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PubMed2005

Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.

Adenocarcinoma, Clear Cell↗
PubMed2002

Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells.

Genomic imprinting is an epigenetic mechanism that causes functional differences between paternal and maternal genomes, and plays an essential role in mammalian development. Stage-specific changes in the DNA methylation patterns of imprinted genes suggest that their imprints are erased some time during the primordial germ cell (PGC) stage, before their gametic patterns are re-established during gametogenesis according to the sex of individuals. To define the exact timing and pattern of the erasure process, we have analyzed parental-origin-specific expression of imprinted genes and DNA methylation patterns of differentially methylated regions (DMRs) in embryos, each derived from a single day 11.5 to day 13.5 PGC by nuclear transfer. Cloned embryos produced from day 12.5 to day 13.5 PGCs showed growth retardation and early embryonic lethality around day 9.5. Imprinted genes lost their parental-origin-specific expression patterns completely and became biallelic or silenced. We confirmed that clones derived from both male and female PGCs gave the same result, demonstrating the existence of a common default state of genomic imprinting to male and female germlines. When we produced clone embryos from day 11.5 PGCs, their development was significantly improved, allowing them to survive until at least the day 11.5 embryonic stage. Interestingly, several intermediate states of genomic imprinting between somatic cell states and the default states were seen in these embryos. Loss of the monoallelic expression of imprinted genes proceeded in a step-wise manner coordinated specifically for each imprinted gene. DNA demethylation of the DMRs of the imprinted genes in exact accordance with the loss of their imprinted monoallelic expression was also observed. Analysis of DNA methylation in day 10.5 to day 12.5 PGCs demonstrated that PGC clones represented the DNA methylation status of donor PGCs well. These findings provide strong evidence that the erasure process of genomic imprinting memory proceeds in the day 10.5 to day 11.5 PGCs, with the timing precisely controlled for each imprinted gene. The nuclear transfer technique enabled us to analyze the imprinting status of each PGC and clearly demonstrated a close relationship between expression and DNA methylation patterns and the ability of imprinted genes to support development.

Animals↗
PubMed1999

Median artery revisited.

This study confirms that the median artery may persist in adult life in 2 different patterns, palmar and antebrachial, based on their vascular territory. The palmar type, which represents the embryonic pattern, is large, long and reaches the palm. The antebrachial type,which represents a partial regression of the embryonic artery is slender, short, and terminates before reaching the wrist. These 2 arterial patterns appear with a different incidence. The palmar pattern was studied in the whole sample (120 cadavers) and had an incidence of 20%, being more frequent in females than in males (1.3:1), occurring unilaterally more often than bilaterally (4:1) and slightly more frequently on the right than on the left (1.1:1). The antebrachial pattern was studied in only 79 cadavers and had an incidence of 76%, being more frequent in females than in males (1.6:1); it was commoner unilaterally than bilaterally (1.5:1) and was again slightly more prevalent on the right than on the left (1.2:1). The origin of the median artery was variable in both patterns. The palmar type most frequently arose from the caudal angle between the ulnar artery and its common interosseous trunk (59%). The antebrachial pattern most frequently originated from the anterior interosseous artery (55%). Other origins, for both patterns, were from the ulnar artery or from the common interosseous trunk. The median artery in the antebrachial pattern terminated in the upper third (74%) or in the distal third of the forearm (26%). However, the palmar pattern ended as the 1st, 2nd or 1st and 2nd common digital arteries (65%) or joined the superficial palmar arch (35%). The median artery passed either anterior (67%) or posterior (25%) to the anterior interosseous nerve. It pierced the median nerve in the upper third of the forearm in 41% of cases with the palmar pattern and in none of the antebrachial cases. In 1 case the artery pierced both the anterior interosseous and median nerves.

Adult↗
PubMed1985

Physiological properties and pattern of innervation of regenerated muscles in the rat.

The regeneration of fast and slow muscles was compared following "mincing" and replacement into their own or alien muscle bed. At intervals varying from 2 to 9 weeks the tension developed by the regenerated muscles was assessed and compared to that developed by the muscles from the contralateral unoperated side. This parameter was then taken as an indication of recovery. The regenerated muscles never developed more than half of the tension of the control muscles. Muscles regenerated in the bed of extensor digitorum longus became fast-twitch muscles and muscles regenerated in the bed of soleus became slow-twitch muscles, no matter whether they originated from an extensor digitorum longus or soleus "mince". The regeneration of the muscle tissue in the place of extensor digitorum longus developed better than in the place of soleus. The pattern of innervation of the regenerated muscles was analysed using a combined cholinesterase silver stain. Many of the regenerated fibres had more than one end plate and some end plates more than one axon terminal. These results show that in adult animals muscle redevelopment can occur, but only to a limited extent. Moreover, on reinnervation of regenerated muscle fibres the axons do not assume their original pattern of innervation.

Animals↗
PubMed1996

2-D Crystallization of the Rhodococcus 20S Proteasome

The 2D crystallization method using a liquid-liquid interface has been applied to the Rhodococcus 20S proteasome. Two types of ordered arrays were obtained, both large enough for high-resolution analysis. The first one is a hexagonal close-packed array, whereas the second one has fourfold symmetry. By image analysis based on a real space correlation averaging technique, the close-packed array was found to be hexagonally packed but the molecules had complete rotational freedom. The fourfold array is, however, a true crystal with p4 symmetry. Lattice constants are a = b = 20.0 nm and the unit cell of this crystal contains two proteasomes. The diffraction pattern computed from the original picture shows the spots up to (4.5) that correspond to 3.1 nm resolution. After applying an unbending procedure, the diffraction pattern shows spots extending to 1.8 nm resolution.

Journal Article↗
PubMed2000

Testing the extent of sequence similarity among viroids, satellite RNAs, and hepatitis delta virus.

A Monte Carlo method was used to test the extent of sequence similarity among viroids, satellite RNAs, and hepatitis delta virus. This analysis revealed that there is insufficient sequence similarity among these pathogens to support the hypothesis that they have a common evolutionary origin. Furthermore, while definite patterns of sequence similarity were observed among some viroids, there was a clear lack of overall similarity, indicating that a monophyletic origin for even this group cannot be reliably supported from sequence data alone.

Biological Evolution↗
PubMed1999

The ancient and divergent origins of the human pathogenic trypanosomes, Trypanosoma brucei and T. cruzi.

This study presents new findings concerning the evolution of the human pathogens, Trypanosoma brucei and T. cruzi, which suggest that these parasites have divergent origins and fundamentally different patterns of evolution. Phylogenetic analysis of 18S rRNA sequences places T. brucei in a clade comprising exclusively mammalian trypanosomes of African origin, suggesting an evolutionary history confined to Africa. T. cruzi (from humans and sylvatic mammals) clusters with trypanosomes specific to Old and New World bats, T. rangeli and a trypanosome species isolated from an Australian kangaroo. The origins of parasites within this clade, other than some of those from bats, lie in South America and Australia suggesting an ancient southern super-continent origin for T. cruzi, possibly in marsupials; the only trypanosomes from this clade to have spread to the Old World are those infecting bats, doubtless by virtue of the mobility of their hosts. Viewed in the context of palaeogeographical evidence, the results date the divergence of T. brucei and T. cruzi to the mid-Cretaceous, around 100 million years before present, following the separation of Africa, South America and Euramerica. The inclusion in this study of a broad range of trypanosome species from various different hosts has allowed long phylogenetic branches to be resolved, overcoming the limitations of many previous studies. Moreover, T. brucei and the other mammalian tsetse-transmitted trypanosomes appear, from these data, to be evolving several times faster than T. cruzi and its relatives.

Animals↗
PubMed1992

Facilitation of pattern recognition by cuing foveation with the luminance centroid as origin of the frame of reference.

The strategy for visual information processing must vary with the specific situation. We assume that in recognition of pre-learnt letter-like patterns under time-pressure conditions, mechanisms of selective attention are involved. We propose that, with simple stimuli, foveation is to the luminance centroids of such patterns, and if normally the latter has to be computed by the brain, cuing such information should improve performance. This assumption was tested on three subjects with five stimuli. In confirmation of the working hypothesis, we found significant improvements in performance (P = 0.01 or better) for each of the stimuli, with cuing to 'relevant' as compared with 'irrelevant' sites, and also when the point of foveation was nearer to the 'nodal' site. It is concluded that in pattern recognition processes, nodal regions are computed, the luminance centroid for example, for simple pattern stimuli.

Fovea Centralis↗
PubMedDate not supplied

Limbs and tail as evolutionarily diverging duplicates of the main body axis.

Contrasting hypotheses have been proposed to explain the pervasive parallels in the patterning of arthropod and vertebrate appendages. These hypotheses either call for a common ancestor already provided with patterned appendages or body outgrowths, or for the recruitment in limb patterning of single genes or genetic cassettes originally used for purposes other than axis patterning. I suggest instead that body appendages such as arthropod and vertebrate limbs and chordate tails are evolutionarily divergent duplicates (paramorphs) of the main body axis, that is, its duplicates, albeit devoid of endodermal component. Thus, vertebrate limbs and arthropod limbs are not historical homologs, but homoplastic features only transitively related to real historical homologs. Thus, the main body axis and the axis of the appendages have distinct but not independent evolutionary histories and may be involved in processes of homeotic co-option producing effects of morphological assimilation. For instance, chordate segmentation may have originated in the posterior appendage (tail) and subsequently extended to the trunk.

Animals↗
PubMed1979

Malignant fibrosarcomatous mesothelioma and benign pleural fibroma (localized fibrous mesothelioma) in tissue culture: a comparison of the in vitro pattern of growth in relation to the cell of origin.

Two cases of fibrous mesothelioma are presented. The first is a malignant tumor containing bundles of spindle-shaped cells with a dense reticulin network and nests of epithelial-like cells. The second is a benign tumor made up of spindle-shaped cells arranged in bundles with abundant reticulin and collagen fibers. Tissue culture in the first case revealed plagues similar to those formed by epithelial tumors. The second case had a fibroblastic pattern with single isolated spindle-shaped cells. These findings confirmed the mesothelial nature of fibrosarcomatous mesothelioma and supported the view that the so-called localized fibrous mesotheliomas could be fibroblastic neoplasms derived from the submesothelial connective tissue.

Adult↗
PubMed1998

Concurrent replication and methylation at mammalian origins of replication.

Observations made with Escherichia coli have suggested that a lag between replication and methylation regulates initiation of replication. To address the question of whether a similar mechanism operates in mammalian cells, we have determined the temporal relationship between initiation of replication and methylation in mammalian cells both at a comprehensive level and at specific sites. First, newly synthesized DNA containing origins of replication was isolated from primate-transformed and primary cell lines (HeLa cells, primary human fibroblasts, African green monkey kidney fibroblasts [CV-1], and primary African green monkey kidney cells) by the nascent-strand extrusion method followed by sucrose gradient sedimentation. By a modified nearest-neighbor analysis, the levels of cytosine methylation residing in all four possible dinucleotide sequences of both nascent and genomic DNAs were determined. The levels of cytosine methylation observed in the nascent and genomic DNAs were equivalent, suggesting that DNA replication and methylation are concomitant events. Okazaki fragments were also demonstrated to be methylated, suggesting that the rapid kinetics of methylation is a feature of both the leading and the lagging strands of nascent DNA. However, in contrast to previous observations, neither nascent nor genomic DNA contained detectable levels of methylated cytosines at dinucleotide contexts other than CpG (i.e., CpA, CpC, and CpT are not methylated). The nearest-neighbor analysis also shows that cancer cell lines are hypermethylated in both nascent and genomic DNAs relative to the primary cell lines. The extent of methylation in nascent and genomic DNAs at specific sites was determined as well by bisulfite mapping of CpG sites at the lamin B2, c-myc, and beta-globin origins of replication. The methylation patterns of genomic and nascent clones are the same, confirming the hypothesis that methylation occurs concurrently with replication. Interestingly, the c-myc origin was found to be unmethylated in all clones tested. These results show that, like genes, different origins of replication exhibit different patterns of methylation. In summary, our results demonstrate tight coordination of DNA methylation and replication, which is consistent with recent observations showing that DNA methyltransferase is associated with proliferating cell nuclear antigen in the replication fork.

Animals↗
PubMed1994

Multiple embryonic origins of gonadotropin-releasing hormone (GnRH) immunoreactive neurons.

Experiments were conducted to test the hypothesis that gonadotropin-releasing hormone immunoreactive (GnRH-ir) and FMRFamide-ir neurons present in the brain and nervus terminalis originate in the embryonic olfactory placode. The olfactory placodes were bilaterally extirpated in stage 26 or stage 29 embryos of the axolotl, Ambystoma mexicanum, which were then reared for 4-8 months before they were examined immunohistochemically. In experimental subjects with bilateral loss of olfactory epithelia, nerves and bulbs, there was complete absence of GnRH- and FMRFamide-ir neurons in the terminal nerve, and in septal and preoptic areas, and complete absence of large diameter peptidergic fibers associated with the TN-septo-preoptic system. However, GnRH-ir perikarya in the posterior tubercle, and FMRFamide-ir perikarya in the ventral hypothalamus, and small diameter peptidergic fibers were not affected by placodal ablation. These results support the hypothesis that contrary to recent reports, GnRH-ir neurons have more than one embryonic origin. Region-specific patterns of staining with antisera directed against different molecular forms of GnRH support the interpretation that GnRH-ir neurons of placodal origin express mammalian GnRH, whereas GnRH-ir neurons of non-placodal origin, in the posterior tubercle, express chicken GnRH II.

Ambystoma mexicanum↗
PubMed2005

Physical fitness, body composition, blood pressure, and blood metabolic profile among young Guatemalan adults.

We assessed the distribution of several risk factors related to health: muscular strength (handgrip strength), cardiovascular endurance (step test), flexibility (sit and reach test), anthropometry and body composition, blood pressure, fasting plasma glucose, lipid profile, and hemoglobin in a cohort of Guatemalan adults who were born in four rural villages between 1962 and 1977. By 2002 approximately 32% had migrated to Guatemala City or elsewhere in the country. Men are more physically fit and leaner than women. Fatness, poor physical fitness, and metabolic syndrome are highly prevalent in women living in both rural and urban areas. Risk profiles worsen with increasing age. Men who migrated to Guatemala City have lower physical fitness, greater fatness and systolic blood pressure, and worse lipid profile than men who still live in their original villages. Such a pattern was not evident in women, except that blood pressure was higher in urban women than in women who lived in their original villages.

Adult↗
PubMed1998

The limited difference between keratin patterns of squamous cell carcinomas and adenocarcinomas is explicable by both cell lineage and state of differentiation of tumour cells.

AIM: To study the differentiation of epithelial tissues within their histological context, and to identify hypothetically, on the basis of keratin pattern, the putative tissue origin of a (metastatic) carcinoma. METHODS: Using well characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19, which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and 14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas originating from various epithelial tissues were characterised. RESULTS: The predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In addition, these keratins were also abundantly present in squamous cell carcinomas of the lung, cervix, and rectum and, to a lesser extent, of the larynx, oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10, 13, and 14 were present in almost all squamous cell carcinomas, but also focally in some of the adenocarcinomas studied. CONCLUSIONS: There is a limited differential expression of distinctive keratin filaments between squamous cell carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that originate from columnar epithelium by squamous metaplasia gain the keratins of squamous cells but retain the keratins of columnar epithelial cells. However, the simultaneous expression of two of three squamous keratins (4, 10, and 13) identifies a squamous cell carcinoma, and thus might be useful in solving differential diagnostic problems.

Adenocarcinoma↗
PubMed1987

Origin and utilization of volatile fatty acids and lactate in the rabbit: influence of the faecal excretion pattern.

Interrelations between bacterial metabolites (volatile fatty acids, lactate) in the gut contents and the blood in relation to the faecal excretory cycle (soft or hard faeces) were studied in anaesthetized rabbits. It appeared that the level of organic acids in the alimentary tract varied cyclicly with the faecal excretion pattern. The lactate entering the portal circulation originates from the stomach, while the volatile fatty acids (VFA) originate from the hind-gut. Net absorption from the digestive tract and hepatic utilization of fermentation acids were greater when the rabbits produced hard faeces (hard-phase) compared with soft faeces (soft-phase). Propionate and butyrate reaching the liver were almost quantitatively removed; acetate and lactate were available for extra-hepatic tissue metabolism. Whatever the excretion pattern the levels of VFA in the arterial circulation remained remarkably constant; blood lactate, however, was lower during the soft-phase. Absorption of bacterial metabolites, like their metabolism in the liver, showed a circadian rhythm parallel to the changes in the activity of the adrenal glands, i.e. the activity was enhanced during the hard-phase.

Animals↗
PubMed1980

Changes in the differentiation pattern of oral mucosal epithelium following heterotopic connective tissue transplantation in man.

Anterior palatal connective tissue was transplanted into wound beds created within the alveolar mucosa of the lower anterior vestibulum in seven adults females. Six months postoperatively, the epithelial lining of the inverted transplants was biopsied and compared histologically, histometrically, and stereologically to the neighboring mucosal epithelium. The data suggest that (1) connective tissue of the lamina propria is primarily responsible for the structural specificity of the overlying epithelium, (2) inductive stimuli are not confined to superficial layers but also originate from deep portions of the lamina propria, (3) these stimuli influence both the epithelial differentiation and the type of epithelium-connective tissue interface, and (4) the epithelial response to the inductive stimuli in man may depend on the individual type of epithelial differentiation pattern originally prevailing at the recipient site. The transplant-lining epithelium assumed features resembling that of the hard palate in subjects with an alveolar mucosal epithelium with cheek-type characteristics. In subjects with an alveolar epithelium displaying a mixed differentiation pattern, the transplant-lining epithelium continued to generate a mixed pattern or else shifted to more palate-like characteristics.

Adult↗
PubMed1986

[Electroencephalographic study of 40 patients with subacute sclerosing panencephalitis].

Among viral diseases, subacute sclerosing panencephalitis is one of the most frequent in Iran (more than 300 cases in two neurological centers and for the last ten years). This paper is devoted to an electroencephalographic study of 40 patients: visual analysis of EEG rhythms (frequency, amplitude, lability, morphology), effects of activation methods, description of pathological EEG patterns (periodic paroxysmal complexes in 38 cases; slow or fast spikes, polyspikes and bifrontal or diffuse spikewaves in 9 cases; localized comitial abnormal patterns in 5 cases; bifrontal delta rhythm in 13 cases). From this description, we suggest an hypothesis of a diffuse localisation at the origin of periodic paroxysmal patterns: the periodic discharge of immune complexes from cerebral tissue into the cerebral circulation would constitute a synchronizing system which periodically modifies the blood-brain barrier permeability.

Adolescent↗
PubMed1997

Bovine cells infected in vivo with Theileria annulata express CD11b, the C3bi complement receptor.

Bovine cells from cattle infected with Theileria annulata were phenotyped with monoclonal antibodies recognizing bovine leukocyte antigens. Macroschizont-infected, transformed cell lines prepared from peripheral blood mononuclear cells of cattle, infected with sporozoites, were assessed by flow cytometry; parasitized cells in tissues from infected cattle were examined by immunocytochemical techniques. Co-expression of markers for different cell lineages by the cell lines precluded a definite conclusion as to their phenotypic origins. For, while the pattern of leukocyte antigens expressed by these in vivo-derived schizont-infected cells, which included CD11b, was indicative of a myeloid origin, the possibility that they were NK cells could not be excluded. The monoclonal antibody (MAb) IL-A15, which recognizes CD11b, reacted with a high proportion of parasitized cells in sections of tissues from infected cattle at all stages of acute disease. Mononuclear cells infected with parasites at all stages of differentiation, from macroschizont to microschizont, expressed CD11b. Such parasitized cells occurred throughout the lymphoid tissues, being found in the thymus, spleen and lymph nodes, particularly the prescapular node draining the site of infection, the hepatic, mesenteric and precrural nodes, as well as in the reticulo-endothelial tissue of the liver, kidney, lung, abomasum, adrenal and pituitary glands. These observations provided the first evidence for a myeloid origin for the parasitized T. annulata cells found in infected bovine tissues and blood and suggested a mechanism whereby schizonts could transfer from cell to cell during mechanical infection with schizont-infected cells.

Animals↗