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At least 19 recordsLinked to original sources
PubMed2026

Relationships among mechanisms in psychosocial treatments for chronic pain: mechanism to mechanism lagged effects and relationships with outcomes.

Results suggest that psychosocial treatments for chronic pain work via several mechanisms, and that they often do so to similar degrees and in similar ways. Extant research, however, has focused on individual and/or independent effects of mechanisms on outcomes. Whether successful outcomes are also partly because of sequential and meaningful relationships among and between mechanisms-mechanism-to-mechanism effects-has not been examined. Secondary analyses were conducted of an RCT that compared cognitive therapy, mindfulness-based stress reduction, and behavior therapy to treatment as usual in a sample (N = 521) of people with chronic low back pain. Results of hierarchical linear modeling revealed that (1) Treatment Condition × Mechanism interactions predicting changes in other mechanisms were nonsignificant; (2) lagged prior session mechanism changes predicted next session changes in another mechanism; (3) lagged relationships between pain catastrophizing and pain self-efficacy were reciprocal, whereas links between lagged pain catastrophizing and mindfulness changes and lagged pain catastrophizing changes and behavioral activation changes were unidirectional; and (4) individual differences in the strengths of mechanism-to-mechanism relationships predicted pre- to post-treatment changes in outcomes. Results reveal heretofore hidden therapeutic processes that cognitive therapy, mindfulness-based stress reduction, and behavior therapy may share. Namely, that mechanism-to-mechanism lagged effects do indeed emerge beyond mechanism-to-outcome effects. Findings show not only that mechanisms may change in definable sequences relative to each other but that individual differences in the strengths of mechanism-to-mechanism relationships may themselves be predictive of outcomes.

Humans↗
PubMed1979

Electrical and mechanical response in biventricular mechanical alternans.

Mechanical alternans of various degrees is produced by rapid heart rates, slower rates in failing hearts and can be brought about by a single extra systole. It has also been shown that the two ventricles may exhibit different degrees of mechanical alternation. The present study was planned to clarify the possible mechanism inducing this latter phenomenon. For this reason myocardial tension was recorded simultaneously from the two ventricles as well as through a miniature strain gage capable of measuring electrogram and myocardial tension of a small area -- just adjacent to a stimulating electrode. The heart was driven at a steady heart rate through one electrode and very late premature beats were applied at various coupling times at another site through an electrode attached to the miniature strain gage. It was found that the degree of mechanical alternans is markedly different at the sites of measurements in either ventricle. These changes could be related to the time interval elapsed between the application of the electrical stimulus and the occurrence of the mechanical response.

Animals↗
PubMed1977

[Animal experimental investigations for determining the duration of the "mechanical-effective period" of muscle action potentials and of the "electro-mechanical latency period" of "fast fibres" of external ocular muscles (author's transl)].

A report is given of an animal experimental study for determination of the duration of the "mechanical effective period" of the muscle fiber membrane action potential and the "electromechanical latency period" of "fast fibers" of the external ocular muscles in rabbits in vivo. The studies were carried out with an internationally standardized glass microelectrode technique. The statistical values are based on 250 tests employing the superposition technique. The mean "mechanical effective period" of the muscular fiber membrane action potential was determined with SE=0.52 ms, SD 0.08 ms. The confidence thresholds were 99% statistically reliable with 0.43 ms and 0.55 ms. According to these studies, the duration of the "mechanical effective period" of the "fast fibers" of the external ocular muscles was only one-third off the "mechanical effective period" of the skeletal muscles. The mean duration of the "electromechanical fast-fiber latency period" was calculated with SE=1.97 ms, SD=0.30 ms. The confidence threshold was 99% statistically reliable with 1.86 ms and 2.08 ms. The "electromechanical latency period" of the "fast fibers" of the external ocular muscles was therefore significantly less than the skeletal muscles, lying under the 50% limit of the "electromechanical latency period" of the analogous skeletal musculature. These studies permit determination of the most important electrophysiological parameters which define a threshold value of maximal speed in vision direction changes.

Action Potentials↗
PubMed2026

Molecular mechanisms underlying drug resistance in protozoan parasites: emerging mechanisms and therapeutic perspectives.

Protozoan parasitic infections, including malaria, leishmaniasis, and human African trypanosomiasis, remain major global public health challenges. In the absence of highly effective vaccines, disease control relies primarily on chemotherapy; however, the emergence and spread of drug-resistant parasite populations increasingly threaten treatment efficacy. This review synthesizes current evidence on the molecular mechanisms underlying drug resistance in Plasmodium, Leishmania, and Trypanosoma species through a systematic analysis of literature. The review identifies four interconnected mechanisms that drive the evolution of drug resistance. First, altered drug transport enables parasites to regulate intracellular drug concentrations through mutations, loss, or amplification of membrane transporters, including PfCRT in Plasmodium and AQP2 in Trypanosoma brucei. Second, target modification and genomic plasticity promote resistance through point mutations in drug targets, such as dhfr and dhps in Plasmodium, while kinetoplastids, particularly Leishmania, exploit extensive genomic plasticity, including aneuploidy, gene amplification, and translational reprogramming, to facilitate rapid adaptation under drug pressure. Third, metabolic reprogramming enhances parasite survival by increasing intracellular thiol production, strengthening antioxidant defense systems, and reshaping central carbon and lipid metabolism to mitigate drug-induced stress. Finally, stress response and persistence mechanisms enable subpopulations of parasites to enter dormant, persister-like states characterized by reduced metabolic activity and slowed proliferation, thereby evading both host immune responses and chemotherapeutic agents. Collectively, these findings demonstrate that drug resistance is a dynamic, multifactorial evolutionary process rather than a single molecular event. Addressing this growing challenge requires integrating genomic surveillance, molecular diagnostics, mathematical modeling of resistance transmission, and mechanistic insights into parasite persistence into future drug discovery and disease control strategies. Such an integrated approach is essential for improving the durability of antiprotozoal therapies and advancing global efforts to control neglected protozoan diseases.

antiprotozoal therapy↗
PubMed1975

On the mechanism of ketogenesis and its control. Purification, kinetic mechanism and regulation of different forms of mitochondrial acetoacetyl-CoA thiolases from ox liver.

1. Two mitochondrial forms of acetoacetyl-CoA thiolases designated as enzyme A and enzyme B were crystallized from ox liver. They could be shown to be homogenous by polyacrylamide gel electrophoresis. 2. In direction of acetoacetyl-CoA cleavage enzyme A shows a double competitive substrate inhibition when acetoacetyl-CoA is varied at different fixed CoA concentrations. With enzyme B a parallel kinetic pattern is obtained when acetoacetyl-CoA is varied at different fixed CoA concentrations. In direction of acetoacetyl-CoA synthesis both enzymes show linear reciprocal plots of initial velocities against acetyl-CoA concentrations in absence of CoA. These initial velocity kinetics in the forward and in the reverse direction are in accordance with a ping-pong mechanism of reaction for both enzymes involving an acetyl-S-enzyme as intermediate. 3. Under saturating concentrations of substrate, the ratios of acetoacetyl-CoA synthesis/aceto-acetyl-CoA cleavage is 0.31 for enzyme A and 0.08 for enzyme B. The maximum velocity in direction of acetoacetyl-CoA synthesis of enzymes A and B are 0.43 mumol X min-1 X unit thiolase-1 and 0.10 mumol X min-1 X unit thiolase-1, respectively. 4. Both enzymes show nearly the same affinity for acetyl-CoA. The Km values are 91 muM (enzyme A) and 80 muM (enzyme B). 5. Coenzyme A and acetoacetyl-CoA both act as inhibitors in direction of acetoacetyl-CoA synthesis: coenzyme A is a nonlinear competitive inhibitor of both enzymes. Acetoacetyl-CoA exerts a negative cooperativity on enzyme A (nH = 0.63) and is a competitive inhibitor for enzyme B (Ki = 1.6 muM). 6. The catalytic and regulatory properties of the acetoacetyl-CoA thiolases A and B are discussed in terms of their proposed role in regulating ketogenesis. Intracellular fluctuations of acetoacetyl-CoA/3-hydroxybutyryl-CoA ratios, resulting in a suspension of inhibition of both enzymes at high NADH/NAD ratios, are postulated as a control mechanism of ketogenesis in addition to mechanisms already known.

Acetyl-CoA C-Acetyltransferase↗
PubMed1977

The mechanism of the inactivation of human fibroblast interferon by mechanical stress.

Interferon derived from human fibroblasts is readily inactivated during agitation and filtration. This inactivation has been shown to be largely a product of mechanical stress, and has been studied in detail by subjecting interferon to controlled shear stress using a rotational viscometer. The possible mechanism of this phenomenon is discussed.

Cell Line↗
PubMedDate not supplied

Theorectical mechanisms for synthesis of carcinogen-induced embryonic proteins: III. The tRNA methylases; methylation mechanism and function.

It is contended that redundant repressed tRed) with carcinogens in adult cells. Supportive evidence, especially from molecular model building, is presented for a mechanism of tRNA methylation. In this mechanism the adenine moiety of S-adenosyl-L-methionine base-pairs with uracil for all tRNA methylations. Furthermore it is proposed that such methylations are required during the transcription of a tRNA molecule in order to limit the number of possible conformers that can occur before further development of the molecule takes place. This theory of the function for methyl groups is discussed in the light of the properties found for hypomethylated tRNAs.

Animals↗
PubMed2026

Comparative proteomic analysis reveals the pathological mechanisms of overuse achilles tendinopathy and the therapeutic mechanisms of ESWT and PRP.

BACKGROUND: Achilles tendinopathy is a common musculoskeletal disorder with limited self-repair capacity. Although extracorporeal shock wave therapy (ESWT) and platelet-rich plasma (PRP) are widely used, their therapeutic mechanisms remain unclear. METHODS: A rat model of overuse Achilles tendinopathy was established by uphill treadmill running. Tendon morphology and structure were assessed by ultrasound and histology, and proteomic profiling was performed to identify differentially expressed proteins (DEPs) and enriched pathways. RESULTS: Ultrasound revealed subcutaneous edematous infiltration after overuse, and histology showed disorganized collagen fibers and altered cellular density. Compared with the normal group, the injury group showed 429 DEPs, which were enriched in pathways related to actin cytoskeleton and complement and coagulation cascades. Both ESWT and PRP treatments ameliorated these overuse-induced pathological changes. Compared with the rest group, the ESWT group showed 30 DEPs, while the PRP group showed 244, with 17 DEPs overlapping between the two comparisons. In the ESWT group, enriched pathways included actin cytoskeleton organization, protein stabilization, and sulfur metabolism. In the PRP group, enriched pathways included FcγR-mediated phagocytosis, lysosome, and endoplasmic reticulum protein processing. Compared with the normal group, the ESWT group showed 32 DEPs, whereas the PRP group showed only one (Serpina6), which was the only protein shared between the two comparisons. CONCLUSION: ESWT and PRP improve tendon healing in overuse Achilles tendinopathy through different molecular mechanisms. The PRP group showed a proteomic profile more similar to the normal group than the ESWT group. These findings provide a molecular basis for optimizing clinical treatment strategies.

Animals↗
PubMed1979

Striated sphincter participation in distal passive urinary continence mechanisms: studies in male subjects deprived of proximal sphincter mechanism.

Striated urethral sphincter function was studied in passive incontinent and continenet male subjects who were deprived of the proximal sphincter mechanism. Functional assessment of striated urethral sphincter include electromyography and electrostimulation. Varying degrees of diminished striated sphincter excitability and reflex activity were observed in passive incontinent male subjects who also had varying degrees of somatomotor neuron lesions. The studies indicate that the participating role of periurethral striated musculature in distal passive continence mechanisms cannot be ignored.

Aged↗
PubMed1977

Mechanism of action of adenosylcobalamin: glycerol and other substrate analogues as substrates and inactivators for propanediol dehydratase--kinetics, stereospecificity, and mechanism.

A number of vicinal diols were found to react with propanediol dehydratase, typically resulting in the conversion of enzyme-bound adenosylcobalamin to cob(II)alamin and formation of aldehyde or ketone derives from substrate. Moreover, all are capable of effecting the irreversible inactivation of the enzyme. The kinetics and mechanism of product formation and inactivation were investigated. Glycerol, found to be a very good substrate for diol dehydratase as well as a potent inactivator, atypically, did not induce cob(II)alamin formation to any detectable extent. With glycerol, the inactivation process was accompanied by conversion of enzyme-bound adenosylcobalamin to an alkyl or thiol cobalamin, probably by substitution of an amino acid chain near the active site for the 5'-deoxy-5'-adenosyl ligand on the cobalamin. The inactivation reaction with glycerol as the inactivator exhibits a deuterium isotope effect of 14, strongly implicating hydrogen transfer as an important step in the mechanism of inactivation. The isotope effect on the rate of product formation was found to be 8.0. Experiments with isotopically substituted glycerols indicate that diol dehydrase distinguishes between "R" and "S" binding conformations, the enzyme-(R)-glycerol complex being predominately responsible for the product-forming reaction, while the enzyme-(S)-glycerol complex results primarily in the activation reaction. Mechanistic implications are discussed. A method for removing enzyme-bound hydroxycobalamin that is nondestructive to the enzyme and a technique for measuring the binding constants of (R)- and (S)-1,2-propanediols are presented.

Adenosine↗
PubMed1978

Pancreatic hormones and plasma glucose: regulation mechanisms in the goose under physiological conditions. II. Glucose-glucagon and glucose-insulin feed-back mechanisms.

We have studied the pancreatic hormone-glucose feed-back mechanisms by infusing glucagon (G), insulin (I) and glucose into normal fasting geese. The controls received saline. Whilst a NaCl 9% infusion is devoid of effect, the pancreatic hormones, used at physiological doses, modify the plasma glucose level, glucagon being hyperglycaemic and insulin hypoglycaemic. In addition, a physiological increase in plasma glucose provokes a drop in plasma glucagon and a rise in plasma insulin, thus a marked decrease in the G/I ratio. The results show that the pancreatic hormone-glucose feed-back mechanisms are effective under physiological conditions.

Animals↗
PubMed1977

Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.

Tolerance can be induced in adult mice by a single intravenous injection of 0.5 mg dinitrophenylated bovine gamma globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody-forming cells in partially tolerant animals and a prompt reversibility on cell transfer. The overall properties of this unresponsive state are consistent with the hypothesis that it is mediated by the production of small amounts of high affinity antibody in response to the tolerance-inducing injection of antigen. In contrast, the unresponsiveness induced in reconstituted, irradiated mice by the same procedure was characterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected and mixed cell transfer studies were consitent with the view that this unresponsive state represented a B-lymphocyte clonal deletion. The presence or absence of T lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolernace induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible "high affinity"-type tolerance is obtained such as is typical of normal intact animals. Restorationof a "normal" response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. It is suggested that the structural integrity of the lymphoid tissue is critical in determining whether B cell will be rendered tolerant after exposure to antigen in vivo.

Age Factors↗
PubMed1978

Studies of the chemo-mechanical conversion in artificially produced streamings. I. Reconstruction of a chemo-mechanical system from acto-HMM of rabbit skeletal muscle.

Steady and uniform streamings (SUS) of HMM solutions were set up in the presence of Mg-ATP in a circular slit, on both side-walls of which a Millipore filter was fixed; F-actin filaments from rabbit skeletal muscle were bound onto the Millipore filter by cyanogen bromide in the flow. The direction of the SUS was specificially determined by that of the flow during the fixing of F-actin and was independent of the direction of the initial velocity applied externally to the HMM solutions. The SUS continued for about 90 min with a velocity of about 20 mum/s at 20 degrees C. There was a strong correlation between the acto-HMM ATPase activity and the velocity of SUS when the salt concentration was varied. Moreover, this was also the case when the ATPase activity was controlled by Ca2+, when native tropomyosin was bound to F-actin in the circular slit. Careful examination led to the conclusions that F-actin filaments are fixed on the Millipore filter with a specific polarity and that a chemo-mechanical system had been successfully reconstituted in our "stream cells," in which chemical energy from ATP is converted to the mechanical energy of streaming.

Actins↗
PubMed1977

Cochlear micromechanics--a mechanism for transforming mechanical to neural tuning within the cochlea.

A linear mathematical model is proposed which will account for the differences observed between mechanically measured data of Rhode (1971) for basilar membrane motion, and the responses of neural tuning curves (Kiang et al., 1974). We show that theoretical tuning curves may be derived from mechanical responses by forming the difference between the pressure across the basilar membrane and its displacement. Some ramifications of this proposal are discussed. We then propose a hypothetical physical model which could perform such a function.

Acoustics↗
PubMed1977

Mechanical work in terrestrial locomotion: two basic mechanisms for minimizing energy expenditure.

The work done during each step to lift and to reaccelerate (in the forward direction) and center of mass has been measured during locomotion in bipeds (rhea and turkey), quadrupeds (dogs, stump-tailed macaques, and ram), and hoppers (kangaroo and springhare). Walking, in all animals (as in man), involves an alternate transfer between gravitational-potential energy and kinetic energy within each stride (as takes place in a pendulum). This transfer is greatest at intermediate walking speeds and can account for up to 70% of the total energy changes taking place within a stride, leaving only 30% to be supplied by muscles. No kinetic-gravitational energy transfer takes place during running, hopping, and trotting, but energy is conserved by another mechanism: an elastic "bounce" of the body. Galloping animals utilize a combination of these two energy-conserving mechanisms. During running, trotting, hopping, and galloping, 1) the power per unit weight required to maintain the forward speed of the center of mass is almost the same in all the species studied; 2) the power per unit weight required to lift the center of mass is almost independent of speed; and 3) the sum of these two powers is almost a linear function of speed.

Animals↗
PubMed1975

The fungicidal mechanisms of human monocytes. I. Evidence for myeloperoxidase-linked and myeloperoxidase-independent candidacidal mechanisms.

We tested the ability of human peripheral blood monocytes to kill Candida albicans and Candida parapsilosis. Evidence that multiple fungicidal mechanisms operate in normla monocytes was found. Normal monocytes ingested and killed viable C. albicans, and could iodinate heat-killed C. albicans. Both functions were defective in monocytes from subjects with myeloperoxidase deficiency or chronic granulomatous disease. Methimazole, isoniazid, and aminotriazole inhibited iodination by normal monocytes without impairing their ability to kill C. albicans, indicating that iodination was not essential to the myeloperoxidase-hydrogen peroxide-mediated fungicidal system of the monocyte. C. parapsilosis, an organism killed with supranormal efficacy by monocytes from a patient with hereditary myeloperoxidase deficiency, was selected to examine the myeloperoxidase-independent fungicidal mechanisms of monocytes. Monocytes were obtained from the blood of normal or leukemic subjects and homogenized in 0.34 M sucrose to yield fractions rich in cytoplasmic granules. These fractions were extracted with 0.01 M citric acid and the soluble components were separated by micropreparative polyacrylamide electrophoresis. Monocytes were found to contain cationic proteins, other than myeloperoxidase, that kill C. parapsilosis in vitro.

Anti-Inflammatory Agents↗
PubMed1979

Mechanical vs. ischemic mechanisms for decompression sickness.

We used 20 kangaroo rats to investigate the effect of exposure to low oxygen levels (0.11 Atm 02 inspired partial pressure) prior to decompression from a steady-state condition. This hypoxia was found to afford significant protection against limb bends as simulated in those animals by tail biting. Yet, it potentiated neurologic symptoms compared with a control exposure on air with the same level of nitrogen supersaturation. However the incidence of simulated limb bends in the same animals was the same with hypoxia as with another control exposure at a pressure estimated to give extravascular bubbles of the same size upon decompression. The results are, therefore, consistent with a simple mechanical basis for limb bends, but are difficult to explain by any ischemic mechanism since a general hypoxia exacerbates any pain produced by oxygen deficiency in the tissues. However, the reverse may be true for some forms of neurologic decompression sickness and the two such cases reported here are consistent with that view, although not statistically significant.

Animals↗
PubMed1979

Molecular mechanism for the initial process of visual excitation. IV. Energy surfaces of visual pigments and photoisomerization mechanism.

Using the twisted conformations of the chromophores for visual pigments and intermediates which were theoretically determined in the previous paper, energy surfaces of the pigment at - 190 degrees C were obtained as functions of the torsional angles theta 9-10 and theta 11-12 or of the torsional angles theta 9-10 and theta 13-14. In these calculations, the existence of specific reaction paths between rhodopsin (R) and bathorhodopsin (B), between isorhodopsin I (I) and bathorhodopsin, and between isorhodopsin II (I') and bathorhodopsin were assumed. It was shown that the total energy surfaces of the excited states had minima C1 at theta 9-10 approximately -10 degrees and theta 11-12 approximately -80 degrees, C2 at theta 9-10 approximately -85 degrees and theta 11-12 approximately -5 degrees, and C3 at theta 9-10 approximately -0 degree and theta 13-14 approximately -90 degrees. These minima are considered to correspond to the thermally barrierless common states as denoted by Rosenfeld et al. Using the total energy surfaces in the ground and excited states, the molecular mechanism of the photoisomerization reaction was suggested. Quantum yields for the photoconversions among R, I, I' and B were related to the rates of vibrational relaxations, radiationless transitions and thermal excitations. Some discussion was made of the temperature effect on the quantum yield. Similar calculations of the energy surfaces were also made at other temperatures where lumirhodopsin or metarhodopsin I is stable. Relative energy levels of the pigments and the intermediates were discussed.

Animals↗