Mucinous Balls Tangled With Mesothelial Cells and MUC2‐Positive Cancer Cells in the Ascites of Pseudomyxoma Peritonei

Pseudomyxoma peritonei (PMP) is characterized by extensive mucinous ascites following rupture of mucinous neoplasms of an intra‐abdominal origin, and contain secreted gel‐forming mucins such as MUC2 and MUC5AC. We encountered a 66‐year‐old Japanese man complaining of abdominal distension. Ascites at the site was gelatinous upon gross examination, and needle aspirate smears showed histiocytes and many mucinous balls wrapped in spindle cells, which were positive for vimentin, pan‐cytokeratin, and podoplanin. The cell block showed several adenocarcinoma clusters, which were positive for MUC2, MUC5AC, CK20, and CDX‐2, and negative for CK7. From these findings, a diagnosis of PMP arising from colon cancer was indicated. Cytoreductive surgery was performed, and the cystic diverticulum was found to be infiltrated by tumor cells in the sigmoid colon that caused PMP. Mucinous balls surrounded by mesothelial cells and MUC2‐positive adenocarcinoma cells are useful clues in the diagnosis of PMP. Diagn. Cytopathol. 2016;44:628–631. © 2016 Wiley Periodicals, Inc.     

Mixed Medullary-Follicular Thyroid Carcinoma : Molecular Evidence for a Dual Origin of Tumor Components

Mixed medullary-follicular carcinomas (MMFCs) are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. The histogenetic origin and possible molecular mechanisms leading to MMFCs are still unclear. To address these questions, we have isolated the two histological components of 12 MMFCs by (laser-based) microdissection, analyzed them for mutations in the RET proto-oncogene and allelic losses of nine loci on six chromosomes, and studied the clonal composition of MMFCs in female patients. Our results provide strong evidence that the follicular and medullary components in MMFCs are not derived from a single progenitor cell, because the seven tumors amenable for analysis consistently exhibited a different pattern of mutations, allelic losses, and clonal composition. We also demonstrate that follicular structures in MMFCs are often oligo/polyclonal and more frequently exhibit hyperplastic than neoplastic histological features, indicating that at least a subset of MMFCs are composed of a medullary thyroid carcinoma containing hyperplastic follicles.     

Origin and Molecular Evolution of Ionotropic Glutamate Receptors

This article provides a review of approaches to identification of the pathways of the molecular evolution of glutamate receptors. Extensive evidence has now accumulated on the homology of glutamate-binding proteins with the ability to function as ligand-activated channels. However, knowledge of the amino acid sequences of the polypeptides forming these channels is a necessary but insufficient condition for identifying their origin and changes during evolution. Natural selection of protein molecules appears to have identified and fixed their functional nature. Molecular and functional approaches should therefore complement each other in studies of protein evolution. Studies of glutamate receptor channels in vertebrates and invertebrates provide an example showing how knowledge of the spatial organization and the details of the mechanisms of operation allows relationships to be identified and possible pathways of the molecular evolution of receptors to be established.     

青光眼分子遗传学的研究进展

青光眼 (glaucoma) 分子遗传学的研究是当前眼科学领域的重要课题,一些青光眼的致病位点和相关基因相继定位于相应的染色体上,并进行基因的克隆、测序、表达、调控及突变分析。目前报道过的与青光眼相关的基因有：TIGR/MYOC基因、OPTN基因、CYP1B1基因、WDR36基因、OPA1基因和LMX1B 基因等,相关的位点有：GLCA、GLCB、GLCC、GLCD、GLCE、GLCF、GLCG、GLC3A等,此文就相关基因的发现、定位、结构、编码产物和突变研究做一综述。     

Molecular Evidence of Mother-to-Infant Transmission of Hepatitis G Virus among Women without Known Risk Factors for Parenteral Infections

Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known risk factors for HGV infection and in 7 of 18 children born to HGV RNA-positive mothers. Molecular evidence of mother-to-infant transmission was obtained only for three of seven children. HGV RNA was also detected in 4 of 42 children born to non-HGV-infected women. Thus, mechanisms other than materno-filial may play an important role in HGV transmission during early childhood.     

Sinonasal Teratocarcinosarcoma: Ultrastructural and Immunohistochemical Evidence of Neuroectodermal Origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Genetic Evidence Concerning the Origins of South and North Ossetians

Ossetians are a unique group in the Caucasus, in that they are the only ethnic group found on both the north and south slopes of the Caucasus, and moreover they speak an Indo‐European language in contrast to their Caucasian‐speaking neighbours. We analyzed mtDNA HV1 sequences, Y chromosome binary genetic markers, and Y chromosome short tandem repeat (Y‐STR) variability in three North Ossetian groups and compared these data to published data for two additional North Ossetian groups and for South Ossetians. The mtDNA data suggest a common origin for North and South Ossetians, whereas the Y‐haplogroup data indicate that North Ossetians are more similar to other North Caucasian groups, and South Ossetians are more similar to other South Caucasian groups, than to each other. Also, with respect to mtDNA, Ossetians are significantly more similar to Iranian groups than to Caucasian groups. We suggest that a common origin of Ossetians from Iran, followed by subsequent male‐mediated migrations from their Caucasian neighbours, is the most likely explanation for these results. Thus, genetic studies of such complex and multiple migrations as the Ossetians can provide additional insights into the circumstances surrounding such migrations.     

Progress in Molecular and Genetic Studies of IgA Nephropathy

Several new findings emerged recently from biochemical, genetic, and molecular studies of patients with IgA nephropathy. It appears that immunoglobulin A1-secreting cells of IgA nephropathy patients produce increased amounts of aberrantly glycosylated IgA1 in which the O-linked glycans in the hinge region are deficient in the content of galactose. The galactose-deficient IgA1 in the circulation is recognized by naturally occurring antibodies with anti-glycan specificity, and immune complexes are formed. These circulating immune complexes escape hepatic degradation and eventually are deposited in the kidney mesangium. Resident mesangial cells bind the IgA-containing immune complexes with the involvement of a novel IgA receptor and become activated. A familial form of IgA nephropathy has been linked to chromosome 6q22-23. Recent progress in molecular analyses of IgA nephropathy thus defines this disease as an autoimmune process with a novel IgA mesangial receptor and certain genetically determined traits.     

Genetic Analysis and Attribution of Microbial Forensics Evidence

Because of the availability of pathogenic microorganisms and the relatively low cost of preparing and disseminating bioweapons, there is a continuing threat of biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the full and robust forensic exploitation and interpretation of microbial evidence from acts of bioterrorism or biocrimes. To respond to the need, greater resources and efforts are being applied to the burgeoning field of microbial forensics. Microbial forensics focuses on the characterization, analysis and interpretation of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or inadvertent agent release. To enhance attribution capabilities, a major component of microbial forensics is the analysis of nucleic acids to associate or eliminate putative samples. The degree that attribution can be addressed depends on the context of the case, the available knowledge of the genetics, phylogeny, and ecology of the target microorganism, and technologies applied. The types of genetic markers and features that can impact statistical inferences of microbial forensic evidence include: single nucleotide polymorphisms, repetitive sequences, insertions and deletions, mobile elements, pathogenicity islands, virulence and resistance genes, house keeping genes, structural genes, whole genome sequences, asexual and sexual reproduction, horizontal gene transfer, conjugation, transduction, lysogeny, gene conversion, recombination, gene duplication, rearrangements, and mutational hotspots. Nucleic acid based typing technologies include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and microarrays.     

分子标记及其在生物遗传多样性研究中的应用

遗传标记(源于DNA序列差异的特征)可以通过很多不同的途径显示出来。随着生化与分子生物技术的发展完善,可以从分子水平上直接显示它的变化-分子标记。分子标记技术具有可靠性,高效性, 因而被广泛应用于多种研究领域。分子标记通常包括同工酶(或蛋白质)和DNA标记。本文综述生化和DNA标记(蛋白/酶,RFLP, RAPD, AFLP, SSR,SNP, SSLP等)技术的原理、发展及应用。     

Molecular Characterisation for Clonality and Transmission Dynamics of an Outbreak of Klebsiella pneumoniae amongst Neonates in a Tertiary Care Centre in South India

Purpose: Sepsis is a significant cause of morbidity and mortality amongst neonates. Klebsiella pneumoniae is a common cause of nosocomial outbreaks causing bacteraemia and having potential of acquiring plasmids enhancing antimicrobial resistance. In the present study, we investigate K. pneumoniae outbreak causing bacteraemia amongst neonates over a span of 2 months. Isolates were characterised for antimicrobial resistance, virulence, molecular typing for clonality and plasmid typing for transmission dynamics, and patient outcome was investigated. Methods: Thirteen isolates of K. pneumoniae were obtained during October–November 2016. Antimicrobial susceptibility testing was performed, and multiplex polymerase chain reaction (PCR) for β-lactamases and PCR for ompK35 and ompK36 were performed. To study hypervirulence, string test and PCR for rmpA and rmpA2 were performed. Multilocus sequence typing and Inc plasmid typing were carried out to study transmission dynamics. Results: Amongst 13 isolates, all isolates harboured bla_SHV and bla_TEM; 12 isolates carried bla_CTX-M-1. ompK35 was present in all, but ompK36 was absent in 12 isolates. Ten isolates belonged to ST48, 6 amongst which contained IncFII (K) plasmid. One isolate each belonged to ST29, ST111 and ST2647 (novel clone). None of the isolates was hypervirulent. Conclusion: Extended-spectrum β-lactamase K. pneumoniae is commonly seen in Indian hospitals and main mechanisms being production of SHV, TEM and CTX-M enzymes as seen in the present study. Outer membrane porins contribute significantly to antimicrobial resistance. Emergence of new clones such as ST2647 implies continuous evolution of the organism and also potential for rapid genetic recombination leading to multidrug resistance. Outbreaks amongst neonates lead to fatal outcome, and stringent hospital infection control is necessary.     

Molecular Genetic Events in Gastrointestinal and Pancreatic Neuroendocrine Tumors

Gastrointestinal and pancreatic neuroendocrine tumors originate from the cells of the diffuse endocrine system. Their molecular genetic mechanism of development and progression is complex and remains largely unknown, and they are different in genetic composition from the gastrointestinal epithelial tumors. The current literature suggests that multiple genes are involved in their tumorigenesis with significant differences for tumors of different embryological derivatives: foregut, midgut and hindgut. The MEN1 gene is involved in initiation of 33% of foregut gastrointestinal neuroendocrine tumors. 18q defects are present almost exclusively in mid/hindgut neuroendocrine tumors. X-chromosome markers are associated with malignant behavior in foregut tumors only. Analysis of poorly differentiated neuroendocrine carcinomas of any site demonstrates high chromosomal instability and frequent p53 alterations similar to other poorly differentiated carcinomas. Several factors played a limiting role in the molecular studies published to date: the tumors are rare and heterogeneous, it is difficult to predict their behavior and prognosis, and several different tumor classifications are used by the investigators in the studies. Future studies need to evaluate molecular genetic composition of large series of gastrointestinal and pancreatic neuroendocrine tumors of each specific tumor type. Understanding of specific genetic alterations characteristic for gastrointestinal and pancreatic neuroendocrine tumors might lead to their improved diagnosis, morphologic and molecular characterization and treatment.