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PubMed1995

The mATPase histochemical profile of rat type IIX fibres: correlation with myosin heavy chain immunolabelling.

In the present study we report a novel histochemical method which, by sequential pre-incubations in alkaline and acidic media, selectively differentiates muscle fibres expressing myosin heavy chain IIX, on the basis of a specific profile for myofibrillar actomyosin ATPase (mATPase) activity. The enzyme reactions were tested for specificity by means of anti-myosin heavy chain monoclonal antibodies, which were characterized on Western blots of muscle homogenates. Enzyme histochemical reactions with the traditional pH buffers were compared to those of the new method and, in conjunction with the immunoreactions, used to confirm the relationship between MyHC expression and the distinct profiles for mATPase. Immunohistochemical reactions demonstrated that the new method only differentiates those fibres expressing myosin heavy chain IIX. The method revealed a continuum in which the intermediate staining intensities corresponded to hybrid fibres expressing myosin heavy chain IIX in combination with either the IIA or IIB forms. Quantitative histochemistry and immunohistochemistry (by image analysis), used to examine the relationship between staining intensities for mATPase and amounts of myosin heavy chain IIX expression, revealed that the new method discriminates well between hybrid fibres expressing variable amounts of the IIX isoform (r2 = 0.93).

Animals↗
PubMedDate not supplied

Investigation of P300 in various forms of epilepsy.

The problem of the late EP components generator localization has not yet been solved. This study aims to find out if a focal cortical epilepsy of the frontal (FLE) or of the temporal lobe (TLE) can modify the P300 component of the evoked response (either visual or auditory). Our data rely mainly on the selective differentiation test of an 80 dB click alternatively applied on the right or left ear, the patient having to give a motor response to those stimuli which have been chosen as target stimuli (probability of administration, 1:4). Under these circumstances, in normal subjects, evoked potentials showed deep P300 and an attenuated N2b in case of target stimulation and high, delayed N2b and an attenuated P300 for the nontarget stimulation, FLE did not abolish the late components of the EP; on the contrary, these were significantly augmented by the task. TLE, in exchange, severely attenuated differences between N2b-P300 components recorded from the scalp in case of target and nontarget stimulation. P300 was even higher at rest (possibly an effect of defective habituation). Rare or rapid stimuli application which was separately investigated gave another type of EPs modification compared to that specific for the auditory discrimination task. These facts are corroborated with the complete abolition of late EP components after lateral brain stem lesions. The conclusion is that N2a component has a reticular brain stem generator while N2b and P3 have initial generators in the temporal lobe (hippocampus).

Adolescent↗
PubMed1996

Contribution to occupational angiopathy diagnosis using special examination method.

The authors presented 1642 cases of professional diseases caused by vibrations (VD) and 435 cases of extremity overload disease (EOD) diagnosed in the years 1974-1993. In addition to the standard rheoplethysmography there were evaluated the results of digital laser Doppler flowmetry (Moor instruments, UK) in 104 workers exposed to vibration (EV) and 25 controls with the age and smoking habit standardisation. In the selected subgroup were used continual measurements of digital blood pressure (Finapress, Ohmeda), digital LD flux and speed and the measuring of digital skin and central body temperature simultaneously. The records before and after 10 min of local cooling test (Rejsek method) and postocclusive hyperemic tests were summarized (computer evaluation, program STATGRAPHICS, T-test). Vasoconstriction to local cooling persisted in EV for longer time. The records of digital skin flux and speed, digital blood pressure reactions of EV were significantly different (EV/controls) also in the 10th min after cooling. Postocclusion hyperemic tests revealed good functional capacity also in EV. Advantages and disadvantages of methods were discussed. The results found by non-invasive methods in VD were in good relation to images obtained by means of radionuclides (clearance and cumulative tests). Cumulative tests (after 99m--pertechnetate i.v.) can be used in the selected differential diagnostic cases of angiopathies to help to distinguish degree of angiospastic and angioparalytic changes in the hands of VD, and also in special cases at angiopathies connected with EOD.

Adult↗
PubMed1998

[Genogeographic primary hypolactasia in the Old World populations].

The geographic distribution of primary hypolactasia (i.e., the genetically determined (LAC*R), age-dependent decrease in lactase activity, which is phenotypically expressed as the intolerance to whole milk), was studied. Data on the distribution of primary hypolactasia and the LAC*R gene frequencies in populations of the Old World are analyzed, with special emphasis on LAC*R distribution in Russia. New data on populations of Kildin Saamis, Mordovian ethnic groups (Mokshas and Erzyas), Udmurtians, Komi-Permiaks, Komi-Zyrians (Komi-Izhem ethnographic group), Northern (Sos'va) Mansis, Northern Khantys, and Russians are described. Gene geographic maps of the LAC*R gene's distribution in populations of the Old World, Europe, and the Ural region were constructed. A map reflecting the amount of the original information on different regions and, therefore, the reliability of the gene geographic maps, is given. In Europe, the interpopulation diversity Gst of the LAC*R gene was significantly higher (0.169) than the average diversity of the European gene pool. The high variation was assumed to result from a potent differentiating selection that affects the gene for primary hypolactasia.

Africa↗
PubMed1988

Effects of ethanol, barbital, and lorazepam on brain monoamines in rat lines selectively outbred for differential sensitivity to ethanol.

The acute effects of ethanol, barbital, and lorazepam on the synthesis and metabolism of brain monoamines were studied in the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) lines of rats, which have been selected for differential motor impairment after ethanol administration. The ethanol-sensitive ANT rats are also more sensitive than the ethanol-insensitive AT rats to the motor impairment caused by barbital and lorazepam. Ethanol increased, whereas barbital and lorazepam decreased, the synthesis of catecholamines in several regions of the brain. Ethanol did not affect the formation of DOPAC, whereas barbital and lorazepam reduced it. Similarly, the accumulation of 5-HTP was increased after administration of ethanol, but was decreased after administration of barbital or lorazepam. Ethanol, barbital and lorazepam decreased the formation of 5-HIAA. The rat lines did not differ in any of these responses. Some differences could, however, be demonstrated between the AT and ANT rats in the effects of the three drugs on the levels of the brain monoamines. Although the importance of these differences in the differential sensitivity to these drugs between the two lines is difficult to determine, the role of central monoaminergic mechanisms cannot be excluded. These findings also suggest that the motor impairment induced by ethanol, barbiturates, and benzodiazepines is probably not primarily based on the monoaminergic systems.

Animals↗
PubMed2002

Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences.

RATIONALE: Rats selectively bred for high intake of a sweet saccharin solution (HiS) consume more ethanol than their low-saccharin intake (LoS) counterparts. The HiS phenotype may be a predictor of abuse of other drugs via other routes of administration. OBJECTIVE: HiS and LoS, male and female rats were tested for acquisition of IV cocaine and heroin self-administration under a fixed-ratio 1 (FR1) schedule, and cocaine-reinforced behavior was examined under a progressive-ratio (PR) schedule. METHODS: Four groups of rats (HiS males and females and LoS males and females) were trained to self-administer IV cocaine (0.2 mg/kg), and another four groups were trained to self-administer heroin (0.015 mg/kg) using an automated autoshaping procedure. Rats were allowed 30 days to reach a criterion whereby a mean of 100 (cocaine) or 20 (heroin) infusions were self-administered during 6-h sessions over 5 consecutive days. RESULTS: The HiS female rats acquired cocaine self-administration significantly more rapidly than the LoS rats, and females of both phenotypes met the acquisition criteria more rapidly than males. In both HiS and LoS cocaine groups a greater percentage of females (compared with males) met the acquisition criteria within 30 days. The only cocaine group in which 100% met the criterion was the HiS females. The female (compared with male) heroin groups showed a more rapid rate of acquisition, but there was no difference due to saccharin phenotype. In each of the four heroin groups 100% of all rats met the criteria within 30 days. Results of the PR schedule in the HiS females and males and LoS females indicated significantly higher break points in the HiS females (compared with HiS males), but there were no differences in females due to phenotype. CONCLUSION: Female rats selectively bred for higher saccharin intake show more rapid and successful acquisition of IV self-administration of a low dose of cocaine than those bred for low saccharin intake. Female rats (compared with males) consistently showed accelerated rates of acquisition and maintenance (PR) of cocaine self-administration and acquisition of heroin self-administration.

Analysis of Variance↗
PubMed1995

Clinical application of differential ventilation with selective positive end-expiratory pressure in adult respiratory distress syndrome.

Differential ventilation in the lateral position with positive end-expiratory pressure (PEEP) selectively applied to the dependent lung (DVSP) has been shown to reduce venous admixture and improve oxygenation without compromising cardiac output in short term studies of patients with acute respiratory failure. We have applied this ventilation technique as a long-term treatment in severe adult respiratory distress syndrome (ARDS) in an open clinical trial. Eleven patients with ARDS of varying aetiology were treated with DVSP for a total of 34 days. Median duration of conventional ventilatory therapy before start of DVSP was 5 days (1 to 18 days), inspiratory oxygen fraction (FIO2) was 0.61 +/- 0.16 (mean +/- s.d.), resulting in a mean arterial oxygen tension (PaO2) of 7.1 +/- 2.1 kPa (PaO2/FIO2 = 11 +/- 4 kPa). A gradual improvement in gas exchange was seen during the first 24 h of DVSP such that PaO2 increased to 8.4 +/- 1.4 with a decreased FIO2 (0.52 +/- 0.14) resulting in an increased PaO2/FIO2 (16 +/- 5 kPa). Five out of the eleven patients survived. No major complication was noted using DVSP as a method. We found a steady improvement in gas exchange over the first 24 hours in most patients. However, mortality rate was no lower than expected. Drawbacks with DVSP were increased demand on staff and difficulties with adequate endo-bronchial suctioning.

Adolescent↗
PubMed2004

Electrical and neurotransmitter activity of mature neurons derived from mouse embryonic stem cells by Sox-1 lineage selection and directed differentiation.

Sx1TV2/16C is a mouse embryonic stem (ES) cell line in which one copy of the Sox1 gene, an early neuroectodermal marker, has been targeted with a neomycin (G418) selection cassette. A combination of directed differentiation with retinoic acid and G418 selection results in an enriched neural stem cell population that can be further differentiated into neurons. After 6-7 days post-plating (D6-7PP) most neurons readily fired tetrodotoxin (TTX)-sensitive action potentials due to the expression of TTX-sensitive Na(+) and tetraethylammonium (TEA)-sensitive K(+) channels. Neurons reached their maximal cell capacitance after D6-7PP; however, ion channel expression continued until at least D21PP. The percentage of cells receiving spontaneous synaptic currents (s.s.c.) increased with days in culture until 100% of cells received a synaptic input by D20PP. Spontaneous synaptic currents were reduced in amplitude and frequency by TTX, or upon exposure to a Ca(2+)-free, 2.5 mm Mg(2+) saline. S.s.c. of rapid decay time constants were preferentially blocked by the nonNMDA glutamatergic receptor antagonists CNQX or NBQX. Ca(2+) levels within ES cell-derived neurons increased in response to glutamate receptor agonists l-glutamate, AMPA, N-methyl-d-aspartate (NMDA) and kainic acid and to acetylcholine, ATP and dopamine. ES cell-derived neurons also generated cationic and Cl(-)-selective currents in response to NMDA and glycine or GABA, respectively. It was concluded that ES-derived neurons fire action potentials, receive excitatory and inhibitory synaptic input and respond to various neurotransmitters in a manner akin to primary central neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

A novel selection regime for differentiation defects demonstrates an essential role for the stumpy form in the life cycle of the African trypanosome.

A novel selection scheme has been developed to isolate bloodstream forms of Trypanosoma brucei, which are defective in their ability to differentiate to the procyclic stage. Detailed characterization of one selected cell line (defective in differentiation clone 1 [DiD-1]) has demonstrated that these cells are indistinguishable from the wild-type population in terms of their morphology, cell cycle progression, and biochemical characteristics but are defective in their ability to initiate differentiation to the procyclic form. Although a small proportion of DiD-1 cells remain able to transform, deletion of the genes for glycophosphatidyl inositol-phospholipase C demonstrated that this enzyme was not responsible for this inefficient differentiation. However, the attenuated growth of the Delta-glycophosphatidyl inositol-phospholipase C DiD-1 cells in mice permitted the expression of stumpy characteristics in this previously monomorphic cell line, and concomitantly their ability to differentiate efficiently was restored. Our results indicate that monomorphic cells retain expression of a characteristic of the stumpy form essential for differentiation, and that this is reduced in the defective cells. This approach provides a new route to dissection of the cytological and molecular basis of life cycle progression in the African trypanosome.

Aconitic Acid↗
PubMed1984

Selective migration of terminally differentiating cells from the basal layer of cultured human epidermis.

How terminally differentiating cells are selectively expelled from the basal layer of epidermis has been a source of interest and speculation for many years. The problem can now be studied in culture, using involucrin synthesis as an early marker of terminal differentiation in human keratinocytes. When keratinocytes are forced to grow as a monolayer by reducing the calcium ion concentration of the culture medium, they still begin to synthesize involucrin. Raising the level of calcium ions induces stratification, and cells that are synthesizing involucrin are selectively expelled from the basal layer. I have found that during calcium-induced stratification no new proteins or glycoproteins are synthesized, and the rate of cell division does not change. Movement of involucrin-positive cells out of the basal layer was found to be unaffected by cycloheximide, tunicamycin, or cytosine arabinoside. These results suggest that keratinocytes growing as a monolayer already have the necessary properties to determine their position when stratification is induced. Addition of calcium simply allows formation of desmosomes and other intimate cell contacts required for stratification. The properties of involucrin-positive cells that determine their suprabasal position include a reduced affinity for the culture substrate and preferential adhesion to other cells at the same stage of terminal differentiation. The molecular basis of these adhesive changes is discussed.

Calcium↗
PubMed1984

Stimulant and depressant properties of sedative-hypnotics in mice selectively bred for differential sensitivity to ethanol.

A genetic analysis of sedative-hypnotic response in selectively bred Long-Sleep (LS) and Short-Sleep (SS) mice showed LS mice to be more depressed by acetaldehyde, ethanol (ETOH), and t-butanol, but less sensitive to pentobarbital. Intermediate inheritance was shown by the two reciprocal F1 hybrids for the alcohols, but dominance to the LS genotype occurred for the aldehyde and the barbiturate. At several subhypnotic doses of ETOH in two experiments, LS mice showed less locomotor stimulation and greater disruption of coordination than the SS mice. The two reciprocal F1 hybrids did not differ from one another and had dose-response curves intermediate to the two parental lines. Study of the effects of t-butanol on locomotor activity revealed a pattern of line differences similar to that for ETOH. The genetic selection for LS and SS mice appears to have differentiated loci that pleiotropically influence a variety of behavioral responses to alcohols.

Analysis of Variance↗
PubMed2004

Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo.

Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1-3 mM) produced a significant increase in the number of bromodeoxyuridine (BrdU)-positive cells in high-density cultures, but did not increase clonal size in low-density cultures. Lithium chloride at 1 mM (within the therapeutic range) also increased the number of cells double-labeled with BrdU antibody and TuJ1 (a class III beta-tubulin antibody) in high-density cultures and the number of TuJ1-positive cells in a clone of low-density cultures, whereas it decreased the number of glial fibrillary acidic protein-positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindin(D28k)-positive cells, and involved a phosphorylated extracellular signal-regulated kinase and phosphorylated cyclic AMP response element-binding protein-dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindin(D28k)-positive neuronal cell type.

Animals↗
PubMed2005

Genetic dissociation between ethanol sensitivity and rapid tolerance in mouse and rat strains selectively bred for differential ethanol sensitivity.

BACKGROUND: The Inbred Long- and Short-Sleep mice (ILS and ISS) and the Inbred High- and Low-Alcohol-Sensitive rats (IHAS and ILAS) were selectively bred for differential alcohol sensitivity with use of the duration of loss-of-righting-reflex test (LORR), with the IHAS and ILS animals being much more sensitive than the ILAS and ISS animals, respectively. The current study was undertaken to determine whether acute sensitivity in these strains is genetically correlated to a rapid tolerance to alcohol, a form of tolerance that is evident 24 hr after a single alcohol dose. METHODS: Separate groups of animals were administered a single pretreatment dose of alcohol (0-6 g/kg for the mice; 0-4 g/kg for the rats). Alcohol sensitivity was tested 24 hr later with the LORR test, and blood ethanol concentration was tested at regain of righting (BECRR). Alcohol-induced hypothermia also was determined in the mice. Independently derived replicate rat strains were used for all experiments (IHAS1, ILAS1; IHAS2, ILAS2); no such replicates exist for the ILS and ISS strains. RESULTS: Alcohol pretreatment caused a dose-dependent decrease in LORR duration accompanied by an increase in BECRR in the ILS strain, but LORR increased in the ISS strain with no effect on BECRR. Both strains became hypothermic during the LORR test on day two, but the only significant effect of alcohol pretreatment was in the ISS strain, in which alcohol-induced hypothermia was enhanced. Alcohol pretreatment caused a significant dose-dependent decrease in LORR duration accompanied by an increase in BECRR in the IHAS1 but not in the IHAS2 strain. In contrast, ILAS1 and ILAS2 strains both showed a significant increase in LORR duration and also a significant increase in BECRR. CONCLUSIONS: Alcohol pretreatment caused a dose-dependent decrease in LORR duration and an increase in BECRR in the IHAS1 and ILS strain, suggesting the development of functional rapid tolerance. In contrast, LORR duration increased in the ILAS1, ILAS2, and ISS groups, but BECRR either increased (ILAS1, ILAS2) or did not change (ISS). These observations suggest that central nervous system sensitivity was decreased in the ILAS1 and ILAS2 groups (i.e., rapid functional tolerance) or unchanged in the ISS strain, but that some pharmacokinetic property also was altered in these strains. Overall, the results do not support a genetic relation between alcohol sensitivity and the development of rapid tolerance.

Alcoholism↗
PubMed2003

Distractibility during selection-for-action: differential deficits in Huntington's disease and following frontal lobe damage.

Selective attention can be measured through analysis of errors and reaction time (RT) for trials in which targets are presented alone compared with trials in which targets and distractors are presented. This study investigated selective attention using a reaching task, in which subjects made rapid reaches to targets. Thirty-seven patients with lesions of the prefrontal cortex (PFC) were compared with 19 healthy age- and IQ-matched volunteers and 18 patients with early-stage Huntington's disease (HD), a neurodegenerative disease primarily affecting the basal ganglia. It was hypothesised that, if fronto-striatal circuits as a whole support selection-for-action, then the pattern of behavioural performance of both patient groups would be similar. Alternatively, if the functional roles of PFC and basal ganglia in selection-for-action are dissociable, then two different patterns would emerge. It was found that that both HD and frontal groups were significantly more distractible than controls for RT, but they had a different pattern of errors. Frontal patients made significantly more touches of the distractor location itself than did controls, while this was not the case for HD. It is argued that a reactive-inhibition mechanism, required in the circumstance of strong distractor activation, is affected by frontal damage, while a lateral-inhibition mechanism, invoked during the recruitment of selective attention, is affected in HD. Additionally, there were significant correlations between the degree of distractibility for RT and the extent of lateral PFC damage, and between cue-generated preparation and lateral PFC damage, thus highlighting the critical importance of lateral, rather than orbital or medial, PFC for attention to action.

Attention↗
PubMed2004

The role of natural selection in genetic differentiation of worldwide populations of Drosophila ananassae.

The main evolutionary forces leading to genetic differentiation between populations are generally considered to be natural selection, random genetic drift, and limited migration. However, little empirical evidence exists to help explain the extent, mechanism, and relative role of these forces. In this study, we make use of the differential migration behavior of genes located in regions of low and high recombination to infer the role and demographic distribution of natural selection in Drosophila ananassae. Sequence data were obtained from 13 populations, representing almost the entire range of cosmopolitan D. ananassae. The pattern of variation at a 5.1-kb fragment of the furrowed gene, located in a region of very low recombination, appears strikingly different from that of 10 noncoding DNA fragments (introns) in regions of normal to high recombination. Most interestingly, two main haplotypes are present at furrowed, one being fixed in northern populations and the other being fixed or in high frequency in more southern populations. A cline in the frequency of one of these haplotypes occurs in parallel latitudinal transects. Taken together, significant clinal variation and a test against alternative models of natural selection provide evidence of two independent selective sweeps restricted to specific regions of the species range.

Animals↗
PubMed1982

Selection and mortality differentials.

The Office of Population Censuses and Surveys Longitudinal Study provides reliable mortality data by a much wider range of characteristics than are available for other national sources. Although it is based on only a 1% sample of the population, it broadens the scope of mortality analysis and permits study of changes in relationships using different aspects of the time dimension. Data from this study have made us increasingly aware of the importance of selection to the interpretation and understanding of observed mortality differentials. Here we focus on that aspect of selection called "health-related mobility," which is associated with the relative health of people acquiring or losing individual characteristics. It is suggested that, for characteristics affected by health-related mobility, mortality differentials would narrow or widen with increased duration of follow-up. One of the basis of this argument the contribution of health-related mobility to mortality differentials by economic position and social class, to regional differentials, and to family and household differentials is investigated. Selection can thus be shown to operate when people change economic position, when they migrate, or when they change marital status. While the effects of these selection processes can be shown to contribute to social class gradients they do not explain regional differentials and contribute only to a limited degree to differentials by marital status. Differentials by household circumstances also reflect the product of selection processes.

Employment↗
PubMed1976

Salsolinol differentially affects mice selected for sensitivity to alcohol.

Salsolinol, a compound putatively formed following alcohol ingestion, differentially decreased the activity of lines of mice after 18 generations of genetic selection for alcohol sensitivity. Low doses of salsolinol produced significantly lower activity levels in the alcohol-sensitive long-sleep (LS) line than in the alcohol-insensitive short-sleep (SS) line. A hypnotic dose of salsolinol induced significantly longer sleeptimes in the LS line than in the SS line. Results are interpreted as supporting the hypothesis that salsolinol-like substances may mediate some of the effects of alcohol on the central nervous system.

Acetaldehyde↗
PubMed1984

Differential ventilation with selective PEEP in bilateral lung disease.

A patient with severe, acute respiratory failure (ARF) due to bilateral lung disease has been treated with a new ventilation concept aimed at improving the vertical match of ventilation and perfusion. The patient suffered from severe hypoxemia in spite of artificial ventilation with high PEEP and high inspired oxygen fraction. He was intubated with a double lumen bronchial catheter and placed in the lateral decubital posture, whereafter each lung was ventilated in accordance with its assumed perfusion, and selective PEEP of 10-15 cm H2O to the dependent and 0-5 cm H2O to the non-dependent lung was applied. Differential ventilation with selective PEEP resulted in a substantial improvement in pulmonary gas exchange in two separate periods of 3-4 days. The technique thus proved to be efficient and also clinically feasible in a standard intensive care unit.

Aged↗