Idiopathic yellow nail syndrome successfully treated with OK-432

A 70-year-old female presented with yellow discoloration of the nail beds of all fingers and toes, as well as bilateral pleural effusions. The patient was diagnosed as having the yellow nail syndrome based on the triad of yellow nails, lymphedema, and pleural effusions. The patient's intractable bilateral pleural effusion was treated with pleurodesis using OK-432. The treatment prevented the accumulation of pleural fluid for a long period of time. Pleural effusion associated with yellow nail syndrome is thought to be difficult to treat; however, this patient's excellent clinical course suggests that pleurodesis with OK-432 could be used to treat the disease in the future.     

Calcium channel blocker, azelnidipine, reduces lipid hydroperoxides in patients with type 2 diabetes independent of blood pressure

Anti-hypertensive agents with antioxidative effects are potentially useful for diabetic patients with hypertension to prevent the onset and progression of their complication. While dihydropyridine-type calcium antagonists are among the frequently used anti-hypertensive drugs, azelnidipine, a novel calcium antagonist, has been reported to have a unique anti-oxidative effect in vitro and in animals. In this study, we measured lipid hydroperoxides in human sample using diphenyl-1-pyrenylphosphine for the first time, and used the value of lipid hydroperoxides as an index of oxidative stress. Then, we compared the antioxidative properties of azelnidipine and amlodipine, a frequently used calcium antagonist in hypertensive diabetic patients. Administration of vitamin C and E for 8 weeks significantly reduced lipid hydroperoxides in erythrocyte membrane in normal subjects. In hypertensive diabetic patients, azelnidipine treatment for 12 weeks induced a more significant fall in erythrocyte lipid hydroperoxide level than amlodipine, though blood pressure during each treatment was comparable. Our data confirm the usefulness of lipid hydroperoxides in erythrocyte membrane as a marker of oxidative stress in vivo, and indicate that azelnidipine has a unique antioxidative property in human.     

Association between trait anxiety and endothelial function observed in elderly males but not in young males

BACKGROUND AND OBJECTIVES: Endothelial function plays a key role in determining the clinical manifestations of atherosclerosis. Recent reports have shown that healthy elderly subjects with higher trait anxiety tend to have heightened risks of atherosclerotic lesions and cardiovascular disease. The present study was intended to examine whether an association exists between trait anxiety and endothelial function in healthy young and elderly subjects. METHODS: This study examined 26 young male and 30 elderly male subjects using brachial artery flow-mediated dilation (FMD) - a non-invasive ultrasound method - to evaluate endothelial function by measuring the dilation responses of vascular smooth muscle to the nitric oxide produced by endothelial cells following hyperemia. RESULTS: A significant negative correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and the percentage change of FMD (%FMD) in the elderly subjects, but not in the young subjects. The elderly subjects showed significantly lower %FMD than the young subjects. CONCLUSION: These results suggest the possibility that trait anxiety is a predisposing risk factor for cardiovascular damage that might, over a long period, induce atherosclerotic lesions.     

Decreased cerebral blood flow and prognosis of Alzheimer's disease: A multicenter HMPAO-SPECT study

PURPOSE: To determine the usefulness of brain perfusion SPECT for evaluating the severity and progression of Alzheimer's disease (AD). METHODS: Eighty-four AD patients were included. At entry, 99mTc-HMPAO-SPECT, the Mini Mental State Examination (MMSE), Mental Function Impairment Scale (MENFIS), and the Raven Colored Progression Matrix (RCPM) were performed for all 84 patients. During the follow-up periods, two individual MMSE evaluations in 34 patients, two MENFIS evaluations in 30 patients, and two RCPM evaluations in 20 patients were performed. Based on the regions of decreased cerebral blood flow demonstrated on 3D-SSP images of SPECT, the cases were classified as type A (no decrease), type B (decreased blood flow in the parietal or temporal lobe), type C (decreased blood flow in the frontal lobe and parietal or temporal lobe), type Pc (decreased blood flow in posterior cingulate gyrus only), and "other types". The types of decreased blood flow, scores on neuropsychological evaluations, and symptom progression were analyzed. RESULTS: The MENFIS, MMSE, and RCPM scores were poorest in type C patients at entry. The degree of decrease of these scores during the follow-up periods was also greatest in type C. The greatest difference between patients with and without rapid progression in SPECT data of the mild AD patients (MMSE score > or = 24) was in the frontal lobe. CONCLUSION: Decreased blood flow in the frontal lobe of AD patients is correlated not only with reduced cognitive function at the time of the evaluation but with rapid progression in the subsequent clinical course.     

S-1 chemotherapy for cancer of the gastric tube used for esophageal reconstruction following surgery for esophageal cancer

We used S-1 chemotherapy to treat 5 patients with cancer of the gastric tube used for esophageal reconstruction through the posterior mediastinal route following surgery for esophageal cancer. The response rate was 40%, the median survival 15 months, and 3 patients still survive. In those 3 patients, the gastric tube cancer was at a resectable stage, but the patients elected to have chemotherapy instead. One patient has survived 21 months after responding completely to 2 cycles of combined chemotherapy with S-1 and cisplatin. Another has survived 15 months after partially respondingto S-1 chemotherapy. And the third has survived 46 months after endoscopic treatment, radiation therapy and S-1 chemotherapy. S-1 chemotherapy thus appears to be an effective treatment for cancer of the gastric tube after surgery for esophageal cancer.     

Non-Hodgkin's lymphoma presenting as multiple bone lesions and hypercalcemia

We report a rare case of a patient with non-Hodgkin's lymphoma who developed multiple bone lesions and hypercalcemia. A 50-year-old woman complained of drowsiness and multiple bone pain on admission. Radiographic examination revealed multiple bone fractures and osteolytic lesions. She was diagnosed with diffuse large B cell lymphoma by biopsy of an inguinal lymph node. Elevation of parathyroid hormone-related protein (PTHrP) and hypercalcemia were confirmed pretreatment, and those serum levels decreased during chemotherapy for lymphoma. However, the disease was resistant to chemotherapy combined with rituximab. These findings suggest that hypercalcemia is associated with PTHrP and the prognosis of patients with bone lymphoma in advanced stage is poor, although it is thought to be a relatively favorable prognosis in localized primary lymphoma of bone.     

Squamous cell carcinoma-derived G-CSF promotes tumor growth and metastasis in mice through neutrophil recruitment and tumor cell proliferation,associated with poor prognosis of the patients

Tumor-derived G-CSF is a well-known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G-CSF in squamous cell carcinoma (SCC). High expression of G-CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR-S1M cells produce considerable amount of G-CSF, which expression is correlated with its metastatic potentials. Deletion of G-CSF in NR-S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR-S1M tumors in the mice. Mechanistically, G-CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR-S1M tumor-bearing mice, accumulation of plasma G-CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8⁺ T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G-CSF produced by NR-S1M cells facilitates tumor progression in mice through bi-functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G-CSF expression.     

Chronic encephalomyelitis virus exhibits cellular tropism and evades pDCs by binding to sialylated integrins as the cell surface receptors

Theiler's murine encephalomyelitis virus (TMEV) causes a chronic demyelinating disease similar to multiple sclerosis in mice. Although sialic acids have been shown to be essential for TMEV attachment to the host, the surface receptor has not been identified. While type I interferons play a pivotal role in the elimination of the chronic infectious Daniel (DA) strain, the role of plasmacytoid dendritic cells (pDCs) is controversial. We herein found that TMEV binds to conventional DCs but not to pDCs. A glycomics analysis showed that the sialylated N-glycan fractions were lower in pDCs than in conventional DCs, indicating that pDCs are not susceptible to TMEV infection due to the low levels of sialic acid. TMEV capsid proteins contain an integrin recognition motif, and dot blot assays showed that the integrin proteins bind to TMEV and that the viral binding was reduced in the desialylated α_Xβ₂. α_Xβ₂ protein suppressed TMEV replication in vivo, and TMEV co-localized with integrin α_M at the cell membrane and TLR 3 in the cytoplasm, suggesting that α_M serves as the viral attachment and entry. These results show that the chronic encephalomyelitis virus utilizes sialylated integrins as cell surface receptors, leading to cellular tropism to evade pDC activation.