Periostin in Eye Diseases.

The transparency of the eye can be disturbed by several eye diseases. It has recently been reported that periostin plays pivotal roles in the pathogenesis of several eye disease, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, pterygia, corneal dystrophy, and chronic ocular allergic diseases. In these diseases, formation of fibro (vascular) tissue plays an important role. Gene expression profiling of human retinal fibro (vascular) membrane revealed significant up-regulation of periostin. The expression of periostin after environmental perturbations, including IL-4 and/or IL-13 induction, can alter normal physiological interactions among fibroblasts, macrophages and ECM protein in the eye. Modulating the expression of periostin by low-molecular weight compounds, antibodies or RNAi directed against the molecule could be a novel therapeutic strategy for inhibiting the progression of those periostin-involved eye diseases.

Neurogenic pulmonary edema following Cryptococcal meningoencephalitis associated with HIV infection.

Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. Only a few cases of NPE after Cryptococcal meningitis have been reported. We report a case of NPE following Cryptococcal meningoencephalitis. A 40-year-old man with no medical history was hospitalized for disturbance of consciousness. Blood glucose level was 124 mg/dL. Non-contrast head computed tomography showed no abnormalities. Lumbar puncture revealed a pressure of over 300 mm H2 O and cerebrospinal fluid (CSF) confirmed a white blood cell count of 65/mm(3) . The CSF glucose level was 0 mg/dL. The patient was empirically started on treatment for presumptive bacterial and viral meningitis. Four days after, the patient died in a sudden severe pulmonary edema. Autopsy was performed. We found at autopsy a brain edema with small hemorrhage of the right basal ganglia, severe pulmonary edema and mild cardiomegaly. Histologically, dilated Virchow-Robin spaces, crowded with Cryptococci were observed. In the right basal ganglia, Virchow-Robin spaces were destroyed with hemorrhage and Cryptococci spread to parenchyma of the brain. No inflammatory reaction of the lung was seen. Finally, acute pulmonary edema in this case was diagnosed as NPE following Cryptococcal meningoencephalitis. After autopsy, we found that he was positive for serum antibodies to human immunodeficiency virus.

Analysis of Dietary Factors Affecting Body Mass Index in Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Body mass index (BMI) is correlated with the outcomes of various metabolic and pathological conditions. To elucidate the factors affecting BMI in elderly persons, we studied elderly persons with and without diabetes mellitus for BMI management target values using receiver operating characteristic (ROC) analysis. METHODS: We conducted a dietary survey targeting 60 elderly outpatients with type 2 diabetes mellitus (diabetes group, 70.1 ± 7.8 years) and 66 elderly persons who participated in a health class offered by the municipality (health class group, 72.5 ± 5.7 years). RESULTS: In the diabetes group, positive correlations were observed between BMI and several variables including blood glucose levels (all P < 0.05), whereas BMI had negative correlations with the third principal component (positive weight for oils and fats). In addition, BMI was negatively correlated with the intake of oils and fats. In the health class group, BMI was positively correlated (all P < 0.05) with grip strength/sixth principal component (positive weight for sweets)/condiments. An analysis of dietary patterns revealed that dietary factors correlated with BMI in each group. The cutoff value of BMI was suggested to be near the normal upper limit or slightly higher in the subject group. CONCLUSION: We considered that BMI management was useful as an indicator for maintaining grip and muscle strength in elderly persons and as an indicator for diabetes care management. From the present study, we may propose the utility of a careful dietary survey as one of the approaches for these aims.

Regulator of G-protein signaling 5 enhances portal vein invasion in hepatocellular carcinoma.

Portal vein invasion (PVI) is a major prognostic factor in hepatocellular carcinoma (HCC). The aim of the present study was to identify molecules that regulate PVI. Sections of cancerous tissue, paired noncancerous tissue and the PVI area were collected from 3 frozen HCC sections, using laser microdissection. The present study focused on 3 upregulated molecules, integrin ß3 (ITGB3), secreted phosphoprotein 1 (SPP1) and regulator of G-protein signaling 5 (RGS5), and 2 molecules that were downregulated in PVI tissue compared with cancer tissue, metallothionein 1G (MT1G) and metallothionein 1H (MT1H), as determined by cDNA microarray analysis. Reverse transcription-quantitative polymerase chain reaction analysis of 32 HCC cases revealed that RGS5 mRNA levels were significantly increased and MT1 G and MT1H mRNA levels were significantly decreased in cancerous tissue compared with noncancerous tissue. However, there was no significant difference in ITGB3 and SPP1 expression. There were no significant differences between the expression of these molecules and any clinicopathologic factors, including PVI. Immunohistochemical staining for RGS5 in 60 HCC cases demonstrated that RGS5 protein levels were higher in cancerous tissue compared with paired noncancerous tissue in 63.3% of HCC cases. Furthermore, high expression of RGS5 in cancerous tissue was significantly associated with PVI and tended to be associated with intrahepatic metastasis. Confluent multinodular type was significantly more frequent in cases with high expression of RGS5 in the cancerous tissue. Therefore, RGS5 may be a useful prognostic biomarker as well as a potential target of molecular therapy to treat HCC.

The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type.

AIMS: The WHO classification describes that combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell subtype (CHC-INT) is composed of tumour cells with features intermediate between hepatocytes and cholangiocytes. However, we previously reported that CHC-INT showed a high positive rate of biliary markers, but the expression of hepatocyte paraffin (HepPar)-1 was low. In this study, we examined the expression of other hepatocyte markers, such as arginase-1 (Arg-1), keratin (K) 8 and K18 in CHC-INT in order to examine the utility of pathological diagnosis in CHC-INT. METHODS: We performed immunohistochemistry (IHC) of Arg-1, K8 and K18 using 32 previously diagnosed as CHC-INT. Immunoreactivity was evaluated with grading from 0 to 4 according to the distribution area of positive cells. The obtained findings of Arg-1, K8 and K18 were compared with those of K7, K19 and HepPar-1. RESULTS: Out of the 32 cases, 22 (68.8%) cases were positive for Arg-1. Twenty-five (78.1%) were positive for K8. The IHC scores of Arg-1 and K8 were significantly higher than those of HepPar-1, but significantly lower than those of K7 and K19. The K18 expression was widely observed in all cases (100%). The IHC score of Arg-1 and K8 in CHC-INT was intermediate between hepatocellular carcinoma and cholangiocarcinoma. CONCLUSIONS: Arg-1 and K8 were good markers to identify intermediate cells between hepatocytes and cholangiocytes. These can be useful markers for pathological diagnosis of CHC-INT, which usually has wide histological diversities, in combination with other hepatocytic and/or cholangiocytic markers.

Evaluation of immunohistochemistry using two different antibodies and procedures for primary lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangement.

Rearrangements of anaplastic lymphoma kinase (ALK) have been recently identified in non-small cell lung carcinomas. Previous studies have revealed characteristic features, including adenocarcinoma histology and mucin production, in ALK-positive lung carcinoma. The present study evaluated immunohistochemistry (IHC) in ALK-positive lung carcinoma using two different antibodies, clone 5A4 and D5F3, and compared the results. On the basis of the aforementioned characteristic features, out of 359 primary lung carcinomas, the ALK status of 14 adenocarcinomas was screened using the intercalated antibody-enhanced polymer (iAEP) method with antibody 5A4, and this was compared with the ALK status obtained using rabbit monoclonal antibody D5F3 and fluorescence in situ hybridization for ALK. Eight cases were demonstrated to be ALK-positive by IHC. Seven cases exhibited ALK rearrangement, which was demonstrated by fluorescence in situ hybridization. The IHC for ALK obtained using D5F3 was comparable with that of the iAEP and exhibited low heterogeneity. This finding suggests that IHC for ALK could be useful in limited tissue samples, such as biopsy specimens or cytology, for the screening of ALK-positive lung carcinoma. In the present study, it was demonstrated that IHC with ALK monoclonal antibody D5F3 was useful for screening lung adenocarcinoma harboring ALK rearrangement.

Pegylated interferon-α2a inhibits proliferation of human liver cancer cells in vitro and in vivo.

PURPOSE: We investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells. METHODS: The effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0-4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined. RESULTS: PEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 µg/kg, 0.06 µg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control. CONCLUSIONS: Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.

Vitrectomy for optic disc pit-associated maculopathy with or without preoperative posterior vitreous detachment.

BACKGROUND: The purpose of this study was to evaluate the efficacy of pars plana vitrectomy for the treatment of optic disc pit-associated maculopathy with or without preoperative posterior vitreous detachment. METHODS: We reviewed the clinical records of four consecutive patients who underwent pars plana vitrectomy in one eye for the treatment of optic disc pit-associated maculopathy, with an emphasis on the preoperative condition of the posterior hyaloid membrane. RESULTS: Two of four eyes were confirmed to have an attached posterior hyaloid membrane, which was subsequently removed during surgery. Following vitrectomy, these two eyes experienced an improvement in visual acuity with complete retinal attachment of the macula. However, the other two eyes, which already had a posterior vitreous detachment at the time of surgery, showed a decrease in visual acuity with persistent maculopathy postoperatively. CONCLUSION: Pars plana vitrectomy for optic disc pit-associated maculopathy was beneficial for improving visual acuity in two eyes without preoperative posterior vitreous detachment but not in two eyes with preoperative posterior vitreous detachment. Our study suggests that preoperative assessment of a posterior hyaloid membrane is clinically important in predicting the surgical outcome of optic disc pit-associated maculopathy.