Hepatoid carcinoma of the skin: spontaneous rat skin hepatoid carcinoma with eosinophilic globules and crystals immunoreactive to α-1-antitrypsin

We present a case of hepatoid carcinoma of the abdominal skin in a male Wistar rat. Histopathologically, this carcinoma resembled human hepatocellular carcinoma with respect to trabecular-sinusoidal structures. Carcinoma tissues contain numerous eosinophilic globules and crystals, and in this case, we found the characteristic eosinophilic globules in the hepatoid carcinoma cells and the crystals in the extracellular portions. Vivid carcinoma cells full of eosinophilic globules were present near the necrotic areas in tumor tissue, wherein quadrate crystals unstained with eosin were observed. PAS staining after diastase digestion revealed that the globules were PAS positive and diastase resistant. In addition, we found that the hepatoid carcinoma cells were immunoreactive for α-1-antitrypsin (anti-A1AT) antibody with the globules and crystals staining peripherally, and a central unstained region. Ultrastructural study of intracytoplasmic globules and extracellular crystals revealed that the fringe of each globule and crystal had no limiting membrane and showed the same level of electron density. These findings suggest that the characteristic crystals in this tumor may have originated from the globules that were emitted from the carcinoma cells after their death as a result of saturation with intracytoplasmic globules.     

The majority of triple-negative breast cancer may correspond to basal-like carcinoma,but triple-negative breast cancer is not identical to basal-like carcinoma

Recently, the concept of basal-like carcinoma has been proposed. However, there are only a few reports about the relationship between triple-negative cancer and basal-like carcinoma. In this article, we report the study of the expression of basal cell markers in 11 triple-negative cancers. Eight tumors (4 metaplastic carcinomas, 2 invasive ductal carcinomas, 1 invasive papillary carcinoma, and 1 medullary carcinoma) were positive for more than three markers among cytokeratins 5, 14, and 17, and p63. Three tumors (2 invasive ductal carcinomas and 1 apocrine carcinoma) were completely negative for all markers. Among 8 tumors positive for basal markers, cytokeratins 5 and 17 were expressed in all 8 tumors, cytokeratin 14 in 6 tumors, and p63 in 7 tumors. Finally, we conclude that the majority of triple-negative cancer may correspond to basal-like carcinoma, but the two entities are not identical. The use of combination immunohistochemistry including cytokeratins 5, 14, and 17 and p63 may contribute to the detection of basal-like carcinoma.     

Synergistic effect of interleukin-6 promoter (IL6 -634C/G) and intercellular adhesion molecule-1 (ICAM-1 469K/E) gene polymorphisms on the risk of endometriosis in Japanese women

PROBLEM: Endometriosis is an immune-related, chronic inflammatory disease with a polygenic predisposition. The aim of this study was to investigate whether the interleukin-6 (IL-6) gene promoter region polymorphism (-634C/G) and the intercellular adhesion molecule-1 (ICAM-1) gene 469K/E polymorphism are responsible in part for the genetic susceptibility to endometriosis. METHODS OF STUDY: The IL-6 -634C/G and ICAM-1 469K/E genotypes were determined in 202 patients with endometriosis and 236 control women by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences in the IL-6 -634C/G or the ICAM-1 469K/E genotypes and allele frequencies between control women and endometriosis patients collectively, or between control women and each clinical subgroup of endometriosis patients. Interestingly, the frequency of ICAM-1 EE homozygotes who concomitantly carried the IL-6 -634G allele was significantly higher in patients with endometriosis (chi(2) = 6.458, P = 0.0396, d.f. = 2). CONCLUSION: Our results suggest that the IL-6 -634C/G and ICAM-1 469K/E polymorphisms synergistically affect the susceptibility for endometriosis in the Japanese population.     

Multiple amino acids in the glycoprotein of rabies virus are responsible for pathogenicity in adult mice

We have reported that the region between amino acids 164 and 303 in the glycoprotein of rabies Nishigahara strain is important for lethality in adult mice. The region contains nine amino acid substitutions between the virulent Nishigahara and the avirulent RC-HL strains. In order to determine key residues for the pathogenicity, two chimeric strains and seven mutants were generated and examined for pathogenicities. The R(G 242/255/268) strain, in which amino acids at positions 242, 255, and 268 were replaced by those from the Nishigahara strain in the genomic backbone of the RC-HL strain, showed the same lethality as that of the Nishigahara strain in mice. Mutants in which one or two of these three amino acids were replaced by those from the Nishigahara strain did not revert to the lethality of the R(G 242/255/268) strain. These results demonstrate that at least these three amino acids are related to enhancement of pathogenicity. It is thought that multiple amino acids of the G protein are related to the pathogenicity of rabies viruses.     

No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population

Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we undertook an extensive case-control association study using a total of 911 unrelated Japanese T2D patients and 876 control subjects. No significant difference was observed in either genotype distribution (P=0.95) or allele frequency (P=0.83) between T2D and control groups. Notably, the frequency of the ancestral Q121 allele, which is also present in other primates, was quite high in African-Americans, and showed a marked ethnic variation (77.3% in African-Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han Chinese). Consequently, the pairwise F_ST value (a classic measure of genetic distance between pairs of population) showed highly significant differentiations between African-American and non-African-American populations (F_ST>0.3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D.An erratum to this article can be found at     

Plasma B-type natriuretic peptide (BNP) measuring

Brain or B-type natriuretic peptide (BNP) is a potent natriuretic, diuretic and vasorelaxant peptide and inhibits sympathetic tone, the renin-angiotensin-aldosterone system, and synthesis of vasoconstrictive molecules. The major source of plasma BNP is the cardiac ventricles. Elevated plasma BNP concentrations correlate with increased left ventricular (LV) filling pressure. Therefore BNP is a useful biomarkers as a screening tool for LV dysfunction. It also is a strong diagnostic indicator for both systolic and diastolic LV dysfunction. Measurement of plasma BNP is proved to be not only an efficient but also a cost effective screening tool for identifying patients with acute dyspnea of unknown etiology.