p38 mitogen-activated protein (MAP) kinase but not p44/p42 MAP kinase is involved in prostaglandin E1-induced vascular endothelial growth factor synthesis in osteoblasts

We investigated the mechanism underlying vascular endothelial growth factor (VEGF) synthesis stimulated by prostaglandin E1 (PGE1) in osteoblast-like MC3T3-E1 cells. PGE1 induced the phosphorylation of both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. SB203580, a specific inhibitor of p38 MAP kinase, inhibited the PGE1-stimulated VEGF synthesis as well as PGE1-induced phosphorylation of p38 MAP kinase. PD98059, an inhibitor of the upstream kinase that activates p44/p42 MAP kinase, which reduced the PGE1-induced phosphorylation of p44/p42 MAP kinase, had little effect on the VEGF synthesis stimulated by PGE1. AH-6809, an antagonist of the subtypes of the PGE receptor, EP1 and EP2, or SC-19220, an antagonist of EP1 receptor, did not inhibit the PGE1-induced VEGF synthesis. H-89, an inhibitor of cAMP-dependent protein kinase, and SQ22536, an inhibitor of adenylate cyclase, reduced the VEGF synthesis induced by PGE1. Cholera toxin, an activator of G(s), and forskolin, an activator of adenylate cyclase, induced VEGF synthesis. SB203580 and PD169316, another specific inhibitor of p38 MAP kinase, reduced the cholera toxin-, forskolin- or 8bromo-cAMP-stimulated VEGF synthesis. However, PD98059 failed to affect the VEGF synthesis stimulated by cholera toxin, forskolin or 8-bromoadenosine-3',5'-cyclic monophosphate (8bromo-cAMP). SB203580 reduced the phosphorylation of p38 MAP kinase induced by forskolin or 8bromo-cAMP. These results strongly suggest that p44/p42 MAP kinase activation is not involved in the PGE1-stimulated VEGF synthesis in osteoblasts but that p38 MAP kinase activation is involved.     

Echocardiographic observation of acute myocarditis with systemic lupus erythematosus

Although myocarditis from a series of autopsies of patients with systemic lupus erythematosus was frequently observed, the incidence of clinically apparent myocardial dysfunction was low. A 30-year-old woman with systemic lupus erythematosus was examined by echocardiography. An acoustic densitometry was followed at the left ventricular posterior wall throughout the clinical course. A decrease in the magnitude of cyclic variation of integrated backscatter (IB) was observed before treatment. Following the combined treatment, steroid and cyclophosphamide, a repeated ultrasonic tissue characterization showed an increase in the magnitude of cyclic variation of IB. It is thought that ultrasonic tissue characterization may be a useful method to evaluate the impairment of contraction, and to follow up the clinical course of myocardial involvement in systemic lupus erythematosus.     

Chronological evaluation of the onset of histologically confirmed interstitial pneumonia associated with polymyositis/dermatomyositis

OBJECTIVE: The present study was designed to determine the chronological sequence of interstitial pneumonia, skin involvement, and muscle involvement associated with polymyositis/dermatomyositis (PM/DM). METHODS: We examined our own cases of histologically confirmed interstitial pneumonia associated with PM/DM. In addition, a review of the literature was done to evaluate other cases of histologically confirmed interstitial pneumonia associated with PM/DM. Lung involvement was the first clinical symptom for all of our 8 patients. RESULTS: Including the literature review and our 8 cases, there were 94 patients with PM/DM in whom interstitial pneumonia was histologically confirmed (36 PM, 50 DM, and 8 amyopathic DM). Chronological evaluation between the diagnosis of PM/DM and lung involvement demonstrated that most lung involvement occurred just before or just after the diagnosis of PM/DM. Interstitial pneumonia was preceded in 35 of 87 evaluable patients [21 cases with PM (61.8%), 14 cases with DM and amyopathic DM (40.2%)]. In 60 of 87 evaluable patients (69.0%), lung involvement occurred as a clinical manifestation at the diagnosis of PM/DM. CONCLUSION: The present data demonstrate that interstitial pneumonia was frequently the initial onset in patients with PM/DM.     

Mitral valve repair for severe mitral regurgitation caused by endomyocardial biopsy

Mitral regurgitation (MR) following endomyocardial biopsy is a rare and severe complication. A 70-year-old man with severe MR due to chordal injury caused by left ventricular endomyocardial biopsy is described. In this patient, a few chordae tendineae of the posterior-median papillary muscle were injured by the biopsy forceps. Due to the chordal rupture, both anterior and posterior leaflets were prolapsed and severe MR developed. MR was successfully treated by artificial chordal replacement using extended polytetrafluoroethylene sutures and ring annuloplasty. This mitral valve repair with artificial chordal replacement was considered suitable to treat MR resulting from iatrogenic chordal injury as the leaflets were not involved in the degenerative process and papillary muscle function was preserved. To avoid MR, the transvenous approach should be used routinely for endomyocardial biopsies; biopsy from the left ventricle is not justified.     

Transthyretin Thr60Ala Appalachian-type mutation in a Japanese family with familial amyloidotic polyneuropathy.

A Japanese case with familial amyloidotic polyneuropathy (FAP) associated with the transthyretin mutation Thr60Ala (Appalachian-type mutation) is described This is the first reported case of a non-Caucasian harboring this type of TTR mutation. The patient developed severe late-onset restrictive cardiomyopathy as well as sensorimotor and autonomic polyneuropathy, which were essentially similar to the previously reported clinical pictures of Appalachian-type FAP.     

Peak VO(2) is more potent than B-type natriuretic peptide as a prognostic parameter in cardiac patients.

BACKGROUND: It is well-known that both B-type natriuretic peptide (BNP) and peak oxygen uptake (VO(2)) are independent predictors of mortality in patients with heart failure. This study investigates the predictive power of BNP and peak VO(2) for survival in cardiac patients. METHODS AND RESULTS: A total of 609 patients with cardiac disease participated in the study. They underwent cardiopulmonary exercise testing to determine peak VO(2), with BNP being measured before exercise testing During 502.5 median follow-up days, 29 patients died of cardiovascular disease. In the univariate Cox proportional hazards analysis, peak VO(2) and BNP were both found to be significant prognostic indices for survival. The time-dependent ROC curve analysis (Heagerty 2006) was applied to 3 predictors: peak VO(2), BNP, and then both, with gender and age as adjusted variables. The area under the curve (AUC) compared with the follow-up period curves of peak VO(2) and the 2 combined variables (ie, BNP and peak VO(2)) were consistently over that of BNP. The integrated AUC indices were 0.80 (peak VO(2)), 0.81 (peak VO(2) and BNP) and 0.70 (BNP), respectively. CONCLUSIONS: These results indicate that peak VO(2) is more potent than BNP for predicting the mortality in patients with mixed cardiac disease.     

Two cases of respiratory infection complicating treatment with infliximab]

Infliximab, an anti-TNF-alpha agent, is highly effective against rheumatoid arthritis and Crohn's disease. However, respiratory infection can occur as a complication. We report two cases complicated by respiratory infection following administration of infliximab. The first case, a 67-year-old woman with rheumatoid arthritis, developed pneumocystis pneumonia after three courses of infliximab therapy. The second case, a 31-year-old man with Crohn's disease, developed pulmonary tuberculosis after four courses of infliximab therapy. Respiratory complications associated with anti-TNF therapy include infectious diseases such as pneumocystis pneumonia, tuberculosis, and bacterial pneumonia. They often lead a fulminant course, and early diagnosis is essential. The final report of a survey of the initial 5000 cases with rheumatoid arthritis treated with infliximab in Japan was released in April 2006; pulmonary infectious complications included 22 cases of pneumocystis pneumonia, 14 cases of tuberculosis, and 108 cases of bacterial pneumonia. The growing use of anti-TNF therapy might lead to increasing pulmonary complications. Accumulation of similar cases is expected to elucidate the mechanism of the complications and methods for effective prophylaxis.     

1,25-Dihydroxyvitamin D3 antagonizes interferon-gamma-induced expression of class II major histocompatibility antigens on thyroid follicular and testicular Leydig cells

Interferon-gamma (IFN gamma) induces production and expression of major histocompatibility complex class II molecules on both marrow-derived and nonbone marrow-derived cell types. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], a seco-steroid derived from vitamin D3, has previously been reported to enhance such expression alone or together with IFN gamma on a number of monocyte/macrophage tumorigenic lines. In contrast, the present studies have found that 1,25-(OH)2D3 inhibited the ability of IFN gamma to induce class II antigen expression on nontransformed rat thyroid follicular epithelial cells (FRTL-5) and mouse testicular Leydig cells (TM3). Although 1,25-(OH)2D3 inhibited the induction of both IA and IE class II locus products, IFN gamma augmentation of class I major histocompatibility complex antigens was not affected. 1,24-(OH)2D3 and 24,25-(OH)2D3 also inhibited class II induction by IFN gamma. Notably, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-(OH)2D3 receptor, indicating that this antagonistic effect probably requires receptor-ligand interaction. Other steroid hormones, such as hydrocortisone or testosterone, had no inhibitory effect on IFN gamma-induced class II expression on Leydig cells. Additionally, the failure of indomethacin to reverse the effect of 1,25-(OH)2D3 and the finding that exogenous prostaglandin E2 did not inhibit class II induction in these cells indicated that prostaglandins are probably not responsible for this anti-IFN gamma activity. In total, these results suggest that an endocrinological mediator is capable of inhibiting class II induction on resident endocrine tissue populations and, therefore, could help to diminish local CD4+ T-cell recognition of these cells.