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Paracentric inversions in man.

The Leuven cytogenetic center experience on paracentric inversions in man is discussed. From a total of 51,000 patients, referred for constitutional chromosome analysis during the period 1970-1985, paracentric inversions were found in 18 index patients. A puzzling finding is the high incidence (26%) of mental retardation and/or congenital malformation in the inversion carrier offspring of phenotypically normal parents with identical chromosomal rearrangements. There was also a high incidence of early fetal loss in the inversion carrier parents. This finding may be explained by an increase of chromosomally unbalanced gametes which result from crossing-over in the meiotic inversion loop. Finally, the possibility of an increased tendency to non-disjunction in paracentric inversion carrier parents is discussed. The most frequent paracentric inversion was inv(3)(p13p25); it was detected in seven unrelated index patients. According to the present experience and the literature data, the breakpoints in paracentric inversions seem to occur preferentially at 1p22, 1p36, 3p13, 3p25, 7q11, and 7q22 regions.

Centromere↗

"Partial trisomy 22 and 11" due to a paternal 11;22 translocation associated with Hirschsprung disease.

The 11;22 translocation seems to be the most frequent, non-Robertsonian, translocation in man. Approximately 50 cases with an unbalanced karyotype 47,XX (or XY),+der(22), t(11q;22q), due to a 3:1 meiotic disjunction in the parental translocation carrier, have been reported in the literature. We present an additional patient with that chromosome aberration, whose father was shown to be the translocation carrier. He presented with many of the more or less typical signs of the syndrome, but had an extraordinary additional finding, namely Hirschsprung disease. Although anal stenosis is a rather frequent finding in the syndrome, Hirschsprung disease has never been described in the literature. Furthermore the most important genetic and cytogenetic data on that chromosome aberration are given, including implications for genetic counselling.

Chromosomes, Human, Pair 11↗

Two cases of trisomy 21 and one XXY case with atypical clinical features.

Three patients with mental retardation and multiple congenital abnormalities are described. Although their clinical appearance was not suggestive of Down's syndrome, chromosome studies showed a non-disjunctional trisomy 21 in two of the patients. The third case had an unsuspected XXY karyotype.

Abnormalities, Multiple↗

Functional organization of the electroreceptive midbrain in an elasmobranch (Platyrhinoidis triseriata). A single-unit study.

The response properties of 322 single units in the electroreceptive midbrain (lateral mesencephalic nucleus, LMN) of the thornback ray, Platyrhinoidis triseriata, were studied using uniform and local electric fields. Tactile, visual, or auditory stimuli were also presented to test for multimodality. Most LMN electrosensory units (81%) are silent in the absence of stimulation. Those with spontaneous activity fired irregularly at 0.5 to 5 impulses/s, the lower values being more common. Two units had firing rates greater than 10/s. Midbrain electrosensory units are largely phasic, responding with one or a few spikes per stimulus onset or offset or both, but the adaptation characteristics of some neurons are complex. The same neuron can exhibit phasic or phasic-tonic responses, depending upon orientation of the electric field. Tonic units without any initial phasic over-shoot were not recorded. Even the phasic-tonic units adapt to a step stimulus within several seconds. Unit thresholds are generally lower than 0.3 microV/cm, the weakest stimulus delivered, although thresholds as high as 5 microV/cm were recorded, Neuronal responses reach a maximum, with few exceptions, at 100 microV/cm and decrease rapidly at higher intensities. LMN neurons are highly sensitive to stimulus repetition rates: most responded to frequencies of 5 pulses/s or less; none responded to rates greater than 10/s. Three distinct response patterns are recognized. Best frequencies in response to sinusoidal stimuli range from 0.2 Hz (the lowest frequency delivered) to 4 Hz. Responses decrease rapidly at 8 Hz or greater, and no units responded to frequencies greater than 32 Hz. Most LMN neurons have small, well defined excitatory electroreceptive fields (RFs) exhibiting no surround inhibition, at least as detectable by methods employed here. Seventy-eight percent of units recorded had RFs restricted to the ventral surface: of these, 98% were contralateral. The remaining 22% of units had disjunct dorsal and ventral receptive fields. Electrosensory RFs on the ventral surface are somatotopically organized. Anterior, middle, and posterior body surfaces are mapped at the rostral, middle, and caudal levels, respectively, of the contralateral LMN. The lateral, middle, and medial body are mapped at medial, middle, and lateral levels of the nucleus. Moreover, the RFs of all units isolated in a given dorsoventral electrode track are nearly superimposable. About 40% of LMN, measured from the dorsal surface, is devoted to input from ventral electroreceptors located in a small region rostral and lateral to the mouth.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Intraspecific metabolic diversity among strains of Burkholderia cepacia isolated from decayed onions, soils, and the clinical environment.

A collection of 218 strains of Burkholderia cepacia (including 18% strain replicates) was assembled from organic soils, decayed onions, and clinical sources. Each strain was characterized for virulence to onion, catabolic ability using the Biolog GN microtiter plate, and several other behaviors. Overall test reproducibility was estimated at 98%. The results obtained using the Biolog GN system corresponded well to those obtained using standard methods. Three coefficients of resemblance (Gower similarity, pattern difference, and Jaccard similarity) were calculated and clustered by the group-average method. The sorted matrices and phenograms, while giving evidence of an underlying phenetic structure to the B. cepacia nomenspecies, gave little evidence of sorting by broad source of isolation. Strains isolated from within fields or samples were frequently found to be similar, however, strains isolated from fields with similar cropping histories were not. The Gower-transformed centroids of ordained clusters were projected in a principal coordinate system and estimates of disjunction were calculated. Strains of B. cepacia were shown to be non-uniformly distributed in taxonomic space. Strains isolated by serial dilution on onion slices formed a tight phenetic cluster which includes the type strain of the nomenspecies and that of a synonymous group (Pseudomonas multivorans); the strains in this phenon were generally virulent to onion and were partially differentiated from others by pectolytic behavior and by the production of diffusible pigment on King's medium A. Further characterization should better resolve the taxonomy of the nomenspecies.

Allium↗

Contribution of transplantations to the understanding of the role of the PLP gene.

We present an overview of the results obtained in a cross-transplantation system using respectively controls, jimpy (jp), and shiverer mutant mice as donors and recipients. Homochronic transplantations (O days into O days) demonstrated that jp environment is non-toxic for non-jp cells and that, contrary to in vitro, jp oligodendrocytes phenotype cannot be modified by environmental factors at this age. Transplantations of embryonic fragments into the newborn brain demonstrated that in contrast to oligodendrocyte precursors contained in fragments of newborn tissue, jimpy embryonic stem cells are sensitive to environmental factors able to modulate the proportion of surviving oligodendrocytes. In addition, these series evidenced a disjunction between the surviving and the myelinating capacity of jp cells demonstrating a pleiotropic effect of the jp mutation on oligodendrocyte biology. Results are discussed with regards to the recent molecular biological finding on the role of the DM20/PLP gene.

Animals↗

A novel omega-conopeptide for the presynaptic localization of calcium channels at the mammalian neuromuscular junction.

Voltage-sensitive Ca2+ channels are essential to transmitter release at the chemical synapse. To demonstrate the localization of voltage-sensitive Ca2+ channels in relation to the site of transmitter release, mouse neuromuscular junctions were double labelled with alpha-bungarotoxin and a novel voltage-sensitive Ca2+ channel probe, SNX-260, a synthetic analog of omega-conopeptide MVIIC. Similar to omega-conopeptide MVIIC, biotinylated SNX-260 blocked nerve-stimulated transmitter release at the mouse neuromuscular junction. Fluorescently-tagged biotinylated SNX-260 labelled the nerve terminal which appeared thinner than and was outlined by acetylcholine receptor clusters as seen in en face view. This SNX-260 labelling was inhibited by preincubation with unconjugated SNX-260. Side-views of the neuromuscular junction indicated that the SNX-260 labelling was on the synaptic side facing the acetylcholine receptor rather than on the nonsynaptic side of the nerve terminal. This presynaptic binding was confirmed by the absence of SNX-260 labelling in denervated muscles following a nerve cut or disjunction after collagenase treatment. Confocal microscopy revealed spots of SNX-260 labelling that may correlate with active zones. The SNX-260 labelling pattern was not affected by preincubation with unconjugated SNX-111 (omega-conopeptide MVIIA), an N-type voltage-sensitive Ca2+ channel blocker. These findings suggest that SNX-260 is a novel probe for localizing non-N type voltage-sensitive Ca2+ channels and that these voltage-sensitive Ca2+ channels are localized near the transmitter release sites at the mammalian motor nerve terminal membrane. The results are consistent with the suggestion that non-N, probably P/Q type voltage-sensitive Ca2+ channels mediate evoked transmitter release at the mammalian neuromuscular junction.

Animals↗

Cellular and matrix changes in drug abuser liver sinusoids: a semiquantitative and morphometric ultrastructural study.

The aim of the present work was to analyse, at the ultrastructural level, the action of heroin of 150 centrilobular sinusoids from liver biopsies of five intravenous drug abusers, who presented clinical and biological manifestations of hepatic impairment. A comparative study of 90 sinusoids from liver biopsies of three control patients was performed. Electron microscopic observations showed a thickening of the sinusoidal wall related to endothelial cell hypertrophy and to fibrosis of the space of Disse. This was generally associated with basement-membrane-like material and hepatocyte microvilli flattening. In addicts, hepatic vascular pole changes were a constant finding, accompanied by interhepatocyte space disjunction and perisinusoidal collagenization. Morphometric assessment confirmed a significant increase of sinusoidal wall surface, endothelial cell body and processes and Ito cell process surface was significantly different between the patient groups. This cellular hypertrophy may represent hyperactivation of the sinusoidal cell functional capacity, triggering the fibrogenesis in the space of Disse. While this mechanical barrier might hinder the free exchange through the space of Disse, it may equally well protect the liver against heroin toxicity.

Adult↗

Analysis using dual-colour fluorescence in situ hybridization of meiotic chromosome segregation in male mice heterozygous for a reciprocal translocation.

Meiotic chromosome behaviour was investigated in male mice heterozygous for the translocation T(7;16)67H. At metaphase I, chain-of-four quadrivalents were present in approximately 80% of the spermatocytes; the bulk of remaining cells contained a ring quadrivalent, with only a few having either a trivalent plus univalent configuration or two bivalents. A low rate of non-disjunction, approximately 5%, was found through analysis of C-banded metaphase II spermatocytes. Using fluorescence in situ hybridization with differentially labelled whole chromosome paints, a wide array of segregation products were observed at metaphase II, depending on whether they arose from alternate, adjacent I, adjacent II orientation at metaphase I or were uninformative for alternative/adjacent I because of the presence of a chiasma in an interstitial pairing segment. Some 62% of the cells fell into this latter category, with only small proportions clearly arising through alternate (1.8%) or adjacent I (0.7%) orientations. Approximately 30% of the cells contained the products of adjacent II orientation. Consideration of the data suggested that most of these cells arose from metaphase I cells that contained a chain quadrivalent. Ring quadrivalents appeared predominantly to orientate in an alternate/adjacent I manner.

Animals↗

Biochemical polymorphisms and phenetic relationships in rodents of the genus Ctenomys from southern Brazil.

Protein variation at 20 loci was analyzed by starch gel electrophoresis in population samples of Ctenomys flamarioni, C. torquatus, C. sp., and C. minutus collected in 25 localities of Southern Brazil. Results show that these four species exhibit higher levels of genetic variability (He = 0.11-0.17) than those reported for most other fossorial rodents. Estimates of similarity coefficients indicate that C. minutus and C. sp. (S = 0.91) are the closest species, while C. flamarioni (S = 0.77) is the most distant from the others. The data presented here support the hypothesis of a relatively recent disjunction of C. minutus from C. sp. Within-species similarity indices are of the same order of magnitude as those found between species. The relatively high levels of heterozygosity observed are not in accordance with the view that subterranean taxa should be less variable than aboveground species due to the uniformity of their environment.

Alleles↗

Work, knowledge and argument in specialist consultations: incorporating tacit knowledge into system design and development.

To understand how video telephone technology could support consultations between pathologists and surgeons, this study looked at what constitutes 'work' in clinical consultations. Using several methods (participant observation, video and interviews), we found pathologists and surgeons both share and do not share similar understandings of what a consultation is, what one should achieve in a consultation, and what in fact constitutes a 'successful' consultation. Furthermore, the same objects of consultation (the products of 'offstage' work) can be used and defined quite differently depending on how a consultation is framed. Differences and disjunctions like these have to be better understood if computer-supported cooperative healthcare work (CSCHW) applications are to be adopted and accepted.

Communication↗

Pavlovian conditioning and rule learning.

The experiment reviewed here was an attempt to show that two differential Pavlovian conditioning designs, namely positive and negative patterning, can best be understood as rule learning. First, it is shown that positive patterning is equivalent to the logical rule of conjunction (AND) and that negative patterning is equivalent to the logical rule of exclusive disjunction (XOR). It is assumed that in order to learn both kinds of discrimination subjects learn to use the according rule. If this is the case, the observed differentiation should be independent of the number of reinforcements for each individual stimulus. Second, subjects should be able to transfer the rule to new stimuli. Forty human subjects were randomly divided into four groups (N = 10 each). Two factors were manipulated independently between subjects: (1) positive vs negative patterning, and (2) 2 vs 4 pairs of trained stimuli. Second interval skin conductance responses were measured. During initial acquisition positive as well as negative patterning occurred independently of number of pairs of trained stimuli (with total amount of training kept constant). Furthermore, AND as well as XOR could be transferred to new stimuli.

Adult↗

Persistence of nucleolar RNA-rich structures and Ph1 duplication in the blastic crisis of chronic myeloid leukaemia.

Nucleolar persistence in metaphase plates is a feature observed in most of the cells in neoplastic processes. Pathological persistence or fragmentation of the nucleoli is thought to be the cause of some numerical chromosomal aberrations due to non-disjunction of the chromatids, with particular involvement of the satellite chromosomes. Thus, a combined selective staining of both the nucleoli (amido black 10B according to Mundkur and Brauer's cytochemical technique) and the chromosomes (neutral red) was applied to the metaphase plates of patients with chronic myeloid leukaemia in the blastic crisis. Duplicated Ph1 was associated with amido black-stained areas at a very high rate in some cases. Since the blastic crisis in chronic myeloid leukaemia is characterized by the appearance of an increased number of immature, highly nucleolated cells, these findings lend support to the hypothesis that the duplication of the Ph1 represents a feature possibly favoured by the pathological persistence of nucleolar RNA-rich structures in the metaphase.

Adult↗

Beyond medical futility: a proposed taxonomy of ultra vires acts in medicine.

When is a physician's act non-medical, and how might such non-medical acts be classified? One approach, analogous to the substantive due process inquiry employed by American courts weighing the constitutionality of legislative acts, would involve consideration of the following questions: 1) Is a legitimate medical goal being pursued? 2) Are the means being employed legitimately medical? 3) Are the goals and means appropriately related? Accordingly, a physician acts medically when employing legitimate and appropriate medical means in pursuit of a legitimate medical goal. In contrast, when the goals pursued or means employed are not legitimately medical, or when the two are not appropriately related, the act is medically ultra vires ("beyond the powers")--that is, an act beyond the physician's power or authority--and consequently non-medical. Medically ultra vires acts may be further sub-classified depending upon which prong of the above trident is defective. Where the goal of the act, though achievable, is not legitimately medical, the act is medically ultra vires because of goal illegitimacy, or medically ultra fines ("beyond the ends"). Where the means employed are not legitimately medical, the act is medically ultra vires because of means illegitimacy, or medically ultra modos ("beyond the means"). Where the means and goals are not appropriately related, the act is medically ultra vires because of means-goals disjunction, or medically ultra nexus ("beyond the connection"). Medical futility (where the medical goal in question, albeit legitimate, cannot be achieved by the act under consideration) represents the paradigmatic example of the latter.

Classification↗

The dynamics of vertical vergence.

We measured the gain and phase of vertical vergence in response to disjunctive vertical oscillations of dichoptic textured displays. The texture elements were m-scaled to equate visibility over the area of the display and were aperiodic and varied in shape so as to avoid spurious binocular matches. The display subtended 65 degrees and oscillated through peak-to-peak amplitudes from 18 arc min to 4 degrees at frequencies from 0.05 to 2 Hz - larger ranges than used in previous investigations. The gain of vergence was near 1 when the stimulus oscillated at 18 arc min at a frequency of 0.1 Hz or less. As the amplitude of stimulus oscillation increased from 18 arc min to 4 degrees, vergence gain decreased at all frequencies, which is evidence of a nonlinearity. Gain declined with increasing stimulus frequency but was still about 0.5 at 2 Hz for an amplitude of 18 arc min. Phase lag increased from less than 10 degrees at a stimulus frequency of 0.05 Hz to between 100 degrees and 145 degrees at 2 Hz. Overall, the dynamics of vertical vergence resemble the dynamics of horizontal vergence and cyclovergence.

Adult↗

Visual-vestibular stimulation interferes with information processing in young and older humans.

Attention has been implicated in postural control and other tasks requiring sensory integration. The purpose of this study was to investigate the role of attention in sensory-motor processing of vestibular and combined visual-vestibular information during seated rotations using a dual-task interference approach. We hypothesized that auditory information processing would be influenced by concurrent visual-ocular, vestibulo-ocular, or combined visual-vestibulo-ocular processing. We further hypothesized that the effect would be greater in older subjects. Twenty older subjects (10 women, 10 men, 69.3+/-3.2 years) and 20 young subjects (10 women, 10 men, 23.5+/-2.9 years) were asked to perform information-processing tasks while they underwent several types of vestibular, visual-vestibular, and ocular motor paradigms. The information-processing tasks were: (1) an auditory simple reaction-time task (SRT), (2) an auditory go-no-go (disjunctive) reaction-time task (DRT), and (3) an auditory forced-choice task (CRT). The visual-vestibular-ocular motor conditions included: (1) no movement/darkness (NO), (2) no movement/fixation (FIX), (3) no movement/pursuit (P), (4) earth-vertical axis rotation (EVAR) in darkness, (5) EVAR with fixation (E-FIX), (6) off-vertical axis rotation (OVAR) in darkness, and (7) OVAR with fixation (O-FIX). Results showed that older subjects had longer reaction times for all combinations of stimulus condition and reaction-time task compared with young subjects. Compared with the NO baseline, reaction times during EVAR were longer for young and older subjects and during OVAR were longer for the young subjects. For FIX and P, the reaction times during P exceeded those during FIX and during NO for both groups. For E-FIX and O-FIX, reaction times did not differ from those during EVAR and OVAR. The interference with information processing by concurrent vestibular stimulation in the dark may be based upon cortical inhibition of auditory processes by vestibular stimulation. Eye movements induced by EVAR showed an increased phase lead during reaction-time tasks, suggesting altered vestibulo-ocular reflex (VOR) dynamics, possibly based on cerebellar-mediated changes in velocity storage. Since fixation of a head-fixed visual target did not add to the effect of rotation in the dark, a further implication of our results is that VOR-fixation while performing a concurrent information-processing task may be accomplished primarily by VOR suppression rather than by VOR cancellation.

Acoustic Stimulation↗

Sound-evoked vestibulo-ocular reflexes (VOR) in trained monkeys.

Acoustic stimulation of the vestibular system has been well documented in humans and has been accepted as a useful tool to diagnose vestibular disorders. The goal of this study was to establish an awake and behaving primate model that might be useful for investigating the neural mechanisms underlying acoustic activation of the vestibular system. We recorded sound-evoked eye movements in monkeys while they performed ocular motor tasks. In the first part of the study, an acoustic click (1 ms, 99 to approximately 125 db peak SPL) was delivered to one of the monkeys' ears while they fixated on visual targets of varying eccentricities and viewing distances. Acoustic clicks were found to evoke well-defined biphasic eye velocity responses. For the movement in the horizontal direction, the first eye velocity peaks were always away from the stimulated ear. For the movement in the vertical direction, however, the directions of the first eye velocity peaks varied from monkey to monkey. This variability was difficult to interpret in the absence of torsional measurement. Thus, our analysis in this report was focused on horizontal eye movements. We found that click-evoked eye movements were disjunctive, with larger first horizontal eye velocity peaks from the eye ipsilateral to the stimulated ear (the amplitude ratio was 1.8 +/- 0.3, n=4). The amplitudes of the first horizontal peaks were also linearly correlated with gaze eccentricity and viewing distance. In the second part of the study, we found that a brief tone-pulse (100 ms, 125 db peak SPL) evoked eye movements that exhibited a well-defined frequency tuning with the most effective stimulating frequencies ranging from 1 K to 1.5 KHz. These data demonstrate that the sound-evoked eye movements in behaving monkeys are well defined and reproducible. This paradigm may be useful for studying the neural mechanisms underlying acoustic activation of the vestibular system.

Acoustic Stimulation↗

A phylogeographic split in Buxus balearica (Buxaceae) as evidenced by nuclear ribosomal markers: when ITS paralogues are welcome.

Sequences from the ribosomal nuclear internal transcribed spacers (ITS) have been widely used to infer evolutionary hypotheses across a broad range of living organisms. Intraspecific sequence variation is assumed to be absent or negliable in most species, but few detailed studies have been conducted to assess the apportionment of ITS sequence variation within and between plant populations. Buxus balearica was chosen as a model species to assess the levels of infraspecific and intragenomic ITS variation in rare and endangered species occurring in disjunct populations around the Mediterranean basin. Intragenomic polymorphic sites were detected for western and eastern accessions of B. balearica and in two accessions of the sister species B. sempervirens. Overall, 19 different ribotypes were found in B. balearica after sequencing 48 clones, whereas 15 ribotypes were detected in 19 clones of B. sempervirens. The integrity and secondary structure stability of the ribosomal sequences suggest that they are not pseudogenes. The high number of ribotypes recovered through cloning suggested that some sequences could be chimeric or generated in vivo by partial homogenization through gene conversion or unequal crossing-over. Average sequence divergence among B. balearica clones was 0.768%, and the most divergent sequences differed by 1.62%. Available evidence does not suggest that B. balearica paralogues have been obtained from other extant Buxus species through interspecific hybridization. The presence of several ribosomal sequences in box implies that the molecular forces driving the concerted evolution of this multigene family are not fully operational in this genus. Phylogenetic analyses of cloned ITS sequences from B. balearica displayed very poor resolution and only two clades received moderate bootstrap support. Despite the marked intragenomic sequence divergence found, ribosomal data suggest a clear phylogeographic split in B. balearica between western and eastern accessions. The distinct, nonchimeric sequences that are postulated as being present in each biogeographic group suggest that box populations from Anatolia (eastern Mediterranean) are relict.

Base Sequence↗