Singly charged ion source designed using three-dimensional particle-in-cell method.

A singly charged ion source (SCIS) has been designed using a newly developed three-dimensional particle-in-cell (PIC) code. The SCIS is to be used in an isotope separation on-line (ISOL) system that provides 11C ions for heavy-ion cancer therapy with simultaneous verification of the dose distribution using positron emission tomography. The SCIS uses low-energy electron beams to produce singly charged carbon ions efficiently and maintain a high vacuum in the ISOL system. Because the SCIS has to realize a production efficiency of 1% if its carbon ions are to be used in the ISOL system, a suitable design for the SCIS was investigated by using the developed PIC code to study the beam trajectories of the electrons and extracted ions. The simulation results show that hollow electron beams are produced in the designed SCIS resulting in a high effective electron current. The results also predict that the designed SCIS would realize ion-production efficiencies (IPEs) of ε SCIS ≃ 6.7% for C O 2 + production from CO2 gas and ε SCIS ≃ 0.1% for C+ production from CH4 gas. Moreover, to examine the validity of the developed code and confirm that the SCIS was able to be designed appropriately, the space-charge-limited current of the electron gun and the total IPE obtained by adding the IPEs of each ion were compared between the experiment and the simulation.

Effects of combination therapy with montelukast and carbocysteine in allergen-induced airway hyperresponsiveness and airway inflammation.

BACKGROUND AND PURPOSE: Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties. EXPERIMENTAL APPROACH: Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty-eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S-carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production. KEY RESULTS: Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid. CONCLUSIONS AND IMPLICATIONS: The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action.

Carbon-ion radiotherapy: clinical aspects and related dosimetry.

The features of relativistic carbon-ion beams are attractive from the viewpoint of radiotherapy. They exhibit not only a superior physical dose distribution but also an increase in biological efficiency with depth, because energy loss of the beams increases as they penetrate the body. This paper reviews clinical aspects of carbon-beam radiotherapy using the experience at the National Institute of Radiological Sciences. The paper also outlines the dosimetry related to carbon-beam radiotherapy, including absolute dosimetry of the carbon beam, neutron measurements and radiation protection measurements.

Soluble interleukin-2 receptor as an indicator of immunological disturbance found in silicosis patients.

Silicosis patients (SILs) possess not only respiratory disorders but also alterations in autoimmunity. To determine an early indicator of immunological disturbance in SILs, the role of serum-soluble interleukin (IL)-2 receptor (sIL-2R) was analyzed. Of ten SILs, immunological clinical parameters such as immunoglobulin (Ig) G, complements, the titer of autoantibodies including anti-nuclear antibodies (ANA), anti-Scl-70 antibody (Ab) and anti-centromere (CM) Ab, and experimental indicators such as serum-soluble Fas, serum IL-2, CD25+ cells in CD4+ or CD8+ fractions, and sIL-2R were divided from respiratory parameters such as percent vital capacity (%VC), percentage of forced expiratory volume in 1 second (FEV1.0%) and v25/Ht (liter/second/m(body height) by a correlation assay. Additionally, a stepwise regression test showed that sIL-2R was correlated with Ig G, ANA and anti-CM Ab. Furthermore, factor analysis revealed that sIL-2R contributed to the subpopulation of SILs with poorer immunological status in the absence of alterations in respiratory status. By defining healthy donors as 1, SILs as 2 and patients with systemic sclerosis as 3 for immunopathological progression status as metric variables, sIL2R and ANA showed a strong positive correlation. This suggests that sIL-2R is a good clinical indicator of immunological disturbance found in SILs without clinical manifestations of any disturbance in autoimmunity. Further analysis using a large-scale number of patients should be performed to confirm these findings.

S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice.

S-carboxymethylcysteine (S-CMC) has been used as a mucoregulator in respiratory diseases. However, the mechanism of action of S-CMC on allergic airway inflammation has not yet been defined. In the present study, BALB/c mice were initially sensitised and challenged to ovalbumin (OVA) and, weeks later, re-challenged with OVA (secondary challenge). S-CMC (5-100 mg.kg-1) was administered from 2 days before the secondary challenge through to the day of assay. Mice developed airway hyperresponsiveness (AHR) 6 h after the secondary challenge and increased numbers of neutrophils were present in the bronchoalveolar lavage (BAL) fluid. At 72 h after secondary challenge, mice again developed AHR, but the BAL fluid contained large numbers of eosinophils. S-CMC treatment was found to reduce AHR and neutrophilia at 6 h, as well as eosinophilia and AHR at 72 h. These effects appeared to be dose dependent. Goblet cell hyperplasia, observed at 72 h, was reduced by S-CMC. In BAL fluid, increased levels of interferon-gamma, interleukin (IL)-12 and IL-10 and decreased levels of IL-5 and IL-13 were detected. In conclusion, the data indicate that S-carboxymethylcysteine is effective in reducing airway hyperresponsiveness and airway inflammation at two distinct phases of the response to the secondary allergen challenge in sensitised mice.

Pneumonitis induced by rifampicin.

An 81-year-old man was admitted to hospital with pulmonary Mycobacterium tuberculosis infection and was treated with rifampicin (RFP), isoniazid (INH), and ethambutol (EB). On day 9 he developed fever and dyspnoea. Chest radiographs showed new infiltration shadows in the right lung. Bronchoalveolar lavage (BAL) was performed and increased numbers of lymphocytes were recovered. Drug induced pneumonitis was suspected so the antituberculous regimen was discontinued and methylprednisolone was administered. The symptoms and infiltration shadows improved. INH and EB were reintroduced without any recurrence of the abnormal shadows. T cell subsets in the BAL fluid and a positive lymphocyte stimulation test for RFP suggest that RFP induced pneumonitis may be related to a complex immunological response.

[Orchiectomy for tuberculous epididymitis: a report of two cases with intractable to antituberculosis treatment].

This paper describes two cases with tuberculous epididymitis. The first case was a 69-year-old man who was admitted to our hospital because of ulceration or right scrotum. Physical examination revealed a hard, rounded, a little bigger than egg-sized mass in the right scrotum. The second case was a 40-year-old man who was admitted to our hospital because of cough, fever and body weight loss. He was treated for pulmonary tuberculosis with isoniazid, rifampicin, streptomycin and pyrazinamide. Six months after admission, he complained of a painless swelling of the right scrotum. Physical examination revealed a hard, rounded, more than egg-sized mass in the right scrotum. Right orchiectomy was performed in these two cases, and they were cured.

Distinct orders of GalNAc incorporation into a peptide with consecutive threonines.

Mucin O-glycosylation is initiated by a transfer of N-acetyl-d-galactosamine (GalNAc) to Ser and Thr residues in polypeptides with a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (pp-GalNAc-Ts). In this paper, four human pp-GalNAc-Ts (pp-GalNAc-T1, T2, T3, and T4) were tested for their preferential orders of GalNAc incorporation into FITC-PTTTPITTTTK, a portion of the tandem repeat of human MUC2. The products were separated by reverse-phase HPLC and characterized by MALDI-TOF MS and peptide sequencing. pp-GalNAc-T1 showed preference for acceptor sites, but the order of the incorporation into these sites seemed to be random. In contrast, the GalNAc incorporation by pp-GalNAc-T2, T3, or T4 was not only site-specific but also according to the specific orders. Furthermore, pp-GalNAc-T2, T3, or T4 had distinct maximum numbers of GalNAc incorporations into this peptide.

Pulmonary lymphoma of large B-cell type mimicking Wegener's granulomatosis.

A 27-year-old man with a primary pulmonary lymphoma of large B-cell type is described. Symptoms involved both the upper and lower respiratory tract. A chest roentgenogram showed a dense mass with cavitation. Transbronchial biopsy specimens revealed no atypical cells, rather they demonstrated granulomatous infiltration and vasculitis consistent with but not conclusively diagnostic of Wegener's granulomatosis. The pulmonary mass became smaller after sulfamethoxazole-trimethoprim therapy. These features suggested Wegener's granulomatosis. However, an open biopsy specimen was diagnostic for diffuse lymphoma of large B-cell type. High-grade pulmonary lymphoma should be considered in the differential diagnosis of patients with clinical and pathologic features suggesting Wegener's granulomatosis.

[A case of schwannoma arising in brachial plexus with intrathoracic extension].

A case of benign schwannoma arising in the brachial plexus with intrathoracic extension was presented. The patient was a 55-year-old man, who was pointed out an abnormal shadow in the left apical region on routine chest X-ray examination. MRI showed that the mass extended to the lowest trunk of the brachial plexus. He had no complaint. Therefore, a diagnostic operation was performed. The tumor was subcapsularly resected with thoracoscopic surgery. Histopathological examination revealed a schwannoma (Antoni type A and B). It should be kept in mind that tumors arising in the brachial plexus are a probable differential diagnosis for tumors at the pulmonary apex, even if no neurological symptoms are seen in the upper extremities.

Expression of MUC1 mucins in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder.

The overall outcome of pT(2) gallbladder carcinoma has not been favorable. Postsurgical recurrence at distant sites occurs in some cases, although the carcinoma was limited to the gallbladder wall. A high level expression of MUC1 mucins with sialylated carbohydrates (sialylated MUC1 mucins) is correlated with poor survival in intrahepatic bile duct carcinoma. In the present study, immunohistochemistry was performed to determine the expression level of sialylated MUC1 mucins, detected by a monoclonal antibody, MY.1E12, in 31 cases of pT(2) gallbladder carcinoma on which curative resections had been performed and to determine the correlation of the expression level of MY.1E12-reactive-MUC1 mucin with mode of recurrence and postsurgical survival. Immunostainings of the MUC1 mucin were recognized in different types of noncancerous pathological epithelia of the gallbladder except for intestinal metaplasia and cancerous epithelia. Immunohistochemical localization was classified into apical, cytoplasmic, and stromal types based on the predominant cellular distribution of MY.1E12-reactive-MUC1 mucin. In 31 cases of pT(2) carcinoma, the localization was apical type in 64%, cytoplasmic type in 71%, and stromal type in 48% of the cases at the deepest invading sites in the subserosal layer. Distant recurrences, i.e., peritoneal dissemination in 8 patients and liver metastasis in 3 patients, were seen in 8 (53%) of 15 cases of pT(2) carcinoma that had > or =10% of the cancerous epithelia showing stromal localization of the MUC1 mucin at the deepest invading sites and in 2 (12%) of 16 cases that had <10% of those showing the stromal localization. The postsurgical survival outcome was significantly poorer in the former than in the latter (P = 0.044). In pT(2) gallbladder carcinoma, the presence of MY.1E12-reactive-MUC1 mucin in the stroma adjacent to the cancerous epithelia in the subserosal layer correlates with the aggressiveness of the disease, such as the tendency to form distant recurrences. This phenotype may serve as a unique biological feature associated with the malignant behavior of pT(2) gallbladder carcinoma.

Compound heterozygosity for alpha-1-antitrypsin (S(iiyama) and QO(clayton)) in an Oriental patient.

Alpha-1-antitrypsin (alpha1AT) deficiency is extremely rare among Orientals. We treated a 37-year-old man with severe pulmonary emphysema associated with a low serum concentration of alpha1AT. Mutation analysis of the alpha1AT gene was performed using a reverse transcription-polymerase chain reaction followed by sequencing. The patient proved to be a compound heterozygote carrying a S(iiyama) deficient allele and a QO(clayton) null allele. This is the first Japanese case of alpha1AT deficiency to arise from such compound heterozygosity in a family with no apparent consanguineous marriage, suggesting that the gene frequency for deficient alleles might be somewhat higher than previously estimated.

Effects of short-term pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease.

Although the rehabilitation of patients with chronic obstructive pulmonary disease (COPD) improves both exercise capacity and quality of life, a standard protocol for COPD patients has not been established. To clarify whether physiologic and quality-of-life improvements can be achieved by an inpatient pulmonary rehabilitation program 5 days per week for 3 weeks, 18 patients with COPD were enrolled in a rehabilitation program. The physical exercise training regimen consisted of respiratory muscle stretch gymnastics and cycle ergometer exercise training. Pulmonary function tests, an incremental ergometer exercise test, a 6-min walking test, and a quality of life assessment by the Chronic Respiratory Questionnaire were administered before and after the program. The peak VO2, an indicator of maximal exercise capacity, did not increase, although the 6-min walking distance, an indicator of functional exercise capacity, increased significantly after rehabilitation. There was a significant improvement in the quality of life in terms of dyspnea, fatigue, and emotional state. These findings suggest that even a 3-week program may be beneficial for COPD patients. Increases in functional exercise capacity, even without an increase in maximal exercise capacity, are helpful for reducing dyspnea and improving quality of life parameters in patients with COPD.

Cardiorespiratory responses during cycle ergometer exercise with different ramp slope increments in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The ramp exercise test has been widely used to evaluate cardiopulmonary responses to an incremental exercise load. This study was performed to clarify whether different slopes of the ramp exercise test influence exercise tolerance, exercise limiting factors, and respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: We applied three different slopes (5 W/min, 10 W/min and 20 W/min) of the ramp exercise test in 9 patients with COPD and evaluated cardiopulmonary responses. RESULTS: There were no significant differences in peak oxygen uptake, anaerobic threshold (AT), minute ventilation, heart rate, arterial oxygen saturation, expired tidal volume, or respiratory rate at the maximal load among the three different ramp exercises tested. AT could be determined in six of nine patients (67%) at the slope of 5 W/min, in 8/9 (89%) at the slope of 10 W/min, and in 9/9 (100%) at the slope of 20 W/min. CONCLUSION: The findings suggest that the ramp slope does not affect exercise tolerance, exercise limiting factors, or respiratory patterns and each of these ramp slopes is useful for the evaluation of COPD. Ramp slopes of 10 W/ min or 20 W/min should be appropriate for the determination of AT.

A horizontal CT system dedicated to heavy-ion beam treatment.

A horizontal helical CT system to be used for 3-D treatment planning and for positioning verification of patients in seated position was installed in the treatment room with a fixed horizontal heavy-ion beam line. The system achieved the expected mechanical consistency and reliability.

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy.

PURPOSE: The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS: An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS: Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.

Bronchial atresia with transient spontaneous disappearance of a mucocele.

We report the transient spontaneous disappearance of a mucocele due to bronchial atresia. Two years before presentation, a chest radiograph showed a hyperlucent right upper lung and a mucocele near the right hilum. A chest radiograph taken 1 year later showed that the mucocele had disappeared leaving an ovoid outline of a dilated bronchus. A chest radiograph obtained 3 months before presentation showed that the mucocele was present again. Atresia of the B3b bronchus of the right upper lobe was noted on thoracotomy. The "disappearance" of the mucocele probably was due to the clearance of mucoid material through collateral airways.

[Three resected cases of pulmonary cryptococcosis].

Case 1 was a 53-year-old female who had a small nodule in the right S3 segment on chest CT. As she was not diagnosed by transbronchial lung biopsy (TBLB), open thoracotomy was performed. Case 2 was a 65-year-old female who had a nodule with pleural indentation in the right S6 segment. As this nodule showed difficulty to differentiate from small lung carcinoma, thoracoscopic surgery was performed. Case 3 was a 63-year-old female who had multiple lesions with cavity in the left S4 and S5 segments, which was preoperatively diagnosed by TBLB. She was performed thoracoscopic partial resection of the lingular segment because of poor response to antimycotic agents. All cases received preventive antimycotic agents for one or two months after the operation. There was no recurrence or postoperative meningitis. Thoracoscopic surgery is the effective procedure for the diagnosis and treatment of the localized pulmonary cryptococcosis.

Visualization of tumor vessels in hepatocellular carcinoma. Power Doppler compared with color Doppler and angiography.

PURPOSE: To assess the visualization of tumor vessels in hepatocellular carcinoma (HCC) by power Doppler sonography. MATERIAL AND METHODS: We examined 40 patients with 47 HCC lesions by means of power Doppler sonography and compared its visualization of tumor vessels with those of color Doppler and angiography. RESULTS: In 38 (81%) of the 47 lesions, power Doppler sonography improved the visualization of tumor vessels compared with color Doppler sonography; in the remaining lesions no significant difference was noted. In lesions located within 7 cm in depth, there was no significant difference between power Doppler sonography and angiography. In 10 (83%) out of 12 small (< or = 2 cm in diameter) lesions and in 11 (85%) out of 13 hypovascular lesions, power Doppler sonography performed considerably better than angiography. In deeper-seated lesions, however, angiography was significantly superior to power Doppler sonography. CONCLUSION: Power Doppler sonography is more sensitive in detecting the fine tumor vessels in most HCCs than color Doppler sonography. In addition, power Doppler sonography can replace angiography in evaluating tumor vascularity in HCCs except in lesions that are deep-seated or located near the heart. In these lesions, angiography can complement power Doppler sonography in demonstrating tumor vessels.