Development of autoimmune insulitis is prevented in E alpha d but not in A beta k NOD transgenic mice

Two lines of E alpha d-expressing NOD mice were established by continuously backcrossing [E alpha d B6 transgenic mice x NOD] F1 to parental NOD or directly microinjecting the E alpha d gene into fertilized NOD eggs. Similarly, A beta k-expressing transgenic NOD mice were produced. Subsequent histological examination of pancreatic tissues revealed that autoimmune insulitis was prevented in E alpha d backcross and transgenic mice but not in A beta k transgenic mice.     

Undifferentiated Carcinoma of the Parotid Gland in a 10-Month-old Child

Malignant salivary gland tumors in children are very rare. This report describes the autopsy of a child with parotid gland cancer. The patient, a 10 month old girl, was admitted to the Nagoya First Red Cross Hospital with facial nerve palsy. lncisional biopsy of a post-auricular tumor was performed, and undifferentiated carcinoma was diagnosed. The patient died 6 months later of respiratory failure due to pulmonary lymphangitis carcinomatosis. Light and electron microscopic and immunohistochemical examinations of the tumor tissue were performed. The tumor cells were arranged in a medullary, sheet-like manner. Keratinization or mucus lakes were not observed. PAS-alcian blue staining demonstrated intracytoplasmic mucus as granules, and also small intercellular droplets of mucus that might otherwise have been unnoticed. Ultrastructurally, some of the tumor cells had tonofilament-like keratin filaments, and also small hollow spaces bounded by microvilli and containing secretory particles. These were stained by antisera against CEA and keratin. These findings are suggestive of differentiation to mucoepider-moid carcinoma. We also review and discuss malignant salivary tumors of epithelial origin in children. Acta Pathol Jpn 40: 149–152, 1990.     

Effect of phorbol myristate acetate (PMA) on diphosphoinositide (DPI) synthesis in rat mast cell granules

Rat mast cell granules were obtained by homogenization of highly purified rat mast cells and isolated in a Percoll gradient. DPI synthesis in rat mast cell granules was assayed by measuring the incorporation of 32P from [gamma 32P] ATP into DPI in the absence of exogenous phosphatidylinositol (PI). Lipids were isolated with methanol/chloroform/HC1 and were separated by thin-layer chromatography on oxalic acid impregnated silica gel plates. DPI areas were identified by staining with iodine, scraped and measured for 32P radioactivity. The addition of PMA to the granules caused an increase of DPI synthesis, which can be catalysed by PI kinase. Neither an inactive phorbol ester, 4-alpha-phorbol-12, 13-didecanoate, nor dimethyl sulfoxide (DMSO) used as a solvent for PMA had any effect. The effect of PMA in the DPI synthesis was dose-dependent and maximal effects were observed at 10-100 ng/ml. Dose-response curves of the effects of PMA in DPI synthesis in the granules corresponded to those of other biochemical effects of PMA in rat mast cells, such as mediator release mediated through the activation of protein kinase C. These results suggest that PMA may directly affect PI kinase or indirectly regulate its activity in rat mast cell granules.     

Extraskeletal mesenchymal chondrosarcoma in a cow

A mesenchymal chondrosarcoma found in a 7-year-old Holstein cow was studied by light and electron microscopy. There was a primary site in the subcutaneous tissue at the base of the neck and metastases in the lungs, pleura, broncho-mediastinal lymph nodes, kidneys and heart. The neoplasm was composed of undifferentiated mesenchymal tissue, myxoid tissue and chondroid tissue. The neoplastic cells of the former two tissues were characterized by desmosome-like junctions and moderate to small amounts of rough endoplasmic reticulum (RER).     

FDG-PET for the evaluation of tumor viability after anticancer therapy

To evaluate positron emission tomography with¹⁸F-fluorodeoxy glucose (FDG-PET) as an diagnostic tool to determine tumor viability after anticancer therapy, fourteen patients were examined by FDG-PET after the end of the treatment. The lesions with residual viable tumor cells showed higher uptake of FDG than surrounding normal soft tissue. The lesions, in which tumor viability was lost or very low, showed higher uptake of FDG in four cases and similar uptake to normal soft tissue in three cases. The residual increased uptake of FDG was considered to be caused by remaining tumor cells and/or inflammatory reaction to anticancer treatment. FDG-PET after anticancer treatment should be interpreted by considering the reaction due to the treatment and the partial volume artifact of PET caused by the limited spatial resolution.     

Liver Targeting of Interferon Through Pullulan Conjugation

Purpose. The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver. Methods. Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2,5-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated. Results. The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7–9 % of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice. Conclusions. IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein.     

Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations

According to linear pharmacokinetics, the time course of plasma concentration of a drug, C_p,is expressed by a sum of exponential functions, C_p= _i=1 ⁿ a_i .This article describes a statistical technique to estimate the number of exponential terms, n,for the time course of drug by the application of Akaike's information criterion (AIC). Plasma concentrations of ethoxybenzamide, sulfisoxazole, bishydroxycoumarin, and diazepam measured following bolus intravenous injection were used as clinical examples for this method. Selection of models is compared between the AIC method and an Ftest method at significance levels of 5% and 1%.     

Continuing Medical Education Activity in Echocardiography

Article Title: Speckle Tracking Global Strain Rate E/E’ Predicts LV Filling Pressure More Accurately Than Traditional Tissue Doppler E/E’ (Echocardiography, 2012;29:403)     

Scimitar syndrome in an infant with right lung hypoplasia,ventricular septal defect,and severe pulmonary hypertension

A 5-month-old boy was presented for surgical repair of scimitar syndrome associated with right lung hyperplasia, severe pulmonary hypertension, ventricular septal defect (VSD), and atrial septal defect. The calculated shunt fraction (Qp/Qs) was 3.1:1.0, pulmonary vascular resistance was 4.6, and the perfusion lung scan showed a marked decrease (11%) in right pulmonary blood flow. Surgical repair was performed through the right fourth intercostal space with the patient supine. The anomalous vein was divided and interposed with a short azygos vein graft, followed by closure of the VSD. Finally, the interposed azygos vein was anastomosed to the left atrium. Although pulmonary artery pressure was normalized at the 2-year follow-up, cardiac catheterization 6 months after the operation demonstrated right pulmonary vein obstruction.