An autopsy case of so-called midline malignant reticulosis followed by extensive dissemination with immunohistochemical evidence for its T cell malignancy

An autopsy case of malignant midline reticulosis (MMR) is reported. The patient, a 42-year-old Japanese male, died after a clinical course of 22 months. Autopsy revealed extensive infiltration of generalized organs by the tumor cells, suggesting that the disease was highly malignant in nature. Staining with monoclonal antibodies against T-cell surface antigens Leu 4 on frozen sections and UCHL1 on paraffin-embedded sections enabled us to examine the phenotype of the tumor cells with good morphological preservation and to verify the T cell nature of the tumor.     

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.     

Cross-regional survey of seasonal affective disorders in adults and high-school students in Japan

BACKGROUND: In Asian countries, there is no epidemiological report on seasonal affective disorder (SAD) in different age groups and different geographic regions surveyed at the same time. The aim of this study was to estimate the prevalence rates of SAD and risk factors for SAD in adults and high-school students, with special reference to the difference of winter SAD between northern and southern regions in Japan. METHODS: A total of 3237 high-school students and 4858 workers living in Japan (31.3-43.5 degrees N) responded to this epidemiological survey using Japanese version of the Seasonal Pattern Assessment Questionnaire (SPAQ). RESULTS: The overall prevalence rates of winter SAD (subsyndromal winter SAD) and summer SAD (subsyndromal summer SAD) in high-school students were 0.91(2.21) and 0.81(2.57)%, respectively. In workers, these rates were 0.45(1.16) and 0.43(0.71)%, respectively. Although no regional difference was noted in high-school students with winter seasonal type, the estimated odds ratio of this type for northern workers was nearly 3-fold higher than the southern counterparts. The prevalence rates of each seasonal type were not significantly different between two sexes in both age groups. No clear dependence on latitude was seen with regard to summer SAD in both age groups. LIMITATIONS: The effect of climate on SAD could not be entirely excluded from geophysical factor as indexed by latitude. CONCLUSIONS: SAD was less common in adults than in high-school students. While latitude was a major determinant of winter type in adults, socio-cultural factors or other contributing factors might affect the development of this type in high-school students.     

Cytokeratin expression in normal human thymus at different ages

Subsets of thymic epithellal cells were examined Immuno-histochemically to determine whether or not their pheno-types change during thymic growth and at early involution in terms of cytokeratin (CK) expression. Five monoclonal antibodies specific for CK4, CK8, CK13, CK18 and CK19 were used and applied for 16 neonatal, three Infantile and one adult thymus speeimen, which had been obtained at autopsy, that were normal macroscopically and microscopicaily. CK4, CK8, CK13, CK18 and CK19 were expressed simultaneously in the cortex, medulla and subcapsular area with the exception of CK4, which showed expression on the adult thymus. Light and electron microscopy showed that CK8 and CK19 expression was overlapped. Thus, It was thought that CK8 and CK19 formed complexes in the cytoplasm of thymic epithelial cells. The Immunoreactivity to CK4, CK13 and CK18 were attenuated or disappeared In the subcapsular area during the early involution stage. Interestingly, two patterns of CK18 expression were observed in the neonatal and Infantile thymus tissues, which Indicated that the thymic microenvironment was changeable even under normal conditions.     

Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53‐ and p16/Rb‐dependent cell cycle regulator proteins

Ovarian mature cystic teratomas (MCT) uncommonly undergo malignant transformation to squamous cell carcinoma (SCC). While alterations in the p53 tumor suppressor gene and protein have been shown, few studies have analyzed other molecular changes leading to this malignant conversion. The purpose of the present study was to investigate 21 samples of SCC arising in MCT for altered expression in known p53‐ and p16/Rb‐dependent cell cycle regulatory proteins, and the association between their expression and cellular proliferation and histological features. Overexpression of the p53 protein was observed in 14 SCC (67%), while four (19%) had point mutations in the p53 gene. Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%). Furthermore, a statistically significant correlation was observed between p53 and Rb overexpression (P = 0.0010), and the overexpression of both p53 and Rb was respectively significantly correlated with increased cellular proliferation. The results indicate that alterations in both the p53 and p16‐Rb pathways are associated with SCC arising in MCT.     

The combination of IFN-alpha2 and IFN-alpha8 exhibits synergistic antiproliferative activity on renal cell carcinoma (RCC) cell lines through increased binding affinity for IFNAR-2.

Although there are at least 13 interferon-alpha (IFN-alpha) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-alpha interactions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-alpha2 and IFN-alpha8 using six renal cell carcinoma (RCC) cell lines. Although IFN-alpha8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-alpha2 and IFN-alpha8. To analyze the interactions between IFN-alpha2 and IFN-alpha8, the receptor-binding kinetics of different combinations of IFN-alpha2 and IFN- alpha8 to the IFN-alpha receptors, IFNAR-1 or IFNAR-2, were measured using a surface plasmon resonance-based biosensor. Unexpectedly, the receptor binding kinetics to IFNAR-2 but not to IFNAR-1 were mutually related to antiproliferative activity and increase in the binding speed (K(a)) for IFNAR-2. Moreover, we observed the increased fluorescence intensity (FI) of biotin-labeled IFN-alpha8 to IFNAR-2 by receptor binding inhibition assay with unlabeled IFN-alpha2 but not the other combinations. These findings indicate that the binding manner of IFN-alpha8 for IFNAR-2 is different from that of IFN-alpha2, suggesting that binding of IFN-alpha8 rather than binding of IFN-alpha2 to IFNAR-2 leads to activation and subsequent antiproliferative activity despite the same antiviral activity in RCC.     

N-Glycosylation contributes to the limited cross-reactivity between hemagglutinin neuraminidase proteins of human parainfluenza virus type 4A and 4B

cDNAs encoding human parainfluenza virus type 4B (hPIV-4B) hemagglutinin neuraminidase (HN) protein were cloned and the nucleotide sequences were determined. A high degree of identity (81.4%) was observed between the nucleotide sequences of hPIV-4A and -4B HN proteins, and an 87.3% identity was found between the deduced amino acid sequences. This degree of identity is considered to be greater than immunological similarity between hPIV-4A and -4B HN proteins determined using monoclonal antibodies. To elucidate the causes of the antigenic difference between HN proteins of hPIV-4A and -4B, we constructed three cDNAs of hPIV-4B HN whose potential N-glycosylation sites were partially or completely the same as in hPIV-4A HN cDNA. We compared the antigenicity of the expressed wild-type and mutant proteins, and found that the antigenicities of the mutant hPIV-4B HN proteins were more similar to the hPIV-4A HN protein than to the non-mutant hPIV-4B HN protein. This study indicated that the antigenic diversity between hPIV-4A and -4B was partly caused by deletion or creation of glycosylation sites, showing that the point mutations resulting in deletion or creation of glycosylation sites is one of the initial steps leading to the division of virus into subtypes. Received: 21 January 2000     

An autopsy case of idiopathic enlargement of the right atrium, and a review of the literature

A 69-year-old man in whom idiopathic enlargement of the right atrium was revealed at autopsy is described. The patient had had cardiomegaly of at least 19 years' duration prior to his death, even though cardiac symptoms were absent. Cause of death was pancreatic carcinoma. Postmortem examination revealed marked and diffuse dilatation of the right atrium and moderate dilatation of the left atrium. Measurement of the cardiac chambers showed that the right and left atria were 7.6 and 4.7 times as large as those of normal hearts, respectively. The volume of either ventricle was about twice the normal value. Histologically, widespread cardiac muscular degeneration and necrosis, diffuse fibrosis, and focal lymphocytic infiltration were found in the right atrium and also, to a lesser degree, in the left atrium. Such pathologic changes were not found in either of the ventricles. The etiology of these muscular changes, which might have been related to atrial enlargement, was unclear. The present case was thought to be consistent with idiopathic enlargement of the right atrium, and a brief review of the literature is given.     

Imaging mitochondrial redox environment and oxidative stress using a redox-sensitive fluorescent protein.

Redox-sensitive green fluorescent protein (roGFP) is a fluorescent protein in which two cysteines are placed adjacently in the barrel structure. Disulfide formation (oxidation) increases the absorption at short wavelengths (410 nm) at the expense of absorption at longer wavelengths (490 nm). The fluorescence ratio indicates reduction/oxidation, i.e., the redox potential at specific cellular locations.