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Shinji Nakao

Publications and source records attributed to Shinji Nakao.

At least 37 records · Page 2Linked to original sources
PubMed2005

Changes in angiogenic growth factor levels after gefitinib treatment in non-small cell lung cancer.

BACKGROUND: To investigate the changes in angiogenic growth factor expression before and after gefitinib treatment, and the association between this expression and response to gefitinib treatment, we measured circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase (MMP) -2 and -9, and tissue inhibitors of metalloproteinase (TIMP) -1 and -2 in patients with non-small cell lung cancer (NSCLC). METHODS: Serum and plasma samples were collected from 52 patients before and after gefitinib treatment. The levels of VEGF, bFGF, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using a sandwich enzyme immunoassay kit. RESULTS: Of the 52 patients, 17 (32.7%) achieved a partial response, 19 (36.5%) had stable disease and 16 (30.8%) had progressive disease. The levels of VEGF, bFGF, MMP-2, MMP-9, TIMP-1 and TIMP-2 did not change significantly after gefitinib treatment, even in responders. The levels of VEGF in volunteers, responders and non-responders were 384 +/- 86.4, 404 +/- 94.3 and 719 +/- 99.8 pg/ml, respectively. The difference between volunteers and responders was not significant (P = 0.540), while the differences between volunteers and non-responders (P = 0.031), and responders and non-responders (P = 0.028) were significant. CONCLUSIONS: Although our results indicate that gefitinib treatment does not affect circulating levels of angiogenic growth factors even in patients who showed a response to gefitinib treatment, low levels of VEGF may predict response to gefitinib treatment in patients with NSCLC.

Adult↗
PubMed2005

Granulocyte colony-stimulating factor-producing malignant pleural mesothelioma with the expression of other cytokines.

We report a 65-year-old man with malignant pleural mesothelioma that produced granulocyte colony-stimulating factor (G-CSF) and other cytokines. At the first presentation, the WBC count was 8600 cells/microl and C-reactive protein (CRP) was 0.6 mg/dl. Seventeen months later, the WBC count had increased to 53,600 cells/microl (93% neutrophils) and CRP to 27.1 mg/dl. The serum concentration of G-CSF had increased to 36.0 pg/dl (normal range, <5.0 pg/dl), interleukin 1beta (IL-1beta) to 46.0 pg/dl (normal range, <10 pg/dl), and IL-6 to 197 pg/dl (normal range, <4.0 pg/dl). The patient died 19 months after the first presentation, and 6 weeks after sudden leukocytosis. At autopsy, a diagnosis of malignant pleural mesothelioma was made. The tumor cells were positive for anti-human G-CSF, granulocyte-macrophage colony-stimulating factor, IL-1beta, and IL-6 antibodies. Malignant mesothelioma may produce G-CSF and other cytokines. Mesothelial cells may have the potential to produce G-CSF and other cytokines in the progress of malignant formation, and this may be a factor influencing the poor prognosis.

Aged↗
PubMed2005

Pulmonary hypertension after splenectomy in hereditary stomatocytosis.

Hereditary stomatocytosis is an autosomal dominant, congenital hemolytic form of anemia, and thromboembolic complications may ensue after a splenectomy is performed in a patient with hereditary stomatocytosis. However, little is known about the relationship between pulmonary hypertension and hereditary stomatocytosis. We describe here a rare case of a patient with hereditary stomatocytosis who developed pulmonary hypertension due to thromboembolic disease after splenectomy. At the first presentation, he was diagnosed with hemolytic anemia, but the cause was unknown, and he was also diagnosed with pulmonary hypertension. Thereafter, we linked his pulmonary hypertension with hemolytic anemia because his red blood cells appeared as leptocytes, acanthytes, and stomatocytes on scanning electron microscopy. It is important to confirm the diagnosis of hemolytic anemia, and splenectomy should be performed with due consideration of whether patients have hemolytic anemia.

Anemia, Hemolytic↗
PubMed2005

Impact of human leucocyte antigen mismatch on graft-versus-host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors.

The impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft-versus-host disease (GVHD) and graft failure after reduced-intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50% in those with two- to three-loci-mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II-IV aGVHD (P=0.01), chronic GVHD (cGVHD) (P=0.05) and graft failure (P=0.033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one-locus-mismatched RICT (51%) and HLA-matched RICT (48%) (P<0.0001). A two- to three-loci mismatch was identified as an independent risk factor for OS (P<0.001), but there was no significant difference in OS between HLA-matched and one-locus-mismatched RICT. HLA incompatibility between the donor and recipient is an important risk factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients with high-risk malignancies who lack HLA-matched related donors.

Acute Disease↗
PubMed2005

Beneficial effects of urokinase on lipopolysaccharide-induced disseminated intravascular coagulation in rats: focus on organ function and endothelin levels.

In a rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC), we used urokinase (UK) in an attempt to clarify the role of fibrinolysis and to investigate changes in plasma endothelin levels. Two kinds of experiment were performed. The first one: experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 h via the tail vein, and two doses of UK (2.0 or 10.0 IU/g/4.5 h) were administered to rats 30 min before infusion of LPS, after which UK infusion was continued for a further 4 h. The second one: experimental DIC was induced by sustained infusion of 1 mg/kg/10 min LPS for 10 min, and two doses of UK (2.0 or 10.0 IU/g/4 h) were administered to rats at 30 min after LPS infusion. The parameters described below were determined at 4 h in the first experiment, at 4 h and 8 h in the second one. The similar results were observed in both kinds of experiment. There were no significant differences in plasma thrombin-antithrombin complex, fibrinogen or platelet number among the three DIC groups, in both kinds of experiment. Plasma levels of D-dimer were significantly increased in the LPS + higher dose of UK group when compared with the LPS group. The increased plasma plasminogen activator inhibitor (PAI) activity seen in the LPS group was significantly suppressed in the groups receiving UK (especially higher dose of UK). In addition, the increased plasma levels of creatinine and alanine aminotransferase seen in the LPS group were significantly suppressed in the groups receiving UK (especially higher dose of UK). Plasma levels of endothelin, known to be a potent vasoconstrictive agent, were markedly elevated by LPS infusion, and were significantly suppressed in the groups receiving UK of both kinds of experiment, in a dose-dependent fashion compared with LPS group. Glomerular fibrin deposition was significantly suppressed in the groups receiving UK when compared with the LPS group. No manifestations of bleeding were observed in any of the groups. Enhanced fibrinolysis and depressed endothelin induced by UK thus appear to play an important role in preventing the development of organ failure in the LPS-induced DIC model.

Animals↗
PubMed2005

Effect of combined therapy of danaparoid sodium and tranexamic acid on chronic disseminated intravascular coagulation associated with abdominal aortic aneurysm.

Chronic disseminated intravascular coagulation (DIC) is a well-known complication of aortic aneurysm. A 63-year-old man with bleeding tendency and a large palpable abdominal aortic aneurysm (AAA) was diagnosed as having fibrinolysis dominant DIC by the excessive activation of both coagulation and fibrinolysis (plasmin -alpha2 plasmin inhibitor complex concentration is usually >4 microg/ml). Although several treatments were tried, DIC could not be controlled until the patient was given combined therapy of danaparoid (1,250 U/12 h, bolus IV) and tranexamic acid (0.5 g x 3/day, oral administration). This therapy may be beneficial when control for bleeding is required without restricting the ambulatory movement of patients by continuous drip.

Anticoagulants↗
PubMed2005

Small follicular lymphoma arising near the ampulla of vater: a distinct subtype of duodenal lymphoma?

A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.

Ampulla of Vater↗
PubMed2005

Isolated hyperkalemia associated with cyclosporine administration in allogeneic stem cell transplantation for renal cell carcinoma.

Two patients with advanced renal cell carcinoma underwent allogeneic hematopoietic stem cell transplantation and received cyclosporine (CSP) as part of their immunosuppressive therapy. Despite adequate renal function, both patients developed hyperkalemia. CSP was the only pharmaceutical agent to which this electrolyte abnormality could be attributed. Evaluation of renal tubule function suggested that CSP-associated isolated hyperkalemia resulted from tubular resistance to aldosterone. We propose that the presence of a single functional kidney may be a risk factor for isolated hyperkalemia due to CSP.

Adult↗
PubMed2005

Complete and durable remission of refractory mantle cell lymphoma with repeated rituximab monotherapy.

We encountered a 53-year-old man with general fatigue. Bone marrow investigations revealed an infiltration of CD20+CD5+CD23- cells and the presence of cyclin D1 lymphoid cells, leading to a diagnosis of mantle cell lymphoma, clinical stage IV. The first 2 lines of chemotherapy, CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone) and fludarabine-cyclophosphamide, produced only a transient decrease in serum lactic dehydrogenase levels, without a clinical remission. Because of the persistence of bone marrow hypoplasia, monotherapy with 375 mg/m2 rituximab was administered. The pancytopenia gradually improved, and a complete remission was obtained after 4 cycles of rituximab. The patient remains in complete remission 21 months after the third rituximab therapy for maintenance.

Antibodies, Monoclonal↗
PubMed2005

Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation.

To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.

Adult↗
PubMed2005

Primary tracheal lymphoma: case report and literature review.

We describe a 20-year-old Japanese woman with anaplastic large cell lymphoma in whom primary tracheal involvement was associated with life-threatening airway obstruction. After debulking surgery, the patient was successfully treated with chemotherapy and radiotherapy. A total of 28 cases of primary tracheal lymphoma were reviewed. Common clinical features included predominance of localized disease, respiratory symptoms resembling acute asthma, absence of hemoptysis, and rapid progression of tracheal stenosis. Various histological subtypes of primary tracheal lymphoma exist and are likely to determine prognosis.

Asthma↗
PubMed2005

Immune pathophysiology of aplastic anemia.

Acquired aplastic anemia (AA) is considered an immune-mediated disease because approximately 70% of AA patients improve with immunosuppressive therapy. However, little is known about the inciting antigens or the mechanisms responsible for the destruction of hematopoietic stem cells by immune system attack. Recent advances in immunologic techniques have promoted our understanding of the pathogenesis of AA and have provided evidence that AA is an organ-specific T-cell-mediated disease localized in the bone marrow. Moreover, antibody screening of patients' serum with a complementary DNA library derived from hematopoietic cells has identified several proteins as candidate autoantigens in AA.

Anemia, Aplastic↗
PubMed2005

Severe community-acquired pneumonia in an intensive care unit: risk factors for mortality.

OBJECTIVE: To evaluate severe community-acquired pneumonia (SCAP) patients in an intensive care unit (ICU) with regard to risk factors for mortality and to compare ICU patients with matched non-ICU patients to evaluate whether our judgement for ICU admission was appropriate or not. MATERIALS AND METHODS: During a 7-year period, all patients with CAP who were admitted to the ICU were examined. They underwent clinical and radiographic evaluations, and two commonly used severity of illness scores were also calculated using the Simplified Acute Physiological Score (SAPS) and the Acute Physiology and Chronic Health Evaluation (APACHE) II methods. To detect risk factors for ICU admission using existing guidelines, each study patient was matched with two patients hospitalized in a general medical ward. RESULTS: Seventy-two patients were identified during the study period. Their mean age was 72.9 years, and 35 patients (48.6%) subsequently died. For the univariate analysis, there were significant differences with the pulse rate > or = 130/min, blood urea nitrogen > or = 30 mg/dl, multilobar shadow, SAPS > or = 13, APACHE II > or = 23, and the occurrence of septic shock between the survivors and those who died. For the multivariate analysis, septic shock (p = 0.0005, odds ratio of 26.6) and blood urea nitrogen > or = 30 mg/dl (p = 0.037, odds ratio of 5.38) were associated with mortality. Regarding the characteristics of different clinical predictions for ICU admission, the revised American Thoracic Society criteria might have been the most accurate. CONCLUSION: Septic shock was associated with high mortality, which is a more accurate and higher predictor of mortality than was physical examination, laboratory or radiographic findings.

Aged↗
PubMed2005

Primary alveolar hypoventilation syndrome complicated with antiphospholipid syndrome.

A 32-year-old woman was transported to our hospital by ambulance because of loss of consciousness and breathing induced by drug intoxication. After general status was recovered, her arterial blood gas analysis under breathing room air revealed hypercapnia and hypoxemia which were caused by hypoventilation. After exclusion of apparent pulmonary, neuromuscular and central nerve diseases, she was diagnosed with primary alveolar hypoventilation syndrome. She had the complication of antiphospholipid syndrome (APS), suggesting the possibility of small lesions of the brainstem due to APS, which were too small to be detected on CT or MRI; these small lesions could cause injuries to the respiratory center.

Adult↗
PubMed2005

Characterization of the prostaglandin biosynthetic pathway in non-small cell lung cancer: a comparison with small cell lung cancer and correlation with angiogenesis, angiogenic factors and metastases.

To investigate the components of the prostaglandin biosynthetic pathway, the characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane synthase (TXS) were examined for autopsied cases with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Autopsied patients (n=120) with lung cancer were examined, of whom 25 had SCLC and 95 had NSCLC. Immunostaining was performed for COX-1, COX-2, hPGDS, mPGES, TXS, CD34, vascular endothelial growth factor (VEGF), and basic fibroblastic growth factor (bFGF). The immunostaining scores of the prostaglandin biosynthetic pathway markers were significantly higher for adenocarcinoma than for SCLC (p<0.0001). In addition, there were significant correlations between two markers of the prostaglandin biosynthetic pathway for cases with SCLC and NSCLC. For NSCLC, the mean immunostaining scores for the prostaglandin biosynthetic pathway markers were significantly higher for cases with high count groups than low count groups for MVD, VEGF and bFGF, except COX-2 and MVD, and COX-2 and bFGF. The mean immunostaining scores for COX-1, COX-2, mPGES, and TXS were significantly higher for cases with more metastatic organs who had NSCLC. Prostaglandin biosynthetic pathway markers may act synergistically and enhance tumor angiogenesis, the expression of angiogenic factors, and metastases in patients with NSCLC.

Adult↗