Systemic lupus erythematosus and blood type.
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ABO Blood-Group System↗
Biomedical subjects
Hiroshi Osawa
Publications and source records attributed to Hiroshi Osawa.
Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture.
BACKGROUND: Chronic low oxygen in the tubulointerstitial area is a crucial cause of renal degradation and tubulointerstitial damage. Previous reports have suggested that the maintenance of renal blood flow plays a role in the suppression of progressive renal damage. Neovascularization is important for the maintenance of blood flow. We studied the production of angiogenic factors by culturing renal proximal tubular epithelial cells (PTEC) under hypoxic conditions. METHODS: Cultured PTEC were exposed to normal and low-oxygen conditions. The levels of angiogenin (ANG) and vascular endothelial growth factor (VEGF) in the cell supernatants were measured by enzyme-linked immunosorbent assay. The messenger RNAs (mRNAs) of ANG and VEGF in the PTEC were examined by real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). The presence of ANG, VEGF and hypoxia-inducible factor-1 (HIF-1) was studied by immunofluorescence techniques. The effect of cobalt chloride (CoCl(2)), which is an HIF-1 inducer, on the production of ANG and VEGF was also examined in order to elucidate the contribution of the HIF-1 pathway to the production of these cytokines. RESULTS: ANG and VEGF were demonstrated to exist in the cell supernatants, and ANG and VEGF mRNAs were detected in the PTEC. Hypoxic conditions stimulated the secretion of ANG (2.5-fold vs normoxia, P<0.001) and VEGF (3.2-fold vs normoxia, P<0.001) by PTEC. Hypoxic conditions increased the mRNA expression of ANG for 6 h (1.38-fold vs normoxia, P<0.05) and VEGF for 24 h (2.04-fold vs normoxia, P<0.01). Hypoxic conditions also enhanced ANG, VEGF and HIF-1 protein expression in PTEC. The CoCl(2) increased the secretion of ANG (5.2-fold vs control, P<0.0001) and VEGF (2.3-fold vs control, P<0.0001) by PTEC. CONCLUSION: Under hypoxic conditions, the ANG and VEGF secreted by PTEC may modulate angiogenesis and vascular remodeling in the renal interstitium via an increase in the production of HIF-1.
Cell Hypoxia↗
Lower limits of hematocrit and mixed venous oxygen saturation ensuring sufficient cerebral oxygenation during hemodilution in rabbits.
OBJECTIVES: We have assessed clinically systemic tissue oxygenation by monitoring mixed venous oxygen saturation (SvO2) in addition to hematocrit (Hct) during cardiopulmonary bypass. Based on results of experimental studies together with clinical experience, we previously defined the lower limits of the critical range as an Hct of 12% and an SvO2 of 46%. However, these values do not provide direct information about cerebral oxygenation. This study was performed to identify critical values for these variables that would be able to ensure sufficient jugular venous oxygen saturation (SjO2), which reflects global cerebral oxygenation. METHODS: Normovolemic hemodilution was performed in ten rabbits. Hct, SvO2 and SjO2 were measured every 7 minutes. The safety limit for cerebral oxygenation was defined as an SjO2 of 50% based on studies of Croughwell et al. and Cook et al. The limit point was defined as 7 minutes before the time that the SjO2 decreased below 50% for the first time. RESULTS: Minimal values for Hct and SvO2 to maintain SjO2 at 50% or more during normovolemic normothermic hemodilution, expressed as the 95% confidence interval, were Hct of 7.4% to 10.0% and SvO2 of 41.8% to 51.4%. CONCLUSION: Adopting the higher values of these pairs, safety limits for cerebral oxygenation would be an Hct of 10.0% and an SvO2 of 51.4%. In conclusion, our experiments in rabbits suggest new safety limits during normovolemic normothermic hemodilution of Hct of 12% and SvO2 of 52%, taking both whole-body and cerebral oxygenation into consideration.
Animals↗
Peripheral neuropathy caused by high-dose cytosine arabinoside treatment in a patient with acute myeloid leukemia.
The central nervous system toxicity of high-dose cytosine arabinoside is well recognized, but the toxicity of cytosine arabinoside in the peripheral nervous system has been infrequently reported. A 49-year-old Japanese man was diagnosed with acute myeloid leukemia. After he achieved complete remission, he received high-dose cytosine arabinoside treatment (2 g/m2 twice a day for 5 days; total, 20 g/m2) as consolidation therapy. The first course of high-dose cytosine arabinoside resulted in no unusual symptoms, but on day 21 of the second course of treatment, the patient complained of numbness in his right foot. Electromyogram and nerve-conduction studies showed peripheral neuropathy in both peroneal nerves. This neuropathy was gradually resolving; however, after the patient received allogeneic bone marrow transplantation, the symptoms worsened, with the development of graft-versus-host disease, and the symptoms subsequently responded to methylprednisolone. Although the mechanisms of peripheral neuropathy are still unclear, high-dose cytosine arabinoside is a therapy that is potentially toxic to the peripheral nervous system, and auto/alloimmunity may play an important role in these mechanisms.
Acute Disease↗
Nephrotic syndrome associated with interferon-beta-1b therapy for multiple sclerosis.
A 43-year-old woman with multiple sclerosis (MS) had nephrotic syndrome 21 months after starting treatment with interferon (IFN)-beta-1b (subcutaneous administration). She had taken no drug except for the IFN-beta-1b. Because nephrotic syndrome may be induced by IFN therapy, the IFN was stopped. Percutaneous renal biopsy revealed that she had minimal change nephrotic syndrome. As nephrotic-range proteinuria, hypoalbuminemia, and general edema were worsening even 2 weeks after cessation of the drug, oral corticosteroid therapy (prednisolone 40 mg/day) was started. The nephrotic syndrome was treated successfully with prednisolone. The dosage of prednisolone was tapered, without a relapse, and then the corticosteroid therapy was stopped. IFN-beta-1b therapy was then resumed, and the patient is in remission for both nephrotic syndrome and MS. Though proteinuria and nephrotic syndrome is a rare adverse effect of IFN-beta-1b therapy, physicians treating MS patients with this agent should pay careful attention to new clinical symptoms and laboratory findings.
Adjuvants, Immunologic↗
Aclarubicin plus behenoyl cytarabine and prednisolone for previously treated acute myeloid leukemia patients.
This study analysed the clinical outcome of salvage therapy consisting of aclarubicin (ACR) plus behenoyl cytarabine (BHAC) and prednisolone (PSL) for patients with acute myeloid leukemia (AML). ACR was administered at a dose of 13 mg/m2 per day for 14 days; BHAC, at 130 mg/m2 per day for 14 days; and PSL was administered orally at a dose of 60 mg/m2 per day for 5 days. Of 47 patients, 25 (53.2%) achieved CR. The CR rates of patients in whom induction failed was 55% and that of relapsed patients was 51.9%. Four patients received allogeneic hematopoietic stem cell transplantation after achieving CR. Five patients achieved long-term survival without relapse. The 10-year relapse-free and overall survival rates were 20% and 10.6%, respectively. ACR in combination with BHAC showed a substantial anti-leukemic efficacy in previously treated AML patients and the role of ACR and BHAC may be considered while devising strategies for AML treatments.
Aclarubicin↗
Roxithromycin inhibits transforming growth factor-beta production by cultured human mesangial cells.
BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in progression of renal injury. However, few materials which inhibit TGF-beta have been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti-inflammatory, immunomodulatory and tissue reparative effects besides its bacteriostatic activity, although the exact mechanism of its anti-inflammatory and immunomodulatory effects was not defined. We examined the effect of ROX on production of TGF-beta and type IV collagen by cultured human mesangial cells (HMC). METHODS: Human mesangial cells were incubated with several concentrations of ROX and TGF-beta and type IV collagen levels in the culture supernatants were measured by enzyme-linked immunoassay. Amount of TGF-beta mRNA was also quantified by using a colourimetric mRNA quantification kit and semiquantitative reverse transcriptase polymerase chain reaction. We also examined the effect of ROX on tyrosine kinase, MAP kinase and NF-kappaB stimulated by thrombin. RESULTS: Roxithromycin (0.1-10.0 microg/mL) inhibited TGF-beta production by HMC in a dose- and time-dependent manner without inducing cell injury. ROX (10.0 microg/mL) also inhibited mRNA expression of TGF-beta in HMC. Thrombin (5 U/mL) stimulated TGF-beta production by HMC and ROX significantly inhibited the stimulating effect of thrombin on TGF-beta production. ROX also inhibited the increment of type IV collagen production stimulated by thrombin. ROX (10.0 microg/mL) suppressed the thrombin-induced NF-kappaB activation, although ROX did not inhibit the activation of tyrosine kinase and MAP kinase by thrombin. CONCLUSION: Roxithromycin has an inhibitory effect on TGF-beta production by HMC possibly via inhibition of NF-kappaB. ROX may be a potential agent for the treatment of glomerulosclerosis.
Anti-Bacterial Agents↗
Intensifying daunorubicin in induction for patients with core binding factor leukemia.
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Adolescent↗
Losartan, an angiotensin-II receptor antagonist, retards the progression of advanced renal insufficiency.
Chronic renal disease with elevated level of serum creatinine (Cr) often progresses to end-stage renal disease. Although blockade of the renin-angiotensin system has been shown to slow the progression of chronic renal disease, it remains uncertain whether one could expect such a renoprotective effect even when the treatment is initiated late in the course of renal disease. The purpose of the present study was to examine the effect of losartan, an angiotensin-II receptor antagonist, on the progression of advanced renal insufficiency. We retrospectively analyzed eight hypertensive patients, whose baseline Cr levels exceeded 2.0 mg/dl (2.2-5.5); the subjects included 6 non-diabetic glomerular diseases, 1 diabetic nephropathy and 1 polycystic kidney disease. Losartan was given at the dosage of 25-50 mg/day. Changes in mean blood pressure (MBP) and serum levels of Cr, potassium (K) and uric acid were evaluated after treatment for 24 weeks. Slopes of reciprocal of serum Cr plotted against time (1/sCr slope), which indicate the rate of renal function loss before and after the treatment period, were compared. There was a significant reduction of 1/sCr slope after losartan (-0.004 +/- 0.002 dl/mg/week before and -0.001 +/- 0.002 dl/mg/week after the treatment, p < 0.05). MBP and serum levels of Cr, K and uric acid were not changed significantly by losartan treatment. However, improvement of 1/sCr slope was correlated to the degree of MBP changes. Based on the available data from 4 patients, proteinuria was decreased in 3 patients. These results suggest that losartan may retard the progression of advanced renal insufficiency.
Adult↗
[Video-assisted thoracoscopic debridement for acute empyema; a low invasive surgery for acute empyema].
BACKGROUND: Recent study reported that thoracoscopic surgery for acute empyema can achieve good results. We performed video-assisted thoracoscopic debridement (VD) in cases diagnosed as having acute empyema when conservative therapies such as administration of antibiotics or continuous thoracic drainage were not successful. METHODS: Two to 4 access ports were inserted into the empyema lumen, and surgery were conducted only under monitoring vision. After removing as much pus, coating, fibrin walls and peel as possible, a chest tube was set in the lumen for drainage. Thirty cases treated in our hospital were reviewed with respect to selected parameters. RESULTS: The interval from onset to surgical treatment was 41.0 +/- 21.0 days. All cases were considered in either fibrinopurulent phase or early organizing phase. Pathogenic bacteria were identified in 8 cases. Surgical duration was 93.1 +/- 26.6 minutes. Hospitalization period was 26.3 +/- 36.4 days. Twenty-seven cases showed improvement after the first VD procedure, while 3 cases required repeat procedures. CONCLUSIONS: VD may achieve good results not only in the fiburinopulurent phase but also in the early organization phase. VD is both low invasive and highly effective for acute empyema.
Acute Disease↗
Roxithromycin is an inhibitor of human coronary artery smooth muscle cells proliferation: a potential ability to prevent coronary heart disease.
Roxithromycin (RXM), a macrolide antibiotic, is used in clinical trials to address secondary prevention of coronary heart disease. However, the effects of RXM on human coronary artery smooth muscle cells (CASMC) proliferation remain unclear. Human CASMC were stimulated with growth medium containing 5% fetal bovine serum and growth factors. RXM at 1 or 10 microg/ml, which are relevant to the therapeutic plasma levels, significantly suppressed mitogen-induced CASMC proliferation, assessed by WST-1 assay and cell counting. Flow cytometry analysis demonstrated that RXM suppressed mitogen-induced G1 to S progression on cell cycle. Western blot showed that RXM inhibited phosphorylation of retinoblastoma gene products, reduced protein levels of cyclin D1 and A, and restored downregulation of cyclin-dependent kinase (CDK) inhibitor p27kip1. The activities of CDK4 and CDK2 were suppressed by RXM without affecting their protein levels. When transfected with both IkappaB kinase alpha and beta constructs as nuclear factor-kappa B (NF-kappaB) activator, CASMC entered S phase at 24 h, and RXM inhibited it. Electrophoretic mobility shift assay and immunostaining of NF-kappaB p65 demonstrated that RXM inhibited mitogen-induced NF-kappaB activation. These results indicate that RXM is an inhibitor of human CASMC proliferation through modulating cell cycle regulatory proteins and inhibiting NF-kappaB signaling pathway.
Anti-Bacterial Agents↗
Hepatitis C virus-associated glomerulonephritis without hepatitis C virus in the blood.
An 82-year-old woman with nephrotic syndrome and a 61-year-old woman with proteinuria and purpura on the lower extremities are reported. Both patients had test results positive for hepatitis C virus (HCV) antibody, but HCV RNA was not detected in the blood of either patient. The kidney biopsy showed membranoproliferative glomerulonephritis with capillary deposition of C3 and immunoglobulin M, indicating HCV-associated glomerulonephritis. These cases are suggestive to study the pathogenesis of this disease.
Adult↗
Septic intramuscular embolism in a neutropenic patient with myelodysplastic syndrome accompanied by asymptomatic septic pulmonary emboli.
Septic embolisms are rare disorders which are associated with increased mortality and morbidity. We describe a rare case of septic intramuscular embolism accompanied by asymptomatic pulmonary embolism in a neutropenic patient. Methicillin-sensitive Staphylococcus aureus (S. aureus) was detected and multiple nodules were revealed in both thighs and lung. Although he was treated with sensitive antibiotics to .S. aureus, the symptoms remained unchanged during the neutropenic period. Fever subsided rapidly and his thigh pain disappeared after neutropenia resolved. A prompt diagnosis and optimal therapeutic decisions are critical for the reduction of mortality.
Embolism↗
Long-term follow-up high-dose chemotherapy (drug-only program) followed by autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas.
PURPOSE: To investigate the feasibility of high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) for aggressive non-Hodgkin's lymphoma (NHL), we conducted HDCT with ASCT using a drug-only protocol without total body irradiation. Previously untreated and treated adult patients with aggressive lymphoma were enrolled onto this study. For the HDCT protocol, we developed the AECC regimen, a drug-only regimen consisting of etoposide, carboplatin, cyclophosphamide, and nimustine (ie, ACNU). Mobilized peripheral blood stem cells were used mainly as a source for ASCT and were used based on collection rates of CD34 cells. PATIENTS AND METHODS: Fifty-six patients were enrolled and assessed for this study. The median length of follow-up was 6.5 years, with a range of 0.2-12.5 years. Retrospective immunophenotypic examination indicated that the majority of the patients were diagnosed with B-cell lymphoma. RESULTS: Before HDCT, 37 patients still had disease (26 partial responses [PRs] and 11 cases of no response), and 19 patients exhibited a complete response (CR) before HDCT with ASCT. Among 56 patients, 37 (66%) exhibited a CR, including patients continuing their first CR and those experiencing a second or further CR, and 11 patients (19.6%) exhibited PR on HDCT with ASCT. Outcomes of patients without CR were significantly poorer than those of the patients with CR, and 7-year overall survival rates of patients with and without CR were 63% and 27.2%, respectively. No patients developed a second malignancy, including leukemia or myelodysplastic syndrome. CONCLUSIONS: High-dose chemotherapy followed by ASCT is one of the available consolidation therapies for aggressive NHL, and additional involved-field irradiation could play a role in the management of patients with NHL who do not exhibit a CR after treatment with HDCT containing a drug-only program.
Adult↗
Side effects of therapy: case 1. Nephrotic syndrome associated with gefitinib therapy.
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Aged↗
Critical values of hematocrit and mixed venous oxygen saturation as parameters for a safe cardiopulmonary bypass.
OBJECTIVE: Mixed venous oxygen saturation (SvO2) is high despite a low hematocrit implies that the relationship between oxygen demand and supply is in a safe state. This study was sought to determine the critical values for hematocrit and SvO2 for safe cardiopulmonary bypass. METHODS: Study 1: To evaluate the limit of hemodilution without cardiopulmonary bypass, normovolemic hemodilution with Dextran 40 (10%) was performed in 14 rabbits. SvO2 was monitored from the right atrium, and the hemodynamic parameters were recorded continuously. Study 2: To determine the critical values for hematocrit and SvO2 during cardiopulmonary bypass, normothermic and hypothermic cardiopulmonary bypass were performed in 13 rabbits and hemodynamic parameters were corrected. RESULTS: Study 1: The heart rate decreased to unsafe levels abruptly, when the SvO2 was < or = 43% or the hematocrit was < or = 10%. The lactate concentration increased when the SvO2 was < or = 46% or the hematocrit was < or = 12%. Study 2: When the hematocrit was < or = 12%, the SvO2 decreased gradually. Even when weaning was possible, the animals with a hematocrit < or = 12% collapsed hemodynamically within 40 minutes after cardiopulmonary bypass. Most of the animals could not be weaned from cardiopulmonary bypass during either normothermic or hypothermic cardiopulmonary bypass when the SvO2 was < or = 46%. CONCLUSIONS: Continuous monitoring of hematocrit and SvO2 provides evidence-based guidelines for safe cardiopulmonary bypass. The lower limits of critical range for a safer cardiopulmonary bypass are hematocrit of 12% and SvO2 of 46%.
Animals↗
A word of caution about the skeletonization of the right gastroepiploic artery.
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Gastroepiploic Artery↗
Tissue factor pathway inhibitor production by human proximal tubular epithelial cells in culture.
Fibrin deposition in the peritubular capillaries and along the tubular basement membrane is commonly observed in several renal diseases and suggests the involvement of blood coagulation in tubulointerstitial damage. It has been demonstrated that tissue factor (TF) is present in tubular epithelial cells of animal models of nephritis. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit TF activity and it is now thought to be produced mainly by the vascular endothelial cells. We examined whether human proximal tubular epithelial cells (PTEC) could produce TFPI and attempted to clarify the regulatory factors affecting TFPI production. Cultured human PTEC were used. The procoagulant activity (PCA) in PTEC lysate was quantified by measurement of the one-stage recalcification time. TFPI in the cell supernatants was measured by ELISA. The mRNA of TF and TFPI in PTEC was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). PCA which is compatible with TF activity was present in the PTEC lysate. TF mRNA and TFPI mRNA were detected in PTEC. The amount of TFPI increased over time in the cell supernatants. Immnoblot analysis revealed 40 kD protein of TFPI, and TFPI antigen was demonstrated in PTEC by immunofluorescence. The concentration of TFPI was significantly increased following incubation with thrombin and heparin in a dose- and time-dependent manner, although the amount of TFPI mRNA was not changed. Our study showed that TFPI is produced in cultured PTEC and added one more cell type that produced TFPI other than endothelial cells. Thrombin and heparin stimulated TFPI secretion from PTEC. TFPI of PTEC may act against generation of thrombin and tubular fibrin formation induced by tissue factor activation. The augmentation of TFPI secretion by heparin may play an important role in the modulation of anticoagulant properties of PTEC.
Anticoagulants↗