To investigate, by focal macular electroretinography (ERG), the change of photopic negative response (PhNR) in the recovery of visual function in patients with optic neuritis.
Focal macular ERG was recorded from nine patients with acute optic neuritis (38.6±10.2 years). The photostimulator device projected 15° visual angle spotlight onto the macula. Focal macular ERG recording was performed at the onset and at 1 month and 6 months after the onset of optic neuritis. The results were compared between each recording for seven of the patients.
All patients decreased in the vision below 20/100 and had central scotoma. Vision improved more than 20/20 within 1 month and full-visual field recovered within 6 months after the onset in all patients. The amplitude of the a-wave, b-wave, and PhNR of focal macular ERG at the onset was significantly attenuated in eyes with optic neuritis (66.8±15.5, 65.8±17.7, and 65.2±14.4% of normal control, respectively). The amplitude of the a-wave and b-wave increased gradually after steroid pulse therapy. The increase in a-wave amplitude was significant at 6 months (P=0.046), whereas the PhNR amplitude did not show any significant change over 6 months after the onset of optic neuritis.
Our results suggest that inflammation at the onset of optic neuritis leads to functional deficits that extend to at least the inner nuclear layers of the retina, and that all but the ganglion cell layers of retina recover.
focal electroretinogram; photopic negative response; optic neuritis; macula
Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus.
Design Meta-analysis of randomised trials.
Data sources Cochrane controlled trials register, Embase, and Medline.
Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I2 statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test.
Results 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups.
Conclusion In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.
Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult.
Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n = 30) and healthy controls (n = 18, plasma; n = 14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n = 10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)‐8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores.
BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9–132.9) v 16.0 ng/ml (IQR 8.9–25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL‐8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL‐8, and neutrophils were significantly greater in patients with ALI of pulmonary origin.
Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL‐8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.
acute lung injury; acute respiratory distress syndrome; interleukin‐8; inflammation; thioredoxin
It is thought that overexpression of epidermal growth factor receptor (EGFR) in non‐small cell lung cancer (NSCLC) might compromise patient survival, presumably by promoting tumour growth by an autocrine mechanism. However, conflicting results have been reported from various laboratories, and the clinical importance of EGFR overexpression remains unsettled.
A meta‐analysis of previous studies was performed to quantitatively review the effects of EGFR overexpression on survival in patients with NSCLC using a DerSimonian‐Laird random effects model. Eighteen studies including 2972 patients were subjected to final analysis.
Overall, positivity for EGFR overexpression differed between histological types: 39% in adenocarcinomas, 58% in squamous cell carcinomas, 38% in large cell carcinomas, and 32% in cancers in a miscellaneous category (p<0.0001). The combined hazard ratio (HR) was 1.14 (95% CI 0.97 to 1.34; p = 0.103), indicating that EGFR overexpression has no significant impact on survival. When only the 15 immunohistochemistry based studies were considered, the combined HR was 1.08 (95% CI 0.92 to 1.28; p = 0.356), again suggesting that EGFR overexpression has no impact on survival. Heterogeneity testing indicated that there was heterogeneity between studies but publication bias was absent, which suggests that the summary statistics obtained may approximate the actual average.
EGFR overexpression was not associated with poorer survival in patients with NSCLC. Specific mutations of the EGFR gene will need further study in terms of survival implications.
epidermal growth factor receptor; lung cancer; overexpression; survival
early stage rheumatoid arthritis; anti‐cyclic citrullinated peptide antibody; magnetic resonance imaging; bone marrow oedema; bone erosion
early stage rheumatoid arthritis; anti‐cyclic citrullinated peptide antibodies; magnetic resonance imaging; bone marrow oedema
Methods: Vascular endothelial growth factor165 (VEGF165), tumour necrosis factor α (TNFα), and interleukin 1ß (IL1ß) were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from three patients with RS3PE syndrome. As controls, serum samples from 26 healthy volunteers, 12 patients with rheumatoid arthritis, 10 patients with systemic lupus erythematosus, 13 patients with polymyositis/dermatomyositis, 13 patients with vasculitis syndrome, and 6 patients with mixed connective tissue disease were also analysed. Synovial hypervascularity of patients with RS3PE syndrome was estimated by rate of enhancement (E-rate) in a dynamic MRI study.
Results: Serum concentrations of VEGF165 (mean (SD) 2223.3 (156.3) pg/ml) were significantly higher in patients with active RS3PE syndrome than in controls before corticosteroid treatment. TNFα and IL1ß levels were similar in patients and controls. Synovial hypervascularity in affected joints and subcutaneous oedema decreased during corticosteroid treatment, in parallel with the fall in serum VEGF165.
Conclusions: VEGF promotes synovial inflammation and vascular permeability in patients with RS3PE syndrome, suggesting that RS3PE can be classified as a VEGF associated disorder.
Aims: To examine histopathological and immunohistochemical changes in lenticules and host of corneal buttons from patients who previously underwent epikeratoplasty for keratoconus.
Methods: 12 penetrating keratoplasty specimens from patients with keratoconus who had previously undergone epikeratoplasty, eight keratoconus, and seven normal corneas were examined. Immunostaining for Sp1, α1-proteinase inhibitor (α1-PI), and α2-macroglobulin (α2M) were performed.
Results: In nine of the 12 lenticules, the keratoconus-like disruptions were found in Bowman’s layer. Peripheral and posterior keratocyte repopulation of the lenticules was observed in all cases. Keratocyte repopulation in the anterior and mid-stromal regions of the lenticules appeared related to the time since epikeratoplasty. Sp1 nuclear staining of the basal and wing epithelial cells was more intense in lenticules and keratoconus corneas than in normal corneas. Lenticular, host, and keratoconus keratocytes showed positive Sp1 staining, whereas staining was absent in normal corneas. Compared to normal corneas, α1-PI and α2M immunostaining was lower in the lenticules, host, and keratoconus specimens.
Conclusions: The epithelial cells and keratocytes repopulated in the lenticules retain keratoconus-like biochemical abnormalities such as upregulation of Sp1 and downregulation of α1-PI and α2M. The authors speculate that both keratocytes and the corneal epithelium may participate in the development of keratoconus.
keratoconus; epikeratoplasty; Bowman’s layer disruption; keratocyte repopulation; Sp1
Background: Very few population based cohort studies have focused on the long term recurrence of stroke.
Objective: To examine 10 year cumulative recurrence rates for stroke in a Japanese cohort according to pathological type and clinical subtype of brain infarction.
Methods: During a 32 year follow up of 1621 subjects ⩾40 years of age, 410 developed first ever stroke. These were followed up prospectively for 10 years after stroke onset.
Results: During follow up, 108 (26%) experienced recurrent stroke. The cumulative recurrence rates were 35.3% at five years and 51.3% at 10 years. The 10 year recurrence rates of subarachnoid haemorrhage (SAH), brain haemorrhage, and brain infarction were 70.0%, 55.6%, and 49.7%, respectively; the difference between SAH and brain infarction was significant (p = 0.004). Most recurrent episodes after SAH or brain haemorrhage happened within a year after the index stroke, whereas recurrence of brain infarction increased consistently throughout the observation period. Cardioembolic stroke had a higher recurrence rate (75.2%) than lacunar infarction (46.8%) (p = 0.049). The 10 year risk of stroke recurrence increased with age after lacunar or atherothrombotic brain infarction, but not after the other types or subtypes. After atherothrombotic brain infarction, cardioembolic stroke, or SAH, the type and subtype of most recurrent strokes were the same as for the index stroke, but recurrence after lacunar infarction or brain haemorrhage showed divergent patterns.
Conclusions: Japanese people have higher recurrence rates of stroke than other populations. Recurrence rate after a first brain infarct increases consistently through the next 10 years.
External manual carotid compression is a non-invasive method to treat patients with cavernous sinus dural arteriovenous fistulae (CS-DAVF). We studied a group of patients with CS-DAVF to identify factors that made cure by compression therapy possible.
We treated 23 patients with CS-DAVF without cortical venous drainage or a recent decline in visual acuity by compression therapy. All were followed up by magnetic resonance angiography (MRA) at one, three, six, and 12 months after treatment and the characteristics of the imaging findings, their neurological symptoms, and the patterns of symptom improvement were examined.
In group A (n=8), cure was achieved by manual carotid compression; in the other 15 patients (group B), cure was not obtained. Group B manifested significantly higher ocular pressure and a significantly longer interval between symptom onset and treatment by manual carotid compression. In group A, venous drainage was via the superior orbital vein (SOV) with/without involvement of the inferior petrosal sinus (IPS); closure of the CS-DAVF occurred within 4.1 months after the start of treatment. In three patients symptom improvement progressed steadily and gradually. The other five cured patients experienced transient worsening of their symptoms at two to four months after the start of treatment, these resolved within four to seven months
Manual carotid compression was effective in patients without retrograde venous CS-DAVF drainage or a severe decline in visual acuity. The factors that rendered cure by compression therapy possible were lower ocular pressure and a shorter interval between symptom onset and the start of treatment. Venous drainage in those patients was exclusively via the SOV without involvement of the IPS.
cavernous sinus, carotid artery, dural arteriovenous fistulae, external compression
Objectives: To characterise cartilage intermediate layer protein (CILP)-induced arthropathy in mice.
Methods: The first and second halves of the nucleotide triphosphate pyrophosphohydrolase (NTPPHase) non-homologous region of human CILP were prepared as recombinant proteins (C1 and C2, respectively), including three overlapping fragments of C2 (C2F1, C2F2, and C2F3). C57BL/6 mice were immunised with these proteins to induce arthritis. In addition, a separate group of mice were immunised repeatedly with the mixture of C1 and C2 to see the effect of chronic immunisation. Arthritis developed in the mice, and cellular and humoral immune responses against CILP were analysed.
Results: Immunisation with C2 and with the mixture C2F1/C2F2/C2F3 caused the severest arthritis to develop in mice. Immunisation with one of C1, C2F1, C2F2, or C2F3 caused milder arthritis, even though each of the fragments carried T cell epitopes. Immunisation either with C1 or C2 alone evoked cellular and humoral immune responses to both the C1 and C2 proteins. Further, the repeated immunisation with the C1/C2 mixture caused tendon calcification and bone irregularity, together with decreased NTPPH activity.
Conclusions: The results show that multiple T cell epitopes are needed for the development of CILP-induced arthritis, and present the characteristic new model of mild arthropathy accompanied by extra-articular calcifications. An immune response to putative murine CILP/NTPPH may be involved in the ectopic calcifications in the arthritic mice.
To diagnose VA dissection, MRA or cerebral angiography, which provides information regarding intra-vascular space, has been performed. We report the acquisition of various information about VA dissection using MRI-BPAS, which is a new diagnostic method.
vertebral artery dissection, MRI-BPAS
Contralateral carotid artery occlusion is thought to represent a significant risk factor in carotid endarterectomy (CEA). There is also evidence that intraoperative and postoperative hypotention may cause contralateral hemodynamic ischemia. As such, contralateral carotid artery occlusion is regarded as a risk factor for carotid angioplasty and stenting (CAS). In this paper, we report on five cases of severe ICA stenosis with contralateral carotid artery occlusions. Cerebral blood flow(CBF) and cerebral vasoreactivity(CVR) of the contralateral carotid artery occlusions were measured before and after CAS. Additionally, the influence that ipsilateral CAS exerted on the occluded side was examined.
123I-IMP SPECT was performed before and after CAS, both at rest and at the time of acetazoramide administration. The CBF was evaluated quantitatively using the ARG method. The mean CBF of the treated side rose from 30.0 ± 7.1 ml/100g/min to 34.4 ± 8.3 ml/100g/min (p<0.05), and the mean CBF of the occluded side similarly rose from 28.3 ± 6.1 ml/100g/min to 31.7 ± 6.4 ml/100g/min (p<0.05). Correspondingly, the regional CVR (rCVR) increased from 5.9% ± 16.3% to 35.0% ± 16.4%(p<0.05) on the treated side, and from 3.7% ± 14.7% to 10.7% ± 16.9% (p<0.05) on the occluded side.
This demonstrates that ipsilateral CAS seems to improve both CBF and CVR on the contralateral occluded side. The fact that some cases developed cross flow from the anterior communicating artery was both remarkable and significant. Where there was poor cross flow from the anterior communicating artery, improvement in cerebral vaso reactivity was limited.
CAS, contralateral carotid artery occlusion, CBF.
Methods: 203 current or ex-smokers (lifelong cigarette consumption (CC) ≥10 pack years) with subclinical and established COPD phenotypes were clinically evaluated and pulmonary function tests and a chest CT scan were performed (smoker group). The non-smoker group consisted of 123 healthy volunteers. CYP2A6 genotypes were determined in both groups.
Results: The percentage of subjects with a CYP2A6del allele (genotype D) was lower in heavy smokers (20.5%, n=88, CC ≥60 pack years) than in light smokers (37.4%, n=115, CC 10–59 pack years, χ2=6.8, p=0.01) or non-smokers (36.1%, n=122, χ2=6.0, p=0.01); lower in ex-smokers (20.7%, n=111) than in current smokers (41.3%, n=92, χ2=10.1, p<0.01); and lower in smokers with a high LAA (low attenuation area) score on the chest CT scan (18.4%, n=76, LAA ≥8.0) than in those with a low LAA score (37.0%, n=127, LAA <8.0, χ2=7.8, p<0.01).
Conclusions: Subjects with the CYP2A6del allele tend not to be heavy habitual smokers but can be light habitual smokers. The CYP2A6del polymorphism may inhibit smokers from giving up smoking, but appears to function as a protective factor against the development of pulmonary emphysema independent of smoking habit.
Aims: To examine the risk factors for age related maculopathy (ARM) in a sample Japanese population.
Methods: In 1998, a cross sectional community survey was conducted among residents of Hisayama. A total of 596 men and 886 women living in Hisayama, Japan, aged 50 years or older consented to participate in the study. Each participant underwent a comprehensive examination that included an ophthalmic examination. The presence of ARM was determined by grading from fundus examination by indirect ophthalmoscopy, slit lamp examination, and colour fundus photographs. Using these cross sectional data, logistic regression analyses were performed to determine the risk factors for ARM. The following 10 possible risk factors were used: age, cataract, hypertension (history), hypertension (history or examination), diabetes, hyperlipidaemia, current smoker, alcohol intake, BMI, and WBC.
Results: ARM was detected in 19.5% of men and 14.9% of women. Men were found to have a significantly higher prevalence of ARM than women. Multiple logistic regression analysis showed that age and hypertension (history or examination) were significantly associated with ARM in men, whereas only age was a significant risk factor for ARM in women.
Conclusions: This study suggests that higher age and male sex are relevant risk factors for ARM in Japan. In addition, hypertension is a relevant risk factor in men.
age related maculopathy; Japanese population; risk factor; population based study
Extent of resection needed to treat lung cancer has long been an issue. The sole randomised controlled trial, reported by the Lung Cancer Study Group, advised against limited resection as standard surgery even for small peripheral non-small-cell lung cancers (⩽3 cm), because of frequent local recurrences. Elsewhere, conflicting results have been reported from different institutions. We therefore conducted a meta-analysis of reported studies to compare survival of stage I patients between limited resection and standard lobectomy. A MEDLINE web search for computer-archived bibliographic data yielded 14 articles suitable for analysis. Combined survival differences (survival rate with lobectomy minus that with limited resection) at 1, 3, and 5 years after resection according to the DerSimonian–Laird random effects model were 0.7% (95% CI, −0.8 to 2.1; P=0.3659), 1.9% (95% CI, −3.7 to 7.4; P=0.5088), and 3.6% (95% CI, −0.4 to 10.5; P=0.3603), respectively. None of these survival differences were significant, indicating that survival after limited resection for stage I lung cancer was comparable to that after lobectomy. However, since interstudy heterogeneity was detected, caution is required in interpretation of the results.
lung cancer; limited resection; segmentectomy; wedge resection; meta-analysis
Type 2 diabetes is preceded by a symptom-free period of impaired glucose tolerance (IGT). Pancreatic B-cell function decreases as glucose intolerance develops. In many patients with IGT, fasting blood glucose is within normal limits and hyperglycaemia occurs only postprandially. We examined whether pancreatic B-cell function changes during acute hyperglycaemia induced by oral glucose loading.
We calculated the insulinogenic index (I.I.) as an indicator of pancreatic B-cell function and measured serum levels of thioredoxin, a marker of cellular redox state, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative stress, during a 75-g oral glucose tolerance test (OGTT) in 45 subjects [24 patients with normal glucose tolerance (NGT), 14 with IGT and seven with Type 2 diabetes].
Thioredoxin levels decreased after glucose loading [66.1 ± 23.7, *59.3 ± 22.4, *49.3 ± 21.2 and *37.7 ± 18.0 ng/mL, fasting (0 min) and at 30, 60 and 120 min, respectively; *P < 0.001 vs. fasting]. In contrast, concentrations of 8-OHdG peaked at 30 min and then gradually decreased (0.402 ± 0.123, *0.440 ± 0.120, †0.362 ± 0.119 and †0.355 ± 0.131 ng/mL, *P < 0.05 vs. fasting, †P < 0.01 vs. 30 min). The insulinogenic index correlated with the change in thioredoxin levels (r = 0.34, P < 0.05). However, there was no relationship with the change in 8-OHdG levels from 0 to 30 min.
Hyperglycaemia in response to oral glucose impairs pancreatic B-cell function with decreasing thioredoxin levels. The augmented oxidative stress induced by hyperglycaemia may affect the cellular redox state. These findings strongly suggest that repeated postprandial hyperglycaemia may play an important role in the development and progression of diabetes mellitus.
blood glucose; impaired glucose tolerance; oxidative stress; postprandial hyperglycaemia
The purpose of this study was to evaluate the effect of endovascular treatment with Guglielmi detachable coils (GDC) on the outcomes of subarachnoid haemorrhage (SAH) patients of poor grades and high ages for each location of aneurysms.
Between 1990 and 2003, 529 SAH cases underwent angiograghy as candidates of early aggressive treatment in our hospital. For the 299 cases in 1990-96 (Group 1), treatment options were early and intensively delayed craniotomy surgery and conservative management, while for the 230 cases in 1997-2003 (Group 2), GDG embolization at acute stage was added to these three treatment options. We compared clinical courses and outcomes of the poor grade (Hunt & Kosnik Grade 4-5) patients and high age (> = 70 years old) patients between two groups for each location of aneurysms.
Introduction of GDC embolization expanded the indication for early treatment in the poor grade patients with anterior communicating artery aneurysm (A-Comm An), the high age patients with internal carotid artery aneurysm (IC An) and all patients with Basilar bifurcation aneurysm (BA-Top An), and has contributed to improvement of their outcomes. To the poor grade patients with middle cerebral artery aneurysm (MCA An), GDC embolization was hardly indicated, because haematoma evacuation concomitantly performed with aneurysm occlusion would be necessary for those patients.
In conclusion, results of treatment with GDC embolization at an acute stage are desirable for poor grade patients with A-Comm An, aged patients with IC An and all patients with BA-Top An. The indication of GDC embolization for the patients with MCA An is limited.
GDC, SAH, outcome, location of aneurysms
We have been using the Guglielmi detachable coils (GDC) since 1997 as one choice of cerebral aneurysm treatment. We have, at the present time, two effective radical treatment methods for acutely ruptured cerebral aneurysms, GDC embolization and conventional surgical aneurysmal neck clipping. There ensued questions about the cost and efficacy of the two strategies. Retrospective analysis was done on a GDC group and a clipping group, with each twenty consecutive patients. The features of the GDC group patients were higher age, and poorer Hunt and Kosnik grades than the other group. All MCA aneurysms were treated with surgical neck clipping, while all the posterior circulation aneurysms were embolized with GDC.
Based on the Japanese Medical Insurance and Payment System, 477,890 points (1 point = ￥10) as a mean was required with the GDC group, and 456,084 points with the neck clipping group, showing no significant difference between the two groups. In the GDC group, the cost of the implanted medical device seemed to raise the total medical expense.
At present, the GDC embolization is the preferred choice of strategies in acutely ruptured cerebral aneurysms, and its preference increases in the surgically difficult cases, very old, or poor grade patients, and in various complicated cases. And, the GDC embolization seems to be satisfactory from the medico-financial viewpoint.
GDC, ruptured cerebral aneurysm, medical insurance, medical expenses
Ruptured vertebral artery dissecting aneurysms (VADA) re-bleed frequently especially during first 24 hours, which makes the prognosis of the patients with this disease poor. Recently endovascular trapping with detachable platinum coils at an acute stage has been done for preventing re-bleeding. However, for the cases with dissecting aneurysm involving the origin of the posterior inferior cerebellar artery (PICA), these methods are hardly indicated because of the risk of ischemic complication in the PICA territory.
We proposed a simple and effective therapeutic method for these cases. We occluded the affected vertebral artery (VA) near its root intending to introduce collateral blood flow from the deep cervical artery into the VA trunk. The controlled antegrade VA flow and retrograde flow from the contralateral VA make a watershed at the dissecting aneurysm, which promotes thrombosis of pseudolumen with preserving the antegrade blood flow of PICA. We treated two cases with ruptured VADA involving PICA, and in both cases thrombosis of aneurysm was obtained without any ischemic complication.
This method would be considered as a treatment of choice to the cases with VADA involving PICA.
endovascular treatment, VA dissecting aneurysm, SAH
photodynamic therapy (PDT); photodynamic diagnosis; hepatocellular carcinoma; chemically induced hepatocellular carcinoma; 5-aminolaevulinic acid; excimer dye laser
OBJECTIVES—To examine whether inhibition of NF-κB induces apoptosis of human synovial cells stimulated by tumour necrosis factor α (TNFα), interleukin 1β (IL1β), and anti-Fas monoclonal antibody (mAb).
METHODS—The expression of proliferating cell nuclear antigen (PCNA), NF-κB, and the presence of apoptotic synovial cells were determined in synovial tissues. Apoptosis of cultured synovial cells was induced by inhibition of NF-κB nuclear translocation by Z-Leu-Leu-Leu-aldehyde (LLL-CHO). The activation of caspase-3 and expression of XIAP and cIAP2 in synovial cells in LLL-CHO induced apoptosis was also examined.
RESULTS—Abundant PCNA+ synovial cells were found in rheumatoid arthritis (RA) synovial tissue, though a few apoptotic synovial cells were also detected in the RA synovial tissues. Nuclear NF-κB was expressed in RA synovial cells. Electrophoretic mobility shift assay showed that treatment of cells with TNFα or IL1β significantly stimulated nuclear NF-κB activity. A small number of apoptotic synovial cells expressing intracellular active caspase-3 were found after treatment of cells with LLL-CHO. Although treatment of RA synovial cells with TNFα or IL1β alone did not induce apoptosis, apoptosis induced by LLL-CHO and caspase-3 activation were clearly enhanced in TNFα or IL1β stimulated synovial cells compared with unstimulated synovial cells. Furthermore, induction of apoptosis of synovial cells with caspase-3 activation by anti-Fas mAb was clearly increased by LLL-CHO. The expression of cIAP2 and XIAP in synovial cells may not directly influence the sensitivity of synovial cells to apoptosis induced by LLL-CHO.
CONCLUSION—The results suggest that NF-κB inhibition may be a potentially important therapeutic approach for RA by correcting the imbalance between apoptosis and proliferation of synovial cells in RA synovial tissue.
BACKGROUND—The role of
Epstein-Barr virus (EBV) in idiopathic pulmonary fibrosis (IPF) is
uncertain. A study was undertaken to detect the virus in IPF as well as
to clarify the influence of EBV on the clinical features of the disease.
lung specimens were obtained from patients with IPF, as well as five
specimens from patients with systemic sclerosis with pulmonary fibrosis
(SSc) and 15 specimens from controls. EBV DNA and EBV latent membrane
protein 1 (LMP1) were detected using the PCR method and
immunohistochemical analysis, respectively.
RESULTS—EBV DNA was
detected in 24 of 25 patients with IPF (96%), in all five patients
with SSc (100%), and in 10 of 14 controls (71%). The detection ratio
was significantly higher in patients with IPF than in controls (p = 0.047, odds ratio (OR) = 9.60, 95% confidence interval (CI) 0.9 to
96.9). Immunohistochemical analysis revealed that cuboidal epithelial
cells were positively stained with anti-LMP1 antibody in nine of the 29 lung specimens from IPF patients. In contrast, neither the patients
with SSc nor the control subjects showed positive staining. In the
follow up periods LMP1 positive patients with IPF died more frequently
from respiratory failure than LMP1 negative patients (4/9 versus 1/20;
p = 0.022, OR =15.20, 95% CI 1.3 to 168.0).
positivity may be associated with more rapid disease progression in IPF.