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At least 19 recordsLinked to original sources
PubMedDate not supplied

[Cellular mechanisms of conditioned reflex integration].

The paper deals with the formation of cellular mechanisms of integration in the course of conditioned reflex elaboration. Primary integration consists in an interaction between the effects of the conditioned (CS) and unconditioned (US) stimuli on neurons, which leads to a stable connection between them. The subsequent, final integration consists in the joining up of these cells into special populations with common functional properties in relation to the paired stimuli. Primary integration is achieved either by the mechanism of addition of the elaborated reaction to the CS to the response to the US, or by joining an adequate reaction to the CS of the elaborated response to the US. The final integration is apparently achieved by the mechanisms of transmition from one neuron to another of the formed connection between the paired stimuli along one path common for the association as a whole.

Animals↗
PubMed1979

Antigenic specificity and cellular mechanisms in leukocyte adherence inhibition analysis of immunity to simple proteins and hapten-protein conjugates.

The hemacytometer leukocyte adherence inhibition (LAI) assay was investigated with respect to immunological relevance, specificity, and cellular mechanisms. Humans were immunized to keyhole limpet hemocyanin, and rats were immunized to dinitrophenyl-bovine gamma-globulin. LAI analysis disclosed classic patterns of immune response kinetics. The LAI response was dose dependent in vitro with no inhibition at relatively high antigen doses. In vitro specificity in rats was restricted to the immunizing conjugate. Cells forming spontaneous E-rosettes were required for LAI reactions. Lymphokine production required the presence of E-rosette-forming cells. E-rosette-forming cells from normal donors lost adherence in the presence of lymphokine. The requirement for T-lymphocytes was confirmed in a human osteosarcoma system using independent criteria. Thus, the hemacytometer LAI depends upon T-lymphocyte collaboration via a lymphokine. It should be distinguished from the tube and microplate variants of LAI analysis because these appear to depend upon different mechanisms.

Animals↗
PubMed1979

The cellular mechanism of leukocyte adherence inhibition.

Human blood leukocytes from three subjects who had been contact sensitized to dinitrochlorobenzene were used in direct and indirect leukocyte-adherence-inhibition (LAI) reactions in an attempt to elucidate the cellular mechanism of reactivity. The leukocytes were separated and purified by standard procedures. In direct LAI, only T cells or populations containing T cells gave positive reactions (significantly reduced adherence) with the antigen. Supernatants from suitable leukocyte-antigen mixtures contained a soluble leukocyte-adherence-inhibition-factor (LAIF) that reduced the adherence of normal leukocytes. Only T cells or populations containing T cells were active in LAIF production; B cells, granulocytes, and monocytes were inactive. The cellular requirement for the action of preformed LAIF was not restricted: all major types of blood leukocytes were susceptible to its effect.

B-Lymphocytes↗
PubMed1977

Cellular mechanisms of the resistance to the induction of immunological tolerance.

Tolerance inducibility was examined in various strains of mice by injecting aggregate-free HGG, followed by challenge with aggregated HGG plus LPS and by assessing spleen PFC numbers. Marked differences were shown between C57BL/6 and DDD mice. The antibody response to HGG was totally suppressed in C57BL/6 mice injected with 0-1 to 1 mg of aggregate-free HGG whereas little suppresssion was observed in DDD mice. Cellular mechanisms of the resistance to tolerance induction in DDD mice were explored. On the injection of 1 mg of aggregate-free HGG, spleen cells were only partially tolerized (at minimum, 21 per cent of control level on 5th day) and thymus cells were suppressed to 40 per cent of the normal responsiveness. No suppression was observed in bone marrow cells. Macrophages do not seem to play a decisive role in the resistance to tolerance induction in DDD mice as the injection of biofiltered HGG or the pretreatment with carrageenan did not ease the resistance. From these data, it was suspected that the resistance to tolerance induction to HGG in DDD mice might be due to the raised threshold of T cells for tolerance.

Animals↗
PubMed1975

Micropuncture analysis of the cellular mechanisms of electrolyte secretion by the in vitro rabbit pancreas.

Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly three times the environmental concentration. The similar characteristics exhibited by HCO3 and acetate secretion indicate that they are secreted by a common mechanism involving active H transport. In vitro acid-base alterations demonstrate that the secretion rate is controlled by the environmental HCO3 concentration and to a much lesser extent by the pCO2. Secretion also requires active Na transport across the mucosal membrane. The effects of ouabain and a low Na environment strongly suggest coupling between the transport of Na and H and a cellular mechanism for electrolyte secretion is proposed involving Na-H exchange mechanisms at both the mucosal and serosal membranes.

Acetates↗
PubMed1979

Cellular mechanisms of prostaglandin action.

The human platelet and erythrocyte differ quite dramatically in relation to the arachidonic acid cascade. The platelet synthesizes its own characteristic products, while the erythrocyte lacks cyclo-oxygenase activity but possesses other metabolic enzymes. In these and other cell types the metabolites are potentially determined by the cascade enzymes, the availability of cofactors, the presence of specific activators and inhibitors, and the selective binding or transport of intermediates. Endogenously synthesized metabolites may have intracellular actions or may be released and exert their effects extracellularly. Study of the cellular mechanisms mediating these effects, like study of the fast-acting hormones, has focused primarily on the cyclic nucleotides and calcium. Considering the diverse activities of several metabolites in the platelet however, these mechanisms seem to need reevaluation or refining. The released cascade metabolites may also act as intercellular signals over a short range. The range depends on their chemical stability in the absence of protective carriers and their selective uptake and metabolism by surrounding cells. Additionally, the effects will reflect the selective interaction of responsive cells with the spectrum of metabolites released. Answering these questions of complex intercellular interactions requires the identification and classification of characteristic responses and the metabolic profile of individual cell types in each tissue. Consequently, this type of analysis may best be done with isolated cells, such as the platelet and erythrocyte.

Arachidonic Acids↗
PubMed1979

Cellular mechanics of dentinal bridge repair using 3H-thymidine.

Cellular reorganization in the pulp following mechanical pulp exposure involves three steps: First, lysis and macrophage resolution of the clot form; second, there is an invasion of the clot area by fibroblasts and endothelial cells, i.e., formation of granulation tissue; third, an organization and differentiation of these cells into functional odontoblasts occurs as early as 9 days after exposure. Autoradiographic results showed an increased DNA synthesis in the fibroblast and endothelial cell populations which coincided with a histologically-observed increase in those populations. A relative increase in fibroblastic activity, as compared to endothelial cell activity, suggested that fibroblasts may be the cells that replace odontoblasts.

Animals↗
PubMed1979

Short and long-term effects of neuroleptics in relation to their cellular mechanism of action.

1. Some mechanisms of action of neuroleptics at cellular level are reviewed, mainly the effects on synaptic transmission and the effects on chromatin. 2. As regard to the effects at synaptic level, a brief review is presented on the available evidence in support of the currently prevailing dopamine hypothesis. 3. Studies carried out on the mechanisms and sites of action of neuroleptics on chromatin show that: a. Behavioral changes caused by psychotropic drugs in experimental animals are associated with chromatin alterations and induced macromolecular syntheses. b. Parkinsonian and possibly drug-induced extrapyramidal symptoms are associated with aberrations in protein synthesis. c. Destabilization under "stress" of the heterochromatin in schizophrenics seems to be due to histone modifications and is partly prevented by neuroleptic treatment.

Antipsychotic Agents↗
PubMed1978

Estimates of cellular mechanics in an arterial smooth muscle.

Estimates of force generation or shortening obtained from smooth muscle tissues are valid for individual cells only if each cell is contracting homogeneously and if cells anatomically arranged in series are mechanically coupled. These two assumptions were tested and shown to be valid for the pig carotid media under certain conditions. Homogeneity of cellular responses in carotid strips was estimated from the motion of markers on the tissue during K+ -induced isometric contractions. When tissues were stretched to L0 (the optimum length for force generation), there was little marker movement on stimulation. However, considerable marker movement was observed on stimulation at shorter muscle lengths, reflecting localized shortening or stretching. The mechanical coupling of the very small cells in the media was determined by measuring the dependence of cell length on tissue length. Tissues were fixed with glutaraldehyde during isometric contractions at various tissue lengths (0.4--1.1 x L0). The fixed tissues were macerated with acid and the lengths of the dispersed cells were measured. Cell lengths were broadly distributed at all muscle lengths. However, the direct proportionality between mean cell length and muscle length (as a fraction of L0) indicated that cells which are anatomically in series are coupled force-transmitting structures. We conclude that valid estimates of cellular mechanical function in this preparation can be obtained from tissue measurements at lengths greater than about 0.9L0.

Animals↗
PubMed2025

Integration of multiple omics reveals key targets and cellular mechanisms for intervention in sarcopenia.

BACKGROUND: Sarcopenia, an age-related syndrome characterized by progressive loss of muscle mass, strength, and function, presents a significant global health burden with limited therapeutic interventions. This study integrates genomic causality, multi-tissue omics, and cellular mediation analyses to identify and prioritize mechanistically grounded therapeutic targets. METHODS: A multi-tiered analytical framework was applied, beginning with two-sample Mendelian randomization (MR) to infer causal relationships between 4907 plasma proteins (cis-pQTLs from 35,559 individuals) and sarcopenia traits in Pan-UK Biobank participants. Bayesian colocalization and transcriptomic validation in human sarcopenia muscle biopsies were employed to prioritize targets. Cellular mediation analysis quantified contributions of immune and stromal cell subtypes to protein-trait pathways using transcriptomic deconvolution. RESULTS: MR identified 1237 plasma proteins causally associated with sarcopenia traits, with six targets (HGFAC, GATM, HMOX2, F2, LMAN2L, HPGDS) validated through colocalization, transcriptomic expression, and sarcopenia-related dysregulation. Cellular mediation revealed immune mechanisms underlying HGFAC's effects, with CD4+ regulatory T cells mediating 3.49 % of its impact on sarcopenia traits. Prothrombin exhibited muscle-protective effects independent of coagulation. CONCLUSION: This study establishes a causal map linking plasma proteins to sarcopenia through immune-stromal interactions. The integration of MR, multi-omics validation, and cellular mediation prioritizes six proteins as actionable targets, supporting repurposing of thrombin inhibitors and development of immunometabolic therapies. The framework bridges genomic causality with cellular pathophysiology, advancing precision strategies for age-related muscle decline.

Humans↗
PubMed1978

Immune reactivity during aging. II. Analysis of the cellular mechanisms involved in the deficient antibody response in old mice.

Analysis was made of the cellular basis of decline in the antibody immune response with advancing age. Employing the cell transfer system, it was found that spleen cells of aged mice have a limited capacity to react to SRBC when transferred into young irradiated recipients. Partial reconstitution was achieved when thymus cells from young untreated donors were applied together with the spleen cells, suggesting that deficiency in T helper cell function is responsible in part for the limited response. Similar studies using the T helper-independent antigen PVP also resulted in low levels of antibodies in the irradiated recipients. Treatment of the spleen cells with anti-theta serum before transfer did not lead to an increased response. Hence, it is suggested that the reduced response is related to limited function in the B cell compartment, and not to function of T suppressor cells. Transfer of bone marrow cells from aged into young irradiated recipients indicated that cells capable of differentiation into antibody-producing cells are available during aging. It is thus maintained that the defect at the B cell level is of a developmental nature.

Aging↗
PubMed1979

A cellular mechanism for the palatal shelf reorientation from a vertical to a horizontal plane in hamster: light and electron microscopic study.

Cellular and subcellular events during reorientation of the palatal shelf in hamster fetuses are described. An alteration in the morphology of the epithelial and the mesenchymal cells is observed during shelf realignment from a vertical to a horizontal plane. The mesenchymal cells elongate and subsequently appear to protrude in the medially bulging palatal shelf. Microtubules, microfilaments and close contacts are associated with elongation of the mesenchymal cells. The cells of the thickened epithelium may play a mechanical role in providing direction to the mesenchymal cells during palatal shelf reorientation. The altered morphology of the mesenchymal cells may be associated with the intrinsic shelf force implicit in Walker and Fraser's theory of palatal shelf reorientation.

Animals↗
PubMedDate not supplied

Pulmonary host defense: coordinated interaction of mechanical, cellular and humoral immune systems of the lung.

The respiratory system has numerous ways to protect lung parenchyma from implantation of bacteria and subsequent infection. Such "natural" defense utilizes the clearing mechanism in the nose, larynx and upper airways and the cellular and humoral immune factors in the lower respiratory tract so effectively that the host is largely unaware of its tireless surveillance. Normal lungs are kept sterile. In contrast, pneumonitis, which represents the fully developed acute inflammatory reaction, signals the ultimate response to virulent bacteria, but can be considered as general failure of host defense also--depending on your viewpont. In between these extremes are gradations of response, which are unnoticed, perhaps. Thus, the inflammatory response in the lung to bacteria requires initiation, modulation and eventually suppression. This report attempts to dissect individual components of this response and to examine cell products which may have regulatory functions.

Antibodies, Bacterial↗
PubMed1976

Cellular mechanism of endotoxin unresponsiveness in C3H/HeJ mice.

B cells from C3H/HeJ mice fail to respond to an endotoxin (LPS K235) which is mitogenic for normal mice including the closely related C3H/HeN strain. The cellular basis for this unresponsive state has been investigated. The C3H/HeJ mice have normal numbers of B cells, which are capable of normal responses to other B cell mitogens, such as polyinosinic acid (Poly I). Addition of normal macrophages or spleen cells fails to reconstitute the normal response. Furthermore, neither macrophages nor spleen cells from the C3H/HeJ strain suppress the normal C3H/HeN spleen cells. Finally, spleen cells enriched for B cells by the removal of macrophages or T cells demonstrate the same differences in responsiveness to LPS. These results indicate that LPS unresponsiveness is a defect of the B cell itself and not due to suppressor cells or the absence of helper cells. When LPS is added to Poly I-stimulated cultures, there is additional enhancement of the response of normal C3H/HeN spleen cells. However, LPS causes a dose-dependent suppression of the Poly I response of C3H/HeJ spleen cells. This suppression is dependent on the time of addition of LPS to the Poly I-stimulated cultures. These data are interpreted as indicating that the binding of LPS to the membrane of C3H/HeJ B cells results in their inactivation or suppression, and that this is the basis of LPS unresponsiveness in this mouse strain.

Animals↗
PubMed2021

Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.

Cellular pathways that repair chromosomal double-strand breaks (DSBs) have pivotal roles in cell growth, development and cancer. These DSB repair pathways have been the target of intensive investigation, but one pathway - alternative end joining (a-EJ) - has long resisted elucidation. In this Review, we highlight recent progress in our understanding of a-EJ, especially the assignment of DNA polymerase theta (Polθ) as the predominant mediator of a-EJ in most eukaryotes, and discuss a potential molecular mechanism by which Polθ-mediated end joining (TMEJ) occurs. We address possible cellular functions of TMEJ in resolving DSBs that are refractory to repair by non-homologous end joining (NHEJ), DSBs generated following replication fork collapse and DSBs present owing to stalling of repair by homologous recombination. We also discuss how these context-dependent cellular roles explain how TMEJ can both protect against and cause genome instability, and the emerging potential of Polθ as a therapeutic target in cancer.

Animals↗