Implementing Faraday effect measurement constraints into the Grad-Shafranov equilibrium fitting code EFIT.

A new tool for the exploration and diagnosis of the internal magnetic field of plasmas in the DIII-D tokamak in the form of a constraint on the EFIT (Equilibrium Fitting) Grad-Shafranov code based on the Faraday-effect Radial Interferometer-Polarimeter (RIP) diagnostic is presented, including description, verification, and sample application. The physics underlying the diagnostic and its implementation into EFIT are discussed, and the results showing the verification of the model are given, and the model's limitations are discussed. The influence of the diagnostic's input on the resulting equilibrium parameters is characterized. The effect of electron density profile refinement is evaluated and found to be negligible. A sample application of the diagnostic is shown, indicating that the RIP constraint has similar effects on the equilibrium as motional Stark effect constraints do.

Expression of intercellular adhesion molecule 1 on pancreatic beta-cells accelerates beta-cell destruction by cytotoxic T-cells in murine autoimmune diabetes.

Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) by being involved in the extravasation of lymphocytes from the circulation into the inflamed pancreas. However, the mechanism of beta-cell destruction by which expression of ICAM-1 on beta-cells may facilitate adhesion of effector cells still remains to be elucidated. Several lines of evidence suggest that this adhesion molecule is involved in the destruction of pancreatic beta-cells by killer lymphocytes in the NOD mouse, which shows an autoimmune diabetic syndrome similar to that of human IDDM. Immunohistochemical study under light microscopy demonstrated that all of the mononuclear cells infiltrating the islets strongly expressed ICAM-1 and leukocyte function-associated antigen 1 (LFA-1), a counterreceptor of ICAM-1, whereas ICAM-1 expression on islet cells was not apparent. However, immunohistochemical staining under electron microscopy revealed that islet beta-cells adjacent to infiltrating lymphocytes were clearly stained by an anti-ICAM-1 monoclonal antibody (mAb). Flow cytometric analysis showed that the ICAM-1 expression on NOD islet cells and NOD-derived insulinoma cells (MIN6N8a) was inducible by interferon (IFN)-gamma or tumor necrosis factor-alpha. These cytokines had an additive effect on the ICAM-1 induction. Susceptibility of MIN6N8a cells to lysis by a NOD islet-derived CD8+ cytotoxic T-cell clone was greatly enhanced by IFN-gamma pretreatment, and this enhancement was abolished by anti-ICAM-1 and anti-LFA-1 mAbs. When both mAbs were administered into NOD mice with spontaneous or adoptively transferred diabetes, the development of diabetes was significantly prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of continuous and intermittent cold (SART) stress on sympathoadrenal system activity in rats.

We compared sympathoadrenal responses to intermittent cold (SART) stress (in which cold exposure is interrupted by 4-hourly intervals daily at room temperature) with those to continuous cold (-3 degrees C) stress. Plasma levels of dihydroxyphenylalanine (DOPA), catecholamines and their metabolites as well as tyrosine hydroxylase (TH) activities in sympathetically innervated tissues were examined in rats exposed to each stressor for 1 day or for 5 days. Neither SART nor continuous exposure to cold for 1 day or 5 days altered plasma epinephrine (EPI) levels. However, norepinephrine (NE) and dihydroxyphenylglycol (DHPG) levels increased markedly during exposure to these stressors. On the first day of SART or continuous cold stress, NE levels were increased similarly, but the increments in DHPG levels were greater during SART stress. Since DHPG is formed in neurons, neural reuptake of NE may be more enhanced on the first day of SART stress than on the first day of continuous cold stress. After 5 days of SART stress plasma NE levels were significantly higher than those found after 5 days of continuous cold exposure. Plasma levels of DHPG were elevated to the same extent in both 5 days SART- and continuously cold-stressed rats, whereas plasma levels of methoxyhydroxyphenylglycol (MHPG) increased only by 5 days SART stress. Even at 1 h after the removal from 5 days SART stress, increased plasma levels of NE, DHPG and MHPG were still evident. These results suggest that 5 days SART stress elevates extraneuronal O-methylation of DHPG, and that NE turnover is more greatly increased by SART stress than by continuous cold stress. Plasma levels of DOPA, dopamine, dihydroxyphenylacetic acid and homovanillic acid also increased after either SART or continuous cold stress for 1 day and 5 days. Adrenal TH activities were significantly increased in rats exposed to SART or continuous cold stress for 1 day and 5 days, but in brown fat TH activity was elevated only in rats exposed to 5 days of continuous cold. Both SART and continuous cold stress are selective and potent stimuli for activation of the sympathoneural system, apparently without significant adrenomedullary EPI release. The increase of TH activity in the brown fat pad as well as of plasma NE and its metabolites is probably a result of adaptation to cold. It appears that even short intervals of return to a normal environmental temperature, as in SART, are sufficient to diminish sympathetic adaptation to cold.

Release of inflammatory mediators by noxious stimuli; effect of neurotropin on the release.

Anesthetized rats were perfused with saline in the subcutaneous space of the hind paw and the release of inflammatory mediators induced by noxious stimuli was studied. Not only immunoreactive bradykinin (BK) but also histamine, serotonin (5-HT) and immunoreactive prostaglandin E2 (PGE2) were found to be released into the perfusate when the paw was pinched. Neurotropin, used clinically as an analgesic and anti-allergic drug in Japan, inhibited the release of BK in dose-dependent manner without altering the release of histamine, 5-HT and PGE2. The maximal inhibition of BK release was observed 60 min after p.o. administration of neurotropin. Indomethacin failed to inhibit the release of BK.

A novel function of islet-derived CD8+T cells in initiating and developing autoimmune insulin-dependent diabetes mellitus in non-obese diabetic (NOD) mice.

Accumulated studies revealed that CD4+T cells were initially required for diabetes in NOD mice, whereas interaction of CD4+T/CD8+T cells is not fully understood. To address this question, we established islet-derived CD4+T cells and CD8+T cells from NOD mice. One NOD neonate that received CD4+T cells developed diabetes and insulitis with CD8+T cells. Administration of cyclophosphamide to non-diabetic recipients accelerated the development of diabetes, while none of the mice with anti-CD8 antibody did so. Similarly, it was observed that neonates that received islet-derived CD8+T cells developed diabetes and obvious insulitis mainly with CD4+T cells. Administration of anti-CD4 antibody with transfer of CD8+T cells inhibited insulitis. These results imply that CD8+T cells function as an initial element to recruit CD4+T cells to islets as well as a final effector.

Changes in muscarinic acetylcholine receptors in the isolated duodenum from repeatedly cold-stressed rats and the effect of neurotropin.

In rats repeatedly cold-stressed by specific alternation of rhythm in environmental temperature (SART-stressed rats), the contractile response to acetylcholine (ACh) of the isolated duodenum was remarkably decreased, whereas the contractile responses to K+, Ba2+ and Ca2+ were comparable to those in non-stressed rats. The amount of [3H]quinuclidinyl benzilate in the duodenum of SART-stressed rats was about 50% of that in non-stressed rats, but the KD value remained unchanged. Long-term administration of hexamethonium prevented the changes in SART-stressed rats. The daily treatment with Neurotropin, an extract isolated from inflamed rabbit dermis inoculated with vaccinia virus, dose-dependently prevented the changes in SART-stressed rats. However, Neurotropin had no effect on the ACh-induced decrease in muscarinic ACh receptor (m-ACh.R) in cultured vas deferens of guinea pig. These results suggest that down-regulation of m-ACh.R in duodenum by SART stress may be associated with enhanced activity in the parasympathetic center. Moreover, Neurotropin is thought to prevent the down-regulation of m-ACh.R throughout the central nervous system.

Heavy metals in emergent trees and pioneers from tropical forest with special reference to forest fires and local pollution sources in Sarawak, Malaysia.

Leaf samples of tropical trees, i.e. Dryobalanops lanceolata (Kapur paji), Dipterocarpaceae and Macaranga spp. (Mahang), Euphorbiaceae were analyzed for 21 chemical elements. The pioneer Macaranga spp. exhibited higher concentrations for the majority of elements compared to the emergent species of Dryobalanops lanceolata, which was attributed to the higher physiological activity of the fast growing pioneer species compared to emergent trees. Lead showed rather high concentrations in several samples from the Bakam re-forestation site. This is suggested to be caused by emissions through brick manufacturing and related activities in the vicinity. A comparison of Dryobalanops lanceolata samples collected in 1993, 1995 and 1997 in the Lambir Hills National Park revealed that certain heavy metals, i.e. Co, Cu, Mn, Ni, Pb and Ti showed higher values in 1997 compared to the previous years, which could indicate an atmospheric input from the haze caused by the extensive forest fires raging in Borneo and other parts of Southeast Asia.

[A clinical study of fluconazole in pulmonary aspergillosis].

Fluconazole is a novel triazole antifungal agent. Its in vitro antifungal activity against Aspergillus spp. is rather weak, but in vivo animal protection studies in mice with Aspergillus infections showed that the activity of fluconazole was about 15 times as potent as that of ketoconazole. We have studied the clinical efficacy and the safety of fluconazole given to 6 patients with chronic intractable respiratory disease, pulmonary aspergillosis, at an oral dose of 400 mg once daily for 23 days to 110 days (70 days on the average). Patients were selected from those who fulfilled 2 of the following 3 criteria: 1) those with chest X-ray evidence of fungus ball, 2) those from whom Aspergillus was continuously isolated through culture of their sputum, 3) those with evidence of serum precipitinogen against Aspergillus. Clinical efficacies were good in 2 patients out of 6 with marked contraction of fungus balls, fair in 2 with slight contraction of fungus balls or improvement of clinical symptoms, and failed in 2. Side effects and laboratory parameter abnormalities possibly considered to be related to fluconazole were not observed in any of the patients enrolled in the study, suggesting the safety in a long-term usage of the drug.

[Clinical effectiveness of cefoperazone for respiratory infections of elderly patients, focusing on its safety on renal function].

Clinical effectiveness of cefoperazone (CPZ) was studied for 46 elderly patients with respiratory infections. 1. Clinical efficacy rate of CPZ was 80.6% (29/36). 2. Adverse reactions occurred in 2 patients as systemic rush and fever. Laboratory abnormalities were observed in 5 patients. These included elevation of transaminase value. 3. The serum concentration of CPZ at 12 hours after administration of 2 g CPZ was not reflected in creatinine clearance and total bilirubin, and those 2 values appeared to have little effects on CPZ excretion. 4. The administration of CPZ at 4 g/day for less than 3 weeks had no effects on the renal function. As a result of this study, CPZ was found to have little undesirable effect on renal functions and to be a useful drug for the treatment of respiratory infections in elderly patients.

[Tuberculosis sequelae].

Although pulmonary tuberculosis decreased remarkably by antituberculous chemotherapy, we have had a lot of patients associated with sequelae who need medical treatment for many symptoms several or dozens years later. Moreover, in these days the delayed detection of pulmonary tuberculosis that is still an important problem may cause new sequelae. However, we have not had the clear definition of tuberculosis sequelae. Then I would like to definite the tuberculosis sequelae as follow. In a narrow sense, the sequelae is a pathological status that is caused by many patho-anatomical change in the healing process of pulmonary tuberculosis and need clinical treatment for many symptoms. The pulmonary tuberculosis sequelae include secondary infection such as aspergillosis, atypical mycobacteriosis and bacterial airway infection. In a broad sense, the sequelae also represent a pathological status with many symptoms after treatment that is caused by injuries in various organs with tuberculosis. I pointed out the problems of sequelae at this conference sixteen years ago. These problems may be beyond the category of tuberculosis study, but are extremely important for chest physicians.

[A case of inflammatory bronchial polyp associated with pulmonary and bronchial tuberculosis].

A 67-year-old man was admitted to our hospital because of cough and sputum. Chest X-ray revealed cavity and consolidation in the right upper lobe. Microscopical examination of stained specimens of sputum disclosed acid-fast bacilli (Mycobacterium tuberculosis). Cough and sputum resolved and cultures of sputum did not yield M. tuberculosis a month after administration of antituberculosis agents. However, a mass shadow in the right upper lobe was found 3 months later. Bronchofiberscopy revealed a polyp with a stalk at the orifice of right upper bronchus, which was elastic, soft in consistency, smooth surfaced, and movable. The pathological findings of the polyp showed non-specific inflammatory granulation which suggested to be inflammatory bronchial polyp. It was appeared in the healing process of bronchial tuberculosis.

[Pathology of bronchopulmonary aspergillosis].

This paper concerns the morphology of 3 types of bronchopulmonary aspergillosis: saprophytic aspergillosis (SPA), invasive aspergillosis (IVA) and allergic bronchopulmonary aspergillosis (ABPA)/allergic bronchopulmonary mycosis (ABPM). To know whether Aspergillus (ASP) in SPA only colonizes in preexisting cavities or presents significant pathogenecity, we examined 38 surgical specimens of SPA and 10 post-tuberculous open cavities (PT-OC). Macroscopically, SPA cavities had macroscopic ulcers (81.6%) and bronchi originating from the cavities (68.4%), in contrary to PT-OC that had neither of them. Microscopically, SPA cavities showed shallow ulcers (100%), coagulation necrosis (42.1%) and granulomatous reaction (52.6%), although ASP invasion to the viable lung tissue couldn't be discovered. The lung tissue around the SPA cavities showed various inflammation caused by transbronchial ASP dissemination from the cavities. We concluded that (1) SPA should be considered chronic destructive infection by ASP, but not colonization, (2) SPA couldn't be differentiated in quality from semi-invasive/chronic necrotizing pulmonary aspergillosis, and both should be categorized into secondary bronchopulmonary aspergillosis. Respecting IVA, we investigated 10 autopsy cases. In those cases, the disease was brought about in the lungs having no preexisting lesions. Three forms were distinguished; (1) 5 cases in that coagulation necrosis was a main feature (CN-IVA). (2) 2 cases having lung balls in cavitary lesions (LB-IVA), and (3) 3 cases showing suppurative lesions (SP-IVA). In CN-IVA and LB-IVA cases, ASP invaded to the viable lung tissue. But in 2 cases of SP-IVA, fungal hyphae were identified only in necrotic lesions but not in the viable tissue. Because the "invasive" was vague in definition, we should categorized these cases into primary bronchopulmonary aspergillosis. To determine the primary lesion of ABPA/ABPM, 5 lobectomy specimen were examined. All cases had hard or firm mucous plugs in the proximal bronchi, peripheral to which we found inflammation with tissue eosinophilia (bronchocentric granulomatosis with tissue eosinophilia : 5 cases, xanthogranuloma-like lesions : 2 cases, eosinophilic pneumonia : 2 cases and organizing pneumonia : 4 cases). Conglomerates of degenerated eosinophils, sometimes showing fir-structure, and fungal hyphae were recognized in both of mucous plugs and the peripheral lesions. We concluded that the mucous plug was the primary lesion of ABPA/ABPM.

[Tuberculosis sequelae: secondary bacterial infections].

Bacterial infections is one of the most important complications in the patients with pulmonary tuberculosis. We reported the causative microorganisms in these cases with special reference to various clinical features and presented the recommended treatment and prophylaxis against respiratory bacterial infections in the patients with pulmonary tuberculosis sequelae. In 1988 and 1989, 63 patients with tuberculosis sequela were demonstrated to have been infected with respiratory pathogenic bacteria by the quantitative sputum culture method (greater than or equal to 10(7)/ml) in Tokyo National Chest Hospital. The male/female ratio of these patients was 3.5, and their average age was 62.5 years. Causative microorganisms of the secondary infections in the patients with tuberculosis sequela were essentially similar in those with other lower respiratory tract infections, i.e., chronic bronchitis, bronchiectasis, diffuse panbonchiolitis, chronic pulmonary emphysema, etc. Pseudomonas aeruginosa, other glucose-nonfermentative Gram-negative bacilli (GNF-GNB), and glucose-fermentative Gram-negative bacilli (GF-GNB) were the major pathogenic bacteria responsible for the chronic respiratory failure and/or fatal outcome in the post-tuberculous patients. Patients with complications, including aspergillosis, atypical mycobacteriosis, bronchial asthma, and so forth, showed no specific causative microorganism for the secondary infections except frequent isolation of Haemophilus influenzae. Our clinical observations clearly demonstrated that there were differences between the causative microorganisms in patients hospitalized during 1988 to 1989 and those in patients without admission. Gram-negative bacilli, including P. aeruginosa, GNF-GNB and GF-GNB, and Staphylococcus aureus were predominant in hospitalized patients. On the contrary, Streptococcus pneumoniae, H. influenzae, and Branhamella catarrhalis were major pathogenic bacteria in patients without hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

[Management of cesarean section under replacement therapy with factor VIII concentrates in a pregnant case with congenital combined deficiency of factor V and factor VIII].

The congenital combined deficiency of Factor V and Factor VIII, a rare bleeding disorder, was identified in a 25-year-old woman. She was admitted to our hospital with a complaint of genital bleeding. Her prothrombin time and activated partial thromboplastin time were prolonged. She had low levels of Factor V coagulant activity (F. V:C) 14%, and Factor VIII coagulant activity (F. VIII:C), 12%, and normal levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor (Rcof) and Protein C antigen. Her Protein C inhibitor level was slightly low. Her Rcof, vWF:Ag and F. VIII:C were elevated following administration of 1-deamino-8-D-arginine-vasopressin (DDAVP), but her F. V:C remained unchanged. Four years later, her F. VIII:C rose to 70% during the course of her pregnancy, but her F. V:C value remained low. It was expected that the vaginal delivery would be possible at the termination of pregnancy. Premature rupture of the membranes and an anomaly of rotation appeared in the course of delivery, however, and cesarean section was accomplished without excess bleeding under replacement therapy with Factor VIII concentrates. These findings suggested that DDAVP and Factor VIII concentrates were useful for management of her delivery. However the mechanisms of the rise of plasma F. VIII:C during pregnancy in a case with congenital combined deficiency of Factor V and Factor VIII are unclear.

[B-chronic lymphocytic leukemia/prolymphocytic leukemia (CLL/PL)--a case report].

A 48-year-old male was admitted to our hospital on April 20, 1989 because of general fatigue and abdominal fullness. Physical examination showed hepatomegaly, massive splenomegaly, and systemic lymphadenopathy. Hematological findings revealed WBC 73,000/microliters, RBC 289 x 10(4)/microliters, Hb 8.0g/dl, and platelet 9.1 x 10(4)/microliters. WBC differential count demonstrated a mixture of 63% matured small lymphocytes and 32% prolymphocytoid cells. Bone marrow aspiration was unsuccessful with a dry tap. Surface marker analysis of peripheral blood lymphoid cells disclosed that they were positive for anti-HLA-DR, CD 5, CD 19, CD 20, CD 21, CD 25, Sm-IgM, Sm-IgD, and Sm-K. He was diagnosed as B-CLL/PL, and treated with VEPA with partial remission. CLL/PL which was advocated by Melo in 1986 is regarded as a distinct clinical entity intermediate between CLL and PLL in clinical and laboratory features. Our case is interesting with regard to good response to combination chemotherapy, though most cases of CLL/PL have a resistance to standard chemotherapy.

[A chemotherapy regimen including CDDP in patients with bronchogenic carcinoma--a comparison between bronchial artery infusion and intravenous administration].

Forty patients with lung cancer were treated using two methods. One was transbronchial artery infusion (BAI) of CDDP and the other was intravenous administration of CDDP with VDS, ACNU or etoposide. There was no difference in response rate between the two groups. The response rate was higher in patients with squamous cell carcinoma compared to these with adenocarcinoma. Compared with the combination group, BAI patients had fewer adverse effects, such as myelosuppression, alopecia, nausea and vomiting. Thus, it was concluded that CDDP is very effective for patients with lung cancer and that CDDP administered by BAI is useful for hilar-type squamous cell carcinoma.

[Pathologic reconsideration on allergic bronchopulmonary aspergillosis and mycosis].

We examined lung specimens that fulfilled the pathological criteria of Bosken and were obtained from 5, patients with allergic bronchopulmonary aspergillosis/mycosis (ABPA/M). A finding common to all 5 was the presence of hard mucous plugs containing numerous eosinophils and fungal hyphae in the bronchi, showing central bronchiectasis. Bronchocentric granulmatosis with tissue eosinophilia (4 cases), xanthogranulomatous lesions (3 cases), eosinohilic pneumonia (2 cases) and organizing pneumonia (3 cases) were recognized only in bronchi distal to the mucous plugs (BMP). Almost normal lung parenchyma could be seen in some areas distal to the BMP. We found clusters of degenerated eosinophils (CDE) showing a "fir-tree like structure" and fungal hyphae in both the mucous plugs and the peripheral lesions. Most CDEs were free in the exudate and were not engulfed by macrophages. The presence of fungi in the mucous plugs may have caused marked inflammation in the wall around the BMP, which may have made the walls fragile and caused central bronchiectasis. The fungi in the mucous plugs may have caused the peripheral lesions via aerogenous dissemination. For this reason, we conclude that ABPA/M is an infectious disease, and that the primary lesion in ABPA/M is the formation of mucous plugs. Therefore, the presence of mucous plugs containing fungi and many eosinophils is diagnostic of ABPA/M.