Clear cell carcinoma arising in a cesarean section scar. Report of a case with fine needle aspiration cytology

BACKGROUND: Clear cell carcinoma arising in a cesarean section scar is an extremely rare disease. To the best of our knowledge, there is no published report on the aspiration cytology. CASE: A 56-year-old woman presented with a mass in a cesarean section scar. Initially an abdominal desmoid was considered, but the features of fine needle aspiration (FNA) cytology suggested an adenocarcinoma. The resected tumor was histologically composed of clear cell carcinoma showing cystic, solid and papillary patterns. CONCLUSION: FNA cytology of masses arising in a surgical scar can be a useful tool in obtaining an accurate pathologic diagnosis of a malignant neoplasm.     

Isolation of cathepsin B inhibitory peptides,Cabin-A1 and -A2, from a tryptic and chymotryptic hydrolysate of human serum albumin

Two novel peptides that inhibit cathepsin B were isolated from a tryptic and chymotryptic hydrolysate of human serum albumin, and designated as Cabin-A1 and -A2. Cabin-A1 and -A2 were purified by reversed-phase HPLC and identified as Ser-Leu-His-Thr-Leu-Phe and Phe-Gln-Asn-Ala-Leu, respectively. These peptides correspond to f(65-70) and f(403-407) of human serum albumin. Human albutensin A (Ala-Phe-Lys-Ala-Trp-Ala-Val-Ala-Arg), which corresponds to f(210-218), was also isolated as a potent cathepsin B inhibitor. Synthetic Cabin-A1, -A2, and human albutensin A showed dose-dependent inhibition of cathepsin B, with K(i) values of 2.4, 290, and 3.8 microM, respectively.     

Visualization of inositol 1,4,5-trisphosphate receptor type III with green fluorescent protein in living cells

Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ channel that releases Ca2+ into the cytosol and its subcellular distribution is believed to have significant effects on Ca2+ signalling. We constructed a plasmid vector containing full-length rat type 3 IP3R linked to GFP (GFP-IP3R) for expression in mammalian cells. Western blot analyses revealed that the expressed fusion protein contained both GFP and full-length type 3 IP3R. Fluorescence confocal microscopy showed that the fluorescence of GFP-IP3R3 was distributed to reticular network structures, even after cell permeabilization with saponin. We further visualized intracellular membranes with DiOC6, a vital fluorescent marker for intracellular membranes, and provide evidence that the distribution of GFP-IP3R3 overlaps with the distribution of the endoplasmic reticulum. Our results indicate that GFP-IP3R3 can be used to visualize IP3R in living cells, and pave the way for subsequent mutational and functional studies.     

CYTOPLASMIC MASSES PRESERVED IN EARLY HOLOCENE DIATOMS: A POSSIBLE TAPHONOMIC PROCESS AND ITS PALEO‐ECOLOGICAL IMPLICATIONS1

In Lake Suigetsu, central Japan, greenish/light‐brown granules identified as cytoplasmic masses had been preserved in siliceous cell walls of freshwater diatoms in annual layers of lacustrine muds since the early Holocene. The lacustrine muds consisted of alternating dark‐colored (rich in diatom valves, clay, and organic matter) and light‐colored (mainly diatom valves) laminae. The greenish/light‐brown granules were predominately preserved in frustules of the genus Aulacoseira preserved in the dark‐colored laminae. The dark‐colored laminae were inferred to have formed annually under stratified water caused by surface water warming in summer that caused the formation of an organic‐rich anoxic layer on the lake bottom that favored granule preservation. The good preservation of cytoplasmic masses in dark‐colored laminae suggested a cause for diatom assemblage periodicity, a phenomenon that was commonly noted in temperate lakes: the cells containing these masses could be potential seed stocks for subsequent spring blooms. Frustules of the most abundant granule‐containing species, Aulacoseira nipponica (Skvortzow) Tuji, in the dark‐colored laminae of the Early Holocene muds were abundant in the overlying light‐colored laminae, suggesting that these species reproduced abundantly in springtime yielding a massive diatom bloom.     

A Novel Zinc Finger Protein, Zic, Is Involved in Neurogenesis, Especially in the Cell Lineage of Cerebellar Granule Cells

Abstract: To clarify the mechanism of cerebellar development, we have cloned a gene, named zic, encoding a zinc finger protein that is expressed abundantly in granule cells throughout development of the cerebellum. zic has a significant homology to the zinc finger domain of the Caenorhabditis elegans tra1 gene, the Drosophila cubitus interruptus Dominant gene, and the human GLI oncogene. An in situ hybridization study revealed that zic showed a restricted expression pattern in the granule cells and their putative precursor cells. It is also expressed at an early embryonic stage in the dorsal half of the neural tube. The expression pattern and nuclear localization were confirmed by immunohistochemical study. Furthermore, the bacterially expressed zic protein containing the zinc finger domains bound to the GLI -binding sequence. These findings suggest that zic is one of a number of nuclear factors involved in both differentiation in early development and maintenance of properties of the cerebellar granule cells.     

Molecular evolution of the major capsid protein VP1 of enterovirus 70.

Nucleotide sequences of the genome RNA encoding capsid protein VP1 (918 nucleotides) of 18 enterovirus 70 (EV70) isolates collected from various parts of the world in 1971 to 1981 were determined, and nucleotide substitutions among them were studied. The genetic distances between isolates were calculated by the pairwise comparison of nucleotide difference. Regression analysis of the genetic distances against time of isolation of the strains showed that the synonymous substitution rate was very high at 21.53 x 10(-3) substitution per nucleotide per year, while the nonsynonymous rate was extremely low at 0.32 x 10(-3) substitution per nucleotide per year. The rate estimated by the average value of synonymous and nonsynonymous substitutions (W.-H. Li, C.-C. Wu, and C.-C. Luo, Mol. Biol. Evol. 2:150-174, 1985) was 5.00 x 10(-3) substitution per nucleotide per year. Taking the average value of synonymous and nonsynonymous substitutions as genetic distances between isolates, the phylogenetic tree was inferred by the unweighted pairwise grouping method of arithmetic average and by the neighbor-joining method. The tree indicated that the virus had evolved from one focal place, and the time of emergence was estimated to be August 1967 +/- 15 months, 2 years before first recognition of the pandemic of acute hemorrhagic conjunctivitis. By superimposing every nucleotide substitution on the branches of the phylogenetic tree, we analyzed nucleotide substitution patterns of EV70 genome RNA. In synonymous substitutions, the proportion of transitions, i.e., C<==>U and G<==>A, was found to be extremely frequent in comparison with that reported on other viruses or pseudogenes. In addition, parallel substitutions (independent substitutions at the same nucleotide position on different branches, i.e., different isolates, of the tree) were frequently found in both synonymous and nonsynonymous substitutions. These frequent parallel substitutions and the low nonsynonymous substitution rate despite the very high synonymous substitution rate described above imply a strong restriction on nonsynonymous substitution sites of VP1, probably due to the requirement for maintaining the rigid icosahedral conformation of the virus.     

Interleukin 6-producing malignant mesothelioma

Systemic amyloidosis of the amyloid A (AA) type, is occasionally associated with various neoplasms, but the cause is still unclear. We obtained interleukin 6 (IL-6)-producing cells designated YO from a primary culture of a malignant peritoneal mesothelioma of epithelial type obtained from a 62-year-old woman. Post mortem examination revealed that the patient had systemic amyloidosis of the AA type. The supernatant media of YO cells, as well as recombinant human IL-6, successfully induced nonneoplastic liver cells to produce serum AA (SAA). Our data suggest that IL-6 produced by the tumor cells may have played an important role in the paraneoplastic syndrome of AA amyloidosis in this patient.     

Molecular clearance of ataxin-3 is regulated by a mammalian E4

Insoluble aggregates of polyglutamine-containing proteins are usually conjugated with ubiquitin in neurons of individuals with polyglutamine diseases. We now show that ataxin-3, in which the abnormal expansion of a polyglutamine tract is responsible for spinocerebellar ataxia type 3 (SCA3), undergoes ubiquitylation and degradation by the proteasome. Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Expression of E4B promoted degradation of a pathological form of ataxin-3. In contrast, a dominant-negative mutant of E4B inhibited degradation of this form of ataxin-3, resulting in the formation of intracellular aggregates. In a Drosophila model of SCA3, expression of E4B suppressed the neurodegeneration induced by an ataxin-3 mutant. These observations suggest that E4 is a rate-limiting factor in the degradation of pathological forms of ataxin-3, and that targeted expression of E4B is a potential gene therapy for SCA3.     

The elongation and contraction of actin bundles are induced by double-headed myosins in a motor concentration-dependent manner

The aqueous solution structure of the full-length recombinant ovine prion protein PrP(25-233), together with that of the N-terminal truncated version PrP(94-233), have been studied using vibrational Raman optical activity (ROA) and ultraviolet circular dichroism (UVCD). A sharp positive band at approximately 1315 cm(-1) characteristic of poly(L-proline) II (PPII) helix that is present in the ROA spectrum of the full-length protein is absent from that of the truncated protein, together with bands characteristic of beta-turns. Although it is not possible similarly to identify PPII helix in the full-length protein directly from its UVCD spectrum, subtraction of the UVCD spectrum of PrP(94-233) from that of PrP(25-233) yields a difference UVCD spectrum also characteristic of PPII structure and very similar to the UVCD spectrum of murine PrP(25-113). These results provide confirmation that a major conformational element in the N-terminal region is PPII helix, but in addition show that the PPII structure is interspersed with beta-turns and that little PPII structure is present in PrP(94-233). A principal component analysis of the ROA data indicates that the alpha-helix and beta-sheet content, located in the structured C-terminal domain, of the full-length and truncated proteins are similar. The flexibility imparted by the high PPII content of the N-terminal domain region may be an essential factor in the function and possibly also the misfunction of prion proteins.