Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behçet's disease (BD) in Japan

BD is prevalent in the area of the Silk Route. It has been shown that hsp are involved in the T cell activation in patients with BD in the UK, where this disease has developed sporadically. We have thus examined whether the T cell response to the hsp-derived peptides may be induced in patients with BD in Japan, an east pole of the Silk Route. As with patients in the UK, the human 60-kD hsp peptide 336–351 also yielded vigorous proliferation of T cells in Japanese patients with BD, but neither in normal subjects nor in patients with rheumatoid arthritis (RA); there was significant association between proliferation by this peptide and the presence of ocular lesion, but not any other symptoms of BD. To clarify whether the peptide stimulates T cells as a polyclonal activator, a specific antigen or a superantigen-like substance, we analysed T cell receptor (TCR) usage of responding T cells by means of MoAbs specific for TCR Vβ subfamily and polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP)-based technique. We found that T cells with certain TCR Vβ subfamilies (including Vβ5.2–3, 8, 13.6, 18, 21.3) were increased in circulation and responded to the hsp peptide in an antigen-specific fashion. In addition, TCR Vβ gene-amplified products of freshly isolated T cells of patients with BD formed several bands in the PCR-SSCP analysis; some of them became prominent after stimulation with the peptide. This suggests that T cells in patients with this disease have already been expanded oligoclonally in vivo, which may be a result of stimulation by triggering antigens, including the hsp peptide. In addition, hsp peptide stimulation induced proinflammatory cytokine mRNA expression in peripheral blood mononuclear cells, including IL-8, tumour necrosis factor-alpha (TNF-α) and TNF-β in eight out of eight patients studied. Taken together, the results suggest that hsp antigen may play a role in the pathogenesis of BD, not only in the area of the Silk Route, but also outside the Silk Route area.     

Adult T‐cell leukemia/lymphoma in a 21‐year‐old man

Adult T‐cell leukemia/lymphoma (ATL) is malignancy of mature T cells that caused by infection with human T‐cell leukemia virus type I (HTLV‐I). Leukemogenesis of ATL cells considered to involve a multistep oncogenic process, resulting in a very long latency period. But, we report here the case of a 21‐year‐old man having suffered from recurrent stomatititis who has already developed acute‐type ATL. ATL generally occurs after a long latency period, and the present case in a young man is thus very rare.     

A Case of Thrombosed Giant Aneurysm of the Azygos Anterior Cerebral Artery: Clipping under Monitoring of Motor Evoked Potentials of the Lower Extremities

Giant aneurysms of the distal anterior cerebral artery (ACA), especially the azygos ACA, are rare. We treated a patient with giant aneurysm of the azygos ACA who underwent aspiration of thrombus and clipping under monitoring of motor evoked potentials of the lower extremities (L-MEPs), resulting in remarkable recovery of motor and intellectual function. A 72-year-old male was admitted with left motor weakness persisting for 2 weeks. Neurologically, disorientation and intellectual impairment were also noted. Imaging disclosed a 60-mm diameter aneurysm with heterochronous thrombi arising from the distal bifurcation of the azygos ACA. One month after the onset, radical surgery was scheduled. The azygos ACA was secured and the aneurysm was dissected, and the distal parts of the azygos ACA were confirmed. After removal of the thrombus, the neck was reconstructed with eight clips. L-MEPs disappeared due to occlusion of the azygos ACA for 20 minutes but reappeared after 22 minutes and normalized 78 minutes after reperfusion. Motor weakness improved entirely with mini-mental state examination score of 29 points at 1 month after surgery. One year later, Wechsler Adult Intelligence Scale-Third Edition and Wechsler Memory Scale-Revised scores reached normal levels. Review of reported cases found this aneurysm tends to occur in males in their 50s to 70s presenting with mass sign. Decompression of the aneurysm in the frontal lobe and monitoring of L-MEPs during temporary occlusion of the ACA are important.     

Electroporation in a Model of Cardiac Defibrillation

INTRODUCTION: It is known that high-strength shock disrupts the lipid matrix of the myocardial cell membrane and forms reversible aqueous pores across the membrane. This process is known as "electroporation." However, it remains unclear whether electroporation contributes to the mechanism of ventricular defibrillation. The aim of this computer simulation study was to examine the possible role of electroporation in the success of defibrillation shock. METHODS AND RESULTS: Using a modified Luo-Rudy-1 model, we simulated two-dimensional myocardial tissue with a homogeneous bidomain nature and unequal anisotropy ratios. Spiral waves were induced by the S1-S2 method. Next, monophasic defibrillation shocks were delivered externally via two line electrodes. For nonelectroporating tissue, termination of ongoing fibrillation succeeded; however, new spiral waves were initiated, even with high-strength shock (24 V/cm). For electroporating tissue, high-strength shock (24 V/cm) was sufficient to extinguish ongoing fibrillation and did not initiate any new spiral waves. Weak shock (16 to 20 V/cm) also extinguished ongoing fibrillation; however, in contrast to the high-strength shock, new spiral waves were initiated. Success in defibrillation depended on the occurrence of electroporation-mediated anodal-break excitation from the physical anode and the virtual anode. Some excitation wavefronts following electrical shock used a deexcited area with recovered excitability as a pass-through point; therefore, electroporation-mediated anodal-break excitation is necessary to block out the pass-through point, resulting in successful defibrillation. CONCLUSION: The electroporation-mediated anodal-break excitation mechanism may play an important role in electrical defibrillation.     

Role of Vagal Control in Vasovagal Syncope

SUZUKI, M., et al .: Role of Vagal Control in Vasovagal Syncope. The vasovagal reaction is thought to be caused by sympathetic withdrawal and vagal augmentation. While measurements of muscle sympathetic nerve activity support sympathetic withdrawal in tilt induced syncope, the results of previous attempts to quantify vagal control using spectral analyses of heart rate variability (HRV) remain controversial. The sampling period used in the HRV studies is related to the discordant results. In the present study, HRV was computed every second using wavelet transformation to clarify the role of vagal control in tilt induced syncope during the 80-degree head-up tilt test (positive: 10 patients with vasovagal syncope; negative: 10 patients with vasovagal syncope, and 10 control subjects). Autonomic modulations were assessed using the absolute power of the low frequency (LF) (0.04–0.15 Hz) and high frequency (HF) (0.15–2.00 Hz) oscillatory components of R-R variability. Although the LF did not change during the tilt procedure, a decrease in the systolic arterial pressure (SAP) and increases in the R-R interval and HF were observed for the last 30 seconds before the tilt induced syncope in the tilt-positive group. Analyzing the hemodynamic measurements and spectral indices for the last 5 minutes preceding the tilt induced syncope, the study found that the SAP, R-R interval, and HF changed simultaneously during the 30-second period immediately before the tilt induced syncope. Further, the HF was positively correlated with the R-R interval and negatively correlated with the SAP. In conclusion, continuous spectral analysis of the R-R interval demonstrated increased vagal influence on the heart in tilt induced syncope. (PACE 2003; 26[Pt. I]:571–578)     

PROGRESSIVE SYSTEMIC SCLEROSIS ASSOCIATED WITH CUTANEOUS AMYLOIDOSIS

A 43-year-old woman presented with a 3-year history of Raynaud's phenomenon and a six-month history of numbness in both arms. Sclerosis was noted on the entire body surface. The skin of the face was smooth and the lips were constricted (Fig. 1). The fingers and hands were atrophic and sclerotic, and full extension of the fingers and metacarpal joints was impossible (Fig. 2). There was pigmentation on the dorsal aspect of the hands. From the nape to the upper back, pruritic wavy, rippled or reticular pigmented macules in addition to sclerosis were noted (Fig. 3). Other parts of her skin did not show such a wavy pigmentation. Physical examination revealed no specific findings in the lung, heart, and abdomen. Neurologic examination was unremarkable. Motor function including muscle tonus was normal.
Laboratory studies disclosed that the complete blood count and tests of hepatic and renal function were within normal limits. Antinuclear antibody was I:80 and showed a speckled pattern, antitopoisomerase 1 antibody, anticen-tromere antibody, anti-Sm antibody and anti-RNP antibody were all negative, and the CH50 was 31.5 units/ml; C3 was 59.4 mg/dL; and C4, 17 mg/dL. Radiologically the chest and esophagus were normal.
Pulmonary function and electro-cardiogram were also normal. Histologic examination of a skin biopsy obtained from the upper back revealed that the collagen bundles throughout the dermis were thickened, homogenous, and closely packed. In the upper dermis, a small number of inflammatory cells around blood vessels was observed. Eosinophilic homogeneous masses were seen in the papillary dermis and upper dermis (Fig. 4). These homogeneous masses were positive to Dylan' (Fig. 5), Congo red, and thioflavin T staining. Therefore, the diagnosis of cutaneous macular amyloidosis was made.     

Effects of treadmill training on the arteriolar and venular portions of capillary in soleus muscle of young and middle-aged rats

The effects of a 6-week programme of endurance training on soleus muscle capillarity were examined, in terms particularly of the proportions of arteriolar and venular capillaries and their capillary domain area, in young (3-week-old) and middle-aged (54-week-old) Wistar rats. Exercise protocols for the young training group were: 10–22.5 m min^?1, 60 min day^?1 for 6 days a week, with a gradient of 7 degrees during the final 2 weeks; for the middle-aged training group, the protocols were: 10–20 m min^?1, 50 min day^?1 for 6 days a week. In both young and middle-aged training groups, the density of arteriolar capillaries was significantly increased (P<0.05), but that of venular and intermediate capillaries was decreased slightly. The proportion of arteriolar capillaries therefore was significantly (P<0.05) increased, from 63.9 to 73.1%, in young rats and from 33.0 to 48.4%, in middle-aged rats after training. The increase in the proportion of arteriolar capillaries is an advantageous adaptation to exercise-induced increases in oxygen demand. In both young and middle-aged rats, capillary domain area and Krogh's tissue cylinder radii in all capillary portions decreased after training. These results suggest that adaptive changes in oxygen transport system, identified as an increase in the arteriolar capillary and a reduction in diffusion distance for oxygen, were observed in middle-aged as well as in young rats. However, capillary angiogenesis induced by exercise appeared to be greater in young than in middle-aged rats.     

Increased IL-6 and IL-8 in bronchoalveolar lavage fluids (BALF) from patients with sarcoidosis: correlation with the clinical parameters

A variety of cytokines have been implicated in the pathogenesis of pulmonary sarcoidosis, but the exact roles of IL-6 and IL-8 are not yet clear. We studied these cytokine levels in BALF from patients with pulmonary sarcoidosis, idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial lung disease and control subjects. IL-6 and IL-8 levels were significantly elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with control subjects. Subjects with sarcoidosis had significantly increased levels of both cytokines compared with controls when the cytokine values were corrected by the total albumin content and the two cytokine levels correlated with each other (r=0.876). BALF IL-6 levels correlated with percent lymphocytes and percent CD3⁺ cells. Moreover, when sarcoidosis patients were divided into three groups, those who needed steroid therapy or had progressive disease showed increased cytokine levels in BALF over stable or improved patients. These observations suggest that locally derived IL-6 and IL-8 were increased in sarcoidosis and correlated with activity of this granulomatous lung disease.