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PubMedDate not supplied

Artifactual distortion of cells simulating metastatic small cell carcinoma in the bone marrow.

Artifactual distortion of hematopoietic elements in histologic preparations and smears of bone marrow aspirates simulating metastatic small cell carcinoma has been recently described. The clinical, pathologic, and immunohistochemical features in 12 such cases have been studied by us. In all these cases, bone marrow smears and histologic sections showed multiple small clusters of atypical, hyperchromatic cells suspicious for metastatic small cell carcinoma. Immunohistochemical stains showed focal positivity of the suspicious cells for leukocyte common antigen (LCA), anti-hemoglobin A (Hem A) and anti-erythrocyte membrane antigen (ERM), and negative staining for epithelial membrane antigen (EMA) and neuron specific enolase (NSE). Clinical follow-up of two years did not demonstrate any evidence of a primary small cell carcinoma in the lung or elsewhere. Comparison of these 12 cases with four cases of transbronchial biopsy-proven metastatic small cell carcinoma to the bone marrow showed that this artifact had a tendency to be located at the periphery of the marrow particles, unlike the true metastatic carcinoma cells which were predominantly found within the marrow particles and replacing the hematopoietic elements. The results of our immunohistochemical studies appear to indicate that these cells correspond to aggregated nuclei and cytoplasmic remnants from erythroid as well as myeloid and lymphoid cells. The main importance of identifying this artifact lies in avoiding confusion with metastatic small cell carcinoma, a distinction that may be very difficult to establish on morphologic grounds alone. Immunohistochemical stains and a thorough clinical follow-up are necessary for arriving at the correct diagnosis.

Adolescent↗
PubMed1977

Characteristics of drug abusers in an adolescent in-patient psychiatric facility.

Characteristics related to the abuse of drugs in 143 adolescents who had been institutionalized in an inpatient psychiatric facility were investigated. A factor analysis generated the following clusters: (1) multiple drug usage, (2) male narcotics procurement, (3) drug history, (4) prognostic index, (5) family drug usage, (6) entrepreneurial procurement of drugs, and (7) social procurement of drugs. Results also indicated that our patients are coming to us at increasingly younger ages and that patients admitted in 1969 appear more seriously involved in drug abuse than those admitted before or after this time.

Adolescent↗
PubMed1997

Effect of hydroxyl radical scavenging capacity on clustering of DNA damage.

We have shown previously that the thiol N-(2'-mercaptoethyl)-1,3-diaminopropane (WR-1065) can attenuate the formation of strand breaks associated with ionizing radiation. The mechanism of this protection is predominantly the reduction of DNA radical species which otherwise would attenuate the chemical repair of DNA radical species which are strand break precursors. We had observed that the presence of a hydroxyl radical scavenger during irradiation resulted in a decrease in the ability of WR-1065 to attenuate the formation of strand breaks. Since ionic compounds are known to affect the binding of the dicationic WR-1065 with the polyanion DNA, the effect of the scavenger was initially attributed to its polar nature having a similar effect on the interaction of WR-1065 with DNA, and not as a consequence of its ability to scavenge hydroxyl radicals. After examining additional scavengers, we now conclude that an increased hydroxyl radical scavenging capacity does attenuate the repair of strand break precursors to some extent. The probable explanation for this observation is that an increased scavenging capacity results in a greater degree of radical clustering on the DNA, and that these clusters of multiple radicals are repaired more slowly than are single radical species.

DNA Damage↗
PubMed2004

Energy distributions in multiple photon absorption experiments.

Photofragmentation experiments on molecules and clusters often involve multiple photon absorption. The distributions of the absorbed number of photons are frequently approximated by Poisson distributions. For realistic laser beam profiles, this approximation fails seriously due to the spatial variation of the mean number of absorbed photons across the laser beam. We calculate the distribution of absorbed energy for various laser and molecular-beam parameters. For a Gaussian laser beam, the spatially averaged distributions have a power-law behavior for low energy with a cutoff at an energy which is proportional to fluence. The power varies between -1 for an almost parallel laser beam and -5/2 for a divergent beam (on the scale of the molecular beam). We show that the experimental abundance spectra of fullerenes and small carbon clusters can be used to reconstruct the distribution of internal energy in the excited C60 molecule prior to fragmentation and find good agreement with the calculated curves.

Journal Article↗
PubMed1990

Profound spatial clustering of polyps in individuals with multiple nonmalignant polyps of the stomach and duodenal bulb: a combined endoscopic and radiographic study.

An individual's simultaneous nonmalignant gastroduodenal polyps were profoundly spatially clustered in a combined endoscopic and radiographic study of 41 consecutive patients. With endoscopic polyp localization, clustering was demonstrated using a nonparametric test of clustering (Kruskal-Wallis statistic with 40 degrees of freedom = 113.35, probability of observing this extreme statistic with no clustering less than 0.0005) and a parametric test of clustering (F test statistic with 40 and 104 degrees of freedom = 17.05, probability of observing this extreme statistic with no clustering less than 0.0005). In the 26 patients with radiographic polyp localization, polyp clustering was confirmed with the same statistical techniques (e.g., Kruskal-Wallis statistic with 25 degrees of freedom = 88.2, probability of observing this extreme statistic with no clustering less than 0.0005). In patients whose largest polyp was in any given region, there was an increased likelihood that their other polyps would be in that same region. For example, at endoscopy, the nine patients whose largest polyp was in the duodenal bulb had 13 of 15, or 87% +/- 9% (SE), of their other polyps in the duodenal bulb. In contrast, the 11 patients who, at endoscopy, had their largest polyp in the proximal stomach had 2 of 30, or 7% +/- 5% (SE), of their other polyps in the duodenal bulb. Polyp clustering was not dependent on the number of gastroduodenal polyps, or patient age or sex. Patients with at least one hyperplastic polyp, one adenomatous polyp, or with both types of polyps also exhibited profound polyp clustering. These findings suggest that local factors may be important in the pathogenesis of multiple polyps of the stomach and duodenal bulb. In particular, these findings suggest a possibly closer relationship between hyperplastic and adenomatous gastroduodenal polyps than previously appreciated.

Aged↗
PubMed2005

Geometric and electronic structures of multiple-decker one-end open sandwich clusters: Eu(n)(C8H8)n- (n = 1-4).

We have measured the photoelectron spectra of the multiple-decker 1:1 sandwich clusters of Eu(n)(COT)n- (n = 1-4; COT = 1,3,5,7-cyclooctatetraene), synthesized in the gas phase, and studied theoretically the bonding scheme, charge distribution, valence orbital energies, and photodetachment energies. We calculated the ground electronic state X- and the first excited electronic state A-, both of which have strong ionic bonding and a characteristic charge distribution. Moreover, we found that the valence orbital energies of Eu (6s) and COT (L delta) depend strongly on cluster size and their positions in the clusters. With the calculated vertical detachment energies for these valence orbitals, we assigned the peaks in the experimental photoelectron spectra and analyzed the origin of their interesting behavior by employing simple point charge models. From these analyses, it became clear that the characteristic behavior of the spectra is due to the strong ionic bonding and the charge distribution. In addition, using the point charge models, we estimated the vertical detachment energies of the one-dimensional polymer [Eu(COT)]infinity-.

Journal Article↗
PubMed1999

[Neural cluster structure with single component prediction in multiple variable systems for X-ray fluorescence spectrometry].

A neural cluster structure with single component prediction (NCSCP) was proposed for X-ray fluorescence spectrometry in a multivariable system. The neural cluster structure is built by the collection of a group of neurons which have close relationships among one another. In X-ray fluorescence analysis, the structure is constructed by choosing the elements in which there exist serious matrix effects, and deleting the components containing large noise. The predictability of the neural cluster structure was compared with that of the classical backward error propagation algorithm with single component prediction. The results show that the neural cluster structure is significantly superior to the classical algorithm in prediction accuracy, antidisturbance and the predictabilty to outliers.

English Abstract↗
PubMed2005

Multiple sclerosis in Tayside, Scotland: detection of clusters using a spatial scan statistic.

Debate continues over the relative importance of genetic factors over infectious agents in the aetiology of multiple sclerosis (MS). Detection of clusters of MS in space and time in the Tayside region of Scotland, UK would provide valuable evidence for the movement of infectious agents into a genetically susceptible population. A spatial scan statistic was used to detect, locate and provide a robust statistical test of any clusters found, without prior knowledge of their location or size. This was applied to a population-based MS register for the Tayside region of Scotland from 1970 to 1997, allowing for age at symptom onset, gender, population density and social deprivation. There were a total of 772 cases during the study period; an annual incidence of 72 per 100000. The mean age of symptom onset was 35.7 (SD = 10.5) and 73.8% of cases were women. There was a general increase in cases over time probably reflecting gradually better detection and diagnosis. There was a peak around the mid-1990s and some evidence of periodicity. There was a highly significant temporal cluster between 1982 and 1995 (P = 0.002) for the whole region. Additionally, a significant spatial cluster for the time period 1993-1995 was found centred in the rural area south-west of Perth (P=0.016). Significant temporal and spatial-temporal clusters are consistent with exogenous factors contributing to the distribution of MS in Tayside, Scotland.

Adult↗
PubMed2005

Prognostic implication of isolated tumor cells and micrometastases in regional lymph nodes of gastric cancer.

AIM: To determine the prognostic significance of isolated tumor cells (ITCs) and lymph node micrometastases in gastric cancer. METHODS: Hematoxylin and eosin-stained slides of lymph node dissections of 632 consecutive gastric cancers were reviewed. Cytokeratin immunostaining was performed in 280 node-negative cases and 5 cases indefinite for lymph node metastases. Lymph node metastases were divided into ITCs, micrometastases, or macrometastases, according to the sizes of tumor deposits in largest dimension. ITCs were further classified into four groups according to metastasis pattern. RESULTS: Lymph node metastases were identified by immunostaining in 58 of 280 node-negative cases (20.7%) and were not significantly associated with patient survival (P = 0.3460). After cytokeratin immunostaining, 196 cases were classified as pN1, which consisted of 20 cases with micrometastases detected by immunostaining (pN1mi(i+)), 34 cases with only micrometastases (pN1mi), and 142 cases with pN1 with one or more macrometastases (pN1). Cases with pN1mi and pN1mi(i+) had a significantly better prognosis than the cases with pN1 (P = 0.0037). ITCs were found in 38 of these 58 cases, and could be divided into four groups: 12 cases with only a single cell pattern, 7 cases with multiple individual cells, 5 cases with single small cluster, and 14 cases with multiple small clusters. Among these four groups, cases with ITCs of multiple individual cell pattern showed the worst survival (median survival: 28 mo, P<0.0001). CONCLUSION: Both size and pattern of lymph node metastases can give prognostic information on the survival of gastric cancer patients.

Humans↗
PubMed2002

Hox cluster organization in the jawless vertebrate Petromyzon marinus.

Large-scale gene amplifications may have facilitated the evolution of morphological innovations that accompanied the origin of vertebrates. This hypothesis predicts that the genomes of extant jawless fish, scions of deeply branching vertebrate lineages, should bear a record of these events. Previous work suggests that nonvertebrate chordates have a single Hox cluster, but that gnathostome vertebrates have four or more Hox clusters. Did the duplication events that produced multiple vertebrate Hox clusters occur before or after the divergence of agnathan and gnathostome lineages? Can investigation of lamprey Hox clusters illuminate the origins of the four gnathostome Hox clusters? To approach these questions, we cloned and sequenced 13 Hox cluster genes from cDNA and genomic libraries in the lamprey, Petromyzon marinus. The results suggest that the lamprey has at least four Hox clusters and support the model that gnathostome Hox clusters arose by a two-round-no-cluster-loss mechanism, with tree topology [(AB)(CD)]. A three-round model, however, is not rigorously excluded by the data and, for this model, the tree topologies [(D(C(AB))] and [(C(D(AB))] are most parsimonious. Gene phylogenies suggest that at least one Hox cluster duplication occurred in the lamprey lineage after it diverged from the gnathostome lineage. The results argue against two or more rounds of duplication before the divergence of agnathan and gnathostome vertebrates. If Hox clusters were duplicated in whole-genome duplication events, then these data suggest that, at most, one whole genome duplication occurred before the evolution of vertebrate developmental innovations.

Animals↗
PubMed1998

Multiple sequences from downstream of the J kappa cluster can combine to recruit somatic hypermutation to a heterologous, upstream mutation domain.

Recruitment of somatic hypermutation to the Ig kappa locus has previously been shown to depend on the enhancer elements, Ei/MAR and E3'. Here we show that these elements are not sufficient to confer mutability. However, hypermutation is effectively targeted to a chimeric beta-globin/Ig kappa transgene whose 5' end is composed of the human beta-globin gene (promoter and first two exons) and whose 3' end consists of selected sequences derived from downstream of the J kappa cluster (Ei/MAR, C kappa + flank and E3'). Thus, multiple downstream Ig kappa sequences (all derived from 3' of the J kappa cluster) can combine to recruit mutation to a heterologous mutation domain. The location of this hypermutation domain is defined by the position of the transcription start site and this applies even if the Ig kappa Ei/MAR is positioned upstream of the promoter. Hotspots within the mutation domain are, however, defined by local DNA sequence as evidenced by a new hotspot being created within the beta-globin domain by a mutation within the transgene. We propose that multiple, moveable Ig kappa sequences (that are normally located downstream of the transcription start site) cooperate to bring a hypermutation priming factor to the transcription initiation complex; a mutation domain is thereby created downstream of the promoter but the local sequence defines the detailed pattern of mutation within that domain.

Animals↗
PubMed1987

Amplification of a chorion gene cluster in Drosophila is subject to multiple cis-regulatory elements and to long-range position effects.

We have used P-element transformation to study cis-acting elements involved in the control of amplification of the third chromosome chorion gene cluster (66D12-15) in Drosophila melanogaster. To reduce position effects large fragments (5.7 to 12 kb; kb = 10(3) bases) of chorion DNA and the 7.2 kb ry+ fragment were used to "buffer" these putative elements from sequences at the insertion site. Nevertheless, even the longest constructs were profoundly affected by the insertion sites and showed amplification levels ranging from undetectable to higher than in the endogenous locus. Any amplification was tissue and temporally correct and extended into the neighboring ry+ sequences. Analysis of amplification levels at various points along two constructs bearing the same 10 kb chorion insert in opposite orientations showed maximal levels occurring at one end of the chorion fragment, irrespective of whether that end was buffered at the middle of the transposon or exposed close to the insertion site. The maximally amplifying region encompasses the amplification control element (ACE), which has been shown to be necessary for amplification, in agreement with its putative role as a replication origin. We have additionally identified amplification-enhancing elements present elsewhere in the 10 kb chorion fragment, which are needed for attainment of high copy number. These elements, distinct from the ACE, have been only coarsely localized within two 2.25 to 2.3 kb regions. Some interesting sequence similarities between these two regions and the ACE element are pointed out.

Animals↗
PubMed2004

Prevalence of multiple chronic disease risk factors. 2001 National Health Interview Survey.

BACKGROUND: Four common factors--cigarette smoking, risky drinking of alcoholic beverages, physical inactivity, and overweight--contribute substantially to chronic disease prevalence. METHODS: We used data from the 2001 National Health Interview Survey to provide an up-to-date picture of multiple risk factor prevalence and clustering in the U.S. population. We conducted a multinomial logit analysis to examine the independent association between each covariate and the dependent ordinal risk factor variable with three levels (none or one risk factor, two risk factors, and three or four risk factors). RESULTS: Seventeen percent of the sample of 29,183 subjects had three or more risk factors. For the entire sample, the mean number of risk factors was 1.68 (95% confidence interval [CI]=1.66-1.70). Many demographic and health factors were significantly associated with the mean number of risk factors including gender, age, ethnic/racial categories, education, martial status, presence of chronic diseases, level of mental distress, country of birth, and presence and type of health insurance. Using the risk factor score as the ordinal dependent variable, adjusted odds for having a risk score of three or four versus zero or one were as follows: men aged <65, 2.49 (95% CI=2.29-2.72); education attainment of high school graduate or less, 3.24 (95% CI=2.86-3.67); and individuals with high levels of mental distress, 2.06 (95% CI=1.65-2.58). CONCLUSIONS: Our analyses confirm earlier reports of the high prevalence of multiple, clustered behavioral risk factors and underline the challenge this presents for primary care and public health systems.

Adult↗
PubMed1989

The new generation of serotonergic anxiolytics: possible clinical roles.

Serotonin has been implicated in mediating diverse physiologic and psychologic processes. The anatomy and complex pharmacology of brain-serotonin systems enables this neurotransmitter to broadly affect normal and abnormal behaviors. It appears that serotonin plays a role in multiple psychopathologies, including anxiety, depression, mood disorders, aggressive acting out, alcohol-related syndromes, and disinhibitory disorders characterized by impulsivity. It would not be surprising, therefore, if drugs that alter the dynamics of serotonergic neurotransmission prove to be effective in multiple clinical settings. Such agents may treat broad symptom clusters common to multiple nosologic categories. The new generation of serotonergic anxiolytics, including buspirone, gepirone, ipsapirone, and SM-3997, which interact potently with 5-hydroxytryptamine-1A receptors, may prove to be such symptom cluster drugs. There is a scientific rationale for exploring the clinical utility of these agents in anxiety, depression, mood disorders, aggressive syndromes, and alcohol-related disorders.

Animals↗
PubMed1999

Influence of a replication enhancer on the hierarchy of origin efficiencies within a cluster of DNA replication origins.

DNA replication origins in animal cells sometimes occur in clusters. Often one of the multiple origins within these clusters fires more frequently than the others. The reason for this hierarchy remains unknown. Similar origin clusters occur in the fission yeast, Schizosaccharomyces pombe. One such cluster is located near the ura4 gene on chromosome III and contains three origins: ars3002, ars3003, and ars3004. In their natural chromosomal context (ars3003 is about 2.5 kb upstream of ars3002 and ars3004 is adjacent to ars3002 on the downstream side) their initiation frequencies display a striking hierarchy: ars3002 >> ars3003 >> ars3004. Here, we describe experiments that reveal a 400 bp replication enhancer within ars3004, adjacent to ars3002. The enhancer is essential for ars3004 origin function in a plasmid, but even with the enhancer ars3004 is an inefficient origin. The enhancer is not essential for ars3002 plasmid origin activity, but dramatically stimulates this activity, converting ars3002 from an inefficient plasmid origin to a very efficient one. It also stimulates the plasmid origin activity of ars3001 and ars3003 at all tested positions and orientations on both sides of each autonomously replicating sequence (ARS) element. If ars3002 is redefined to include the enhancer, then the relative activities of the three ARS elements as single origins within separate plasmids or as origins when all three ARS elements are present in a single plasmid is the same as the chromosomal hierarchy. Thus, this replication enhancer defines the relative activities of the three origins in the ura4 origin region. Similar enhancers may affect relative activities in the origin clusters of animal cells.

Cell Count↗
PubMed2002

Gene expression profiles in young adult Ciona intestinalis.

Comparison of 12,230 expressed sequence tags (ESTs) of 3' ends of cDNA clones derived from young adults of Ciona intestinalis allowed us to categorize them into 976 independent clusters. When the 5'-end sequences of 10,400 ESTs of the 976 clusters were compared with the sequences in databases, 406 of the clusters showed significant matches ( P < E-15) with reported proteins with defined functions, while 117 showed matches with putative proteins for which there is not enough information to categorize their function, and 453 had no significant sequence similarities to known proteins. The 406 clusters with sequence similarity to proteins with defined functions consisted of 304 clusters related to proteins with functions common to many kinds of cells, 73 related to proteins associated with cell-cell communication and 29 related to transcription factors. Spatial expression of all of the 976 clusters was examined by a newly improved whole-mount in situ hybridization method. A total of 430 clusters did not show distinct in situ hybridization signals, while 122 clusters showed ubiquitous distribution of signals, and 253 clusters showed signals in multiple tissues. The remaining 171 clusters showed signals specific to a certain organ or tissue: 16 showed epidermis-specific expression, 3 were specific to the neural complex, 1 to heart, 6 to body-wall muscle, 94 to pharyngeal gill, 3 to esophagus, 26 to stomach, 1 to intestine and 21 to endostyle. Many of these organ-specific genes encode proteins with no sequence similarity to known proteins. The present analysis thus highlights characteristic gene expression profiles of Ciona young adults and provides not only molecular markers for organs and tissues but also transcriptomic information useful for further genomic analyses of this model organism.

Animals↗
PubMed2006

Signatures for multi-alpha-condensed states.

An experimental way of testing Bose-Einstein condensation of alpha clusters in the atomic nucleus is reported. The enhancement of cluster emission and the multiplicity partition of possible emitted clusters could be direct signatures for the condensed states. The barrier for the emission of clusters, such as (8)Be and (12)C(O(+)(2)), is calculated and compared with the barrier for the sequential emission of 2 or 3alpha particles from the compound nucleus. For the calculations, a simple approach using a folded Woods-Saxon potential is used.

Journal Article↗