Membrane anomalies of neoplastic cells

Neoplastic cells exhibit numerous membrane anomalies. Those involving the plasma membrane have attracted the greatest attention, although ample evidence indicates that the membranes of mitochondria, endoplasmic reticulum and lysosomes are also profoundly implicated. The information on these topics is briefly reviewed and it is concluded that of the multiple membrane anomalies observed, those responsible for high aerobic lactate production, abnormal plasma membrane transport and release of hydrolytic enzymes may figure prominently in malignant behaviour, i.e. invasiveness and metastasis. It is proposed that the membrane polymorphism of neoplastic cells can be explained in terms of the Changeux membrane lattice hypothesis. In particular it is suggested that the concerted behaviour of tumor cell membranes might deviate from normal due to one or more of the following processes: (a) insertion of a new protein (or lipid); (b) alteration of existing proteins (or lipids); (c) change in the proportion of phospholipid; (d) change in the proportion of glycolipid; (e) change in the proportion of cholesterol; (f) change in the steady-state of membrane ligands. The validity of this proposal is evaluated in terms of recent advances in membrane molecular biology.     

Role of the nucleus accumbens and the striatum in the production of turning behaviour in intact rats

Recent knowledge of the mechanisms underlying turning or circling behaviour in intact rats is reviewed. Most interest has been directed towards the striatum because of the classical hypothesis that turning behaviour results from lateral differences in the activity of the bilateral nigrostriatal pathway. However, the assumption that asymmetrical activation of the striatum is a necessary condition for dopamine-dependent turning behaviour has been questioned by several studies showing that unilateral injection of amphetamine or dopamine receptor agonists into the nucleus accumbens, a target of the mesolimbic dopaminergic system, also produces reliable circling away from the side of injection. Apart from discussing differences in stepping patterns of turning and discussing the role of the dopamine D1/D2 receptor interaction, the present survey focuses attention upon the two-component hypothesis, especially in relation to our recent studies in which activities of dopamine D1 and D2 receptors in the striatum and the nucleus accumbens have been manipulated separately in intact rats. It is hypothesized that turning behaviour is produced by asymmetry within nucleus accumbens circuits which involve neuronal connections from the nucleus accumbens to the A9 cell area, which in turn projects to the ventrolateral striatum that determines the direction of turning.     

Mentoring relationships of New Zealand nurses: an empirical study (Part 1)

A national, random, postal survey (n = 298) of mentoring behaviour among New Zealand nurses was undertaken. The initial research problem was to seek an explanation for the apparent lack of mentoring in New Zealand nursing. However, as the study evolved the lack of agreement concerning the definition of mentoring became a major research obstacle. A new conceptual framework of mentoring grounded in the work of Kathy Kram (1985) was devised. A quantitative global measure of mentoring behaviour (the TMS score) was used to measure levels of mentoring behaviour. This score was used as the dependent variable in subsequent statistical tests of: the definitional hypothesis-the study's validity check; the peer mentoring hypothesis which explored selected dynamics of mentor protégé relationships, and four allied research questions. The conceptual framework and approach are discussed in part one.     

évolution des comportements agressifs entre 17, 29 et 41 mois dans la population québécoise.

Several hypotheses on antisocial behaviour development have been based on individuals who are old enough to go to school. The present study's objectives were to verify some of these hypotheses in the transition from 17-29-41 months of age. Data for two aggressive behaviours (i.e. fighting, physically assaulting others) were collected in a sample that represented Quebec children. First, results suggest that in accordance with the socialization hypothesis, the propensity to show frequent aggressive behaviour is more consistent among boys between the ages of 29 and 41 months, while the propensity not to manifest such behaviour is more consistent among girls. Second, results suggest that under the precocity hypothesis, the propensity for frequent aggressive behaviour is more consistent in children between the ages of 29 and 41 months who already showed the same tendency at the age of 17 months. Third, under the severity hypothesis, results also show that aggressive behaviour is more consistent between 29 and 41 months in children who manifest it often. However, the contrary is true among the majority of children who do not manifest such behaviour at the age of 17 months. Fourth, results show that under the turn for the worse hypothesis, there are slightly more children who start manifesting frequent aggressive behaviour between 29 and 41 months, than there are children who stop manifesting such behaviour. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Con A cytotoxicity: a model for the study of key signaling steps leading to lymphocyte apoptosis in AIDS?

Lymphocytes respond to mitogens, viruses and other activation agents with hydrogen peroxide or reactive oxygen bursts which may originate at or near the cell membrane. It has been shown that a very small increase in the ratio of Con A cells results in a rapid switchover from mitogenicity to cytotoxicity. It is hypothesized that the change from mitogenicity to cytotoxicity correlates with the strength and duration of the hydrogen peroxide or reactive oxygen bursts which in turn depends on the number of molecules of the activation agent bound per cell. This hypothesis is presented and discussed in the context of the apoptosis (programmed cell death) and pro-oxidant-antioxidant hypothesis of CD4+ T-cell and B-cell subpopulation depletion in AIDS.     

Frequency tuning of basilar membrane and auditory nerve fibers in the same cochleae

Responses to tones of a basilar membrane site and of auditory nerve fibers innervating neighboring inner hair cells were recorded in the same cochleae in chinchillas. At near-threshold stimulus levels, the frequency tuning of auditory nerve fibers closely paralleled that of basilar membrane displacement modified by high-pass filtering, indicating that only relatively minor signal transformations intervene between mechanical vibration and auditory nerve excitation. This finding establishes that cochlear frequency selectivity in chinchillas (and probably in mammals in general) is fully expressed in the vibrations of the basilar membrane and renders unnecessary additional ("second") filters, such as those present in the hair cells of the cochleae of reptiles.     

Response of Neisseria gonorrhoeae to Bdellovibrio species

We have previously proposed that if the two half-layers of a membrane are different in their protein and lipid compositions, they may respond differently to some membrane perturbation (the bilayer couple hypothesis). This hypothesis has been applied to explain the changes in shape of human erythrocytes that are produced by a variety of amphipathic compounds. These compounds are presumed to intercalate by their hydrophobic ends into the lipid portions of the membrane; if the compounds are anions, the binding is preferentially to the outer half of the bilayer, if cations, to the inner half. It is proposed that such preferential binding causes an expansion of one half-layer relative to the other, with a corresponding change in cell shape. The predicted sidedness of these shape changes is now demonstrated in experiments with methochlorpromazine and 2,4,6-trinitrophenol. Under appropriate nonequilibrium or equilibrium or equilibrium conditions, both of these compounds are shown to be either crenators or cup-formers of the intact erythrocyte, depending upon which side of the membrane they are concentrated in. These results therefore strongly support the bilayer couple hypothesis.     

Chilling invokes different morphologies in two Salmonella enteritidis PT4 strains

The reduction in chemical preservatives in food processing has resulted in more refrigerated (chilled) products. However, the effect of chilling on Salmonella enteritidis PT4 isolates has received relatively little attention. This study investigates the effect of chilling on two Salm. enteritidis PT4 isolates, denoted E and I. These isolates differ in their tolerance to heat, acidification, survival on surfaces, and behaviour in animal models. E routinely shows greater tolerance and pathogenicity than I. Chilling invokes profound cell elongation and heterogeneity in E which corresponded to a 90% sublethal injury; neither such substantial cell elongation nor significant injury was seen in I. The ability to recover resistance to desoxycholate coincided with a reduction to normal cell size. Incomplete cell division and failure of the septum to form is a likely hypothesis for cell elongation although outer membrane changes could be responsible. Possible links are suggested between cell elongation of the hat- and acid-tolerant strain and pathogenicity.     

Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL

The adaptive significance of repeated withinpair copulations is not well understood. We analysed the copulatory behaviour of 16 pairs of solitary-nesting American kestrels, Falco sparverius, in southern Quebec (Canada), and the achieved reproductive success (paternity) of 21 kestrel families determined by DNA fingerprinting, in terms of four hypotheses. (1) The paternity assurance hypothesis, which suggests that males copulate frequently to avoid being cuckolded, was rejected because there were few extrapair copulation attempts (<1% of all copulations observed), withinpair copulations were not timed during the fertile period and mate attendance did not increase as the fertile period approached. (2) The immediate material benefits hypothesis, which suggests that females trade copulations for food, was refuted because copulations most often occurred without food transfers, especially outside the fertile period. (3) The female mate guarding of males hypothesis, which suggests that females distract their mates from other mating opportunities by copulating frequently, was rejected because extrapair copulation attempts were infrequent, male and female solicitation frequencies were similar and females did not differ in the timing or frequency of solicitations. (4) The mate assessment hypothesis, which suggests that assessment of mate quality is mediated via copulation, most closely predicted the behaviour observed since withinpair copulations were frequent outside the fertile period and at pair formation, males and females solicited similar numbers of copulations and pairs did not differ significantly in solicitation or copulation frequency. In line with this hypothesis we found that only one brood was extrapair, probably the result of mate replacement.Copyright 1998 The Association for the Study of Animal Behaviour     

Biological membranes as bilayer couples. III. Compensatory shape changes induced in membranes

We have previously proposed the hypothesis that asymmetric membranes behave like bilayer couples: the two layers of the bilayer membrane can respond differently to a particular perturbation. Such a perturbation, for example, can result in the expansion of one layer relative to the other, thereby producing a curvature of that membrane. In experiments with erythrocytes and lymphocytes, we now demonstrate that different membrane perturbations which have opposite effects on membrane curvature can compensate and neutralize one another, as expected from the bilayer couple hypothesis. This provides a rational basis, for example, for understanding the effects of amphipathic drugs on a variety of cellular phenomena which involve shape changes of membranes.     

Solid-liquid interfacial tensions by the dihedral angle method. A mathematical approach

An elaboration of Smith's relationship is presented, in order to relate the experimental behaviour of the dihedral angle 2θ with temperature to the values of solid-liquid and solid-solid interfacial tensions and to their dependence on temperature. It is shown that, in the general case, the hypothesis, usually made, of a linear dependence of interfacial tensions on temperature is not correct. A criterion to evaluate the signs of the temperature coefficients of interfacial tensions from the shape of the dihedral angle vs temperature curve is given, and two equations which allow to compute interfacial tensions in the experimental temperature range, are also reported.     

Experimental developments in movement disorders: update on proposed free radical mechanisms

A possible physical explanation of the echinocyte -spheroechinocyte red blood cell (RBC) shape transformation induced by the intercalation of amphiphilic molecules into the outer layer of the RBC plasma membrane bilayer is given. The stable RBC shape is determined by the minimization of the membrane elastic energy, consisting of the bilayer bending energy, the bilayer relative stretching energy and the skeleton shear elastic energy. It is shown that for a given relative cell volume the calculated number of echinocyte spicula increases while their size decreases as the number of the intercalated amphiphilic molecules in the outer layer of the cell membrane bilayer is increased, which is in agreement with experimental observations. Further, it is show that the equilibrium difference between the outer and the inner membrane leaflet areas of the stable RBC shapes increases if the amount of the intercalated amphiphiles is increased, thereby verifying theoretically the original bilayer couple hypothesis of Sheetz and Singer (1974) and Evans (1974).     

Ankle performance after ankle fracture: a randomized study of early mobilization

Low concentrations of some neutral dipeptides, such as L-Ala-L-Ala, rapidly disrupt rat liver lysosomes. The phenomenon has been attributed to an osmotic imbalance generated by the production of amino acids in the lysosome by lysosomal dipeptidase activity. This hypothesis is challenged by testing several pairs of dipeptides available in both D- and L-forms and a range of dipeptides whose susceptibility to lysosomal dipeptidase activity is known. A good correlation was found between the lytic ability of dipeptides and their capacity to cross the lysosome membrane and be hydrolysed by lysosomal dipeptidase. The osmotic-imbalance hypothesis is critically evaluated in the light of the results and of recent information concerning the carrier-mediated transport of amino acids and dipeptides across the lysosome membrane. It is concluded that intralysosomal generation of amino acids remains the most plausible explanation of the lytic activity of dipeptides, and that the dipeptide porter(s) in the lysosome membrane must have higher Km than the amino acid porters.     

Differences between hospital patients with alcohol problems referred for counselling by physicians' routine clinical practice versus screening questionnaires

AIMS: To test the hypothesis that screening for alcohol-related disorders in a general hospital with questionnaires generates a target group of patients for alcohol counselling which differs from patients referred by physicians' routine clinical practice. DESIGN: A prospective study with follow-up after 12 months. SETTING: Medical and surgical wards of a general hospital. PARTICIPANTS: A sample of 298 patients detected by screening questionnaires (CAGE, MAST) was compared with a sample of 87 patients referred by physicians. MEASUREMENTS: The main measurements were a diagnostic interview (SCAN), two questionnaires to estimate the severity of dependence and the motivation to change drinking behaviour (RCQ, LAS), and socio-demographic variables. Outcome criteria were utilization of remedial programmes, decreases in hazardous and excessive drinking and abstinence rates. FINDINGS AND CONCLUSIONS: Patients referred by physicians were more often separated and unemployed, were more likely to be alcohol-dependent and to be more severely dependent, had a higher rate of alcohol-related diseases as reasons for admission, were more often motivated to change drinking behaviour, had a higher participation rate in remedial programmes and more often exhibited improvements in drinking behaviour compared with the sample identified by screening questionnaires. However, there was evidence of improvements in drinking in both samples. Data show that while screening reaches a less problematic sample with lower motivation to change, it is a worthwhile activity which extends the spectrum of patients eligible for brief interventions.     

Motion of Crystal Particles by the Electromagnetic Vibrations in Mg-Cu-Y Bulk Metallic Glasses

The method for producing Mg-Cu-Y and Fe-Co-B-Si-Nb bulk metallic glasses using electromagnetic vibrations is effective in forming the metallic glass phase. Disappearance or decrement of clusters by the electromagnetic vibrations applied to the liquid state is considered to cause suppression of crystal nucleation, because the electromagnetic vibrations vibrate the clusters vigorously in the melt. The purpose of this study was to investigate motion of the crystal particles by the electromagnetic vibrations in Mg-Cu-Y bulk metallic glasses. The electromagnetic vibration force vibrated the crystal particles or the clusters that become crystal nuclei in the melt, because the electric current for the electromagnetic vibrations concentrates in those. Thus, the electromagnetic vibrations were found to select vibration particles from the melt. Moreover, it was considered that composites for which second phases or other compounds are dispersed into the metallic glass phase or a nanostructure phase can be produced by the electromagnetic vibration process. This article is based on a presentation given in the symposium entitled “Bulk Metallic Glasses IV,” which occurred February 25–March 1, 2007 during the TMS Annual Meeting in Orlando, Florida under the auspices of the TMS/ASM Mechanical Behavior of Materials Committee.     

Effects of GABA, glycine, picrotoxin and bicuculline methochloride on rubrospinal neurones in cats

A microelectrophoretic study was performed of the actions of GABA and glycine, and of their antagonists on rubrospinal neurones. GABA and glycine depressed antidromic and synaptic potentials, hyperpolarized the cell membrane and increased the membrane conductance. GABA was more effective than glycine. Corticorubral IPSPs and the GABA-induced membrane hyperpolarization could be reversed by intracellular application of hyperpolarizing currents. Picrotoxin and bicuculline methochloride antagonized inhibitory GABA actions and the corticorubral IPSP or the corresponding extracellular positive field potential. The results support the hypothesis that GABA is the transmitter of the corticorubral inhibition in the cat.     

Role of local amyloidosis of the fundus oculi tissues in the pathogenesis of senile maculopathy

Histological, histochemical, and electron microscopic studies of tissues of the fundus oculi in 111 eyes with senile maculopathy revealed amyloid in the nodules. Bruch's membrane, and between the basal membrane of retinal pigmented epithelium and the internal collagen layer of Bruch's membrane in the center of the fundus oculi. The detected amyloid incorporations are referred to senile amyloidosis and reliably differ from amyloid in generalized amyloidosis. Comparative analysis of morphologic changes in tissues of the macular and paramacular areas of the fundus oculi and of the incidence of amyloid incorporations in them permit us to propose that accumulation of local senile amyloid is conductive to development and aggravation of senile maculopathy. A relationship between the degree of pigmented epithelium degeneration and accumulation of amyloid in the fundus oculi was revealed. The authors put forward a hypothesis of the pathogenesis of some stages of senile maculopathy, in which the principal role in the formation and deposition of abnormal protein, amyloid, is played by degenerative cells of pigmented epithelium. It is followed by amyloid destruction of Bruch's membrane and accumulation of amyloid under it and the basal membrane of pigmented epithelium. this in its turn, promoting neovascularization and formation of fibrovascular membrane.