Expression of BAFF and BAFF-R in the synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: The elevated expression of B-cell-activating factor belonging to the TNF family (BAFF) is associated with systemic autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the distribution of BAFF and its receptor BAFF-R in the cells residing in the rheumatoid synovium. METHODS: The expression of BAFF and BAFF-R in synovial tissues obtained from 12 RA patients was examined by immunohistochemistry and flow cytometry. The mRNA expression of these molecules was determined by reverse transcriptase polymerase chain reaction (RT-PCR). Soluble BAFF levels were measured with an enzyme-linked immunosorbent assay (ELISA). Fibroblast-like synoviocytes (FLS) purified from the RA (RA-FLS) were co-cultured with peripheral B cells. The degree of apoptosis in the B cells was measured to assess the effects on the viability of the B cells. RESULTS: The RA synovium showed focal or diffuse infiltration of mononuclear cells (MNCs), and one specimen showed germinal centre (GC)-like structures. Synovial sublining cells, but not lining cells, expressed BAFF. These sublining cells were negative for BAFF-R. BAFF and BAFF-R were expressed in B and T cells extracted from the RA synovium. Notably, RA-FLS spontaneously expressed cytoplasmic BAFF after 4-6 passages; however, they did not express BAFF or BAFF-R on their cell surface. RA-FLS could support the survival of B cells by preventing their apoptosis, but its effect on B cells might not be BAFF dependent. CONCLUSIONS: BAFF and BAFF-R are widely expressed in the RA synovium. The cells residing in the RA synovium might affect each other through BAFF.

A retrospective study of the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody (anti-CCP) retrospectively in patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-CCP were measured retrospectively in 131 patients with RA and 90 patients with non-RA rheumatic diseases using a commercially available kit. All sera were collected from patients during the 22-year period, 1982-2004. To analyze the fluctuation in anti-CCP levels, 17 RA patients were selected on the basis of showing a significantly higher anti-CCP level in a serum sample taken at the first visit (> 80 U/ml), and availability of preserved serum samples that had been taken from each patient at 10 time points. RESULTS: The test gave a sensitivity of 88% (115/131) and a specificity of 81% (73/90). The longitudinal study of 17 RA patients showed that anti-CCP levels were elevated at the first visit in 12 (71%) patients and then decreased gradually, whereas those in the other five (29%) patients fluctuated substantially. In both cases, anti-CCP levels tended to fluctuate in parallel with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, reflecting the spontaneous aggravation of arthritis and the efficacy of anti-rheumatic drugs. The courses of three representative RA patients are illustrated in detail along with their therapeutic regimens, and these further confirm the correlation of anti-CCP levels with laboratory parameters (ESR and CRP) as well as the activity of arthritis. CONCLUSION: Measurement of serum anti-CCP levels was found to be useful for not only the diagnosis but also the management of RA.

Relationship between gait and clinical results after high tibial osteotomy.

Thirty-two patients with primary osteoarthritis of the medial compartment of the knee were studied prospectively to assess the relationship between clinical results, limb alignment, and adduction moment of the knee. Clinical and radiographic examination and gait analyses were performed preoperatively and repeated at 6 months and at 1, 3, and 6 years after high tibial osteotomy. The preoperative peak adduction moment was high in 25 patients and low in seven. In both groups, the adduction moment of the knee decreased at 6 months after surgery but increased after that period. Alignment of the affected knee in both groups remained valgus after surgery (average femorotibial angle, 167 degrees-169 degrees). Clinical outcome in both groups improved after surgery and remained unchanged after 1 year. The peak adduction moment of the knee for the whole group significantly correlated with alignment and foot angle before and 6 years after surgery but did not correlate with stride length and walking velocity. In addition, only alignment was associated significantly with clinical results at 6 years. These results suggest that the preoperative peak adduction moment of the knee does not correlate with clinical or radiographic outcomes of high tibial osteotomy, provided sufficient valgus alignment is achieved at surgery.

[Epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer with applying a method of case-control study--a study of a efficient screening programme for stomach cancer].

An epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer was conducted with applying a method of case-control study. And also in order to carry out an efficient screening programme, the age groups who should be intensively recommended to receive screening and an optimal screening time interval since the last test were analyzed. 527 cases of men and 273 of women, dying of stomach cancer in the years 1981-1989 in the Awa region of Chiba prefecture, were identified from Chiba Cancer Registry. For each case, 3 controls were drawn at random from Awa living residents (about 162000 inhabitants at 1989 national census), with being matched strictly according to the district of residence, sex and born within 3 years of birth-year. For both cases and controls, the information about the screening history until the date of diagnosis of the case in each matched set was collected respectively from comparison with the screening certification. The results showed a relative risk of 0.417 (99% CI 0.284-0.612) in ever screened men compared with never screened and 0.480 (99% CI 0.280-0.823) in women. The significant reduction in risk was intensively observed on age groups 40-74 years among men and 50-69 years among women and the protective effect continued at most in the following three years since last screening. For an efficiency of screening programme, these age groups should be intensively recommended to receive screening and it is allowable that an optimal screening time interval since last negative test is at most 3 years for general attendance.

The effect of hemoglobin and its metabolites on energy metabolism in cultured cerebrovascular smooth-muscle cells.

Cerebral arteries in spasm have been found to contain low levels of adenosine triphosphate (ATP), and it has been postulated that this change in levels results from hypoxia produced by arterial encasement in clotted material. This study was undertaken to determine whether any of four blood-derived agents, ferrous hemoglobin, methemoglobin, hemin, or bilirubin, is capable of reducing energy levels in cerebral artery smooth-muscle cells. Twenty-four-hour exposure of cultured canine basilar artery cells to ferrous hemoglobin and bilirubin led to a significant decline in ATP levels (to 8.9 nmol/mg protein and 2.8 nmol/mg protein, respectively) versus control (16.6 nmol/mg protein); methemoglobin and hemin showed no effect. Bilirubin but not hemoglobin was found to interfere with electron transport and with creatine phosphokinase activity in intact cells; however, bilirubin showed no inhibitory effect on this enzyme in cell-free conditions. The findings indicate that hemoglobin and bilirubin may be responsible for diminished energy levels in cerebral arteries. These observations also suggest that bilirubin may exert its effect on ATP by impairing mitochondrial function.

Bilirubin levels in subarachnoid clot and effects on canine arterial smooth muscle cells.

BACKGROUND AND PURPOSE: Previous studies have suggested that bilirubin is a potential contributor to cerebral vasospasm. The purpose of this investigation was to determine whether bilirubin accrues in subarachnoid clot, whether its vasoconstrictive effect could involve a direct action on arterial smooth muscle cells, and, if so, whether bilirubin affects their Ca2+ uptake. METHODS: Subarachnoid clots were analyzed for bilirubin using high-performance liquid chromatography. The length and 45Ca2+ uptake of vascular smooth muscle cells enzymatically dissociated from canine carotid arteries were measured before and after exposure to bilirubin solution. Additional experiments were conducted on cultured smooth muscle cells from canine basilar artery and on ATP-depleted cardiac myocytes. RESULTS: Mean +/- SE bilirubin concentration in experimental clot was 263 +/- 35.7 mumol/L. Vascular smooth muscle cells exposed to bilirubin showed progressive shortening (P < .01) and an increased uptake of 45Ca2+ (P < .001). Contraction was prevented by Ca(2+)-free media but not by verapamil. Experiments with heart myocytes showed that bilirubin caused an increased uptake of 45Ca2+ but not of [14C]sucrose. CONCLUSIONS: The results indicate that bilirubin accrues in subarachnoid clot, that it exerts a direct constrictive effect on arterial smooth muscle cells, and that this effect is associated with an increased uptake of Ca2+. Studies on heart myocytes suggest that the Ca2+ uptake induced by bilirubin could be due to a selective increase in membrane permeability to Ca2+.

Hemin: levels in experimental subarachnoid hematoma and effects on dissociated vascular smooth-muscle cells.

Although hemin is known to exert toxic effects on a variety of cell types, its possible participation in the genesis of cerebral vasospasm has received little attention. The authors measured the concentration of hemin in experimental subarachnoid clot and studied its effects on the morphology and 45Ca++ uptake of vascular smooth-muscle cells dissociated from canine carotid artery. Craniectomies were performed in five dogs under general anesthesia, and 3 to 5 ml of autologous whole blood was deposited in the supraclinoid subarachnoid compartment. The concentration of hemin recovered by Folch extraction from clotted material removed 7 days after surgery was 390 +/- 247 microM (mean +/- standard error of the mean). Mean vascular smooth-muscle cell length after 40 minutes of exposure to 50 microM hemin was 37.3 +/- 1.2 microns (control 51.6 +/- 1.6 microns) (p < 0.01). The mean percent permeation of 45Ca++, measured by a dual label technique, of cells exposed to hemin was 200.9% +/- 23% (control 102.9% +/- 4.3%) (p < 0.01). These findings indicate that hemin accrues in subarachnoid hematoma, that it exerts a constrictive effect on vascular smooth-muscle cells, and that this effect is associated with an increased uptake of Ca++. This study demonstrates that hemin should be included in the list of potential agents that participate in the development of cerebral vasospasm.

Mutism after removal of a vermian medulloblastoma: cerebellar mutism.

A case of mutism after removal of a vermian medulloblastoma from a 4-year-old girl is reported. Postoperatively, the patient was mute without disturbance of consciousness, language comprehension, or lower cranial nerve function. Computed tomography scans demonstrated no abnormal findings except for the surgical lesion in the posterior fossa. The mutism lasted for 78 days, followed by a period of dysarthria, but she gradually became fluent. The mechanism of "cerebellar mutism" is briefly discussed.

Multiple intracranial xanthogranulomas--case report.

A 58-year-old female was admitted to our hospital with nausea, vomiting, and gait disturbance of 1 year duration. Postcontrast computed tomographic scans demonstrated enhanced lesions in the left cerebellopontine angle (CPA), the retrosellar region, the right parasellar region, and the left parietooccipital convexity. The left parieto-occipital tumor was totally removed in the first operation and the left CPA tumor was partially removed in the second. The histological diagnosis of both tumors was xanthogranuloma. She also had cutaneous lesions (subcutaneous nodules without tenderness) and an ureteral stenosis possibly due to the retroperitoneal involvement. A skin biopsy demonstrated infiltration of xanthoma cells and foamy cells in the dermis. A gallium scintigram demonstrated an abnormal uptake in the thoracic cavity, liver, and bones. From these findings, systemic Weber-Christian disease was diagnosed. Another unique aspect was that the serum IgE levels were increased during postoperative hospitalization. This suggests that abnormal immunological conditions are related to this disease and that intracranial xanthogranulomas are a manifestation of systemic Weber-Christian disease.

The effect of atherosclerosis on endothelium-dependent relaxation in the aorta and intracranial arteries of rabbits.

The effect of hypercholesterolemia on vascular responsiveness was studied in isolated rabbit arteries. The arteries of animals maintained on a cholesterol-rich (1%) diet for 6 months had more pronounced intimal lesion than those receiving the diet for 3 months. The aortas were more severely damaged than the carotid or basilar arteries. Segments of the arteries were mounted in organ chambers for isometric tension recording or for measurement of the endothelium-derived relaxing factor. Endothelium-independent relaxation induced by glyceryl trinitrate was not affected even in the most severely damaged arteries; endothelium-dependent relaxation in response to acetylcholine (ACh) and A23187 was progressively inhibited as the degree of fatty streak formation increased. In the carotid arteries, mean (+/- standard deviation) relaxation induced by 10(-5) M of ACh (expressed as a percentage of the maximum relaxation induced by 10(-4) M of papaverine) decreased from 87.33% +/- 6.30% in control tissues to 60.90% +/- 4.64% in vessels from animals subjected to 6 months of hypercholesterolemia (p less than 0.01); in the aortas, mean relaxation due to 10(-5) M of ACh was 85.08% +/- 8.03% in control tissues and 41.35% +/- 13.68% in hypercholesterolemic tissues (p less than 0.01). In the carotid arteries, mean relaxation induced by 10(-7) M of A23187 decreased from 95.81% +/- 3.58% in control tissues to 55.95% +/- 2.81% in hypercholesterolemic tissues (p less than 0.01); in the aortas, relaxation in response to 10(-7) M of A23187 was 73.73% +/- 4.35% in control tissues and 29.35% +/- 6.77% in hypercholesterolemic tissues (p less than 0.01). Intimal lesions were not produced in the basilar arteries even in rabbits with 12 months of hypercholesterolemia, and endothelium-dependent relaxation was preserved.