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PubMed1996

[Reduced sympathetic nervous system activity during the cluster period of cluster-headache].

Cluster headache is a rare, very severe disorder that is clinically well characterized with a relatively poorly understood pathophysiology. Alterations of the hypothalamic-pituitary axis due to chronobiological changes, such as typical temporal pattern of both cluster periods and attacks, point to a central etiopathogenesis. Multiple local and systemic autonomic symptoms are compatible with an altered balance of the sympathetic and parasympathetic nervous system. In this connection, too, a central etiology is postulated. To evaluate the activation of the sympathetic nervous system, in 12 cluster headache patients we investigated the plasma catecholamines norepinephrine and epinephrine four times a day (7.00, 12.00, 17.00, 23.00) in the cluster period. In the cerebrospinal fluid we determined the transmitters norepinephrine, epinephrine, dopamine and the metabolites homovanillic acid (HVA), vanillymandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA). Values of plasma norepinephrine in the morning (p < 0.01), in the evening (p < 0.01) and the daily mean value (223.8 = 58.3 nmol/ml) were significantly decreased in the cluster headache group in comparison to the control group (328.8 = 53.0 nmol/ml, p < 0.01). The plasma epinephrine showed no significant changes. In the CSF of cluster headache patients norepinephrine (p < 0.05), HVA (p < 0.01), and 5-HIAA (p < 0.01) were significantly decreased. Plasma norepinephrine was correlated with CSF values of HVA and 5-HIAA. The longer the duration of the disease, the lower the values of HVA and 5-HIAA in the CSF of cluster headache patients. Moreover, plasma norepinephrine showed a significant correlation with the duration, the intensity and the frequency of the attacks. The results of this study implicate decreased activity of the sympathetic nervous system with alteration of circadian rhythmicity during the cluster period. The decreased CSF transmitter values may support the hypothesis of a central etiopathogenesis of cluster headache. Moreover, plasma norepinephrine seems to be involved in triggering and continuing the attacks. The anatomical region in which this interface of sympathetic and neurogenic inflammatory processes might be located is the trigemino-vascular system.

Adult↗
PubMed2000

Multiple contact kernel for diffusionlike aggregation

The Brownian kernel is usually assumed to describe pure diffusion-limited cluster-aggregation processes. In this work, we show that this assumption is correct for simulated data. For experimental data, however, significant deviations were observed although the system was aggregated at an electrolyte concentration well above the critical coagulation concentration. This indicates that residual cluster-cluster interactions are not completely absent in real experimental systems. In order to improve the description of the experimental data, we developed a kernel that considers a monomer-monomer sticking probability explicitly and accounts for the possibility of multiple monomer-monomer contacts in the cluster collision area. The proposed kernel agrees excellently with the experimental cluster-size distribution and the corresponding scaling function.

Journal Article↗
PubMedDate not supplied

The power of focused tests to detect disease clustering.

Statistical tests have been proposed for determining whether incident cases of adverse health effects are 'clustered' together. Several procedures, termed 'focused', specifically analyse disease surveillance data around pre-specified putative sources of environmental hazard. Little has been done to compare the performance of various proposed methods on actual models of clustering. Analytic power functions are derived for three tests of focused clustering. These functions are based on the probabilistic structure of the clustering tests and do not require simulation. The three tests are compared with respect to statistical power on hypothetical data where monotone multiplicative increases in disease risk near a putative hazard define disease clusters of varying intensity.

Cluster Analysis↗
PubMed1998

A novel portable perfused manometric system for recording of small intestinal motility.

The development of solid-state catheters with miniature pressure transducers and portable dataloggers with a large memory capacity has allowed recording of gastrointestinal motility in ambulant subjects. Developments in silicone rubber extrusion technology made it possible to build a perfused manometric system, using a perfused manometric assembly requiring a low volume of perfusate. In the present study the feasibility of recording and automated analysis of small intestinal motility using a perfused multiple lumen manometric system was evaluated in seven healthy volunteers. Pressures were recorded from 12 sideholes arranged in four clusters spaced at 10-cm intervals from the catheter tip. Each channel was perfused at 0.15 mL min-1 with degassed water by a portable, low-compliance, perfusion pump. The 12 sidehole recording channels were connected to external transducers mounted on a belt. Pressure data were stored in two dataloggers. Motility was recorded in the sitting (30 min), and supine (30 min) position, during walking (30 min) and postprandially (90 min). Using purpose-built software baseline variations were corrected for and manometric variables (number of pressure waves, mean amplitude and motility index) calculated. Bench testing of the manometric assembly showed a median baseline pressure offset of 4.2 kPa (range 3.7-10.1) and upon occlusion a rise rate of 27.8 kPa sec-1 (range 19.7-30.8). Changes in body position affected baseline pressures so that compared to the supine position changes in baseline pressure varied between 1.5 +/- 0.7 kPa and 1.9 +/- 0.6 kPa during sitting (P < 0.02), and between 1.7 +/- 0.7 kPa and 1.5 +/- 0.9 kPa during walking (P < 0.03). Manometric recordings obtained during the fasting period showed an increase in small intestinal motor activity during walking. In the postprandial period no differences in motility variables were observed within one cluster and in time. Recording of small intestinal motility with a multiple-channel silicone rubber manometric assembly with a portable perfusion system is a feasible technique which is relatively inexpensive. Computer-assisted data processing allows for adequate elimination of artefacts and automated numerical analysis.

Adult↗
PubMed1997

Familial papillary thyroid cancer: a case report.

Familial occurrence of medullary thyroid cancer is well known in families as an isolated malignancy or in association with multiple endocrine neoplasia syndrome type II. Conversely, papillary thyroid cancer almost always presents sporadically except for reports of familial clustering in individuals with radiation exposure, inherited syndromes of colonic polyposis or multiple harmatomas, and rarely in monozygotic twins. We report a case of papillary thyroid cancer diagnosed incidentally in a 53-year-old woman who underwent surgery for excision of an adenomatous nodule. It was noted that her mother suffered from a similar thyroid malignancy some 33 years ago, and several of her maternal relatives had either Graves' disease or hypothyroidism. The possible existence of this familial entity and its likely genetic basis is discussed.

Biopsy, Needle↗
PubMed1994

Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8+ CTL in vivo with peptide vaccine constructs.

CTL are a critical component of protective immunity against viral infections, but requirements for in vivo priming of CTL are not completely understood. Covalent linkage of a helper determinant to a CTL determinant, analogous to that required for cognate help for antibody production, does not appear to be necessary in vitro, but its necessity has not been extensively explored in vivo, especially at a molecular level. We previously defined peptides encompassing multideterminant regions of HIV-1 gp160 (cluster peptides) recognized by Th from mice and humans of multiple MHC types. To investigate the requirement for Th in the development of CTL in vivo, in the context of developing a synthetic peptide vaccine for HIV active in multiple strains of mice, we immunized with compound peptides representing an immunodominant CTL epitope, P18, of gp160, co-linearly synthesized at the C-terminus of three cluster peptides. Spleen cells from compound-peptide-immunized mice of three MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules exhibited enhanced gp160-specific CD8+ CTL activity and CD4+ Th. In contrast, immunization with P18 alone or a mixture of cluster peptide and P18 elicited only marginal CTL activity. These results imply a requirement for determinant linkage in CTL induction in vivo similar to that already well recognized for cognate help for antibody induction. The results also define promising peptide HIV vaccine candidates for induction of CTL, as well as neutralizing antibodies, in diverse MHC types.

AIDS Vaccines↗
PubMed2003

Genotype-environment interactions at quantitative trait loci affecting inflorescence development in Arabidopsis thaliana.

Phenotypic plasticity and genotype-environment interactions (GEI) play a prominent role in plant morphological diversity and in the potential functional capacities of plant life-history traits. The genetic basis of plasticity and GEI, however, is poorly understood in most organisms. In this report, inflorescence development patterns in Arabidopsis thaliana were examined under different, ecologically relevant photoperiod environments for two recombinant inbred mapping populations (Ler x Col and Cvi x Ler) using a combination of quantitative genetics and quantitative trait locus (QTL) mapping. Plasticity and GEI were regularly observed for the majority of 13 inflorescence traits. These observations can be attributable (at least partly) to variable effects of specific QTL. Pooled across traits, 12/44 (27.3%) and 32/62 (51.6%) of QTL exhibited significant QTL x environment interactions in the Ler x Col and Cvi x Ler lines, respectively. These interactions were attributable to changes in magnitude of effect of QTL more often than to changes in rank order (sign) of effect. Multiple QTL x environment interactions (in Cvi x Ler) clustered in two genomic regions on chromosomes 1 and 5, indicating a disproportionate contribution of these regions to the phenotypic patterns observed. High-resolution mapping will be necessary to distinguish between the alternative explanations of pleiotropy and tight linkage among multiple genes.

Arabidopsis↗
PubMed2003

The internal structure of the phenomenology of auditory verbal hallucinations.

BACKGROUND: Auditory verbal hallucinations (AVH) do not have uniform pathological significance. They affect patients with different brain disorders, and vary along multiple phenomenological dimensions. Evidence indicates that some of the phenomenological variables have specific neural substrates. Therefore, a comprehensive characterization of the phenomenological variations of AVH and the interrelationship between these variables was undertaken. METHOD: Twenty phenomenological variables were identified; on each AVH had a binary value (present or absent). Information about 11 of these variables were obtained from 30 patients. Hierarchical cluster (HC) and multidimensional scaling (MDS) analyses were performed to investigate the hidden structure and dimensions of these variables. RESULTS: HC yielded two main clusters with further sub-clusters in each. The first cluster included hallucinations with low linguistic complexity, repetitive content, attributed to self, located in outer space, and associated with different kinds of control strategies. The second cluster included hallucinations with high linguistic complexity, systematized content, multiple voices, attributed to others, and located in inner space. In MDS, three dimensions were identified: linguistic complexity, self-other attribution, and inner-outer space location. CONCLUSION: The patterns of clustering and dimensional configuration of AVH characteristics were in accord with intuitive expectation and validated the patients' descriptions of their experiences. These findings could reflect aspects of the neural mechanisms of AVH. For example, the presence of neural specificity for each phenomenological variable, intermediate neural commonality for groups of variables, and a final common pathway for all subtypes of AVH. Another example is a differential level of language dysfunction according to the linguistic complexity of AVH.

Adult↗
PubMed1995

Fighting as a marker for multiple problem behaviors in adolescents.

PURPOSE: Behaviors that put adolescents at risk frequently occur together. To help identify high-risk adolescents, we analyzed a national, self-reported behavior survey of high school students to assess the suitability of fighting as a marker for students with multiple problem behaviors. METHODS: A cross-sectional cluster survey of 11,631 U.S. high school students in 1990 was used to compare the prevalence of recent problem behaviors among all students and those who fight. RESULTS: One (8%) of every 12 students was in a fight during the 30 days before the survey. Reported problem behaviors were prevalent among fighters: during the previous 12 months, 24% attempted suicide; during the previous 30 days, 26% carried a firearm, 13% used cocaine, and 39% drove a motor vehicle while intoxicated; during the previous 3 months 41% had two or more sex partners; and 45% had sexual intercourse and did not use a condom the last time they had sex. Of all students, fighters accounted for 22% of those who reported attempting suicide, 49% carrying a firearm, 46% using cocaine, 18% driving while intoxicated, 25% having sex with multiple partners, and 11% not using condoms. Three or more of these six problem behaviors were reported by 26% of the fighters. The problem behaviors were all positively correlated, and the first principal component accounted for 35% of the total variation among the individual variables.

Adolescent↗
PubMed2006

Plasmid pCAR3 contains multiple gene sets involved in the conversion of carbazole to anthranilate.

The carbazole degradative car-I gene cluster (carAaIBaIBbICIAcI) of Sphingomonas sp. strain KA1 is located on the 254-kb circular plasmid pCAR3. Carbazole conversion to anthranilate is catalyzed by carbazole 1,9a-dioxygenase (CARDO; CarAaIAcI), meta-cleavage enzyme (CarBaIBbI), and hydrolase (CarCI). CARDO is a three-component dioxygenase, and CarAaI and CarAcI are its terminal oxygenase and ferredoxin components. The car-I gene cluster lacks the gene encoding the ferredoxin reductase component of CARDO. In the present study, based on the draft sequence of pCAR3, we found multiple carbazole degradation genes dispersed in four loci on pCAR3, including a second copy of the car gene cluster (carAaIIBaIIBbIICIIAcII) and the ferredoxin/reductase genes fdxI-fdrI and fdrII. Biotransformation experiments showed that FdrI (or FdrII) could drive the electron transfer chain from NAD(P)H to CarAaI (or CarAaII) with the aid of ferredoxin (CarAcI, CarAcII, or FdxI). Because this electron transfer chain showed phylogenetic relatedness to that consisting of putidaredoxin and putidaredoxin reductase of the P450cam monooxygenase system of Pseudomonas putida, CARDO systems of KA1 can be classified in the class IIA Rieske non-heme iron oxygenase system. Reverse transcription-PCR (RT-PCR) and quantitative RT-PCR analyses revealed that two car gene clusters constituted operons, and their expression was induced when KA1 was exposed to carbazole, although the fdxI-fdrI and fdrII genes were expressed constitutively. Both terminal oxygenases of KA1 showed roughly the same substrate specificity as that from the well-characterized carbazole degrader Pseudomonas resinovorans CA10, although slight differences were observed.

Bacterial Proteins↗
PubMed1998

Contribution of serine residues to constitutive and agonist-induced signaling via the D2S dopamine receptor: evidence for multiple, agonist-specific active conformations.

Dopamine D2 receptors contain a cluster of serine residues in the fifth transmembrane domain that contribute to activation of the receptor as well as to the binding of agonists. We used rat D2S dopamine receptor mutants, each containing a serine-to-alanine substitution (S193A, S194A, S197A), to investigate the mechanism through which these residues affect activation of the receptor. Activation of the mutant receptor S194A was abolished in an agonist-dependent manner, such that dopamine no longer inhibited cAMP accumulation in C6 glioma cells or activated G protein-regulated K+ channels in Xenopus laevis oocytes, whereas the efficacy of several other agonists was unaffected. Dihydrexidine did not inhibit cAMP accumulation at either S193A or S194A. The decreased efficacy of dihydrexidine at S193A and S194A and dopamine at S194A was associated with a decreased ability to detect a GTP-sensitive high affinity binding state for these agonists. The ability of dopamine to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate binding via S194A also was decreased by approximately 50%. Finally, constitutive stimulation of [35S]guanosine-5'-O-(3-thio)triphosphate binding and inhibition of adenylate cyclase by the D2S receptor was reduced by mutation of either S193 or S194. These data support the existence of multiple active receptor conformations that are differentially sensitive to mutation of serine residues in the fifth-transmembrane domain.

Animals↗
PubMed1999

Familial clustering of reflux symptoms.

OBJECTIVE: A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett' s esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. METHODS: A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. RESULTS: Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p = 0.007) or low LOS pressure (27%, p = 0.01) or Barrett's esophagus (30%, p = 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. CONCLUSIONS: Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.

Adult↗
PubMed1994

Incongruous item generation effects: a multiple-cue perspective.

In a series of studies, generation effects were obtained under encoding conditions designed to induce incongruous, unrelated item generation. Experiments 1 and 2, using free- and cued-recall measures, respectively, provided evidence that this unrelated generation effect was due to response-specific processing. Experiment 3 demonstrated a lack of relation between free recall and indices of clustering. A preliminary protocol study suggested that Ss generate multiple items in their search for appropriate unrelated responses. In Experiments 4 and 5, conditions designed to produce more extensive multiple generations demonstrated enhanced free recall. These results supported a multiple-cue account of facilitated recall for incongruous item generation. The multiple-cue perspective is consistent with traditional conceptualizations of memory, such as the principle of congruity, and contemporary distinctions between cue-target relational and item-specific processing.

Adult↗
PubMed1995

Visual topography in primate V2: multiple representation across functional stripes.

The second visual cortical area (V2) of the primate is composed of repeating thin, pale, and thick cytochrome oxidase stripes containing primarily color-selective, broad-band oriented, and disparity-selective cells, respectively. We have now examined topography in V2 with respect to these functional subdivisions. Our data suggest that there are multiple, interleaved visual maps in V2, one for each of the color, orientation, and disparity domains. The same region of visual space is re-represented by each stripe within a stripe cycle, resulting in discontinuities or "jumps back" in representation at stripe borders. Adjacent stripe cycles represent adjacent regions of space such that the visual map is continuous from one stripe to the next like stripe. Receptive field size and scatter are significantly larger for thin stripes than for thick stripes. Unexpectedly, our data suggest two types of pale stripes within each stripe cycle, one with scatter similar to thin stripes and another to thick stripes. Some evidence also suggests the presence of multiple maps within individual stripes in V2. Consistent with functional clustering within single stripes (Ts'o et al., 1990b), we have recorded re-representations and topographic discontinuities coincident with functional borders within single stripes. These results suggest that multiple and interleaved mapping may be a common organizational strategy for representing multiple functional domains within a single cortical area.

Animals↗
PubMed2000

Masticatory mucosa in subjects with different periodontal phenotypes.

AIMS: The aim of the present investigation was to study thickness of masticatory mucosa and gingival width in subjects with different periodontal phenotypes. METHODS: Periodontal phenotypes were defined with the aid of cluster analysis of standardised parameters including mean gingival thickness and width as well as ratio of crown width to its length at maxillary canines, lateral and central incisors of 40 young adults with healthy periodontal conditions. RESULTS: 3 groupings could be observed. Clusters A1 and A2 comprised 75% of all subjects. They were characterised by thin gingiva and a slender tooth form. Clusters A1 and A2 were differentiated by gingival width. Cluster B comprised 11 subjects with relatively thick and wide gingiva and a quadratic tooth shape. In general, characteristics of the frontal sextant in the maxilla were also found in other parts of the dentition. Thus, mean thickness of masticatory mucosa as well as gingival width and crown form differed significantly among clusters. In addition, cluster B subjects had a significantly greater mean periodontal probing depth. Multiple linear regression analysis was employed to identify significant factors influencing palatal mucosal thickness. Women had considerably thinner palatal mucosa than men. Furthermore, cluster affiliation had a significant influence on thickness of palatal mucosa. Thickest tissue was found in the premolar region, whereas the mucosa over the root prominence of the first molar represented an anatomical barrier for graft harvesting. CONCLUSIONS: Thickness of masticatory mucosa strongly depends on gender and the periodontal phenotype.

Adult↗
PubMed1993

Severe limb abnormalities: analysis of a cluster of five cases born during a period of 45 days.

We report on 5 individuals with severe limb abnormalities born in our hospital within a period of 45 days. Detailed clinical descriptions, photographs, and radiographs are presented. Etiological evaluations included genetic background, obstetric history, invasive procedures during pregnancy, maternal infectious diseases or maternal hyperthermia, drug use before and during pregnancy, and occupational or recreational exposures of both parents.

Abnormalities, Multiple↗
PubMed1996

A not quite as quick but much cleaner alternative to the Expanded Programme on Immunization (EPI) Cluster Survey design.

BACKGROUND: Although the Expanded Programme on Immunization (EPI) cluster survey methodology has been successfully used for assessing levels of immunization programme coverage in developing country settings, certain features of the methodology, as it is usually carried out, make it less-than-optimal choice for large, national surveys and/or surveys with multiple measurement objectives. What is needed is a 'middle ground' between rigorous cluster sampling methods, which are seen as unfeasible for routine use in many developing country settings, and the EPI cluster survey approach. METHODS: This article suggests some fairly straightforward modifications to the basic EPI cluster survey design that put it on a solid probability footing and render it easily adaptable to differing and/or multiple measurement objectives, without incurring prohibitive costs or adding appreciably to the complexity of survey operations. The proposed modifications concern primarily the manner in which households are chosen at the second stage of sample selection. CONCLUSIONS: Because the modified sampling strategy maintains the scientific rigor of conventional cluster sampling methods while retaining many of the desirable features of the EPI survey methodology, the methodology is likely to be a preferred 'middle ground' survey design, relevant for many applications, particularly surveys designed to monitor multiple health indicators over time. The fieldwork burden in the modified design is only marginally higher than in EPI cluster surveys, and considerably lower than in conventional cluster surveys.

Humans↗
PubMedDate not supplied

Premeiotic clusters of mutation and the cost of natural selection.

Haldane stated that there is a cost of natural selection for new beneficial alleles to be substituted over time. Most of this cost, which leads to "genetic deaths," is in the early generations of the substitution process when the new allele is low in frequency. It depends on the initial frequency and dominance value, but not the selection coefficient, of the advantageous allele. There have been numerous suggestions on how to reduce the cost for preexisting genetic variation that goes from disadvantageous, or neutral, to advantageous with a change in the environment. However, the cost of natural selection for new alleles that arise by mutation is assumed to be high, based on the assumption that new mutant alleles arise in natural populations as single events [1/(2N) of the total alleles]. However, not all mutant alleles arise as single events. Premeiotic mutations occur frequently in individuals (germinal mosaics), giving rise to multiple copies of identical mutant alleles called a "cluster" (C) with an initial allele frequency of C/(2N) instead of 1/(2N). These clusters of new mutant alleles reduce the cost of natural selection in direct proportion to the relative size of the cluster. Hence new advantageous alleles that arise by mutation have the greatest chance of going to fixation if they occur in large clusters in small populations.

Computer Simulation↗