Lupus nephritis: varying complement-fixing properties of immunoglobulin G antibodies to antigens of cell nuclei.

Relative complement-fixing activity of antibodies to nuclear antigens, including DNA, were determined in serums of 15 patients with, and 65 patients without, active lupus nephritis, by comparing titers obtained in two methods. High complement-fixing activity of antibody was found in the nephritis group and low activity in the others. Results with immunoglobulin G fractions were similar.

Detection of Pb-LIII edge XANES spectra of urban atmospheric particles combined with simple acid extraction.

Pb-LIII edge XANES spectra of atmospheric particles are directly obtained by fluorescent XAFS spectroscopy using a 19-element solid state detector (SSD). Particulate sample was collected on a quartz fiber filter using a high-volume air sampler, and the filter was cut into small pieces (25x25 mm). Then, surface layer of the filter piece was scaled and accumulated in order to enhance the particle density per filter unit. Use of 10 pieces of the surface layer enables the measurement of Pb-LIII edge XANES spectra on beamline BL01B1 at SPring-8, Hyogo, Japan. The shape of the Pb-LIII edge XANES spectra of the particulate sample is similar to the shapes of the spectra for PbS, PbCO(3), PbSO(4) and/or PbCl(2). Additionally, the filter sample is also divided into water-soluble, 0.1 M HCl-extractable, and residual fractions of Pb compounds by a simple acid extraction procedure. We discuss the possibility of Pb speciation in the particulate samples with combination of highly sensitive XANES spectroscopy and simple acid extraction.

Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis.

We have identified a novel autoantibody reactive with all three classes of RNA polymerases, well-characterized nuclear enzymes, in sera from patients with systemic sclerosis (SSc). After incubation with [35S]methionine-labeled HeLa cell extracts, 14 of 275 SSc sera immunoprecipitated 12 or 14 proteins with similar molecular weights as those of several subunit proteins of eukaryotic RNA polymerases I, II, and III. Purified IgG from these two types of sera inhibited RNA transcription catalyzed by RNA polymerases I, II, and III in vitro. Immunoblot analysis using RNA polymerase-enriched fraction showed that the majority of these sera reacted with 42- or 25-kD protein. Anti-RNA polymerase antibody was highly specific to SSc, especially to diffuse cutaneous SSc. Clinical features associated with this antibody included a high frequency of heart and kidney involvement and a poor survival rate at 5 yr after first visit. These findings indicate that the autoantibody to three classes of RNA polymerases is a new marker for a unique subset of diffuse cutaneous SSc.

[Lung resections for lung cancer with idiopathic pulmonary fibrosis].

PURPOSE: The aim of this study was to investigate the postoperative complications after lung resections for lung cancer with idiopathic pulmonary fibrosis (IPF). MATERIAL AND METHODS: There were 23 patients who underwent lung resections for lung cancer with IPF. There were 8 major complications. Acute exacerbation of IPF occurred in 4 cases, pulmonary edema in 1 case, bronchofistula in 1 case, bacterial pneumonia in 1 case, prolonged hypoxia in 1 case. Three cases died due to acute exacerbation of IPF (2 cases) and bronchofistula (1 case). RESULTS: There were 4 complications among 7 patients who underwent wedge resections and 4 complications among 16 patients who underwent lobectomy. All the 4 complicated cases who underwent wedge resections had low preoperative percent forced vital capacity (%VC) for 79+/-6%. For the patients who had lobectomy, the preoperative %VC and predicted postoperative %VC was significantly different between the 2 groups of complicated patients and uncomplicated ones (p < 0.05). For the prevention of acute exacerbation of IPF, we used clarithromycin in 11 cases, steroid in 2 cases, ulinastatin in 2 cases. However, the acute exacerbation was occurred in 4 cases. CONCLUSIONS: For the patients of lung cancer with IPF who had low preoperative %VC, even wedge resections should be carefully indicated.

Inhibition of topoisomerase I by antibodies in sera from scleroderma patients.

Purified type I topoisomerase from calf thymus as well as nuclear and cytoplasmic extracts from EGF-stimulated human and mouse fibroblasts in cell culture efficiently convert supercoiled plasmid DNA to the relaxed form. The purified IgG fraction from the sera of Japanese patients with the rheumatic disease scleroderma were shown to inhibit this relaxation activity. Thus, these patients likely produce autoantibodies to topoisomerase I. In addition, the human, bovine and murine enzymes share antigenic determinants recognized by the antisera.

Fatty acid imaging with 123I-15-(p-iodophenyl)-9-R,S-methylpentadecanoic acid in acute coronary syndrome.

UNLABELLED: 123I-15-(p-iodophenyl)-9-R,S-methylpentadecanoic acid (9-MPA) has recently been developed as a tracer for myocardial fatty acid uptake. The aim of this study, which was performed as part of a phase III clinical trial of 9-MPA, was to test the usefulness of 9-MPA for the assessment of myocardial viability in patients with acute coronary syndrome (ACS). METHODS: Fifteen patients with ACS who had undergone direct percutaneous transluminal coronary angioplasty were examined. Myocardial SPECT with 9-MPA and 99mTc-sestamibi and low-dose dobutamine echocardiography were performed within 2 wk after onset. The 9-MPA images were obtained 10 and 60 min after tracer administration, and sestamibi imaging was begun 60 min after the injection. The left ventricle was divided into 9 segments, and 9-MPA and sestamibi uptake were scored from 0 (normal) to 3 (no activity) in each segment. Lower uptake of 9-MPA than of sestamibi was defined as a mismatch. Myocardial segments showing improvement in wall motion during low-dose dobutamine infusion (5-10 microg/kg/ min) were considered viable. RESULTS: The 9-MPA images were of high quality for all patients. Myocardial uptake of 9-MPA was lower in ischemic myocardium than in nonischemic myocardium (58.2%+/-14.2% versus 91.9%+/-6.5%, P<0.0001). Clearance of 9-MPA from ischemic myocardium was slower than that from nonischemic myocardium (10.2%+/-11.7% versus 19.1%+/-5.9%, P<0.01). A mismatch was seen in 10 of 15 patients, and 18 of 20 (90%) mismatched segments were defined as viable by dobutamine echocardiography. Conversely, 18 of 20 (90%) matched segments did not show any improvement in function during dobutamine stimulation (P<0.0001). Uptake of 9-MPA in nonviable segments was lower than that in dysfunctional but viable segments (P<0.05), and 9-MPA clearance from nonviable segments was slower than that from viable segments (P<0.05). CONCLUSION: The imaging characteristics of 9-MPA for SPECT are excellent, allowing noninvasive assessment of myocardial fatty acid uptake. Myocardial imaging with 9-MPA may reveal impaired fatty acid uptake in dysfunctional but viable myocardium and thus provide useful information for clinical decision making in ACS.

Specificity of antibodies to single-stranded (ss) DNA in SLE patients with anti-phospholipid syndrome.

Although the concept of anti-phospholipid syndrome has been proposed in patients with SLE and other rheumatic diseases, the immunological mechanism is still controversial. Recently, the crossreactivity between anti-cardiolipin antibody and anti-ssDNA antibodies has been discussed in relation to this syndrome. In the present study, the specificity such as the avidity and the crossreactivity of anti-ssDNA antibodies was examined to find a clue to clarify the question why all of anti-cardiolipin antibody positive patients do not have any specific clinical features, thrombosis and spontaneous abortion. The avidity of IgG anti-ssDNA antibodies was examined by salt elution studies in solid phase ELISA. The avidity of anti-ssDNA antibodies tended to be lower in 10 patients with specific features than in other 10 patients without those features. The crossreactivity of affinity purified IgG anti-ssDNA antibodies was investigated by competitive ELISA. Purified anti-ssDNA antibodies from 4 patients without specific features were slightly inhibited by negatively charged phospholipids, cardiolipin and phosphatidylserine, whereas purified anti-ssDNA antibodies from 2 patients with specific features, who were considered to have anti-phospholipid syndrome, were little inhibited by these phospholipids. The above results suggest that the specificity of anti-ssDNA antibodies appears, at least partly, in different manners whether specific features are present or absent in anti-cardiolipin antibody positive patients. Moreover, anti-ssDNA antibodies and anti-phospholipid antibodies may form separate groups of antibodies in patients with anti-phospholipid syndrome.

Initial predictors of survival in patients with systemic sclerosis (scleroderma).

We conducted a retrospective study of 86 patients with systemic sclerosis (SSc) to clarify the initial predictors of survival at the first visit to the hospital. A life-table analysis of survival was performed concerning 137 items from their histories, physical examinations, and laboratory data. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years. Ten items were found to be the initial predictors of survival in patients with SSc. Of these 10 items, 9 items showed significant differences within 5 years of the first visit to the hospital. Patients with resting electrocardiographic abnormalities, such as atrial or ventricular arrhythmias, or conduction disturbances, pulmonary fibrosis on the chest x-ray films, or decreased vital capacity had significantly lower survival rates. However, patients with anti-centromere antibody had a significantly better survival rate. In addition, males, aged patients over 65 years old, and patients with proteinuria, leucopenia, or hypergammaglobulinemia had significantly lower survival rates. Only patients with proximal scleroderma at the first visit to the hospital had a significantly lower survival rate after 8 years. These results are useful in predicting individual patients at risk of shortened survival and in managing these patients.

Effects of preoperative chemotherapy and radiation therapy on human bronchial blood flow.

OBJECTIVE: We investigated the relationship between bronchial mucosal blood flow around the area of lung resection and the state of healing of the bronchial stump in patients after chemotherapy with or without radiation therapy. METHODS: Ninety patients with primary lung cancer were divided into the following 3 groups: group A, 72 patients who had no preoperative therapy; group B, 10 patients who had chemotherapy; and group C, 8 patients who had chemoradiation (60 Gy) therapy. Bronchial mucosal blood flow was measured preoperatively, intraoperatively, and postoperatively (days 8-10) with a laser Doppler flowmeter. RESULTS: In groups A and B bronchial mucosal blood flow was preserved sufficiently around the surgical site, and the healing of the bronchial stump was satisfactory. On the contrary, preoperative blood flow in group C was 70% of the preoperative value in group A and decreased further intraoperatively. Healing of the bronchial stump was poor, and a bronchopleural fistula occurred in one patient of group C. CONCLUSION: Preoperative chemoradiation therapy may adversely affect bronchial mucosal blood flow and healing of the bronchial stump, although lymphadenectomy and preoperative chemotherapy had little effect. It is recommended that the bronchial stump should be covered with pedicled viable tissue after chemoradiation therapy for prophylaxis against bronchial complications.

Thoracoscopic wedge resection of blebs under local anesthesia with sedation for treatment of a spontaneous pneumothorax.

We performed thoracoscopic wedge resections of blebs with a stapling device under local anesthesia with sedation in 34 consecutive patients who presented with spontaneous pneumothoraces. The indications for surgery included the absence of parietal pleural adhesions and knowledge of the precise bleb location prior to the procedure. Prior to surgery, 0.5% lidocaine was administered into the pleural space, and IV butorphanol tartrate and diazepam were administered to reduce pain and anxiety during the procedure. In our series, the thoracoscopic procedure resulted in favorable outcomes in all but two patients. There was no evidence of hemodynamic instability or arterial blood gas abnormalities encountered during the procedure. Minor postoperative complications were seen in only three patients (two with air leakage and one with transient atelectasis). One patient had a recurrence of his spontaneous pneumothorax 3 months following the procedure. Therefore, the overall success rate was 91%. We compared the results of this therapeutic modality (group 1) with those of 38 patients who underwent the procedure under general anesthesia (group 2) during the same period. The length of hospital stay was shorter in group 1 than in group 2 (4.5 +/- 1.3 vs 5.8 +/- 1.1 days; p < 0.01). Thoracoscopic wedge resections under local anesthesia are safe and offer the benefit of shorter hospital stays. We believe that this thoracoscopic technique will further simplify the surgical treatment of pneumothoraces without incremental risks.

Recovery and limitation of exercise capacity after lung resection for lung cancer.

OBJECTIVE: To assess the effects of pulmonary resection for lung cancer on postoperative recovery and limitation of exercise capacity. METHODS: Eighty-two patients (20 pneumonectomies, 62 lobectomies) underwent spirometric pulmonary tests and exercise capacity tests preoperatively, and at 3 months and more than 6 months after the operation. RESULTS: In the lobectomy group, FEV1 vital capacity (VC), and maximum oxygen consumption (VO2max) decreased significantly 3 months after the operation and improved after more than 6 months, but did not reach the preoperative values. In the pneumonectomy group, FEV1 VC, and VO2max decreased 3 months after the surgery and the values did not recover thereafter. In comparison with preoperative values, the functional percentage losses after more than 6 months for lobectomies and pneumonectomies were 11.2% and 36.1% for FEV1, 11.6% and 40.1% for VC, and 13.3% and 28.1% for VO2max, respectively. Postoperatively, maximal minute ventilation (VEmax), the maximal heart rate percentage, and maximal O2 pulse during the exercise test significantly decreased in both the lobectomy and pneumonectomy groups. Nevertheless, VEmax and O2 pulse improved more than 6 months after lobectomy compared with the value at 3 months, but not after pneumonectomy. Breathing reserve did not differ before and after surgery in the lobectomy group, although it decreased significantly after surgery in the pneumonectomy group. Subjectively, postoperative exercise after lobectomy was limited by leg discomfort (64% at more than 6 months after surgery); after pneumonectomy, exercise was limited by dyspnea (60%). CONCLUSIONS: These results suggest that there are differences between lobectomy and pneumonectomy for lung cancer in terms of recovery and limitation of exercise capacity.

Epithelial regeneration and preservation of tracheal cartilage after tracheal replacement with cryopreserved allograft in the rat.

OBJECTIVE: We investigated the origin of the epithelium in transplanted cryopreserved tracheal allografts in rats and tried to clarify the mechanism by which immunogenicity is reduced in this procedure. METHODS: Tracheal transplantation was performed with PVG rats (allele at the RT1 locus: c) used as donors and ACI rats (allele at the RT1 locus: a) as recipients. After resection of a 5-ring segment of the cervical trachea of an ACI rat, the trachea was reconstructed with the cryopreserved tracheal segment of a PVG rat (n = 6). No immunosuppressive agents or steroids were given. Histologic changes were determined and immunohistochemical staining was performed to investigate major histocompatibility complex class I antigens of the transplanted tracheal segment. RESULTS: Two months after tracheal transplantation, 6 surviving ACI rats were killed. Histologically, the epithelium and tracheal cartilage of the transplanted cryopreserved segment displayed normal structure. Immunohistochemical staining showed that the major histocompatibility complex class I antigen of the ACI rat was expressed in the epithelium of the transplanted segment and that the class I antigen of the PVG rat was expressed in the cartilage of the transplanted segment. CONCLUSIONS: After transplantation of the cryopreserved trachea, the epithelium of the transplanted cryopreserved segment originated from the recipient epithelium whereas the cartilage retained the structure of the donor trachea. We hypothesize that transplantation of a cryopreserved trachea leads to the growth of the recipient's epithelium over the donor trachea, thereby reducing the antigenicity of the transplant.

Protection against lipid peroxidation induced during preservation of lungs for transplantation.

The questions of whether oxygen-derived free radicals are induced during preservation of lungs and, if so, how such radicals might relate to reperfusion injury were investigated by means of an isolated canine lung model. Lungs were obtained from 16 mongrel dogs and divided into groups 1 (n = 6), 2 (n = 5), and 3 (n = 5). The lungs of groups 1, 2, and 3 were flushed through the pulmonary artery with Euro-Collins solution alone, the solution with superoxide dismutase (120,000 U/L), and the solution with allopurinol (1 mmol/L), respectively, at 4 degrees C and then stored for 4 hours in the respective solutions at 4 degrees C with clamped bronchi. They were then reperfused for 2 hours by means of an isolated lung model. Lung lipid peroxidation was sequentially determined. The lung functional status was assessed by systolic pulmonary arterial pressure and end-inspiratory airway pressure. The lung edema was assessed by lung wet/dry weight ratio. Lipid peroxidation was induced after 1 hour of preservation and the first 30 minutes of the reperfusion in group 1 and only 2 hours of the reperfusion in group 2, whereas no induction was observed in group 3. Values for systolic pulmonary arterial pressure and end-inspiratory pressure in group 1 were significantly higher than those in group 3 (p < 0.05). The lung wet/dry weight ratio in group 1 was significantly higher than that in groups 2 and 3 (p < 0.05). The present results indicate that the administration of free radical scavengers in the preservation may effectively improve conditions for lung transplantation.

In vitro comparison between Argon Beam Coagulator and Nd:YAG laser in lung contraction therapy.

BACKGROUND: The Argon Beam Coagulator (ABC) and neodymium:yttrium-aluminum garnet (Nd:YAG) laser are used for lung tissue contraction. Assessing the damage of treated lung tissue is helpful in choosing devices for pulmonary volume reduction by pneumoplastic procedures. METHODS: We assessed the damage of in vitro lung lobes resected at operation for pulmonary carcinoma. Samples were irradiated with noncontact Nd:YAG laser and ABC. One hundred forty-four samples obtained from 24 lobes were examined by light microscopy. The lung tissue showing destructive degeneration at the pleura and slight coagulation at the residual parenchyma was defined as showing "air leak pattern" based on a previously reported experiment of the air inflation test. RESULTS: At the power of clinical use (Nd:YAG, 15 W; ABC, 80 W), most of the visceral pleura treated with the Nd:YAG laser was classified as presenting amorphous degeneration, and that treated with ABC showed destructive degeneration. Air leak pattern occurred in all samples treated with ABC. At the power of 40 W, ten (42%) of 24 visceral pleuras irradiated with the Nd:YAG laser were classified as presenting destructive degeneration, and of those irradiated with the ABC, 18 (75%) showed destructive degeneration (p < 0.05). Air leak patterns were found in 3 (13%) of the samples treated with the Nd:YAG laser and in 16 (63%) of those treated with the ABC (p < 0.05). CONCLUSIONS: The ABC had more potential to damage the pleura and less potential to produce underlying parenchymal coagulation in the lung tissue than did the Nd:YAG laser. This information may be useful in the selection of devices for pulmonary volume reduction by pneumoplastic procedures.

In vitro study of ablated lung tissue in Nd:YAG laser irradiation.

BACKGROUND: Neodymium:yttrium-aluminum garnet lasers are used to reduce lung volume. An assessment of the relationship between the histologic and gross findings in the lung irradiated by a laser would be helpful in laser-assisted pneumoplastic procedures. METHODS: In vitro lung lobes surgically resected for pulmonary carcinomas were irradiated with a neodymium:yttrium-aluminum garnet laser at three energy levels in three modes: contact rubbing, contact pointing, and noncontact. Pleural degeneration in 216 samples from 24 lobes was classified as coagulative, amorphous, or destructive. At all energy levels, the laser was applied for 1.5 seconds. RESULTS: Noncontact mode at 7.5 W or 15 W and contact rubbing at 5 W caused coagulative or amorphous degeneration but no destructive degeneration. The energy level correlated with the color of the degenerated pleura. The incidence of destructive pleural degeneration, which led to air leaks as revealed by an air inflation test, was 0% in pink and white samples, 59% in brown samples, and 100% in black samples (p < 0.0001, white versus brown samples). CONCLUSIONS: In neodymium:yttrium-aluminum garnet laser ablation of lung tissue, the color of the degenerated pleura correlates with the intensity of the applied laser energy and the degree of pleural degeneration.

Effects of warm ischemia and cryopreservation on cartilage viability of tracheal allografts.

BACKGROUND: For clinical use of a cryopreserved tracheal allograft, it is important to evaluate cartilage viability. We assessed cell viability of the cartilage in a cryopreserved tracheal allograft by measurement of Na2 35SO4 incorporation. We also investigated the effects of warm ischemic time on tracheal cartilage viability. METHODS: The tracheas from Lewis rats were harvested and preserved at different warm ischemic times from cardiac death to preservation (0, 1, 2, 4, 6, 9, and 12 hours, each group n = 8). The cartilage was labeled with 4 muCi/mL of Na2 35SO4. The specimen was hydrolyzed in 0.5 mol/L NaOH, and a solution of the extracts was then counted by liquid scintillation counter. Tracheas were transplanted into Brown Norway rats. RESULTS: 35Sulfur incorporation in the cartilage decreased as warm ischemic time increased. In addition, 35Sulfur incorporation decreased from 76% to 67% after cryopreservation. Histologic examinations of the normal tracheal cartilage before preservation and after thawing were done in all the groups. After transplantation, the cartilage had severe fibrous changes, and its layer was almost nonobservable in the 9- and 12-hour groups. CONCLUSIONS: The viability of the tracheal cartilage decreased with warm ischemic time and from 76% to 67% after cryopreservation. In the rat tracheal transplantation model, a cryopreserved tracheal allotransplant could be done safely with a graft that was cryopreserved within 6 hours of warm ischemic time.

Tracheal replacement with cryopreserved tracheal allograft: experiment in dogs.

BACKGROUND: It has been difficult to perform tracheal allotransplantation without immunosuppression. To determine whether cryopreserved trachea can be used in tracheal replacement, we evaluated the viability of cryopreserved tracheal allografts in a canine model of immunosuppressant-free transplantation. METHODS: Cryopreserved tracheal allografts, which had been frozen to -80 degrees C in a programmed freezer and then stored in liquid nitrogen (-196 degrees C) (group 1, n = 6), fresh tracheal autografts (group 2, n = 5), and fresh tracheal allografts (group 3, n = 4) were transplanted into the thoracic segment of the trachea using an omental flap without immunosuppressive agents. RESULTS: All dogs in groups 1 and 2 survived, but in group 3, all 4 died of airway obstruction between 1 month and 2 months after operation. Histologically, the cryopreserved allografts displayed normal epithelium and cartilage, but the fresh allografts showed chronic inflammatory changes, no epithelium, and no cartilage. CONCLUSIONS: Cryopreserved tracheal allografts maintain their structural integrity after transplantation. The cryopreservation process seems to reduce the allogenic response of the trachea in canine models. Therefore, we believe the cryopreserved tracheal allograft is an excellent choice for tracheal replacement.

Management of malignant tracheobronchial stenosis with metal stents and Dumon stents.

BACKGROUND: Tracheobronchial stenosis caused by malignancy is a life- threatening problem. Stenting is one of the treatment modalities and recently has been used widely for the management of such stenosis, but we do not have a clear guide as to which stent should be selected. METHODS: We evaluated 25 patients (19 men, 6 women; mean age, 60.7 years; range, 34 to 77 years) received 24 metal stents (four covered with silicone rubber) and three Dumon stents. All 25 patients had severe dyspnea because of airway stenosis caused by malignant tumors. RESULTS: Among the 25 patients, airway obstruction due to extrinsic compression by tumor developed in 11 and was treated with a bare metal stent. The airway remained patent in 10 patients. In 16 patients with intraluminal tumor invasion, nine lesions were treated with a bare metal stent, four lesions with a covered metal stent, and the remaining three lesions with a Dumon stent. Recurrent stenosis did not occur in any patient with a covered metal stent or a Dumon stent. However, restenosis occurred in 4 patients with a bare metal stent, all of whom received laser therapy. In all patients, stenting immediately relieved dyspnea. Six patients lived for 32 days to 53 months after stenting, and 19 patients died of primary malignancies with a mean survival of 131.9 days. CONCLUSIONS: Metal stents are effective in treating malignant extrinsic tracheobronchial compression. The use of covered metal stents or Dumon stents is preferable for intraluminal stenosis due to malignant growth.

Thrombocytopenia responsive to warfarin in a patient with systemic sclerosis--systemic lupus erythematosus overlap.

We report a patient with overlapping systemic sclerosis-systemic lupus erythematosus who developed refractory thrombocytopenia and recurrent thromboses. Coagulation and platelet labeling studies revealed that platelets were being consumed by the thrombus formation, and anticoagulation with warfarin dramatically increased the platelet count. This case report suggests that platelet consumption due to thrombus formation is one of the causes of thrombocytopenia in patients with rheumatic disease.

Brasiliquinones A, B and C, new benz[alpha]anthraquinone antibiotics from Nocardia brasiliensis. I. Producing strain, isolation and biological activities of the antibiotics.

New benz[alpha]anthraquinone antibiotics (brasiliquinones A, B and C) with an ethyl group at C-3 were isolated. The producer was identified as Nocardia brasiliensis. The antibiotics were active against Gram-positive bacteria including Mycobacterium sp., but not active against Gram-negative bacteria or fungi. They were also active against multiple drug-resistant P388/ADR tumor cells.