Antiinflammatory properties of the new antirheumatic agent 4-acetylaminophenylacetic acid

The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.     

A surgical case of atrial septal aneurysm associated with rheumatic mitral and tricuspid disease and coronary-pulmonary artery fistula

A case of atrial septal aneurysm associated with combined valvular disease and coronary-pulmonary fistula (C-PA fistula) was presented. The patient successfully underwent mitral valve replacement, excision and closure of the aneurysm, tricuspid annuloplasty and closure of C-PA fistula. Atrial septal aneurysm is a rare anomaly and its natural course is thought to be generally good without significant clinical symptoms. However, complications such as cerebral and pulmonary embolism, or occlusion of the atrioventricular vales by the prolapsed aneurysm were reported to occur in small number of cases. In this case, diagnosis of the aneurysm was made by 2-D and Doppler echocardiography and further confirmed by cineangiography. Routine echocardiographic examinations will serve as useful noninvasive method for detection and follow up study of this anomaly.     

Clinical and hemodynamic sequelae of mitral prostheses evaluated by Doppler echocardiography]

To determine the relative superiority of a prosthesis in the mitral position, in vivo hemodynamics were examined by Doppler echocardiography, and the results were compared with other types of mechanical mitral valves including 63 Bj?rk-Shiley convexo-concave (BS) values, 30 Duromedics (DM) valves, and 58 Medtronic Hall (MH) valves. For this comparison, the following indices were evaluated: peak velocity of mitral flow (PV), mitral valve orifice area (MVA), mitral valvular regurgitation, New York Heart Association (NYHA) classification, pulmonary capillary wedge pressure (PC), cardiac index (CI) and valve-related complications. On Doppler echocardiograms, PV ranged from 1.2 to 2.0 m/sec with a mean of 1.6 m/sec. There was no evident relationship between the PV and the valve size in each type of prosthesis, and no significant difference in the PVs among the valves. The mean MVA was 2.6 cm2 (25 mm DM, 25 mm MH), which was regarded satisfactory from a clinical standpoint. MVA increased with the increase in the valve size in all types of valves, and of all sizes, MVA was larger in the DM and MH groups than in the BS group. Similarly, the incidence of valvular regurgitation was relatively low in all groups, and the degree of regurgitation proved to be grade II or less in all cases. As for the clinical results, clinical symptoms (NYHA) and hemodynamic states (PC, CI) improved postoperatively, with the differences among the types of prosthetic valves being insignificant. The incidences of thromboembolism, valvular thrombosis, valve failure and prosthetic endocarditis were relatively low in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between the thromboxane A2 receptor gene and susceptibility to cerebral infarction.

The risk of cerebral infarction (CI) in an individual is dependent on the interplay between genetic risk factors and environmental influences. Binding of thromboxane A2 (TXA2) to its receptor (TP) modulates thrombosis/hemostasis and plays a significant role in the pathogenesis of CI. The aim of the present study was to investigate the relationship between human TP gene single nucleotide polymorphisms (SNPs) and haplotypes and CI in a Japanese population. A genetic association study was performed in 194 CI patients and 365 non-CI subjects by specifically characterizing 6 SNPs in the human TP gene (rs2271875, rs768963, rs2238634, rs11085026, rs4523 and rs4806942). Analysis demonstrated that there were significant differences in the overall distribution of genotypes and dominant or recessive models of rs2271875 and rs768963 between the CI and the non-CI groups. Multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with CI (p = 0.029), even after adjusting for confounding factors (odds ratio: 2.41). Further, the C-T-C haplotype of rs768963-rs2238634-rs4806942 was significantly more frequent in the CI group (23.0%) than in the non-CI group (17.7%). These results suggest that specific SNPs and haplotypes may have utility as genetic markers for the risk of CI and that TP or a neighboring gene is associated with the increased susceptibility to CI.     

Autoantibodies specifically detected in patients with polymyositis/dermatomyositis]

Polymyositis/Dermatomyositis (PM/DM) is a chronic inflammatory disorder that culminates in injury to the skin and muscle and, sometimes, is accompanied by interstitial lung disease (ILD). A number of autoantibodies are associated with myositis, including those specific for aminoacyl-tRNA synthetase (anti-ARS), signal recognition particle (anti-SRP), and Mi-2. These autoantibodies have proven to be useful in the diagnosis and classification of the diseases and are predictive of prognosis. It has been known that certain patients may have typical DM skin manifestations without clinical evidence of myositis for at least 2 years (Clinically Amyopathic DM; C-ADM). Although classical myositis-related antibodies are well known, specificities related to C-ADM have not been examined in detail. Therefore, we have examined sera from 15 Japanese patients with C-ADM to identify additional autoantibodies associated with this disease. Eight sera of C-ADM patient recognized a polypeptide of approximately 140 kDa and we named this new antibody specificity anti-CADM-140. Anti-CADM-140 antibodies were detected in 8 of 42 patients with DM, but not in patients with other connective tissue diseases or idiopathic pulmonary fibrosis. It is noteworthy that DM patients with anti-CADM-140 had significantly more rapidly progressive ILD when compared to patients without anti-CADM-140 (50% vs 6%, P=0.008). Further studies of the pathogenicity of these autoantibodies specificity may provide insight into the pathogenic mechanisms of PM/DM accompanied by rapidly progressive ILD.     

MULTICENTER STUDY DESIGN OF THE EX VIVO EVALUATION OF ENDOCYTOSCOPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Optical technological innovations enable us to visualize cellular nuclei endoscopically. Herein is described a protocol design for a multicenter study for the ex vivo evaluation of endocytoscopy. The present study was performed by the Endoscopy Forum Japan study group.     

Dynamic Interaction of Craniofacial Structures during Head Positioning and Direct Laryngoscopy in Anesthetized Patients with and without Difficult Laryngoscopy

Background: We lack fundamental knowledge of the mechanisms of difficult laryngoscopy despite its clinical significance. The aim of this study was to examine how head positioning and direct laryngoscopy alter arrangements of craniofacial structures.

Methods: Digital photographs of the lateral view of the head and neck were taken at each step of head positioning and direct laryngoscopy in age- and body mass index-matched patients with (n = 13) and without (n = 13) difficult laryngoscopy during general anesthesia with muscle paralysis. The images were used for measurements of various craniofacial dimensions.

Results: Both simple neck extension and the sniffing position produced a caudal shift of the mandible and a downward shift of the larynx, resulting in an increase of the submandibular space. Direct laryngoscopy during the sniffing position displaced the mandible and tongue base upward and caudally, and the larynx downward and caudally, increasing the submandibular space and facilitating vertical arrangement of the mandible, tongue base, and larynx to the facial line. These structural arrangements in response to direct laryngoscopy were not observed in patients with difficult laryngoscopy, whereas head positioning produced similar structural arrangements in patients with and without difficult laryngoscopy.     

Activated caspase expression and apoptosis increase in keloids: cytochrome c release and caspase-9 activation during the apoptosis of keloid fibroblast lines

To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo.