A monoclonal antibody (1G10) recognizes a novel human mesangial antigen.

We have identified a unique mesangial matrix protein of the human glomerulus by using a monoclonal antibody, 1G10, generated against culture human glomerular cells. By immunofluorescence, the antigen recognized by 1G10 (1G10 antigen) is present in mesangium and smooth muscle tissue and cannot be detected in any other tissue examined. Immunoelectron microscopy of glomeruli indicated that 1G10 antigen is present exclusively in the mesangial matrix at the endothelial-mesangial interface. The 1G10 antigen is also expressed by cultured mesangial cells, but not by cultured glomerular epithelial cells, umbilical endothelial cells or fibroblasts. 1G10 did not react with the mesangial matrix proteins [fibronectin (FN), laminin (LAM), collagen types I, III, IV, V, and VI (Col I, III, IV, V, VI), heparin sulfate proteoglycan (HSPG), or thrombospondin (TS)] present under normal and diseased states or smooth muscle antigens (myosin, actin), but did react with a 4 M urea extract of renal cortex and a 0.3% deoxycholate extract of isolated glomeruli. Two dimensional immunoblot analysis using the urea extract demonstrated the binding of 1G10 to an approximately 200 KDa polypeptide with pI 6.0. On one dimensional immunoblot this band did not show cross react with polyclonal antisera to FN, LAM, Col IV, V, VI, HSPG or TS. This mesangial matrix component is trypsin and periodate sensitive, suggesting that it has the character of glycoprotein. In renal biopsy specimens from patients with mesangial proliferative glomerulonephritis (GN) and membranoproliferative GN, the expression of the 1G10 antigen increased along with mesangial hypercellularity or increased accumulation of mesangial matrix, but decreased in completely sclerosed glomeruli. No significant changes in 1G10 antigen expression was observed in membranous GN or minimal change nephrosis compared to normal glomeruli. This study suggests that the 1G10 antigen may not only be a useful marker for the clinical assessment of GN, but may also serve as a potential tool for the study of the pathogenesis of glomerular diseases characterized by cellular proliferation and mesangial matrix expansion.     

Interstitial irradiation for carcinoma of tongue complicated by chronic renal failure undergoing hemodialysis--a case report

There has been some controversy concerning dose-time correction in continuous irradiation at low dose rates. We present the results of carcinoma of the tongue in a patient complicated by chronic renal failure, for which he was undergoing hemodialysis three times a week. This patient was treated with a single implant but with a doubling of 137Cs needles for double strength. The actual dose was given in a shorter treatment time than recommended, with the dose-time adjustment following the Paterson-Parker system. The patient has been alive and well for eight years.     

Treatment of squamous cell carcinoma of the head and neck with multi-drug chemotherapy and radiotherapy

Multi-drug chemotherapy containing cisplatin has been reported to be one of the most active chemotherapy regimens in advanced or recurrent head and neck squamous cell carcinoma. In this study, the current status of clinical investigation of combination chemotherapies is reviewed. And our data are presented in head and neck cancer with multi-drug chemotherapy containing cisplatin. Thirty-five patients of stage 3-4 and 70 patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated by multi-drug chemotherapy containing cisplatin, and radiotherapy and/or operation. The overall response rate was 71.4%, with 17.1% complete remission in previously untreated, locally advanced patients and 31.4% in recurrent or metastatic patients. Problems of chemotherapy combined with radiotherapy and future direction of clinical study in locally advanced or recurrent head and neck cancer are discussed.     

Concurrent Adult T-Cell Leukemia and Acute Myeloblastic Leukemia

A 49-year-old man developed adult T-cell leukemia (ATL) andacute myeloblastic leukemia (AML) at the same time. Using Southernblotting analysis, the leukemic cells of the ATL were foundto contain the human T-cdl leukemia virus type I (HTLV-I) proviralgenome, whereas those of the AML did not, indicating the HTLV-Inot to be associated with the AML oncogenesis. At the initialpresentation, the serum anti-HTLV-I antibody was judged on screeningby a routine particle-agglutination (PA) test and an indirectimmunofluorescence assay (IF) to be negative. By Western blottinganalysis, however, the serum was proved to be positive for anti-HTLV-Iantibody. These results indicate that a routine PA-test andan IF way show false negative reactions on very rare occasionsof low antibody titer. This is the first report of a coincidenceof ATL with another type of leukemia.     

Chemotherapy for lung cancer patients

The number of lung cancer-related deaths has increased since the 1960 and has become the leading cause of cancer-related death in Japan. It is anticipated that the number will double in the next 20 years. Chemotherapy is a hopeful systemic therapy because of distant metastases due to lung cancer. Platinum based doublets remain the standard of care for the first-line treatment of metastatic NSCLC. As salvage chemotherapy for patients, the effectiveness of docetaxel has been confirmed. The standard chemotherapy for extensive SCLC is the combination of cisplatin and irinotecan or etoposide. Recently, randomized trials have shown that platinum-based chemotherapy has the potential to improve survival among patients with completely resected NSCLC. Recent advances in molecular biology and genetics have created new molecular targeted therapies for lung cancer. New anti-cancer agents, including gefitinib, erlotinib, bevacizumab, pemetrexed and amrubicin, are being developed currently.     

Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats

Studies were performed to test the hypothesis that reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) contribute to the pathogenesis of aldosterone/salt-induced renal injury. Rats were given 1% NaCl to drink and were treated with one of the following combinations for 6 weeks: vehicle (0.5% ethanol, SC, n=6); aldosterone (0.75 microg/H, SC, n=8); aldosterone plus a selective mineralocorticoid receptor antagonist; eplerenone (0.125% in chow, n=8); aldosterone plus an antioxidant; and tempol (3 mmol/L in drinking solution, n=8). The activities of MAPKs, including extracellular signal-regulated kinases (ERK)1/2, c-Jun-NH2-terminal kinases (JNK), p38MAPK, and big-MAPK-1 (BMK1) in renal cortical tissues were measured by Western blot analysis. Aldosterone-infused rats showed higher systolic blood pressure (165+/-5 mm Hg) and urinary excretion of protein (106+/-24 mg/d) than vehicle-infused rats (118+/-3 mm Hg and 10+/-3 mg/d). Renal cortical mRNA expression of p22phox, Nox-4, and gp91phox, measured by real-time polymerase chain reaction, was increased in aldosterone-infused rats by 2.3, 4.3, and 3.0-fold, respectively. Thiobarbituric acid-reactive substances (TBARS) content in renal cortex was also higher in aldosterone (0.23+/-0.02) than vehicle-infused rats (0.09+/-0.01 nmol/mg protein). ERK1/2, JNK, and BMK1 activities were significantly elevated in aldosterone-infused rats by 3.3, 2.3, and 3.0-fold, respectively, whereas p38MAPK activity was not changed. Concurrent administration of eplerenone or tempol to aldosterone-infused rats prevented the development of hypertension (127+/-2 and 125+/-5 mm Hg), and the elevations of urinary excretion of protein (10+/-2 and 9+/-2 mg/day) or TBARS contents (0.08+/-0.01 and 0.11+/-0.01 nmol/mg protein). Furthermore, eplerenone and tempol treatments normalized the activities of ERK1/2, JNK, and BMK1. These data suggest that ROS and MAPK play a role in the progression of renal injury induced by chronic elevations in aldosterone.     

Infected acute subdural hematoma associated with invasive pneumococcal disease

A previously healthy 68-year-old woman presented with a rare case of subdural empyema which developed at the site of preceding acute subdural hematoma (SDH). She was first admitted for treatment of an acute SDH after a fall. Since she was neurologically intact and the SDH volume decreased with conservative management, she was discharged 9 days after admission for follow up as an outpatient. Three days after discharge, she unexpectedly returned with worsening headache and altered mental status. Brain computed tomography (CT) showed increased SDH volume. Her condition deteriorated rapidly after presentation, with further increase in SDH volume. Copious pus in addition to the SDH was evacuated by emergency drainage, establishing the diagnosis of subdural empyema. Streptococcus pneumoniae was identified from bacterial cultures. Despite improvement in postoperative CT findings, she fell into septic shock and died 3 days after the drainage. Autopsy revealed meningitis and lobar pneumonia, and the postmortem diagnosis was invasive pneumococcal disease. Infection of acute SDH resulting in subdural empyema by S. pneumoniae is extremely rare. However, invasive pneumococcal disease is not uncommon in the elderly and tends to cause intracranial bleeding. Considering the high mortality rate of invasive pneumococcal disease and the low vaccination rate among the elderly in Japan, neurosurgeons should ask about the pneumococcal vaccination status.