Autoantibody to transcriptional intermediary factor-1ß as a myositis-specific antibody: clinical correlation with clinically amyopathic dermatomyositis or dermatomyositis with mild myopathy.

BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1ß is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. OBJECTIVES: To evaluate the clinical features of seven cases with anti-TIF-1ß antibodies alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1ß. RESULTS: Anti-TIF-1ß antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1ß antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were confirmed to have anti-TIF-1ß antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1ß antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.

Loss of p53 in stromal fibroblasts enhances tumor cell proliferation through nitric-oxide-mediated cyclooxygenase 2 activation.

Overexpression of cyclooxygenase 2 (COX-2) by stromal fibroblasts plays a critical role in the early stage of carcinogenesis. COX-2 expression is thought to be positively or negatively regulated by inflammatory chemical mediators or tumor suppressors. In this study, the contributions of inducible nitric oxide synthase (iNOS) and p53 to COX-2 expression were examined using mouse embryonic fibroblasts (MEFs) from wild-type, p53-deficient, iNOS-deficient, and p53/iNOS-deficient mice. These MEFs were treated with 1 µg/mL of lipopolysaccharide and 100 IU/mL of interferon gamma for up to 72 h. iNOS and COX-2 expression were analyzed by Western blotting. iNOS was induced earlier (16 h) in p53-deficient MEFs than in wild-type MEFs (48 h). Elevated expression of COX-2 was sustained for a longer duration in the p53-deficient MEFs. In contrast, COX-2 expression was reduced earlier in the iNOS-deficient MEFs. Addition of an exogenous NO donor (0.8 mM of S-nitroso-l-glutathione) to the iNOS-deficient MEFs augmented COX-2 expression. Co-culture with stimulated p53-deficient MEFs promoted cell proliferation of mouse rectal polyploid carcinoma CMT93 cells, but treatment with a COX-2-specific inhibitor counteracted this effect. These results suggest that loss of function of the p53 gene in stromal fibroblasts enhances COX-2 expression by enhancing iNOS expression and the resultant production of NO, contributing to the promotion of tumor growth.

Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma.

BACKGROUND: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E(4) (LTE(4)) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B(4) (LTB(4)) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators. METHODS: Induced sputum, saliva, urine and blood were obtained at baseline from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB(4) and the prostaglandin D(2) metabolite 9alpha,11beta-prostaglandin F(2) were performed and the fraction of exhaled nitric oxide was measured. RESULTS: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB(4) levels between the groups. Levels of urinary LTE(4) and 9alpha,11beta-prostaglandin F(2) increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase. CONCLUSION: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.

Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis.

The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D2 (PGD2). In addition, PGD2 is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F2alpha (8-isoPGF2alpha) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA. Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study. The serum SP-D and urinary eicosanoid (LTE4, PGD2 metabolite (9alpha,11betaPGF2), 8-isoPGF2alpha) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9alpha,11betaPGF2 concentrations in the EAA patients. In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.

Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge.

BACKGROUND: Aspirin challenge of aspirin-intolerant asthma (AIA) patients causes a significant increase in leukotriene E4 (LTE4) concentration in urine. However, knowledge on leukotriene B4 (LTB4) generation in patients with AIA is insufficient. Recent research has demonstrated that exogenously administered LTB4 is excreted as glucuronide into the urine in human healthy subjects. OBJECTIVE: The purpose of this study is to estimate urinary LTB4 glucuronide (LTBG) concentration in the clinically stable condition in healthy subjects and asthmatic patients and to investigate changes in urinary LTBG concentration in patients with AIA after aspirin challenge. METHODS: A provocation test was performed by intravenous aspirin challenge. After urine was hydrolysed by beta-glucuronidase, the fraction containing LTB4 was purified by high-performance liquid chromatography and LTB4 concentration was quantified by enzyme immunoassay. Urinary LTBG concentration was calculated as the difference between the concentration obtained with hydrolysis and that without hydrolysis. RESULTS: (1) After hydrolysis, the presence of urinary LTB4 was verified by gas chromatography-mass spectrometry-selected ion monitoring. (2) The urinary LTBG concentration was significantly higher in the asthmatic patients than in the healthy subjects (median, 5.37 pg/mg creatinine [range 1.2-13] vs. 3.32 pg/mg creatinine [range, 0.14-10.5], P = 0.0159). (3) The patients with AIA (n = 7), but not those with aspirin-tolerant asthma (n = 6), showed significant increases in LTBG and LTE4 excretions after aspirin challenge. (4) When the concentrations after aspirin challenge were analysed simultaneously, a significant linear correlation was observed between urinary LTBG concentration and urinary LTE4 concentration in patients with AIA (Spearman's rank correlation test, r = 0.817, P = 0.0003). CONCLUSION: LTBG is present in human urine, albeit at a concentration lower than urinary LTE4. In addition to a marked increase in cysteinyl-leukotriene production, aspirin challenge induced LTB4 production in AIA patients.

Urinary 3-bromotyrosine and 3-chlorotyrosine concentrations in asthmatic patients: lack of increase in 3-bromotyrosine concentration in urine and plasma proteins in aspirin-induced asthma after intravenous aspirin challenge.

BACKGROUND: Eosinophil peroxidase and myeloperoxidase halogenate tyrosine residues in plasma proteins and generate 3-bromotyrosine (BY) and 3-chlorotyrosine (CY), respectively. OBJECTIVES: (1) To estimate urinary concentrations of BY and CY in asthmatic patients. (2) To investigate BY concentration in relation to urinary leukotriene E4 (LTE4) concentration in order to evaluate the activation of eosinophils in patients with aspirin-induced asthma (AIA). METHODS: BY and CY were quantified with a gas chromatograph-mass spectrometer using (13)C-labelled compounds as internal standards. RESULTS: (1) Activation of eosinophils and neutrophils by immobilized IgG1 induced preferential formation of BY and CY, respectively. (2) A significantly higher concentration of BY was observed in the urine from asthmatic patients than in that from healthy control subjects (45+/-21.7 vs. 22.6+/-10.8 ng/mg-creatinine, P<0.01). CY concentration was also elevated in the urine from asthmatic patients (4.4+/-3.2 vs. 1.5+/-1.0 ng/mg-creatinine, P<0.01). (3) After intravenous aspirin challenge of aspirin-induced asthmatic patients, the concentration of BY in urine did not significantly change. No significant change was also observed in the ratio of BY concentration to total tyrosine concentration in plasma proteins. In contrast, the concentration of urinary LTE4 significantly increased after the intravenous aspirin challenge. CONCLUSION: Determination of BY and CY concentrations may be useful for monitoring the activation of eosinophils and neutrophils in asthmatic patients, respectively. After aspirin challenge of AIA patients, the increased concentration of urinary LTE4 did not accompany changes in BY concentration in both urine and plasma proteins. These results may preclude the activation of eosinophils after aspirin challenge in patients with AIA.

[Long-term results of aortic arch replacement using combination of deep hypothermic circulatory arrest and retrograde cerebral perfusion; comparison of result for atherosclerotic aneurysm and aortic dissection].

Between 1992 and 2001, 73 patients with aortic arch lesion underwent surgical treatment. The aneurysm was characterized by atherosclerosis in 54 patients (TAA) and by aortic dissection in 19 patients (DAA). All patients received graft replacement under combination of deep hypothermic circulatory arrest and retrograde cerebral perfusion. The hospital mortality rate for all patients was 15.6%. The follow-up period of 61 survival patients ranged from 2 to 90 months (mean 33.2 months). The actuarial survival rate was 93.2%, 83.5%, and 79.7% at 1, 3, and 5 years, respectively. No significant difference was noted between TAA and DAA in the actuarial survival rate. The freedom from vascular complication was 97.9%, 95.8%, and 95.8% at 1, 3, and 5 years, respectively. The rate was significant higher in the patients of DAA than in those of TAA (TAA: 100%, 100%, and 100%, DAA: 90.9%, 81.8%, and 81.8%). The freedom from cardiac complication was 96.4%, 89.7%, and 84.1% at 1, 3, and 5 years, respectively. There was no significant difference between TAA and DAA. The freedom from cerebrovascular complication was 100%, 97.6%, and 83.4% at 1, 3, and 5 years, respectively. No significant difference was noted between TAA and DAA. The late result of surgical treatment for the aortic arch using combination of deep hypothermic circulatory arrest and retrograde cerebral perfusion was satisfied. The long-term survival rate was higher in TAA patient than in DAA one. The possibility remained that fatal vascular complication affected the long-term survival rate.

[A case of giant cell tumor originating from the rib].

We have experienced a case of giant cell tumor originating from the rib. A 45-year-old male was admitted to our hospital because of a mass in the left chest wall. A tumor shadow was observed in the left side of chest X ray. Chest CT, bone scintigram showed tumor originating from the left 4th rib. The tumor was suspected giant cell tumor of bone by needle biopsy examination. The tumor was completely resected with chest wall surrounding the tumor. The defect of chest wall was reconstructed with Marlex mesh and the Latissimus dorsi muscle flap. The pathological diagnosis was a giant cell tumor of bone. The patient has been well for two years and one month since surgery, with no signs of recurrence.

Compositional analysis of copoly (DL-lactic/glycolic acid) (PLGA) by pyrolysis-gas chromatography/mass spectrometry combined with one-step thermally assisted hydrolysis and methylation in the presence of tetramethylammonium hydroxide.

Rapid and precise compositional analysis of copoly (DL-lactic/glycolic acid) (PLGA) was performed by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) combined with one-step hydrolysis and methylation in the presence of tetramethylammonium hydroxide (TMAH). Pyrolysis of PLGA with TMAH gave two characteristic products, derivatives of DL-lactic acid and glycolic acid, which directly reflect the average molar composition of PLGA. The analytical results for PLGA samples with various compositional ratios were in good agreement with those obtained by 1H-NMR spectrometry, and the precision was satisfactory.

[Development of a multi-layer ion chamber for measurement of depth dose distributions of heavy-ion therapeutic beam for individual patients].

In heavy-ion radiotherapy, an accelerated beam is modified to realize a desired dose distribution in patients. The setup of the beam-modifying devices in the irradiation system is changed according to the patient, and it is important to check the depth dose distributions in the patient. In order to measure dose distributions realized by an irradiation system for heavy-ion radiotherapy, a multi-layer ionization chamber(MLIC) was developed. The MLIC consists of 64 ionization chambers, which are stacked mutually. The interval between each ionization chamber is about 4.1 mm water. There are signal and high voltage plates in the MILC, which are used as electrodes of the ionization chambers and phantom. Depth dose distribution from 5.09 mm to 261.92 mm water can be measured in about 30 seconds using this MLIC. Thus, it is possible to check beam quality in a short amount of time.

[Relationship between biological activity and heparin-affinity sites of recombinant human basic fibroblast growth factor CS23 mutein].

A recombinant human basic fibroblast growth factor CS23 mutein (rhbFGF-CS23) obtained from Escherichia coli cells has proliferation-stimulating activity for a fetal bovine heart endothelial cell line, ATCC CRL 1395 (biological activity), and strong affinity for heparin (heparin-affinity) similarly to the natural human basic fibroblast growth factor. Plural species having different kinds of heparin-affinity were formed by acetylation of rhbFGF-CS23 with acetic anhydride. To clarify the relationship between the sites with heparin-affinity and the biologically active sites, we have investigated the acetylation sites by peptide mapping and the biological activity of the acetylated species. Consequently, the sites with heparin-affinity in rhbFGF-CS23 are found to be Lys26, Lys119, Lys125, Lys129, and Lys135 in the primary structure, and these sites with heparin-affinity except Lys26 are also clarified to be very important to retain the biological activity of the factor.

Helicobacter pylori infection and atrophic gastritis: a nested case-control study in a rural town in Japan.

A seroepidemiologic, nested case-control study was conducted to evaluate the risk for atrophic gastritis associated with Helicobacter pylori infection. Atrophic gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I level < or = 70 ng/ml and pepsinogen I/pepsinogen II ratio < or = 3.0. Cases were 23 men and 39 women who were not diagnosed with atrophic gastritis in 1987, but who were diagnosed with the condition in 1992. Controls were the 120 men and 282 women who did not meet the serologic criteria for atrophic gastritis in either time period. Neither cases nor controls had a history of upper gastrointestinal operations. Helicobacter pylori infection at the initial survey was associated with a significantly increased risk of atrophic gastritis incidence for both sexes combined (odds ratio = 3.72; 95% confidence interval, 1.78-7.79; P = 0.0005). Cigarette smoking and consumption of alcohol and green-yellow vegetables were not associated with incidence of atrophic gastritis.

Recurrences after the open Bankart repair: a potential risk with use of suture anchors.

Eighty-seven consecutive patients were treated with an open Bankart repair for traumatic, recurrent anterior instability of the shoulder. Forty-six of these patients underwent a transosseous suture technique. Forty-one patients were operated on with suture anchors. After follow-ups that ranged from 18 to 85 months, 7 of the 87 patients showed signs of recurrence and another 14 patients reported apprehension. Compared with the 66 patients without residual instability, these 21 patients were more likely to have been operated on with suture anchors (P < .05), had a greater incidence of hypermobility in joints other than the shoulder (P < .05), and had had a greater number of preoperative episodes (P < .05). In light of this data we recommend the transosseous suture technique for open Bankart repairs. In addition, a cautious and extensive capsular repair may be required when a patient reports frequent subluxations preoperatively or has hypermobility in some joints, if not in the shoulder per se.

Relationship between CT number and electron density, scatter angle and nuclear reaction for hadron-therapy treatment planning.

The precise conversion of CT numbers to their electron densities is essential in treatment planning for hadron therapy. Although some conversion methods have already been proposed, it is hard to check the conversion accuracy during practical therapy. We have estimated the CT numbers of real tissues by a calculational method established by Mustafa and Jackson. The relationship between the CT numbers and the electron densities was investigated for various body tissues as well as some tissue-equivalent materials used for a conversion to check the accuracy of the current conversion methods. The result indicates a slight disagreement at the high-CT-number region. A precise estimation of the multiple scattering, nuclear reaction and range straggling of incident particles has been considered as being important to realize higher-level conformal therapy in the future. The relationship between these parameters and the CT numbers was also investigated for tissues and water. The result shows that it is sufficiently practical to replace these parameters for real tissues with those for water by adjusting the density.

Zinc status relates to hematological deficits in middle-aged women.

OBJECTIVE: The objective of our study was to investigate zinc (Zn) status and the effects of Zn supplementation in relation to iron deficiency anemia in middle-aged women. It is important to define the role of Zn in hematologic abnormalities and to determine the frequency of Zn deficiency. METHODS: Fifty-two Japanese women, selected from a health examination survey on 6200 women, had hemoglobin concentrations below 12.0 g/dl, total iron binding capacity (TIBC) below 390 micrograms/dl and fairly normocytemia. These 52 were divided into three groups and we then compared the hematological status before and after iron (group A) or Zn (group B) or iron plus Zn (group C) supplementation. RESULTS: After treatment, concentrations of hemoglobin (Hb) increased slightly in groups A and B, but not statistically significant. In group C, Hb levels were significantly increased from 10.8 +/- 1.1 to 12.8 +/- 1.1 g/dl. Furthermore, numbers of RBC and reticulocytes, and concentrations of albumin were also increased significantly. Increased values over 1.0 g/dl of hemoglobin levels were noted in four women (26.6%) in group A, three women (14.2%) in group B and 13 women (81.2%) in group C. CONCLUSION: Zn status to some extent can account for hematological abnormalities in middle-aged women. At least 5.0% of middle-aged Japanese women may have Zn deficiency. Normocytic anemia with low TIBC levels may serve as a good indicator of a marginal Zn deficiency.

Modified Bankart procedure for recurrent anterior dislocation and subluxation of the shoulder in athletes.

Thirty-four athletes (34 shoulders) with recurrent anterior glenohumeral instability were treated with a modified Bankart procedure, using a T-shaped capsular incision in the anterior capsule. The inferior flap was advanced medially and/or superiorly and rigidly fixed at the point of the Bankart lesion by a small cancellous screw and a spike-washer. The superior flap was advanced inferiority and sutured over the inferior flap. Twenty-five athletes (median age: 22) were evaluated over a mean period of follow-up of 65 months. The clinical results were graded, according to Rowe, as 22 (88%) excellent, 3 (12%) good, and none as fair or poor. The mean postoperative range of movement was 92 degrees of external rotation in 90 degrees of abduction. Elevation and internal rotation was symmetrical with the opposite side. Twenty-four patients returned to active sport, 22 at their previous level. This modified Bankart procedure is an effective treatment for athletes with recurrent anterior glenohumeral instability.