Behçet’s disease complicated by IgA nephropathy with nephrotic syndrome

A 65-year-old woman with a 48-year history of Behçet’s disease associated with nephrotic syndrome is described. Immunofluorescence study revealed IgA nephropathy. Following treatment with an angiotensin II type-I receptor-blocker, an anti-platelet drug, and an HMG-CoA reductase inhibitor, accompanied by dietary restrictions of protein and sodium, proteinuria was markedly decreased. This report describes our experience with a rare entity of Behçet’s disease complicated by nephrotic syndrome due to IgA nephropathy. Routine urine examination and renal biopsy are needed for the detection and diagnosis of renal problems with Behçet’s disease.     

Activation of Fyn tyrosine kinase in the mouse dorsal hippocampus is essential for contextual fear conditioning

Fyn-tyrosine-kinase-deficient mice exhibit defects in the Morris water maze test and long-term potentiation (LTP) induction in the hippocampus, and given that LTP has been postulated as the neural basis for memory formation, Fyn may be required for hippocampus-dependent memory formation. However, how Fyn is involved in the process of memory formation is unclear. To investigate the role of Fyn in hippocampal memory formation, we first tested the behavior of Fyn-deficient mice by contextual fear conditioning. A mouse was placed in a context and a foot shock was delivered, so that the mouse associated the context with the shock. We found that the freezing response of Fyn-deficient mice to the context was impaired at 24 h after conditioning. We then measured freezing at 1 h after conditioning, and found that their short-term contextual fear memory was also impaired. We used Western blotting to examine the mode of Fyn activation in dorsal hippocampal tissue following contextual fear conditioning. Fyn activation peaked as early as 5–10 min after contextual fear conditioning and persisted for at least 40 min. Concomitant increases in tyrosine phosphorylation of several proteins, including NR2B, were also observed, but no increases in tyrosine phosphorylation were observed in Fyn-deficient mice. Thus, both short-term and long-term (24-h) contextual fear memory were impaired in Fyn-deficient mice, and Fyn activation in the dorsal hippocampus transiently increased after contextual fear conditioning. These findings strongly suggest that activation of the Fyn signaling pathway is involved in hippocampus-dependent formation of contextual fear memory.     

Postischemic mild hypothermia alleviates hearing loss because of transient ischemia

The effect of postischemic mild hypothermia on the inner ear has not been clarified. In this study, we investigated whether hypothermia after transient ischemia could prevent cochlear damage and its therapeutic time window. Mongolian gerbils were divided into six groups: a sham-operation group, a normothermia group, and four hypothermia groups in which hypothermia was induced 1-7, 1-4, 3-6, and 6-9 h after reperfusion. Animals subjected to postischemic mild hypothermia within 3 h after reperfusion had attenuated hearing loss and inner hair cell loss. The protective effect was greater when hypothermia was induced earlier and had a longer duration. This implies that mild hypothermia after ischemia could have therapeutic effects for inner ear ischemic damage.     

Providing support to psychiatric patients living in the community in Japan: patient needs and care providers perceptions

Background

Social support programs are a critical component of care for psychiatric patients living in community or residential settings. There is little information, however, on how to optimally deliver these services in the Japanese context.

Methods

We selected ten community life support centers for patients with major mental illness and administered questionnaires to 199 pairs of patients and staff members. These questionnaires consisted of twenty-six items from six categories: difficulties with interpersonal relationships; risks to physical well-being; risks to mental health; difficulties with life skills; challenges regarding living conditions; risks towards community safety. For each of these items, patients were asked whether they had experienced difficulties during the previous month, and staff members were asked the extent to which their patients needed support.

Results

The results demonstrated that staff members tended to understate patients' needs regarding chronic medical conditions (p < 0.01), dietary habits (< 0.01), and excessive smoking or alcohol drinking (< 0.05). On the other hand, staff members recognized patients' needs regarding mental health problems to a greater extent than patients themselves (< 0.05).

Conclusion

Results of this study suggest that social services geared towards specific tasks of daily living form an important component of comprehensive care for psychiatric patients living in community settings in Japan.     

Inverse relationship between matrix remodeling and lipid metabolism during osteoarthritis progression in the STR/Ort mouse

OBJECTIVE: The biologic changes associated with osteoarthritis (OA) are incompletely understood. The aim of this study was to elucidate the molecular mechanisms underlying OA progression in an STR/Ort murine model of spontaneous disease. METHODS: Global patterns of gene expression were assessed using microarray analysis of articular cartilage/subchondral bone from the tibial plateaus of STR/Ort mice at 3, 9, and 12 months of age. The age-dependent severity of osteophyte formation and extent of cartilage damage were determined in the corresponding femurs using microfocal computed tomography and the Mankin histologic scoring system. Pathway analysis was used to identify the functions of genes associated with OA progression, and changes in gene expression were confirmed using immunohistochemistry. RESULTS: Six hundred twenty-one genes were associated with both osteophyte formation and cartilage damage in the STR/Ort joints. Genes involved in the development/function of connective tissue and in lipid metabolism were most significantly enriched and regulated during disease progression. Genes directly interacting with peroxisome proliferator-activated receptor alpha (PPARalpha)/PPARgamma were down-regulated, whereas those genes involved with connective tissue remodeling were up-regulated during disease progression. Associations of down-regulation of myotubularin-related phosphatase 1 (a phosphoinositide 3-phosphatase involved in lipid signaling) and up-regulation of biglycan (a member of the small leucine-rich protein family known to modulate osteoblast differentiation and matrix mineralization) with OA progression were confirmed by immunohistochemistry. CONCLUSION: Since adipogenesis and osteogenesis are inversely related in the developing skeletal tissue, these results suggest that a shift in the differentiation of mesenchymal cells from adipogenesis toward osteogenesis is a component of the OA pathophysiologic processes occurring in the tibial plateau joints of STR/Ort mice.     

Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations

Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoietic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMML with specific RAS mutations may have spontaneously improving disease.     

Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells

The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell-receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.     

Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5

Intravascular large B-cell lymphoma (IVLBCL) is pathologically distinct with a broad clinical spectrum and immunophenotypic heterogeneity. A series of 96 patients with IVLBCL (median age, 67 years; range, 41-85 years; 50 men) was reviewed. Anemia/thrombocytopenia (84%), hepatosplenomegaly (77%), B symptoms (76%), bone marrow involvement (75%), and hemophagocytosis (61%) were frequently observed. The International Prognostic Index score was high or high-intermediate in 92%. For 62 patients receiving anthracycline-based chemotherapies, median survival was 13 months. CD5, CD10, Bcl-6, MUM1, and Bcl-2 were positive in 38%, 13%, 26%, 95%, and 91% of tumors, respectively. All 59 CD10- IVLBCL cases examined were nongerminal center B-cell type because they lacked the Bcl-6+MUM1- immunophenotype. CD5 positivity was associated with a higher prevalence of marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic abnormalities among patients with CD10-IVLBCL. Compared with 97 cases of de novo CD5+CD10-diffuse LBCL, 31 cases of CD5+CD10-IVLBCL exhibited higher frequencies of poor prognostic parameters, except age. Multivariate analysis in IVLBCL revealed that a lack of anthracycline-based chemotherapies (P<.001, hazard ratio [HR]: 9.256), age older than 60 years (P=.012, HR: 2.459), and thrombocytopenia less than 100x10(9)/L (P=.012, HR: 2.427) were independently unfavorable prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity, IVLBCL constitutes a unique group with aggressive behavior.     

A case of adenosquamous gastric carcinoma successfully treated with TS-1, low-dose CDDP and docetaxel as neoadjuvant chemotherapy

The patient was a 66-year-old male with extremely advanced gastric cancer type 3 and diagnosed with adenocarcinoma by endoscopic biopsies specimens. Combined chemotherapy of TS-1, CDDP and docetaxel was prescribed in order for tumor reduction and downstaging. TS-1 (80 mg/m(2)) was administered 28 days followed by 14 days rest as one course. CDDP (8 mg/m(2)) was administered on days 1, 2, 14 and 15 and docetaxel (40 mg/m(2)) was administered on day 1 and 14, followed by 4 weeks rest as one course. After 2 courses of treatment, a CT scan revealed a minor response of tumor reduction. Therefore, total gastrectomy, partial pancreas body and tail resection, and D 2 lymph node dissection were performed. The patient had undergone adjuvant chemotherapy of TS-1 and biweekly docetaxel after surgery with no recurrence for 13 months. Adverse reactions were grade 3 neutropenia and grade 2 diarrhea. Combined chemotherapy of TS-1, low-dose CDDP and docetaxel were intensive and required constant patient monitoring. However, it proved effective and feasible as a neoadjuvant chemotherapy regimen for advanced gastric cancer.     

Bone scanning--who needs it among patients with newly diagnosed prostate cancer?

BACKGROUND: We evaluated the relationship between serum PSA and clinical variables to eliminate bone scanning in patients with prostate cancer having a low probability of bone metastasis. METHODS: The study included 366 patients with newly diagnosed prostate cancer between 1999 and 2005. Bone metastasis was studied for its correlation with various clinical and pathological variables in these patients. RESULTS: Bone metastasis was found in 28 (7.7%) of 366 patients. Fourteen patients had skeletal symptoms related to bone metastasis. The risk for bone metastases increased considerably with increases of PSA level, clinical T stage and Gleason score. The metastasis was not found in 161 patients with serum PSA concentration of 10 ng/ml or lower. In 95 patients with the concentration between 10 and 20 ng/ml only two had the metastasis. These two patients had T2 disease and Gleason scores of 7 or greater. In 204 patients with clinical stage T1 disease, one (0.5%) had the metastasis. In 117 patients with Gleason scores of 6 or less, the metastasis was found in two (1.7%). CONCLUSIONS: For patients with serum PSA levels of 10 ng/ml or lower, bone scanning may be eliminated because of the negligible risk of bone metastases. In addition, scanning may not be necessary for those with PSA levels between 10 and 20 ng/ml, when they have T1 disease and Gleason scores of 6 or lower.