Primary linitis plastica of the colon and rectum

Primary linitis plastica of the colon and rectum is an uncommon entity. Sixty-six cases have been reported in the English literature. Two new cases are reported, one of the transverse colon with widespread metastases and the other of the right colon extending from the appendix to the distal resection margin of the transverse colon. Some clinical and pathologic characteristics of the tumor are discussed, based on a review of the literature.     

Factors associated with frailty in Japanese patients with rheumatoid arthritis: results from the Institute of Rheumatology Rheumatoid Arthritis cohort study

Clinical Rheumatology - This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in...     

Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection.     

Cutaneous Mycobacterium chelonae infection following autologous peripheral blood stem cell transplantation for POEMS syndrome

Although hematopoietic stem cell transplantation (HSCT) may increase the curability of refractory hematologic diseases, it requires complication management due to a long-term immunocompromised state. We experienced a case who received an autologous peripheral blood stem cell transplantation (Auto-PBSCT) for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) and developed cutaneous Mycobacterium chelonae infection. It is clear that attention needs to be paid to prevent bacterial, fungal and viral infection after HSCT. It is also important to keep in mind that tuberculous and nontuberculous mycobacteria (NTM), in rare cases, lead to lethal complications.     

Morphology and biochemistry of the lung from guinea pig after repeated injections of freund’s complete adjuvant

Guinea pigs received 5 daily injections of Freund’s complete adjuvant and the changes in the lung were investigated by light microscope and electron microscope. In the 20th week of experiment, fibrotic changes were found around the granulomata close to the surface of the lung. In addition the fraction of glycosaminoglycans was isolated from the lung and analyzed quantitatively. As a result, a decrease in quantity of hyaluronic acid and an increase in quantity of dermatan sulfate were observed.     

Adjuvant treatments for resectable hepatocellular carcinoma

Hepatocellular carcinoma often recurs even after curative resection. Although some encouraging data showing improvements in recurrence-free times have been reported with the use of intraarterial 131I-lipiodol infusion, retinoids, interferon, or immunotherapy after hepatectomy, there is no consensus regarding standard adjuvant therapy for resectable hepatocellular carcinoma. A novel target agent, sorafenib, which has recently become a standard of care for advanced disease, may also be promising in an adjuvant setting to prevent early recurrence after curative surgery. In future trials, it will be important to identify appropriate target populations for each type of adjuvant approach; that is, an agent with definitive antitumor activity for high-risk patients, and one that shows chemoprevention for low-risk patients.     

Increased blood–brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model

Behavioral and psychological problems are often observed in patients with dementia such as that associated with Alzheimer disease, and these noncognitive symptoms place an extremely heavy burden on the family and caregivers. Although it is well know that these symptoms often are triggered by infection of peripheral organs, the underlying mechanisms for these pathological conditions are still unclear. In this study, using an Alzheimer amyloid precursor protein (APP)-transgenic mouse, we analyzed behavioral changes and brain inflammatory response induced by peripheral administration of lipopolysaccharide. Application of a unique in vivo microdialysis system revealed that the increase in brain inflammatory cytokine (interleukin-6) level was significantly higher in APP-Tg than in wild-type mice after peripheral lipopolysaccharide injection, which was associated with more severe sickness behaviors. The blood–brain barrier became more permeable in APP-Tg mice during peripherally evoked inflammation, suggesting the increased vulnerability of the blood–brain barrier to inflammation in this animal model of Alzheimer's disease. These findings might provide insight into the pathogenesis of noncognitive symptoms in dementia and a basis to develop new therapeutic treatments for them.     

CCL2 is critical for immunosuppression to promote cancer metastasis

We previously found that cancer metastasis is accelerated by immunosuppression during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a critical determinant for both tumor metastasis and immunosuppression induced by Snail⁺ tumor cells. CCL2 is significantly upregulated in various human tumor cells accompanied by Snail expression induced by snail transduction or TGFβ treatment. The Snail⁺ tumor-derived CCL2 amplifies EMT events in other cells including Snail^? tumor cells and epithelial cells within tumor microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail⁺ tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied by lowered expression of costimulatory molecules such as HLA-DR but increased expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive CD4⁺FOXP3⁺ Treg cells, and finally impair tumor-specific CTL induction. In murine established tumor model, however, CCL2 blockade utilizing the specific siRNA or neutralizing mAb significantly inhibits Snail⁺ tumor growth and metastasis following systemic induction of anti-tumor immune responses in host. These results suggest that CCL2 is more than a chemoattractant factor that is the significant effector molecule responsible for immune evasion of Snail⁺ tumor cells. CCL2 would be an attractive target for treatment to eliminate cancer cells via amelioration of tumor metastasis and immunosuppression.     

CD30: from basic research to cancer therapy

Immunologic Research - The FDA recently approved an agonistic anti-CD30 drug conjugate, Brentuximab vedotin, for the treatment for CD30-positive lymphomas. The potent clinical activity of...