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PubMed1988

DNA nucleotide sequence analysis of the PvuII DNA fragment L of the genome of insect iridescent virus type 6 reveals a complex cluster of multiple tandem, overlapping, and interdigitated repetitive DNA elements.

The DNA nucleotide sequence of the PvuII DNA fragment L (0.920 to 0.944 map units (m.u.] of the genome (209 kbp) of insect iridescent virus type 6 was determined. The size of this DNA fragment was 5064 bp with a base composition of 39.79% G + C and 60.21% A + T. The DNA sequence contained many perfect direct repeats of sizes up to 145 bp. In addition to these repetitions, a cluster of four imperfect repetitive DNA elements (R1 to R4) with a complex structural arrangement was detected. R1, R2, and R3 existed in duplicate (two boxes (B] between nucleotide positions 271 and 3466) and their size were as follows: R1-B1/B2 (567/568 bp), R2-B1/B2 (917/931 bp), and R3-B1/B2 (92/88 bp). The R4 repetitive element was found in 12 boxes (between bases 1301 and 4417), which were interrupted at nucleotide positions 1883 to 2236 and 3341 to 3587. These interruptions define three segments (S) harboring boxes B1 to B3 (S1), B4 to B8 (S2), and B9 to B12 (S3). The size of the individual boxes was found to be 239, 233, 107, 244, 222, 242, 242, 148, 240, 242, 242, and 102 bp for R4-B1 to B12, respectively. Five open reading frames (ORFs of 118 to 333 amino acid (AA) residues) were detected. The analysis of the amino acid sequences of the largest ORF revealed that the deduced amino acid sequence of the putative gene product contained two repetitions TR1 (three domains of 50 AA) and TR2 (two domains of 74 AA). Sequences of 43 amino acid residues of ORF 5 (160 to 202 AA) were homologous within the majority of ORFs. A consensus sequence-MANL(X)6 IGSSST(X)6 L(X)1 LGS(X)1 LQISG(X)2 L(X)1 VN- was found in all five ORFs. Although classical canonical and noncanonical transcriptional start signals were detectable, polyadenylation signals were not observed.

Amino Acid Sequence↗
PubMed1997

Molecular and functional analysis of genes required for expression of group IB K antigens in Escherichia coli: characterization of the his-region containing gene clusters for multiple cell-surface polysaccharides.

Escherichia coli group I capsular K antigens are found in two forms on the cell surface. The K(LPS) form is linked to lipopolysaccharide lipid A core, whereas the high-molecular-weight capsular form is assembled independently of lipid A core. Subgroup IB K antigens are generally co-expressed with either the O8 or O9 antigen and, under the appropriate conditions, with the exopolysaccharide, colanic acid. To examine the relationships between the genetic loci and the synthetic pathways for these various cell-surface polymers, the gene cluster responsible for expression of a prototype group IB K antigen (serotype K40) was cloned and the flanking chromosomal regions characterized. Analysis of the six orfs within the cluster indicates features typical of Wzy (Rfc)-dependent O antigens. Synthesis of group IB K antigens is initiated by WecA (Rfe), a UDP-GlcNAc::undecaprenylphosphate GlcNAc-1-phosphate transferase, and the chain length of K40LPS is determined by the wzz gene product. The his-region of the E. coli O8:K40 prototype is almost exclusively devoted to the expression of three different surface polysaccharides. The rfbK40 cluster is located adjacent to the cps (colanic acid synthesis) and rfbO8 (O8 antigen synthesis) loci in the gene order: his-rfbO8/O9-wzz-ugd-gnd-rfbK40-galF-cps. Thus, rfbK40 is in the location occupied by other Wzy-dependent rfb gene clusters, and rfbO8/O9 represents an additional locus.

Antigens, Bacterial↗
PubMed1993

Abnormalities in proximal small bowel motility in patients with cirrhosis.

Because altered intestinal motility could be involved in the pathogenesis of small intestine bacterial overgrowth observed in some patients with cirrhosis, we investigated fasting proximal small bowel motility in 16 cirrhotic patients and 8 healthy controls. In addition, the effects of oral tetracycline administration on duodenal motility were investigated in seven cirrhotic patients with evidence of bacterial overgrowth. The mean duration and characteristics of the migrating motor complex were analyzed. Cyclic activity was observed in all healthy controls. It was absent in two cirrhotic patients showing a prolonged phase 2-like pattern. The duration of cycles was significantly longer in the remaining 14 patients with cirrhosis (166 +/- 19 min) compared with controls (81 +/- 14 min; p < 0.02). This difference was caused by a prolonged phase 2 (138 +/- 19 min in patients with cirrhosis vs. 52 +/- 11 min in controls; p < 0.02). Marked changes in the contraction pattern during phase 2 were noted in cirrhotic patients. They were characterized by multiple clusters (frequency, 12 +/- 1/hr; duration, 38 +/- 3 sec) of contractions (frequency, 11 +/- 1 cpm) separated by quiescent periods (duration, 2.4 +/- 0.2 min). This motility profile filled up 58% +/- 8% of the total duration of phase 2, and it was observed in patients with and without bacterial overgrowth. Treatment with tetracycline was followed by only mild modifications, such as a reduction of the fraction of phase 2 occupied by multiple-clustered contractions. In conclusion, an altered proximal small bowel motility has been observed in patients with cirrhosis. These disturbances appear not to be dependent on the presence of bacterial overgrowth.

Adult↗
PubMed2005

A possible spatial and temporal cluster of multiple sclerosis in the town of Linguaglossa, Sicily.

We carried out an epidemiological survey to determine prevalence and incidence of multiple sclerosis in the little town of Linguaglossa in the Province of Catania. We calculated prevalence rate as point prevalence at 1 January 2001 and incidence during 1991-2000. We studied the frequency of multiple sclerosis in the community of Linguaglossa in a population of 5,422 inhabitants in the 2001 census. The primary sources for the case ascertainment were the general practitioners of Linguaglossa, the local Italian Multiple Sclerosis Association and the neurological departments, Multiple Sclerosis Centers and private neurologists of the province of Catania. We considered as prevalent and incident cases all patients who satisfied the Poser's diagnostic criteria. We detected 11 patients with multiple sclerosis who had had the onset of disease on prevalent day (P.D.). The onset-adjusted prevalence rate was 203/100,000 (95% CI 107-352). Prevalence was higher in women (247/100,000) than in men (154/100,000). From 1991 to 2000, 10 subjects with MS had clinical onset of disease. The mean annual incidence risk was 18.2/100,000 (C. I. 95 % 5.9-42.5). Conversely in the same population prevalence on 1 January 1991 was 37/100,000 while the onset adjusted annual incidence risk during the previous decade (1981-1991) was 3.6/100,000. Prevalence and incidence rates of MS during the last decade in the little town of Linguaglossa are higher than those found in the same area during the previous ten years and also than those reported in other Sicilian and Italian surveys suggesting a possible cluster of MS.

Adolescent↗
PubMed1998

High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: implications for protocol design of therapeutic antigen-specific vaccination strategies.

Human melanoma cells express several antigens which are recognized by autologous and specific CTL clones in association with HLA-class-I molecules. Many of these antigens represent suitable targets for tumor immunotherapy, since their expression in human melanoma cells is common and highly specific. In order to achieve real clinical success with therapeutic vaccination strategies, one important requirement is the expression of the target antigen by all the tumor lesions of a patient. We have studied this issue by assessing, through an RT-PCR approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic lesions (82%), the homogeneity in the pattern of gene expression within the cluster was complete. Heterogeneity within the same cluster was observed in only 3 out of 17 clusters (18%) and represented only minor features. Our data reveal that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic lesions express the same pattern of antigen-coding genes. These observations have 2 main clinical implications: (i) the antigenic characterization of one single and easily accessible lesion allows identification of optimal targets for an active antigen-specific immunotherapy treatment; (ii) almost all the metastatic lesions are expected to be hit by the immune response eventually induced against the tumor antigen. Moreover, these data suggest that active specific immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in high-risk AJCC-stage-III-melanoma patients.

Antigens, Neoplasm↗
PubMed1975

Studies on the clustering of multiple sclerosis in Finland II: microepidemiology in one high-risk county with special reference to familial cases.

The epidemiology of multiple sclerosis (MS) was investigated in a small selected area within the western high-risk county of Finland. The investigation was extended to the level of single communes, villages and even houses, together with the search for all familial cases born in this district. The results were compared to those obtained for Helsinki, a city of medium-risk for MS. Prevalences by present domicile that exceeded 100 per 1000,000 inhabitants were recorded in several communes of the western high-risk county. The highest prevalence was 174.2. Seventy patients were born in the small high-risk area. This was 25% of the MS patients born in the whole county and much higher than expected (16%). A positive familial history of another MS patient was recorded in 8 cases (11%). They were all living, first-degree relatives. A similar history was found in only 2 cases (2%) among the 99 MS patients born in Helsinki. The birthplaces of the 123 parents of these 70 MS cases could be confirmed. All villages with high MS frequencies were located along the rivers, running through the area. The birthplaces of the patients showed a similar accumulation to the valleys. No conjugal cases were found. If the preponderance of familial cases in the small high-risk area reflects the role of genetic factors in the aetiology of MS, it is only of polygenic nature. The pronounced clustering of the birthplaces in the small high-risk area and, especially, along the rivers also suggests the importance of environmental influences in early childhood.

Child, Preschool↗
PubMed2004

Large-volume radiofrequency ablation of ex vivo bovine liver with multiple cooled cluster electrodes.

Three methods of creating large thermal lesions with cool-tip cluster electrodes were compared. Three cluster electrodes were arranged 4 cm apart in a triangular array. Eight lesions were created ex vivo in fresh bovine liver (from a butcher) with each method: sequential ablation (three electrodes, 12 minutes each); simultaneous activation of electrodes (12 minutes); and rapid switching of power between electrodes (12 minutes), for which an electronic computer-controlled switch was developed. For sequential, rapid switching, and simultaneous methods, lesion volumes were 137.5 cm(3)+/- 22.2, 116.4 cm(3)+/- 15.2, and 22.3 cm(3)+/- 6.4 (P < .05), respectively, and final temperatures at lesion center were 80 degrees C +/- 5, 97 degrees C +/- 8, and 41 degrees C +/- 3 (P < .001), respectively. Because of electrical interference between electrodes, simultaneous method led to little heating at the center between the electrodes and created small discontinuous lesions. Rapid switching created large round lesions by employing multiple electrodes concurrently, which substantially reduced treatment time and resulted in more effective heating between electrodes.

Animals↗
PubMed1995

Familial clustering of multiple measures of adiposity and fat distribution in the Québec Family Study: a trivariate analysis of percent body fat, body mass index, and trunk-to-extremity skinfold ratio.

OBJECTIVE: To assess whether independent or common (pleiotropic) familial factors (i.e., genetic and/or common environment) underlie the observed associations among measures of body mass, body fat, and its distribution. DESIGN: A familial correlation model involves both parents and offspring, and gives rise to three types of familial correlations (spouse, parent-offspring, and sibling). A pattern of significant familial correlations suggests that the trait is determined by familial factors (i.e., genetic and/or environmental heritability). Cross-trait familial correlations are also estimated, both within individuals (intraindividual) and between family members (interindividual). Interindividual cross-trait familial correlations (e.g., trait 1 in parents with trait 2 in offspring) lead to the same type of familial inferences regarding bivariate heritabilities. SUBJECTS AND MEASURES: Measures of total body fat (% body fat-%BF), fat distribution (trunk/extremity skinfold ratio-TER), and body mass index (BMI) were assessed in 1239 individuals from 309 nuclear families participating the Québec Family Study. RESULTS: All three adiposity measures are cross-correlated within individuals. However, interindividual cross-trait correlations, which alone are capable of suggesting common familial determinants, are significant only for BMI with each of %BF and TER (bivariate heritabilities of 10% and 18%, respectively), and not for %BF and TER. CONCLUSION: Although all three adiposity measures are correlated within individuals, there appear to be entirely different underlying genes and/or environmental factors influencing the adiposity phenotypes of total body fat and fat distribution. The BMI, however, apparently shares some familial determinants with both total body fat and fat distribution.

Adolescent↗
PubMed1989

Amplification enhancers and replication origins in the autosomal chorion gene cluster of Drosophila.

Drosophila melanogaster follicle cells over-replicate the chromosomal domain containing the third chromosome chorion gene cluster. Multiple regions of this cluster are needed in cis for attainment of high levels of amplification. We have confirmed the importance of the proposed amplification control element (ACE3) and demonstrated that it can support low levels of follicular amplification in the absence of other elements, but that it lacks detectable activity as a DNA replication origin. We have also demonstrated the existence of additional amplification-enhancing regions (AERs), by analyzing the amplification levels of a series of in situ induced, nested deletions of the chorion cluster. These deletions were induced by P-transposase perturbation of a chorion transposon in a highly amplifying transformed line, and were not accompanied by re-transposition, making possible a quantitative analysis of amplification levels in the absence of chromosomal position effects. Analysis of endogenous replication intermediates in wild-type follicular DNA suggested that at least one of the AERs may be an origin of replication and that amplification uses at least one additional replication origin.

Animals↗
PubMed1997

Posttranslational modification of oat phytochrome A: phosphorylation of a specific serine in a multiple serine cluster.

Phytochrome A (phyA) is a photoreceptor of higher plants which mediates a variety of biochemical and physiological processes in response to red/far-red light. By detailed structural analysis of the peptides of the total tryptic digest of oat phyA, we found that the photoreceptor isolated from red light irradiated seedlings contains only one site of phosphate attachment, in the N-terminal Ser-rich region. The N-terminal tryptic phosphopeptide (residues 1-12) contains eight serine residues, any of which may be phosphorylated. Direct fast atom bombardment mass spectrometry (FAB MS/MS) analysis of the phosphorylated peptide as well as of its phosphate-containing fragment (residues 1-9) was not successful due to their hydrophilic nature and instability of the phosphate bond. beta-Elimination of the phosphorylated tryptic peptide in the presence of ethanethiol converted the phosphoserine residue to S-ethylcysteine that is stable under FAB MS/MS. FAB MS/MS analysis of the modified peptide clearly showed that the phosphate group was attached to Ser7. The in vivo phosphorylation site at Ser7 in oat phyA is discussed for its possible regulatory role in phyA function.

Amino Acid Sequence↗
PubMed2000

Genetic network inference: from co-expression clustering to reverse engineering.

MOTIVATION: Advances in molecular biological, analytical and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-cluster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e. who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.

Animals↗
PubMed2003

Extraction of correlated gene clusters from multiple genomic data by generalized kernel canonical correlation analysis.

MOTIVATION: A major issue in computational biology is the reconstruction of pathways from several genomic datasets, such as expression data, protein interaction data and phylogenetic profiles. As a first step toward this goal, it is important to investigate the amount of correlation which exists between these data. RESULTS: These methods are successfully tested on their ability to recognize operons in the Escherichia coli genome, from the comparison of three datasets corresponding to functional relationships between genes in metabolic pathways, geometrical relationships along the chromosome, and co-expression relationships as observed by gene expression data.

Algorithms↗
PubMed1989

Clustering of multiple sclerosis in Galion, Ohio, 1982-1985.

Epidemiologic evidence indicates that the outbreak of 30-40 cases of multiple sclerosis and other demyelinating syndromes in Galion, Ohio, USA, during 1982-1985 was related to an excess concentration of heavy-metal wastes, especially of cadmium and chromium in sewage and river water. Both multiple sclerosis and myasthenia gravis were diagnosed by board-certified neurologists.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Genetic analysis of incident HIV-1 strains among injection drug users in Bangkok: evidence for multiple transmission clusters during a period of high incidence.

During 1995-1996, 1,209 HIV-1-negative injection drug users (IDUs) attending methadone treatment clinics operated by the Bangkok Metropolitan Administration in Bangkok, Thailand, were enrolled in a prospective cohort study. Through 1998, 133 of these IDUs had seroconverted to HIV-1; 130 of these seroconverters were included in this study. HIV-1 CRF01_AE and subtype B strains accounted for 79% and 21% of the incident infections, respectively. To examine phylogenetic relationships among these incident HIV-1 strains, we used several phylogenetic inference methodologies to analyze the env (C2-V4) sequences in blood samples collected soon after seroconversion. These analyses consistently revealed eight phylogenetic clusters comprising 21 incident strains (bootstrap method, >80%; six CRF01_AE and two subtype B clusters). Two factors were found to be associated with the eight clusters. The first factor was temporal: seven of the eight clusters comprised 17 sequences from IDUs whose estimated dates of seroconversion were within a period of high incidence from July 1996 through January 1997. The second factor was a possible geographic association: four clusters were observed among IDUs who had attended the same methadone treatment clinics. These phylogenetic clusters likely represent subgroups within larger HIV transmission networks among IDUs in Bangkok. Despite prevention efforts, the incidence of HIV-1 infection among the Bangkok IDU population continues to be high. A better understanding of transmission networks and factors associated with such networks can help guide prevention efforts.

Adult↗