Cytosolic phospholipase A2alpha-deficient mice are resistant to collagen-induced arthritis

Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2alpha (cPLA2alpha) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2alpha plays a key role in the development of CIA, we backcrossed cPLA2alpha-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA2alpha-deficient mice compared with wild-type littermates. At completion of the study, >90% of the wild-type mice had developed disease whereas none of the cPLA2alpha-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA2alpha-deficient mice. Although the disease scores differed significantly between cPLA2alpha mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA2alpha in the pathogenesis of CIA.     

An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation

Prostaglandin E (PGE)2 produced by osteoblasts acts as a potent stimulator of bone resorption. Inflammatory bone loss is accompanied by osteoclast formation induced by bone-resorbing cytokines, but the mechanism of PGE2 production and bone resorption in vivo is not fully understood. Using cytosolic phospholipase A2alpha (cPLA2alpha)-null mice, we examined the role of cPLA2alpha in PGE2 synthesis and bone resorption. In bone marrow cultures, interleukin (IL)-1 markedly stimulated PGE2 production and osteoclast formation in wild-type mice, but not in cPLA2alpha-null mice. Osteoblastic bone marrow stromal cells induced the expression of cyclooxygenase (COX)-2 and membrane-bound PGE2 synthase (mPGES) in response to IL-1 and lipopolysaccharide (LPS) to produce PGE2. Osteoblastic stromal cells collected from cPLA2alpha-null mice also induced the expression of COX-2 and mPGES by IL-1 and LPS, but could not produce PGE2 due to the lack of arachidonic acid release. LPS administration to wild-type mice reduced femoral bone mineral density by increased bone resorption. In cPLA2alpha-null mice, however, LPS-induced bone loss could not be observed at all. Here, we show that cPLA2alpha plays a key role in PGE production by osteoblasts and in osteoclastic bone resorption, and suggest a new approach to inflammatory bone disease by inhibiting cPLA2alpha.     

Aggressive NK cell leukaemia after splenectomy: association with CD95-resistant memory T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome

We describe a 44-yr-old Japanese woman with persistent polyclonal T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome (HPS). T cells bearing αβ T-cell receptors (TCR) expressed increased amounts of CD95 and of CD45RO, which are phenotypically memory T cells. The TCR repertoire was broad and diverse. Regardless of CD95 expression, these cells were resistant to CD95-mediated apoptosis. Aggressive natural killer cell leukaemia (ANKL) without an association with Epstein–Barr virus was detected 1 month after therapeutic splenectomy that followed 3 yr of immunosuppressive therapy against HPS. The immunophenotype of these leukaemia cells was CD56, CD16^dim, CD7, CD45RA and they expressed some CD2, CD8 and HLA-DR. Moreover, hyperdiploid clones with complex chromosomal abnormalities were also detected. Latent NK-cell malignancy seemed to cause the CD95-resistant memory T-cell proliferation and splenectomy resulted in overt ANKL progression. There should be careful consideration of the risks versus benefits of splenectomy in HPS, in light of the possibility of fatal leukaemia/lymphoma progression.     

Instructing females to wipe their vulva after bowel movements is unnecessary to prevent cystitis: a short research report

In Japan, females are often taught to wipe their vulva from front to back (FTB) after bowel movements in order to prevent cystitis. In this report, we studied whether vulva care after bowel movements in females is a risk factor for simple cystitis. Moreover, we evaluated factors affecting the method of vulva care after bowel movements in females. We recruited 274 females for this study. We analysed the correlations between the style of vulva care, restroom habits and patient characteristics. In addition, we evaluated the correlation between the incidence of cystitis and the style of vulva care after bowel movements. There were no significant differences in the presence of coexisting diseases (P = 0·766), activities of daily living (ADL's) (P = 0·203), body mass index (BMI) (P = 0·174) or restroom style (P = 0·512). However, a significantly greater number of elderly subjects reported wiping from back to front (P = 0·023). In the cystitis group, 48 females (28%) reported wiping the vulva from back to front after bowel movements. In the control group, 29 females (28%) reported wiping the vulva from FTB after bowel movements. There were no significant differences between these two groups (P = 0·988). Our data demonstrated that instructing females to wipe their vulva from FTB after bowel movements is unnecessary for the purpose of preventing cystitis.     

Effects of adipocytes on the proliferation and differentiation of prostate cancer cells in a 3‐D culture model

Objective: To investigate how the mechanism of adipocyte–prostate cancer cell interaction affects the proliferation and differentiation of prostate cancer cells. Methods: An androgen‐dependent cell line (LNCaP), two androgen‐independent cell lines (PC‐3, DU145), and mature adipocytes harvested from male Wistar rats were used. Cancer cells were co‐cultured with the isolated mature adipocytes in 3‐D collagen gel matrix culture. The morphology and proliferative ability of the prostate cancer cells were examined. With regard to the activation of the phosphatidylinositol 3‐kinase (PI3K) pathway, the expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN), Akt and Bad were determined by immunohistochemistry. Results: LNCaP cells co‐cultured with adipocytes formed larger clusters than those of the control. PC‐3 cells co‐cultured with adipocytes did not form larger clusters, but formed spherical and spindle‐shaped cells. The phosphorylation of Akt in PC‐3 cells was greater in the co‐cultured group compared with the controls, but there were no significant differences in the phosphorylation of Akt with regard to LNCaP and DU145 cells. Conclusions: Adipocytes could modulate the proliferation and differentiation of prostate cancer cell lines. Activation of the PI3K pathway might be involved in the prostate cancer cell–adipocyte interaction.     

“Phosphene”: early sign of vascular compression neuropathy of the optic nerve

Background  

Phosphenes, flashes of light, are a visual phenomenon experienced by patients with ophthalmological disease and normal individuals.     

The effects of neoadjuvant chemotherapy and chemo-radiation therapy on MRI staging in invasive bladder cancer: comparative study based on the pathological examination of whole layer bladder wall

Objective

We evaluated the correlation of radiological findings obtained by MRI study with pathological diagnosis in invasive bladder cancer treated with neoadjuvant chemotherapy, with or without radiation.

Design, Setting, and Participants

Twenty-seven patients, who underwent total or partial cystectomy for invasive bladder tumors, were enrolled into the present study. Eight cases had received neoadjuvant chemotherapy following the staging biopsy (group A), ten cases had received chemo-radiation therapy following the staging biopsy (group B), and nine cases had received preoperative staging biopsy alone (group C). As a final treatment, 12 of the 27 patients underwent total cystectomy and the other 15 patients underwent partial cystectomy. MRI was conducted prior to total or partial cystectomy in each case. The pathological stage was assessed by histological examination of the entire layer of the bladder wall.

Results and Limitations

Tumor stage assessed by MRI was consistent with pathological findings in 16 of the 27 cases (59.3%), while MRI produced over-staging in 7 cases and under-staging in 4 cases. The accuracy of staging was 75.0, 30.0, and 77.8% in groups A, B, and C, respectively. The accuracy of MRI staging in group B was lower than that in group C (P < 0.05). There was no difference in the accuracy of MRI staging between groups A and C.

Conclusion

MRI is useful for the staging of bladder cancer. However, care needs to be taken when staging invasive bladder tumors treated with neoadjuvant chemo-radiation therapy, because inflammatory infiltrations and/or fibrous changes caused by the chemotherapy or chemo-radiation therapy make precise staging with MRI difficult.     

A case of mucopolysaccharidosis IV with lower leg paresis due to thoraco-lumbar kyphoscoliosis.

We treated a patient of type IV mucopolysaccharidosis (Morquio's disease) with lower leg paresis due to kyphoscoliosis. A 65-year-old woman presented with Morquio's disease. A lateral radiograph demonstrated the classic bullet-shaped vertebrae and a 65 degrees thoraco-lumbar kyphosis. After the age of 60, she suffered from numbness in both lower legs and walking disturbance. Bilateral patellae-tendon reflexes were exaggerated. MRI showed compression of the spinal cord around T12 to L2 with a highlighted area of change inside the spinal cord. Myelography and computed tomography after the myelography showed narrowing of the sub-arachnoidal space and deformation of the spinal cord around the T12 to L2 levels. Severe vertebral osteoporosis made it necessary to first perform posterior correction of the kyphosis and fusion. The curve was stabilised with the Luque method from T7 to L4. Her neurological condition markedly recovered, but 1 year after surgery her neurological condition again began to deteriorate, resulting in walking disturbance. For this reason, anterior decompression and fusion through a lateral thoracotomy was undertaken. Decompression of the spinal cord and a bone graft from the iliac crest were attained. The patient's neurological condition again improved, but not as much as immediately after the first operation.