3D kinematic analysis of the acromioclavicular joint during arm abduction using vertically open MRI.

Many researchers have evaluated the motions of the shoulder girdle, especially scapular and humeral motion. However, few reports exist that describe motions of the acromioclavicular joint. The purpose of the present study was to analyze the 3D kinematics of the acromioclavicular joint during arm abduction using 3D MR images obtained by a vertically open MRI. Fourteen shoulders of seven volunteers were examined in seven static positions from 0 degrees to the maximum abduction in a seated position. 3D surface models of the clavicle and scapula were created, and the movements of the acromioclavicular joint from 0 degrees to each position were calculated using the volume-based registration technique. From these calculations, the translations were evaluated and the rotational motions were analyzed using the concept of the screw axis. In the anteroposterior direction, the clavicle translated most posteriorly (-1.9 +/- 1.3 mm) at 90 degrees of abduction and most anteriorly (1.6 +/- 2.7 mm) at maximum abduction. In the superoinferior direction, the clavicle translated slightly superiorly (0.9 +/- 1.9 mm). When analyzing relative motion of the scapula with respect to the clavicle, the scapula generally rotated about a specific screw axis passing through the insertions of both the acromioclavicular and the coracoclavicular ligaments on the coracoid process. The average rotation was 34.9 +/- 8.4 degrees.     

Pyoderma gangrenosum associated with ulcerative colitis and subcutaneous and splenic abscesses

Pyoderma gangrenosum is a rare, chronic, inflammatory ulcerative skin disease of unknown etiology and pathogenesis. It is often associated with systemic disease. We describe a patient with pyoderma gangrenosum associated with ulcerative colitis and aseptic abscesses of the subcutis and spleen, which have been rarely reported previously. These manifestations were cleared by combined therapy with minocycline hydrochloride and diaphenylsulfone.     

Rationale and design for a study using intravascular ultrasound to evaluate effects of rosuvastatin on coronary artery atheroma in Japanese subjects: COSMOS study (Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects).

BACKGROUND: There have been few multicenter studies using intravascular ultrasound (IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. METHODS AND RESULTS: An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. CONCLUSIONS: The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions.     

Effects of methylprednisolone on cortical neural activity, blood flow, and water content in air exposure-induced cerebral edema

The correlation of changes in cortical neuron activity with water content and local cerebral blood flow was investigated in cats with brain edema produced by air exposure. The further effect of high-dose methylprednisolone on these factors was studied. Six hours after exposure of the brain surface to air, the water content of the white matter significantly increased. The local blood flow of the cortex and white matter significantly decreased with significant suppression of cortical neural activity (direct cortical response), indicating that ischemia was responsible for neural suppression. A single, large dose of methylprednisolone (30 mg/kg, i.v.) at the beginning of air exposure significantly reduced brain edema of the cortex and white matter 12 h after air exposure and improved the local blood flow of the cortex. Methylprednisolone also caused a remarkable improvement in cortical neural activity. This steroid effect on cortical neural function may play a role in the rapid neurologic improvement observed with their use in addition to the effect on brain edema.     

Population study of expression of thymidylate synthase and dihydropyrimidine dehydrogenase in patients with solid tumors

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) has been suggested to be sensitivity-limiting factors of 5-fluorouracil therapy in cancer patients. We conducted a large-scale population study on the activity of TS and DPD in patients with various solid tumors. A total of 2590 clinically removed tumors, consisting of 1112 colon, 724 gastric, 520 breast, and 236 non-small cell lung cancers, were provided to measure TS and DPD activity. TS activity in the gastric, colon, and non-small cell lung cancers was significantly higher than in matched non-cancerous tissue (P<0.0002), but there was no difference in TS expression between tumor and non-cancerous tissue from breast cancer patients. Gastric, breast, and non-small cell lung cancers showed significantly higher DPD activity than their corresponding non-cancerous tissues, but colon cancers did not. There was no correlation between TS activity and DPD activity, and thus each enzyme was considered to be an independent sensitivity-limiting factor for 5-fluorouracil therapy. The median TS activity and median DPD activity in all specimens including gastric, colorectal, breast, and non-small cell lung cancers tested were 0.041 and 110.1 pmol/mg protein, respectively. We classified each of the type of carcinoma into 4 groups by using the median activity of TS and DPD as the cutoff values: a low TS/low DPD group, high TS/low DPD group, low TS/high DPD group, and high TS/high DPD group. About 50% of the gastric, 47% of the colon, 70% of the breast and 30% of the non-small cell lung cancers had high TS activity, and 60% of the gastric, 40% of the colon, 48% of the breast, and 87% of the lung cancers had high DPD activity. Moreover, breast cancer was characterized by high TS activity and lung cancer by high DPD activity as compared with gastric and colon cancers, and their high activity levels may influence to the effectiveness of 5-fluorouracil against cancers of these organs. The results for expression of TS and DPD in clinically dissected tumors would be useful to estimate the efficacy of 5-fluorouracil in the treatment of cancer patients.     

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.     

Expression of interferon-gamma-inducible protein-10 in human endometrial stromal cells

Human endometrial stromal cells (ESC) can produce a variety of chemokines, especially after inflammatory stimulation. Interferon-gamma-inducible protein-10 (IP-10) is a potent chemoattractant for lymphocytes, and belongs to the family of non-ELR CXC chemokines. The expression of IP-10 in ESC after stimulation with interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), or lipopolysaccharide (LPS) was evaluated using an enzyme-linked immunosorbent assay and Northern blot analysis. A small amount of IP-10 protein was detected in the culture media of unstimulated ESC. The expression of IP-10 mRNA was detected in ESC. IFN-gamma, IL-1 beta, TNF-alpha and LPS significantly stimulated the expression of IP-10 mRNA and protein in ESC. These results suggest that the production of IP-10 by ESC is regulated by inflammatory mediators. The modulation of IP-10 concentrations in the local environment may contribute to the normal and pathological processes of human reproduction by regulating leukocyte trafficking in the endometrium.     

Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

In the present study, we evaluated the potential of bradykinin (BK) to induce the release of neutrophil and monocyte chemotactic activity (NCA and MCA) and cytokines from an alveolar type II epithelial cell line, A549 cells. BK stimulated A549 cells to release NCA and MCA in a dose- and time-dependent manner (P < 0.001). Checkerboard analysis revealed that both NCA and MCA involved chemotactic and chemokinetic activity. Molecular sieve column chromatography showed three molecular weight masses (near 19 kd, 8 kd, and 400 d) for NCA and several molecular weight peaks (near 66 kd, 25 kd, 19 kd, 16 kd, and 400 d) for MCA. The release of NCA and MCA was inhibited by cycloheximide and lipoxygenase inhibitors (P < 0.01). The NCA and MCA were inhibited by leukotriene B4 (LTB4) receptor antagonist (P < 0.01), and the concentration of LTB4 was high enough for NCA and MCA. Antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) attenuated NCA (P < 0.01), and antibodies to monocyte chemotactic protein-1 (MCP-1), G-CSF, and transforming growth factor (TGF)-β attenuated MCA (P < 0.01). The levels of IL-8, G-CSF, MCP-1, and TGF-β increased time dependently (P < 0.01). BK also stimulated the release of ILeukin-6 from A549 cells (P < 0.001). The receptors responsible for the release of NCA, MCA, and individual chemokines involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate alveolar type II pneumocytes to release inflammatory cytokines, which then may modulate the lung inflammation.