Antiphospholipid antibody-associated haemophagocytic syndrome.
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Adult↗
Biomedical subjects
H Hashimoto
Publications and source records attributed to H Hashimoto.
Primary synovial sarcoma of the kidney.
The authors present two cases of primary synovial sarcoma of the kidney. Both patients had a mass in the upper part of the right kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were soft to rubbery masses measuring 5.5 cm and 5 cm in diameter, respectively. Histologically, both tumors were poorly differentiated synovial sarcoma. The lesions exhibited a hypercellular solid or lobular growth of round, oval, or short spindle cells in variably solid sheets, in intersecting fascicles, or in a haphazard fashion. Areas of solid aggregation or fascicles of the tumor cells alternating with hypocellular myxoid tissues, together with areas displaying a prominent hemangiopericytoma-like pattern, were found. Immunohistochemically, vimentin was diffusely positive and a few tumor cells were positive for cytokeratin, epithelial membrane antigen, and neurofilament. The tumor cells were negative for S- 100 protein, CD34, smooth muscle actin, and desmin, whereas CD56 and CD99 were positive. In both cases, reverse transcription-polymerase chain reaction using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX2 fusion gene transcripts, which are characteristic molecular findings of synovial sarcoma. One patient died 10 months after diagnosis. These tumors are unique cases of primary synovial sarcoma of the kidney confirmed by molecular study.
Biomarkers, Tumor↗
Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines.
Cardiopulmonary bypass (CPB) impairs pulmonary endothelial injury in part by increasing expression of adhesion molecules that results in neutrophil influx. Although numerous proinflammatory cytokines up-regulate these responses, the extent to which systemic and pulmonary proinflammatory cytokines increase remains unknown. We therefore examined systemic and pulmonary gene expression and production of proinflammatory cytokines during CPB. Bronchoalveolar lavage and peripheral blood sampling were performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. We also measured these cytokines in cultured alveolar macrophages and plasma monocytes in standard medium alone, or in the presence of lipopolysaccharide. We found 2- to 20-fold increases in gene expression for these cytokines in both plasma and alveolar leukocytes at the end of surgery. However, the increases were 4-8 times greater in alveolar than plasma leukocytes. Alveolar macrophages obtained at the end of surgery produced 1.5-3 times more IL-6, IL-8, and TNF-alpha than those obtained at the beginning (P < 0.0001). Although plasma monocytes produced more IL-8 at the end of surgery (P < 0.001), TNF-alpha and IL-6 did not increase. The production of all cytokines was 1.5-3 times greater in alveolar macrophages obtained at the end of surgery than in plasma monocytes obtained simultaneously (P < 0.005). Our data thus suggest that CPB provokes a greater pulmonary than systemic inflammatory response.
Actins↗
Neutrophil number and interleukin-8 and elastase concentrations in bronchoalveolar lavage fluid correlate with decreased arterial oxygenation after cardiopulmonary bypass.
Atelectasis is a major cause of decreased arterial oxygenation after cardiopulmonary bypass (CPB). There is a close relationship between atelectasis and inflammatory responses. We therefore tested the hypothesis that neutrophil number and the concentrations of proinflammatory cytokines and elastase in plasma and bronchoalveolar lavage fluid correlate with changes in arterial oxygenation. Bronchoalveolar lavage was performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. Peripheral blood was sampled simultaneously. Arterial oxygenation was quantified by PaO(2)/fraction of inspired oxygen (FIO(2)) and intrapulmonary shunt (Q(s)/Q(t)). PaO(2)/FIO(2) and Q(s)/Q(t) decreased significantly at the end of surgery, whereas neutrophil number, interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and elastase concentrations in the lavage fluid increased significantly. The increase in neutrophil count from the lavage fluid correlated significantly with the increases in IL-8 and elastase concentrations. The increase in neutrophil number and IL-8 and elastase concentrations in the lavage fluid correlated significantly with PaO(2)/FIO(2) and Q(s)/Q(t) at the end of surgery. In contrast, none of the plasma values correlated with these variables. Significant correlation between immune mediators and decreased arterial oxygenation suggests that inflammatory responses in the distal airway are strongly related to a decrease in arterial oxygenation after CPB.
Bronchoalveolar Lavage Fluid↗
Fatal perioperative myocardial infarction in four patients with cardiac amyloidosis.
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Accidents, Traffic↗
Smoking decreases alveolar macrophage function during anesthesia and surgery.
BACKGROUND: Smoking changes numerous alveolar macrophage functions and is one of the most important risk factors for postoperative pulmonary complications. The current study tested the hypothesis that smoking impairs antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery. METHOD: The authors studied 30 smoking and 30 nonsmoking patients during propofol-fentanyl general anesthesia. Alveolar immune cells were harvested by bronchoalveolar lavage immediately and 2, 4, and 6 h after induction of anesthesia and at the end of surgery. The types of alveolar immune cell and macrophage aggregation were determined. The authors measured opsonized and unopsonized phagocytosis. Microbicidal activity was determined as the ability of the macrophages to kill Listeriamonocytogenes directly. Finally, RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin 1beta, 6, and 8, interferon gamma, and tumor necrosis factor alpha were measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. RESULTS: The fraction of aggregated macrophages increased significantly over time in both groups, whereas phagocytosis of opsonized and nonopsonized particles and microbicidal activity of alveolar macrophages decreased significantly. The changes, though, were nearly twice as great as in patients who smoked. Gene expression of all proinflammatory cytokines in alveolar immune cells except interleukin 6 increased 2- to 20-fold over time in both groups. The expression of interleukin 1beta, interferon gamma, and tumor necrosis factor alpha, however, increased only half as much in smokers as in nonsmokers. CONCLUSION: Smoking was associated with macrophage aggregation but markedly reduced phagocytic and microbicidal activity-possibly because expression of proinflammatory cytokines was reduced in these patients. Our data thus suggest that smokers may have a limited ability to mount an effective pulmonary immune defense after anesthesia and surgery.
Anesthesia, General↗
Supplemental intraoperative oxygen augments antimicrobial and proinflammatory responses of alveolar macrophages.
BACKGROUND: The first goal was to test the hypothesis that 100% inspired oxygen maintained for approximately 8 h intraoperatively is not associated with impaired pulmonary oxygenation. The authors also tested the hypothesis that intraoperative inhalation of 100% oxygen augments proinflammatory and antimicrobial responses of alveolar macrophages during anesthesia and surgery. METHODS: The authors studied patients administered 100% oxygen (n = 30) and 30% oxygen (n = 30) during propofol-fentanyl general anesthesia. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery. The authors measured "opsonized" and "unopsonized" phagocytosis and microbicidal activity. RNA was extracted from harvested cells and cDNA was synthesized. The expression of interleukin(IL)-1beta, IL-6, IL-8, interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction. RESULTS: Gene expression of all proinflammatory cytokines except IL-6 increased fourfold to 20-fold over time in both groups. However, expression of TNF-alpha and IL-8, IFN-gamma, and IL-6 and IL-1beta was 2-20 times greater in patients administered 100% than in those administered 30% oxygen. Unopsonized and opsonized phagocytosis and microbicidal activity decreased progressively, with the decreases being nearly twice as great during inhalation of 30% oxygen versus 100% oxygen. CONCLUSION: Inhalation of 100% oxygen improved intraoperative decreases in phagocytic and microbicidal activity possibly because expression of proinflammatory cytokines was augmented. These data therefore suggest that intraoperative inhalation of 100% oxygen augments antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery.
Anesthesia, Intravenous↗
Changes in vasoactive substances during gastric ulcer healing.
In order to study the roles of vasoactive peptides during tissue repair of gastric ulcers, we compared concentrations in tissue surrounding gastric ulcers of endothelin-1(ET-1), adrenomedullin (AM), and transforming growth factor-beta (TGF-beta) among different stages of ulcer development. A total of 82 cases were studied. Ulcers were located in the gastric angulus in 51 cases. All cases were positive for Helicobacter pylori (Hp). Ten cases were in the active stage (GA), 18 were in the healing stage (GH), and 28 were in the scarring stage (GS). As control, 17 cases of Hp-positive gastritis (gast+) and 14 of Hp-negative gastritis (gast-) were studied. The concentrations of endothelin (ET) and TGF-beta were in the order of GH> GA> GS, and those of AM were in the order of GS > GH > GA. On immunostaining, ET stained positively in endothelial cells and vascular smooth muscle cells (VSMCs) during the GH and GS stages, and AM stained positively in histiocytes during GA, GH and GS, and also stained positively in glandular epithelia and smooth muscle fibers during GH and GS. When our results were reviewed with respect to the regulation of vascular tonus and the proliferation of VSMCs, ET and AM were considered to have roles in the regulation of proliferation.
Adrenomedullin↗
Changes of nitric oxide and growth factors during gastric ulcer healing.
We measured the concentrations of vascular endothelial growth factor (VEGF), nitric oxide and endothelin-1 (ET-1) in the gastric mucosa and examined the relationships between these factors. VEGF, nitric oxide and ET participate in angiogenesis and vascular remodeling, important elements of gastric ulcer healing. We studied cases of gastric ulcer as confirmed by endoscopic examination. All 61 cases in the angulus were positive for Helicobacter pylori (Hp). Fifteen cases were active stage (GA), 23 were healing stage (GH), and 23 were scarring stage (GS). As control, 17 cases of Hp-positive gastritis (gast+) and 14 cases of Hp-negative gastritis (gast-) were studied. Biopsy samples taken from the angulus during endoscopic examination were frozen and sliced into thin sections. ET was measured by enzyme immunoassay, VEGF was measured by enzyme-linked immunosorbent assay (ELISA) and nitric oxide was measured in terms of metabolite oxides of nitrogen (NOx) as described by Griess. ET, VEGF and inducible nitric oxide synthase (iNOS) were immunostained. The GA group had the highest concentration of NOx, suggesting that nitric oxide participates in the early stage of mucosal repair. In the GH group, all three factors showed high concentrations, suggesting that all may be involved in increased production. In the GS group, all three factors were significantly lower than in the GA and GH groups. Immunohistochemical studies showed that the distribution of ET- and iNOS-positive cells differed according to the ulcer stage. In particular, ET- and iNOS-positive cells in the vascular wall were primarily endothelial cells during GA and GH and vascular smooth muscle cells (VSMCs) during GS. These findings suggest that endothelial cells produce increased amounts of ET, nitric oxide and VEGF early in ulcer healing, a period of active endothelial cell repair and angiogenesis. During the scarring stage, vascular remodeling may result from the effects of ET and nitric oxide in regulating the proliferation of VSMCs. Our results suggest that VEGF. nitric oxide and ET participate in angiogenesis, vascular remodeling and mucosal regeneration during ulcer healing.
Endothelial Growth Factors↗
Microvascular angiogenesis and apoptosis in the survival of free fat grafts.
OBJECTIVES/HYPOTHESIS: Autologous fat is an ideal material for augmentation in plastic surgery because of its minimal tissue reaction and easy availability, but its long-term graft survival is somewhat unpredictable. This study was conducted to determine how fat grafts get their vascular supply from the recipient bed and why they keep reducing in volume and weight. STUDY DESIGN: Experimental study using animal models. METHODS: The expression of vascular endothelial growth factor (VEGF) in grafted fat tissue was examined by using immunohistochemical staining, and apoptotic cell death in the grafted fat was studied by using terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-uridine triphosphate (dUTP)-biotin nick end-labeling method. Twenty-five Wistar rats were used as models of free fat grafts. Fat tissue taken from inguinal fat pads was grafted to the back skin with an 18-gauge needle injection. RESULTS: The weight of the injected fat was significantly reduced on the 180th day compared with the original weight (32% +/- 10%). VEGF+ cells were observed in fibrous connective tissue of the grafts on days 7 and 30 but not after day 90. Apoptotic cells were also observed on days 7 and 30. CONCLUSIONS: Angiogenic factors including VEGF started to revascularize the graft around day 7, and the extent of the vasculature was not reduced after the revascularization. In addition to necrosis in the graft's early stages, apoptosis induced by many factors in the graft's environment is also, at least in part, a cause of long-term volume reduction of the fat graft. Thus clinical application of angiogenic factors such as VEGF to fat grafts and control of apoptosis may contribute to improvements in fat-grafting techniques.
Adipose Tissue↗
Crystallographic study of intein homing endonuclease II encoded in the archaeal DNA polymerase gene.
Intein homing endonucleases are proteins spliced out from a precursor protein and site-specific enzymes that make double-strand breaks in inteinless alleles. Crystals of intein homing endonuclease II from the hyperthermophilic archaeon Pyrococcus kodakaraensis strain KOD1 (PI-PkoII) have been grown at room temperature using ammonium sulfate as a precipitant. The diffraction pattern of the crystal extends to 3.0 A resolution at room temperature upon exposure to synchrotron X-rays at KEK-PF, Japan. The crystals have symmetry consistent with space group C222(1), with unit-cell parameters a = 107.6, b = 150.5, c = 146.8 A. A full set of X-ray diffraction data were collected to 3.0 A Bragg spacing from a native crystal with an overall R(merge) of 4.8% and a completeness of 96.6%.
Archaeal Proteins↗
[Basic study on anti-bacterial urethral catheter. I. Development of a new anti-bacterial coating material for silicon catheters].
In order to develop a new anti-bacterial urethral catheter, we studied anti-bacterial and anti-adherent coating material suitable for silicon catheters. Several aspects of various silver compounds were examined, including anti-bacterial activity, chemical property and toxicity. Among silver citrate, silver phosphate and silver oxide, which were found to have excellent anti-bacterial activities, silver citrate was regarded as the material of choice for anti-bacterial coating in terms of durable activity and biological safety. It was also found that several surfactants inhibited bacterial adherence to the surface of silicon catheters. Among them soybean lecithin exhibited excellent anti-adherent activity in a dose dependent manner. Finally, a mixture of silver citrate, soybean lecithin and liquid silicon at the ratio of 2:2:8 was regarded as an ideal anti-bacterial coating material for silicon catheters.
Animals↗
[Basic study on anti-bacterial urethral catheter. II. Potency of a new anti-bacterial catheter and its durability in experimental models].
The potency and effectiveness of an anti-bacterial catheter coated with a mixture of silver citrate, soybean lecithin and liquid silicon at the ratio of 2:2:8 were compared with those of commercially available anti-bacterial and conventional urethral catheters. This new anti-bacterial catheter showed a strong activity and excellent durability in ordinary in vitro experimental studies. In the present series we have developed new in vitro experimental models for the evaluation of anti-bacterial catheters in inhibiting bacterial ascent via intraluminal or extraluminal route. The characteristic features of the silver citrate/lecithin catheter, namely strong activity and excellent durability, were confirmed using these new models that mimic urinary catheter-associated clinical infections.
Catheterization↗
Detection of SYT-SSX fusion transcripts in both epithelial and spindle cell areas of biphasic synovial sarcoma using laser capture microdissection.
To investigate the distribution of tumour cells expressing the SYT-SSX fusion gene in biphasic synovial sarcoma, modified reverse transcription polymerase chain reaction (RT-PCR) analysis was performed using microdissected specimens from haematoxylin and eosin stained sections of archival paraffin wax embedded tissues. This modified RT-PCR included a stage with degenerate oligonucleotide primed (DOP) PCR, which randomly amplified cDNA after reverse transcription. SYT-SSX fusion transcripts were detected in both epithelial and spindle cell areas of all three biphasic synovial sarcomas examined. Subsequent sequence analysis confirmed that the detected messages were derived from the SYT-SSX1 fusion gene in two cases and from SYT-SSX2 in one. These results indicate that SYT-SSX fusion transcripts are found in both epithelial and spindle cell areas of biphasic synovial sarcoma, and RT-DOP-PCR-PCR analysis is a useful method for detection of extremely small amounts of mRNA in microdissected samples from archival formalin fixed, paraffin wax embedded tumour tissues.
Adenocarcinoma↗
Cloning of novel soluble gp130 and detection of its neutralizing autoantibodies in rheumatoid arthritis.
In an attempt to isolate disease-associated autoantigens in rheumatoid arthritis (RA), we cloned a new autoantigen named gp130-RAPS, which is a novel soluble form of the IL-6 signal-transducing molecule gp130. gp130-RAPS is a 50-kDa protein translated from alternatively spliced mRNA and has a truncated form of gp130 with a unique sequence, Asn-Ile-Ala-Ser-Phe (NIASF), in its COOH-terminus. We observed serum antibodies to this NIASF sequence frequently in patients with RA, but not in those with other systemic rheumatic diseases or in healthy subjects. In RA, detection of those antibodies was significantly associated with disease activity indices such as serum C-reactive protein (CRP) levels, erythrocyte sedimentation rate, blood platelet counts, and serum IL-6 concentration. In vitro experiments revealed that gp130-RAPS inhibited IL-6 activity, and this inhibition was neutralized by antibodies to the COOH-terminus of gp130-RAPS derived from patients with RA. Thus, autoantibody to gp130-RAPS may play an important role in the progression of RA by promoting IL-6 activity. Inspection of autoantibodies to gp130-RAPS may become a practical clinical test for RA. gp130-RAPS and its autoantibody provide a new clue to the complicated pathogenesis of RA.
Animals↗
Effect of intravenous cyclophosphamide in systemic lupus erythematosus: relation to lymphocyte subsets and activation markers.
Since the mechanism mediating the beneficial effect of intravenous cyclophosphamide (IVCY) in systemic lupus erythematosus (SLE) is unknown, we investigated lymphocyte subsets and markers of activated lymphocytes in patients received IVCY, and compared the results with the effect of steroid pulse. In 55 patients with SLE, 34 patients receiving IVCY [21 cases (61.8%) were responsive] and 25 patients received steroid pulse [21 cases (84.0%) were responsive] (four patients who were resistant to steroid pulse therapy were transferred to IVCY). When the lymphocyte subsets and markers of activated lymphocytes were compared in the responsive and unresponsive group of IVCY, soluble CD4 levels and the ratio of HLA-DP-positive T cells were significantly higher in the unresponsive group. Further, the changes of these markers and costimulatory molecules [LFA-1 (CD11a), ICAM-1 (CD54), CD40 and CD40-ligand (CD154)] were also examined in the responsive patients. The ratio of HLA-DP-positive T cells did not change in the IVCY-responsive group, while it decreased in the steroid pulse therapy-responsive group. The ratio of CD11a on T cells increased and CD54 on B cells decreased in the IVCY-responsive group. The ratio of CD154 on T cells increased in the steroid pulse-responsive group, while it decreased in the IVCY-responsive group. These results suggest that the effect of IVCY is different to that of steroid pulse therapy and mainly related to B cell activation, and that these markers may contribute to predict the responsiveness of IVCY.
Adult↗
The possible role of interleukin-16 in the low incidence of HIV infection in patients with systemic lupus erythematosus.
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CD8-Positive T-Lymphocytes↗
Serum-deprivation induces cell death of rat cultured microglia accompanied with expression of Bax protein.
Expression of Bcl-2 related proteins in rat microglial primary culture was examined. At relative low cell densities, serum deprivation caused cell death and nuclei condensation of cultured microglia. Expression of a pro-apoptotic protein, Bax, but not Bcl-2, was increased by the serum deprivation. SB203580, a specific inhibitor of p38MAPK, prevented both the serum deprivation-induced Bax expression and microglial death. Immunochemical staining showed that microglia expressing a high level of Bax were subjected to apoptosis-like cell death. These observations suggest that Bax expression underlies the apoptosis of cultured microglia after serum deprivation.
Animals↗