An autopsy case of hepatic sarcomatoid tumor: Immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma

A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-α₁-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immuno-histochemistry; many tumor cells were strongly immuno-reactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and u,-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC.     

No association of GSK3beta gene (GSK3B) with Japanese schizophrenia.

Several lines of evidence indicate that glycogen synthase kinase-3beta (GSK3beta) is one of the candidates for schizophrenia-susceptibility factor. However, it has not been reported the association analysis between GSK3beta gene (GSK3B) and Japanese schizophrenia based on linkage disequilibrium (LD). We provide an association analysis using relatively large samples (381 schizophrenia, and 352 controls) after determination of "tag single nucleotide polymorphisms (SNPs)." In this LD mapping, we selected and genotyped for eight polymorphisms (seven SNPs and one diallelic (CAA)(n) repeat), which covered the entire region of GSK3B, and determined two "tag SNPs." In the following association analysis using these two "tag SNPs," we could not find association with Japanese schizophrenia. Furthermore, we also include subgroup analysis considering age-at-onset and subtypes, neither could we find associations. Because our samples provided quite high power, these results indicate that GSK3B may not play a major role in Japanese schizophrenia.     

Live varicella vaccine polarizes the mucosal adjuvant action of cholera toxin or its B subunit on specific Th1-type helper T cells with a single nasal coadministration in mice

This study was undertaken to determine whether the specific Th1- or Th2-cell response to varicella-zoster virus was induced predominantly by a mucosal adjuvant, cholera toxin, in mice. A commercially available live varicella vaccine (Oka strain) and cholera toxin or its B subunit were administered simultaneously via the nasal route. Delayed-type hypersensitivity to the Oka vaccine was induced, but the systemic neutralizing antibody response was low. The delayed-type hypersensitivity evoked after a single administration was relatively higher than that on administration three times. When spleen cells from mice immunized once with the vaccine and cholera toxin or its B subunit were restimulated with the live vaccine in vitro, there was greater thymidine uptake and production of interleukin- 2 (IL-2) than controls, but only a low level of IL-4 production. The production of IL-2 induced by the B subunit of cholera toxin was less than that by cholera toxin and a mutant of Escherichia coli enterotoxin on co-immunization with the vaccine in mice. Cholera toxin and its B subunit have been reported to induce predominantly a specific Th2-type T-cell response to various antigens. However, the Oka vaccine is an antigen that polarizes the activation of specific Th1/Th2-type T cells by cholera toxin or its B subunit to the Th1-type side. Cholera toxin and its B subunit are thus useful mucosal adjuvants for inducing cellular immunity to the Oka vaccine similar to Escherichia coli enterotoxin.     

Ridge filter design for proton therapy at Hyogo Ion Beam Medical Center

At the Hyogo Ion Beam Medical Center (HIBMC) we have developed a new design method for the bar ridge filter used in proton therapy, taking into consideration the scattering and nuclear interaction effects within the filter itself, which are introduced in the design. In our beam delivery system, the bar ridge filter is employed as the range modulator. It is combined with the wobbler system, and produces a three-dimensionally uniform spread-out Bragg peak (SOBP). The design program predicts the three-dimensional dose distribution. Ridge filters of 3-12 cm SOBP in 1 cm increments were designed in the maximum radiation field for 150 MeV and 190 MeV proton beams so that a uniform physical dose area is obtained in the SOBP region three-dimensionally. Measurements were performed with the constructed ridge filters to verify the uniformity and these were compared with the predictions of the design program. The predictions and measurements were found to be in agreement except for the 12 cm SOBP. The uniformities were better than +/- 3.0% for all SOBPs produced. The ridge filters are now clinically in use.     

In vivo study of the effects of cryopreservation on heart valve xenotransplantation.

BACKGROUND: Recent reports have suggested that cryopreservation reduces the immunogenicity of donor tissue. The immunomodulation by cryopreservation might influence on the tissue durability after xenotransplantation. We investigated the in vivo morphologic changes in cryopreserved xenograft (CXG) heart valves. MATERIAL AND METHOD: We transplanted a fresh (fresh xenograft; FXG) and a cryopreserved (CXG) porcine aortic root and a cryopreserved canine (cryopreserved allograft; CAG) aortic root into the abdominal aorta of a dog without any immunosuppressive agents. Explanted grafts on the 21st to 49th days after implantation were analyzed morphologically with light microscopy using some special stains, immunohistochemical analysis, and scanning electron microscopy (SEM). RESULT: Light microscopy showed the absence of smooth muscle cells in the media of the aorta in any group after transplantation. FXG valves did not maintain any cellularity after transplantation. CXG valves contained cellular infiltration in themselves. CAG valves contained numerous fibroblasts, which showed the maintenance of tissue integrity without allowing cellular infiltration. The structure of elastic fibers was well maintained, even in the part of CXG valve with cellular infiltration. Immunohistochemical studies documented the infiltration of T lymphocytes in CXG valves that were labeled by anti-CD3 antibodies. SEM demonstrated that no endothelia were seen on the surface of the valves in any group after transplantation. CONCLUSION: We concluded that the cryopreservation method might provide an immunomodulation of xenogeneic heart valves for transplantation.     

Neural crest origin of clear cell sarcoma of tendons and aponeuroses

Summary In order to clarify the histogenesis of clear cell sarcoma of tendons and aponeuroses (CCS), two cases of human and one nude mouse-transplanted CCS line were studied using an ultrastructural and enzyme cytochemical approach. Most of the tumour cells obtained from the primary and transplanted CCS demonstrated melanosomes in various stages of development within the cytoplasm, whereas no melanosomes could be identified in the metastatic CCS. However, cholinesterase and tyrosinase activities could be demonstrated not only in the melanotic primary and transplanted CCS but also in the amelanotic metastatic CCS. The results therefore support the hypothesis that CCS is a soft tissue tumour derived from the neural crest.     

Sustained interleukin-6 signalling leads to the development of lymphoid organ-like structures in the lung

A variety of pathological changes are seen in lymphoproliferative disorders of the lung but the histogenesis of these abnormalities is not yet fully understood. We previously showed that adenovirus vector-mediated transient expression of both the human interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes, but not the IL-6 gene alone, in the rat lung induced lymphocytic alveolitis. In the present study, we explored the lung pathology of human IL-6 and IL-6R double transgenic mice to elucidate the effects of prolonged IL-6 signalling on the lung. The transgenic animals developed mononuclear cell accumulation in peribronchovascular regions, but little infiltration into alveolar spaces. Immunohistochemical analysis revealed that the cellular accumulations contained not only mixtures of inflammatory cells but also lymphoid tissue-like structures. As the expression of CXCL13/BLC, the indispensable chemokine for lymphoid organogenesis, was recognized in the B cell follicles of the pulmonary lesions, we speculate that this chemokine plays an inductive role in the development of the lymphoid tissue-like structures. These structures were distinguished from bronchus-associated lymphoid tissues (BALTs) by their location and by the lack of lymphoepithelium, which is a characteristic of BALT. These findings imply that IL-6 signalling may play a role in the pathogenesis of lymphoproliferative disorders of the lung.     

A new approach to spike sorting for multi-neuronal activities recorded with a tetrode--how ICA can be practical

Multi-neuronal recording with a tetrode is a powerful technique to reveal neuronal interactions in local circuits. However, it is difficult to detect precise spike timings among closely neighboring neurons because the spike waveforms of individual neurons overlap on the electrode when more than two neurons fire simultaneously. In addition, the spike waveforms of single neurons, especially in the presence of complex spikes, are often non-stationary. These problems limit the ability of ordinary spike sorting to sort multi-neuronal activities recorded using tetrodes into their single-neuron components. Though sorting with independent component analysis (ICA) can solve these problems, it has one serious limitation that the number of separated neurons must be less than the number of electrodes. Using a combination of ICA and the efficiency of ordinary spike sorting technique (k-means clustering), we developed an automatic procedure to solve the spike-overlapping and the non-stationarity problems with no limitation on the number of separated neurons. The results for the procedure applied to real multi-neuronal data demonstrated that some outliers which may be assigned to distinct clusters if ordinary spike-sorting methods were used can be identified as overlapping spikes, and that there are functional connections between a putative pyramidal neuron and its putative dendrite. These findings suggest that the combination of ICA and k-means clustering can provide insights into the precise nature of functional circuits among neurons, i.e. cell assemblies.     

THE PRESENCE OF INTRACYTOPLASMIC CONFRONTING CISTERNAE OF THE ENDOPLASMIC RETICULUM IN OSTEOSARCOMA CELLS IN INTERPHASE

Confronting cisternae of the endoplasmic reticulum recognized in tumor cells of 7 cases of osteosarcoma were presented. They were found in the mitotic cells as well as in the cytoplasms of interphase cells. The more the mitotic cells were observed in 1 μm-thick sections, the more frequently those membranous structures were encountered in the corresponding ultrathin sections. In the interphase cells, such structures were located around Golgi apparatus or close to the nucleus. Occasionally, they were composed of a pair of closely apposed cisternae of the nuclear membrane and the rough endoplasmic reticulum. These results seem to indicate that the nuclear envelope which is disrupted and reformed during mitosis in rapidly proliferating cells takes part in the formation of the confronting cisternae of the endoplasmic reticulum.     

Polycondensation-addition. V. Polyurethan-ureas with asymmetric carbon atoms in the main chain from L- and DL-2-alkyl-2-isocyanatoethyl chloroformates and diamines1

L - and DL-2-Alkyl-2-isocyanatoethyl chloroformates were synthesized by the phosgenation of the corresponding amino alcohols. These optically active or racemic difunctional compounds were submitted to polycondensation-addition with various diamines to form high molecular weight polyurethan-ureas having asymmetric carbon atoms along the main chain. The optically active polyurethan-ureas obtained had slightly higher melting points than the corresponding racemic polymers.