of psychological stress. 相似文献
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