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PubMed1982

Infantile sarcoma with intracytoplasmic filamentous inclusions: distinctive tumor of possible histiocytic origin.

This report describes four malignant tumors originating in infants, (one present at birth), for which a common origin is proposed. The common nature of these tumors was suggested by a remarkable similarity of histologic and ultrastructural features, including the presence of intracellular filamentous aggregates, as well as a shared aggressive clinical course consistent with sarcomatous origin. Two of these neoplasms arose within the kidney and were classified as "rhabdoid" sarcomas, according to the NWTS nomenclature. However, cells from these neoplasms could not be identified as muscular in origin. In culture, these cells demonstrated adherence to substratum, ability to phagocytose particles, and cell surface complement receptors. In addition, the renal tumors contained definite tumor cells positive for muramidase; the liver primary tumor contained only a limited number of such cells, which could not be interpreted as neoplastic. These findings suggest that among the "round-cell sarcomas" of infants and young children, a distinct, highly malignant form may be identified on clinical and morphologic grounds. The possibility that the tumor cells may be linked to the mononuclear phagocyte system was suggested, but not proved, and deserves further study.

Female↗

PubMed1988

Clonal origin of columnar, mucous, and endocrine cell lineages in human colorectal epithelium.

Human colorectal epithelium is composed mainly of columnar, mucous and endocrine cells; origin of these cell lineages from a multi-potential stem cell at the base of the crypt (the Unitarian hypothesis) has been proposed but not yet demonstrated. Gut endocrine cells have variously been considered of neural crest or endodermal origin, but conclusive evidence, particularly in humans, is lacking. It has been shown that in mouse gastrointestinal tract, a single progenitor cell gives rise to both columnar and mucous cells, but it has yet to be demonstrated that such a progenitor cell can also give rise to endocrine cells. Here, a single human rectal adenocarcinoma cell has been shown to differentiate into columnar, mucous and endocrine cells; therefore all epithelial lineages are of clonal origin. Additionally, these results show that human colorectal enteroendocrine cells, at least in neoplastic epithelium, have an endodermal origin.

Adenocarcinoma↗

PubMed1995

Embryonal malignancies of unknown primary origin in children.

BACKGROUND: Little is known about embryonal malignancies of unknown primary origin in children. All such cases referred to a pediatric cancer center over a 30-year period were reviewed to delineate their clinical and prognostic features and to develop recommendations for evaluation and therapy. METHODS: Seventeen patients with embryonal malignancies of unknown primary origin were identified by reviewing the institutional solid tumor database. The medical records, imaging studies, laboratory records, and pathology reports for each patient were reviewed and tabulated. RESULTS: Pathology review confirmed the original histologic diagnosis in 15 of the cases. Final diagnoses after review were rhabdomyosarcoma (n = 9), neuroblastoma (n = 7), and Ewing's sarcoma (n = 1). At initial evaluation, an extensive array of radiologic studies revealed multiple abnormalities in 16 cases. Bone marrow sampling and urinary catecholamine analysis were valuable diagnostic tools. A primary site of origin was identified in five patients: by interval assessments during treatment in two cases, and at autopsy in three. Although the median survival was only 6 months, 3 patients are alive at 12, 15 and 17 years after diagnosis. CONCLUSIONS: An exhaustive search for a primary lesion appears unwarranted in children with disseminated embryonal malignancies. Tumor sampling should be adequate for the pathologic work-up to determine the definitive diagnosis. Although the chances of cure are slight, tumor specific therapy may improve the interval of disease control, the quality of life, and the possibility of long term survival.

Adolescent↗

PubMed1995

Epstein-Barr virus-associated leiomyosarcomas in liver transplantation recipients. Origin from either donor or recipient tissue.

BACKGROUND: Leiomyosarcoma, a mesenchymal malignancy with smooth muscle differentiation, is extremely rare in children. Immunosuppression, due to either antirejection medication in organ transplantation recipients or human immunodeficiency virus infection (HIV), appears to constitute a predisposition. METHODS: Two cases of leiomyosarcoma in pediatric liver transplantation recipients were investigated and compared clinically with respect to site of origin and course of the disease and pathologically by routine histology and electron microscopy, by forensic DNA methodology for origin from donor or recipient tissue, and by EBER-1 in situ hybridization for evidence of latent Epstein-Barr virus (EBV) infection. RESULTS: A 9-year-old male developed a high grade, poorly differentiated leiomyosarcoma in his allografted liver 2 years after transplantation, and despite antineoplastic chemotherapy, he died of metastatic disease. The genotype of his tumor indicated an origin from allografted tissue. A 12-year-old female had a low grade retroperitoneal leiomyosarcoma involving the superior mesenteric vein. After resection, she remained disease free without chemotherapy. The genotype of her tumor indicated an origin from native tissue. In both tumors, latent EBV infection was documented. CONCLUSIONS: Neoplastic smooth muscle proliferation in immunosuppressed liver transplantation recipients is analogous to the more common posttransplantation lymphoproliferative disorder in involving transformation of either engrafted donor tissue or recipient tissue elsewhere in the body, in displaying a wide spectrum of histologic differentiation, grade and clinical behavior, and in exhibiting evidence of latent EBV infection.

Base Sequence↗

PubMed2006

Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin have an annual risk of major vascular events between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with oral anticoagulants is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy. OBJECTIVES: To compare the efficacy and safety of oral anticoagulants and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (searched 16 September 2004). Authors of published trials were contacted for further information and unpublished data. SELECTION CRITERIA: Randomised trials examining long-term secondary prevention after recent ischaemic stroke of presumed arterial origin were selected. The oral anticoagulant therapy had to be of specified intensity with warfarin, phenprocoumon or acenocoumarol versus antiplatelet therapy. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Subgroup analyses with treatment International Normalized Ratio (INR) 1.4 to 2.8 (low intensity), INR 2.1 to 3.6 (medium intensity) and INR 3.0 to 4.5 (high intensity) were performed. MAIN RESULTS: Five trials, with 4076 patients were selected. The data do not allow a robust conclusion on whether anticoagulants are more or less efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation relative risk (RR) 0.96, 95% confidence intervals (CI) 0.38 to 2.42; high intensity anticoagulation RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low or medium intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents. The relative risk for major bleeding complications for low intensity anticoagulation was 1.27 (95% CI 0.79 to 2.03) and for medium intensity anticoagulation 1.19 (95% CI 0.59 to 2.41). However, it was clear that high intensity oral anticoagulants with INR 3.0 to 4.5 were not safe, because they yielded a higher risk of major bleeding complications (RR 9.0, 95% CI 3.9 to 21). AUTHORS' CONCLUSIONS: For secondary prevention of further vascular events after limited ischaemic stroke of arterial origin, there is insufficient evidence to justify the routine use of medium-intensity oral anticoagulants; such treatment should only be used as part of a clinical trial. More intense anticoagulation is not safe and should not be used in this setting. Low-intensity anticoagulation is not likely to be more or less efficacious than aspirin.

Administration, Oral↗

PubMed2002

Parental origin of normal X chromosomes in Turner syndrome patients with various karyotypes: implications for the mechanism leading to generation of a 45,X karyotype.

The parental origin of the X chromosome of 45,X females has been the subject of many studies, and most of them have shown that the majority (60-80%) of the X chromosomes are maternal in origin. However, studies on the parental origin of normal X chromosomes are relatively limited for Turner syndrome (TS) females with sex chromosome aberrations. In this study, we used PCR-based typing of highly polymorphic markers and an assay of methylation status of the androgen receptor gene to determine the parental origin of normal X chromosomes in 50 unbiased TS females with a variety of karyotypes. Our results showed a higher paternal meiotic error rate leading to the generation of abnormal sex chromosomes, especially in the case of del(Xp) and abnormal Y chromosomes. Isochromosome Xq and ring/marker X chromosomes, on the other hand, were equally likely the result of both maternal and paternal meiotic errors. A thorough review of previous results, together with our data suggests, that the majority of TS karyotype are caused by paternal meiotic errors that generate abnormal sex chromosomes, and that most 45,X cells are generated by mitotic loss of these abnormal sex chromosomes, resulting in maternal X dominance in these cells.

Chromosomes, Human, X↗

PubMed1995

Parental origin of the extra haploid chromosome set in triploidies diagnosed prenatally.

The parental origin of the additional chromosome complement in a total of 17 cases of triploidy was determined mainly using highly polymorphic microsatellites. Maternal origin of the triploidy was demonstrated in most cases. To the best of our knowledge, this is the first systematic evaluation of the parental origin of chromosome sets in fetuses who survived until a cytogenetic diagnosis was established. In contrast to previous investigations this study documented a predominance of maternal origin of the extra haploid set mainly due to longer survival time for digynic triploidies. The concept of 2 distinct fetal phenotypes in triploidy is clearly supported by this study.

Adult↗

PubMed2003

Disclosing the mechanisms of origin of de novo short-arm duplications of chromosome 9.

Three de novo short-arm duplications of chromosome 9 were investigated by fluorescence in situ hybridization (FISH) and genotyping of microsatellite loci with the aim of disclosing their mechanisms of origin. Two of these duplications were identified as direct and one as an inverted duplication, and they comprised nearly the entire 9p. In the two dirdup(9p), the distal breakpoints were mapped to subtelomeric sequences, whereas the proximal break boundaries were defined by pericentromeric sequences. The maternal origin of both duplications was demonstrated, and the presence of three different alleles in distal loci indicated that these rearrangements must have occurred prezygotically. In the invdup(9p), the proximal breakpoint was mapped at the alphoid sequences, which were partially duplicated on the tip of the rearranged 9p; subtelomeric and telomeric sequences were not detected, allowing the distal breakpoint to be mapped proximally to subtelomeric sequences. Genotyping of microsatellite loci allowed us to conclude that this invdup(9p) chromosome had a paternal origin. Homozygosity throughout the duplicated segment pointed to its probable postzygotic formation. Chromatid rearrangements appeared to have originated these 9p duplications, involving pericentromeric and subtelomeric sequences. These rearrangements might have been the result of recombination events between homologous repeats in these segments.

Adolescent↗

PubMed1992

Origin of the Koreans: a population genetic study.

A population genetic study was undertaken to investigate the origin of Koreans. Thirteen polymorphic and 7 monomorphic blood genetic markers (serum proteins and red cell enzymes) were studied in a group of 437 Koreans. Genetic distance analyses by both cluster and principal components models were performed between Koreans and eight other populations (Koreans in China, Japanese, Han Chinese, Mongolians, Zhuangs, Malays, Javanese, and Soviet Asians) on the basis of 47 alleles controlled by 15 polymorphic loci. A more detailed analysis using 65 alleles at 19 polymorphic loci was performed on six populations. Both analyses demonstrated genetic evidence of the origin of Koreans from the central Asian Mongolians. Further, the Koreans are more closely related to the Japanese and quite distant from the Chinese. The above evidence of the origin of Koreans fits well with the ethnohistoric account of the origin of Koreans and the Korean language. The minority Koreans in China also maintained their genetic identity.

Alleles↗

PubMed1979

The origin of fasciculations in motoneuron disease.

The collision technique was used to determine the origin of distal fasciculations in 25 motor units from 9 patients with amyotrophic lateral sclerosis and 6 with other diseases involving motoneurons. Fasciculations originated in the nerve proximal to the knee or elbow in 15 and distally in 2; multiple sites of origin were found in 8 motor units. The origin was not related to the presence or absence of electromyographic evidence for collateral sprouting or lesions in descending suprasegmental pathways.

Adult↗

PubMed2002

Missing Omo L338y-6 occipital-marginal sinus drainage pattern: ground sectioning, computer tomography scanning, and the original fossil fail to show it.

The Omo L338y-6 occipital region has been recently studied by White and Falk (1999), who claim that it shows a readily identifiable enlarged left occipital-marginal sinus (O/M). These observations are contrary to the direct observations of previous investigators (Rak and Howell, 1978; Kimbel, 1984; Holloway, 1981; Holloway, 1988). White and Falk (1999) further argue that the presence of this enlarged O/M strongly suggests that the Omo L338y-6 hominid was indeed a "robust" Australopithecus. We used direct sectioning and CT scanning to analyze magnified sections of a high-quality first-generation cast of the newly cleaned original fossil. These methods fail to show any evidence of a morphological landmark that can be interpreted as an enlarged O/M, either as an eminence or a sulcus. In contrast, the same techniques used with both SK 1585 and OH5 ("robust" Australopithecus with an enlarged O/M) show extremely visible and palpable enlarged O/M's. Examination of the original Omo fossil confirms that it lacks an O/M. This evidence clearly shows that an enlarged O/M cannot be identified on either the original fossil or a first-generation cast, although this does not rule out the possibility that the Omo L338y-6 hominid was a "robust" Australopithecus. We believe that the differences between observers regarding this feature are most probably due to displacement caused by a crack and the different source materials employed, i.e., the difference between a first-generation cast of the original fossil and a third- or fourth-generation cast of the endocast made two decades ago.

Animals↗

PubMed2002

Motility proteins and the origin of the nucleus.

Hypotheses on the origin of eukaryotic cells must account for the origin of the microtubular cytoskeletal structures (including the mitotic spindle, undulipodium/cilium (so-called flagellum) and other structures underlain by the 9(2)+2 microtubular axoneme) in addition to the membrane-bounded nucleus. Whereas bacteria with membrane-bounded nucleoids have been described, no precedent for mitotic, cytoskeletal, or axonemal microtubular structures are known in prokaryotes. Molecular phylogenetic analyses indicate that the cells of the earliest-branching lineages of eukaryotes contain the karyomastigont cytoskeletal system. These protist cells divide via an extranuclear spindle and a persistent nuclear membrane. We suggest that this association between the centriole/kinetosome axoneme (undulipodium) and the nucleus existed from the earliest stage of eukaryotic cell evolution. We interpret the karyomastigont to be a legacy of the symbiosis between thermoacidophilic archaebacteria and motile eubacteria from which the first eukaryote evolved. Mutually inconsistent hypotheses for the origin of the nucleus are reviewed and sequenced proteins of cell motility are discussed because of their potential value in resolving this problem. A correlation of fossil evidence with modern cell and microbiological studies leads us to the karyomastigont theory of the origin of the nucleus.

Animals↗

PubMed2004

The evolutionary origins and significance of vertebrate left-right organisation.

In the last few years, an understanding has emerged of the developmental mechanism for the consistent internal left-right structure, termed situs, that characterises vertebrate anatomy. This involves largely vertebrate-conserved (i.e. 'phylotypic') gene expression cascades that encode 'leftness' and 'rightness' in appropriate tissues either side of the embryo's midline soon after gastrulation. Recent evidence indicates that the initial, directional symmetry breaking that initiates these cascades utilises mechanisms that are conserved or at least closely related in different vertebrate types. I describe a scenario whereby the capacity for directional modification of an otherwise bilateral body plan can be viewed as an adaptive innovation rather closely connected with vertebrate origins, enabling optimal 'design' for very active lifestyles. But an alternative scenario, while retaining the view that situs and indeed other vertebrate functional lateralisations are deeply adaptive, proposes that they originated in the co-optation of left-right developmental information inherited from a very early stage in metazoan diversification. It is proposed that a remote chordate ancestor lost its original or 'ur-bilaterian' symmetry to pass through an altogether non-symmetrical stage, and that the vertebrate dorsoventral midline plane is not descended from that original one. I review the considerable evidence in favour of this scenario, and discuss its wider implications for directional asymmetries across the Metazoa.

Anatomy↗

PubMed1978

Origin and length of left main coronary artery: its relation to height, weight, sex, age, pattern of coronary distribution, and presence or absence of coronary artery disease.

The distance from the base of the left coronary sinus to the origin of the left main coronary artery was measured in 54 patients. The length of the left main coronary artery and the pattern of arterial dominance were determined in the last 37 patients. These variables were correlated with height, weight, age, sex, and presence or absence of coronary artery disease. Average distance from the basis of the left coronary sinus to the origin of the left main coronary artery was 19.4 +/- 2.7 mm. Average length of the left main coronary artery was 9.7 +/- 4.3 mm. There was a large inherent variability between distance from the base of left coronary sinus to the origin of the left main coronary artery and height of the subjects. Other variables did not show positive correlation. Similar large variability was noticed between of the left main coronary artery and height of the subjects. Thus, from these observations it was not possible to predict the distance from the base of the left coronary sinus to the origin of the left main coronary artery or the length of the left main coronary artery using height or any other variable. The importance of these findings in relation to coronary angiography is discussed.

Adult↗

PubMed1996

Anomalous origin of the right coronary artery from the pulmonary trunk: is surgical reimplantation into the aorta a method of choice?

The origin of the right coronary artery (RCA) from the pulmonary trunk (PT) is a rare congenital anomaly. Although most of the patients remain asymptomatic, prophylactic reimplantation of the RCA into the aorta has been recommended to prevent an adverse outcome. The report describes postoperative results in two patients following uneventful RCA reimplantation. A 47-year-old man, with coexisting diffuse atherosclerotic involvement of the left coronary artery, remained symptomatic despite the establishment of a two-coronary system. The second patient, a 36-year-old woman, with isolated anomalous origin of the RCA from the PT, continued to present with myocardial ischemia on exertion. The original observation of an angiographic "slow-flow" phenomenon in the reimplanted RCA in both patients implies the impairment of myocardial microvessels. These findings give rise to the question of whether the reimplantation of the anomalous artery is really superior to simple ligation of its origin in order to relieve the "coronary steal" effect.

Adult↗

PubMed2005

Original and reviewed nuclear grading according to the Fuhrman system: a multivariate analysis of 388 patients with conventional renal cell carcinoma.

BACKGROUND: The objective of the current study was to evaluate the reproducibility of the Fuhrman nuclear grading system as well as its independent predictive value in a series of patients with conventional renal cell carcinoma (RCC). METHODS: The authors selected 388 patients who had undergone surgical treatment for conventional RCC between 1986 and 2000. Pathology slides from the selected patients were reviewed by a single pathologist, who reassigned a Fuhrman nuclear grade and assessed the presence of tumor necrosis. The pathologist was blinded to both the original pathologic diagnosis and follow-up data. The kappa statistic was used to evaluate concordance between original and reviewed nuclear grades. The log-rank test was used for univariate analyses, and a Cox proportional hazards model was used for multivariate analyses. RESULTS: The original Fuhrman nuclear grade was Grade 1 (G1) in 111 patients (28.6%), G2 in 141 patients (36.3%), G3 in 108 patients (27.8%), and G4 in 28 patients (7.3%). After pathology slide review, nuclear grades were reassigned as follows: G1 in 49 patients (12.6%), G2 in 138 patients (35.6%), G3 in 150 patients (38.7%), and G4 in 51 patients (13.1%). The grade of concordance was moderate (kappa=0.44; P <0.001). Univariate analyses identified three separate prognostic categories defined by nuclear grade (G1 and G2 vs. G3 vs. G4). Both the original and the reviewed Fuhrman nuclear grading systems were capable of independently predicting disease-specific survival in patients with conventional RCC. CONCLUSIONS: The interobserver reproducibility of Fuhrman nuclear grading was moderate. The substantial overlap in survival curves for G1 and G2 tumors provided an opportunity to cluster those categories, and the resulting three-tiered nuclear grading system was an independent predictor of cause-specific survival in patients with conventional RCC. Other independent predictors of survival included pathologic stage and tumor necrosis status.

Adult↗

PubMed1978

Sequence of neuron origin in experimentally distorted brains of chick embryos.

The effects of proliferative disorders on the time and sequence of neuron origin in the optic tectum were studied in chick embryos in which "overgrowth" had been experimentally induced, Sixteen normal and fourteen abnormal embryos ranging in age from four through ten days of incubation were each given a single dose of thymidine[3H]. Comparisons were then made between 16-day normal and abnormal chick embryos with respect to the distribution tectum midway between its rostral and caudal boundaries. In the normal and abnormal tecta layers I-IV were generated on days 3-6. Differences occurred in the generation of the remaining layers. In the normal embryos layers V-VII arose on days 5-8 and layers VIII-XV on days 4-7; in the abnormal embryos layers V-VII originated on days 6-8 and layers VIII-XV on days 5-8. In addition to the delay in onset of neuron origin, the abnormal tectum also showed distorted lamination, particularly in layers VIII-XV which constitute the superficial regions of the stratum griseum and fibrosum superficiale. Despite the defect in time and sequence of neuron origin, the rostroventrolateral to caudodorsomedial gradient of maturity characteristic of the normal tecta was not disturbed in the abnormal tecta.

Age Factors↗

PubMed1983

Overall distribution of substance P-containing nerves in the wall of the cerebral arteries of the guinea pig and its origins.

The overall distribution of substance P-like immunoreactivity (SPI) in the wall of the cerebral arteries and their origins were investigated in the guinea pig by using whole-mounts. Two types of SPI fibers were seen: one forming dense fiber bands and located among the periadventitial nerves, and the other forming a meshwork. The SPI fibers located in the periadventitial nerves often leave these nerves to form a meshwork of SPI fibers of varying density according to the diameter or location of the blood vessels. The present study suggests that: (1) SPI fibers located on the circle of Willis and its branches originate from SPI cells in the trigeminal ganglion; (2) SPI fibers of the rostral one-third of the basilar artery originate partly from trigeminal SPI cells; and (3) SPI fibers in the caudal two-thirds of the basilar artery originate exclusively from other SPI cells, apart from the trigeminal ganglion.

Animals↗