Interaction of poly(styrene sulfonic acid) with the alternative pathway of the serum complement system

Bioartificial pancreas, in which the islets of Langerhans are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement reaction. In this study, we examined the effects of poly(styrene sulfonic acid) (PSSa) on the alternative pathway of the serum complement system to identify the mechanism(s) involved. PSSa was dissolved in pooled normal human serum (NHS), and the mixtures were incubated at 37 degrees C for 30 min. Complement activities in sera were determined by hemolytic assays. Amounts of complement activation products released were determined by ELISA. Interactions of PSSa with complement components and fragments were examined with electrophoresis and immunoblotting. From these examinations, it appeared that the manner of PSSa effects on the alternative pathway (AP) highly depends on its concentration. PSSa seemingly acted as an activator when its concentration was 0.005 g/dl to 0.05 g/dl, while it acted as an inhibitor when its concentration was more than 0.1 g/dl. In terms of activation or inhibition of the AP, forming complex of PSSa with factor H induced activation, and that with factor D induced inhibition.     

Genomic alterations in primary cutaneous melanomas detected by metaphase comparative genomic hybridization with laser capture or manual microdissection: 6p gains may predict poor outcome

To clarify the correlation of genomic alterations with clinical and histological features, we performed metaphase comparative genomic hybridization analysis on 20 primary cutaneous melanomas, which were obtained by laser capture or manual microdissection, and 16 melanoma cell lines. There were no differences in the average number of aberrations between acral melanomas (AM) and non-AM, although gains of 5q and 11q13 were more frequent (P=0.05) and 10q loss was less frequent (P=0.01) in AM than in non-AM. Although tumor thickness is considered a measurable estimate of clinical expression, there were no differences in the average number of aberrations among 4 groups, classified by thickness of the tumor. While the majority of aberrations were equally distributed among the 4 groups, 6p gains were found only in the thickest tumors. Patients with 6p or 1q gains had a lower overall survival rate than those without them (P=0.0002 or P=0.013). While gains of 1q, 2q, 3p, 3q, 7q, 20p, and 20q were more frequent in the cell lines than in the primary tumors (P<0.01), losses of 6q, 9p, 10p, and 10q were equally found in both cell lines and primary tumors. The present study showed that chromosomal aberrations had already occurred in the thinner tumors, and that 6p and 1q gains may be a prognostic factor.     

Immunohistochemical and immunochemical study of amyloid in liver affected by systemic Alambda amyloidosis with antibodies against three different regions of immunoglobulin lambda light chain

The purpose of the present paper was to investigate the heterogeneous nature of amyloid deposits in the liver, by immunohistochemical and immunochemical examination of liver samples from cases of immunoglobulin lambda light chain amyloidosis (Alambda amyloidosis) with antibodies generated against the peptides corresponding to the three different regions of the lambda light chain. Amyloid deposits in the hepatic artery tended to react better with anti-lambda(118-134) than with anti-lambda(159-175). Amyloid deposits in the space of Disse tended to react weakly or partially with anti-lambda(118-134) but well with anti-lambda(159-175). Amyloid deposits in the portal vein reacted relatively well with both antibodies. By western blotting of water-extracted amyloid in which amyloid deposits were not stained with anti-lambda(118-134) immunohistochemically, the three antibodies detected 27 kDa bands consistent with the full-length Ig lambda chain and some smaller bands. These findings indicate that amyloid deposits may not be homogeneous in the liver of AL amyloidosis, and that molecular heterogeneity of amyloid fibril protein or a difference in the mode of deposition results in the histopathological heterogeneity of AL amyloid deposits even within a single patient.     

Identification of normal and neoplastic stem cells by the multicolor lineage tracing methods

Adult stem cells and embryonic (ES) and induced pluripotent stem (iPS) cells are two major focus areas of stem cell research. Studies on adult stem cells are important not only as sources for regenerative medicine but for analyzing the mechanisms of tissue homeostasis, tissue repair after injury, cancinogenesis, and aging. On the other hand, ES and iPS cells are mainly important for regenerative medicine. However, many adult stem cells, especially those in low‐turnover tissues, have remained unidentified. We have been working on the development of methods using multiple fluorescent markers, to improve the accuracy of lineage‐tracing analyses of adult stem cells and their fetal progenitors. With this method, we were able to identify lingual epithelial stem cells (LESCs). By using the same strategy, we could potentially identify candidate cancer stem cells. In this review, we would like to introduce how the multicolor lineage tracing method could be used in various stem cell studies.     

Approximate Entropy of Respiratory Movements in Human Newborns during Different Sleep States

Previous studies have reported that the respiratory cycle of healthy newborns is more irregular during active sleep. This study aimed to apply non-linear analysis to examine the irregularity of respiratory movement in newborns at different sleep states. The respiratory movement signals from an abdominal band during quiet and active sleep were analyzed using approximate entropy (ApEn). The breathing interval of active sleep was significantly shorter than that of quiet sleep [1.30 (0.17) s vs. 1.58 (0.11) s; (P < 0.03)]. The ApEn of respiratory movements during active sleep were significantly larger than that during quiet sleep [0.785 (0.135) s vs. 0.678 (0.083) s; (P < 0.05)]. We found that the ApEn of respiratory movement in healthy newborns could detect irregularities in respiration during sleep.     

Cytologic findings and differential diagnoses of primary thyroid MALT lymphoma with striking plasma cell differentiation and amyloid deposition

We report two cases of thyroid mucosa‐associated lymphoid tissue (MALT) lymphoma with associated amyloid protein deposition. While other primary thyroid neoplasms sush as medullary carcinoma and plasmacytoma with associated amyloid protein are known to occur and have been previously described by fine‐needle aspiration cytology (FNAC), to our knowledge, the current cases are the first of thyroid MALT lymphoma with amyloid deposition to be detailed in the cytopathology literature. Case 1 was a 73‐year‐old female with chronic thyroiditis. FNAC suspected MALT lymphoma. The amyloid material was not noticed, nevertheless it existed. Case 2 was a 71‐year‐old female with a nodule of the thyroid. Malignant lymphoma and medullary carcinoma were suspected by FNAC. The possibility of medullary carcinoma was excluded by a measurement of serum calcitonin and carcinoembryonic antigen. After follow‐up for two years, the nodule was diagnosed as MALT lymphoma associated with plasma cell differentiation and amyloidosis by the fourth FNAC. When we encounter small round cell tumors associated with amyloid in thyroid FNAC, we should consider not only medullary carcinoma but also MALT lymphoma. Diagn. Cytopathol. 2014;42:73–77. © 2013 Wiley Periodicals, Inc.     

Transient heating of expressed breast milk up to 65°C inactivates HIV‐1 in milk: A simple,rapid, and cost‐effective method to prevent postnatal transmission

The postnatal transmission of human immunodeficiency virus (HIV) from mothers to children occurs through breastfeeding. Although heat treatment of expressed breast milk is a promising approach to make breastfeeding safer, it is still not popular, mainly because the recommended procedures are difficult to follow, or time‐consuming, or because mothers do not know which temperature is sufficient to inactivate HIV without destroying the nutritional elements of milk. To overcome these drawbacks, a simple and rapid method of heat treatment that a mother could perform with regular household materials applying her day‐to‐day art of cooking was examined. This structured experiment has demonstrated that both cell‐free and cell‐associated HIV type 1 (HIV‐1) in expressed breast milk could be inactivated once the temperature of milk reached 65°C. Furthermore, a heating method as simple as heating the milk in a pan over a stove to 65°C inhibited HIV‐1 transmission retaining milk's nutritional key elements, for example, total protein, IgG, IgA, and vitamin B₁₂. This study has highlighted a simple, handy, and cost‐effective method of heat treatment of expressed breast milk that mothers infected with HIV could apply easily and with more confidence. J. Med. Virol. 85:187–193, 2013. © 2012 Wiley Periodicals, Inc.     

Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type: immunohistochemical studies and mutation analysis of the p53 gene

Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type fulfilling the 1999 WHO criteria is rare. Here, we report a case of this type of tumor determined entirely by histological examinations. A 57-year-old man was incidentally found to have a demarcated 3cm mass in his lower lobe of the right lung. The tumor was composed of tall columnar cells containing cytoplasmic mucins, cuboidal cells without mucins, and intermediate cell types with lepidic growth patterns. Tumor cells were distributed within a region of 2cm in diameter, and no stromal, vascular, or pleural invasion was observed. Immunohistochemically, both the mucinous and nonmucinous components were positive for cytokeratin 7, TTF-1, and E-cadherin, and negative for cytokeratin 20, consistent with the results for nonmucinous bronchioloalveolar carcinoma. No mutations were detected in exons 5-8 of the p53 gene. The present tumor was composed mainly of morphologically mucinous bronchioloalveolar carcinoma, but presented different immunohistochemical profiles of ordinary mucinous bronchioloalveolar carcinoma. This case suggests that the mucinous component in bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type has characters dissimilar to conventional mucinous bronchioloalveolar carcinoma, and is probably derived from the nonmucinous component.