SEARCH · PubMed Health

Results for “Deep generative model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed2005

An integrated modelling and multicriteria analysis approach to managing nitrate diffuse pollution: 2. A case study for a chalk catchment in England.

The site-specific land use optimisation methodology, suggested by the authors in the first part of this two-part paper, has been applied to the River Kennet catchment at Marlborough, Wiltshire, UK, for a case study. The Marlborough catchment (143 km(2)) is an agriculture-dominated rural area over a deep chalk aquifer that is vulnerable to nitrate pollution from agricultural diffuse sources. For evaluation purposes, the catchment was discretised into a network of 1 kmx1 km grid cells. For each of the arable-land grid cells, seven land use alternatives (four arable-land alternatives and three grassland alternatives) were evaluated for their environmental and economic potential. For environmental evaluation, nitrate leaching rates of land use alternatives were estimated using SHETRAN simulations and groundwater pollution potential was evaluated using the DRASTIC index. For economic evaluation, economic gross margins were estimated using a simple agronomic model based on nitrogen response functions and agricultural land classification grades. In order to see whether the site-specific optimisation is efficient at the catchment scale, land use optimisation was carried out for four optimisation schemes (i.e. using four sets of criterion weights). Consequently, four land use scenarios were generated and the site-specifically optimised land use scenario was evaluated as the best compromise solution between long term nitrate pollution and agronomy at the catchment scale.

Agriculture↗

PubMed2005

Multiscale brain modelling.

A central difficulty of brain modelling is to span the range of spatio-temporal scales from synapses to the whole brain. This paper overviews results from a recent model of the generation of brain electrical activity that incorporates both basic microscopic neurophysiology and large-scale brain anatomy to predict brain electrical activity at scales from a few tenths of a millimetre to the whole brain. This model incorporates synaptic and dendritic dynamics, nonlinearity of the firing response, axonal propagation and corticocortical and corticothalamic pathways. Its relatively few parameters measure quantities such as synaptic strengths, corticothalamic delays, synaptic and dendritic time constants, and axonal ranges, and are all constrained by independent physiological measurements. It reproduces quantitative forms of electroencephalograms seen in various states of arousal, evoked response potentials, coherence functions, seizure dynamics and other phenomena. Fitting model predictions to experimental data enables underlying physiological parameters to be inferred, giving a new non-invasive window into brain function that complements slower, but finer-resolution, techniques such as fMRI. Because the parameters measure physiological quantities relating to multiple scales, and probe deep structures such as the thalamus, this will permit the testing of a range of hypotheses about vigilance, cognition, drug action and brain function. In addition, referencing to a standardized database of subjects adds strength and specificity to characterizations obtained.

Axons↗

PubMed1986

Microcorrosion casting of the human respiratory acinus.

Microcorrosion casts demonstrating the respiratory acini of human lungs were produced using Tensol Cement No. 70 (a methyl methacrylate mixture). Lung casts were made from foetuses of 19 weeks' gestation to term, a child of 5 years and two adults. Tensol Cement No. 70 was found to infuse the most peripheral airspaces without tissue penetration and could be airdried. Attempts using Batson's medium were hampered by permeation of the airway walls and inability to withstand airdrying. Despite the use of autopsy material, good cell impressions were seen. At 19 weeks' gestation, the respiratory acinus is simple with only two or three generations of rather tubular respiratory bronchioles. In later intra-uterine development, the number of generations of intra-acinar airways increases and the most peripheral airspaces expand to form initially shallow but later cup-shaped saccules. At all ages, the proximal airways of the acinus have regularly-spaced deep cell impressions suggesting a cuboidal/columnar epithelium while the distal airspaces have less frequent shallow cell impressions suggesting a flattened epithelium. Measurements of the maximum diameter of the most peripheral airspaces show an approximate doubling of size between 19 weeks' gestation and term and a further doubling by the age of 5 years.

Adult↗

PubMed1991

Localization of the P3 sources using magnetoencephalography and magnetic resonance imaging.

In this study, two related issues were addressed: first, whether the P3 component of auditory evoked responses, obtained in the context of an oddball paradigm, and its magnetoencephalographically recorded counterpart (P3m) are generated by the same intracranial sources; and, second, whether these sources, modeled as equivalent current dipoles, can be localized in particular brain structures using magnetic resonance imaging. The study involving 8 normal adult subjects resulted in the following findings. (1) Both the similarities and differences in wave form characteristics of the simultaneously recorded P3 and P3m can be best accounted for by common intracranial sources. (2) Several successively activated single-dipolar sources, rather than a single source, account for the entire evolution of the P3m component. (3) Most of these sources were localized in the vicinity of the auditory cortex in all subjects, although some sources appeared to be in deeper structures, possibly the lateral thalamus. (4) The successive activation of sources followed an orderly medial-to-lateral course. These results suggest that activity responsible for the surface-recorded P3 (and P3m) component may be initiated in deep structures, but it quickly spreads over and is sustained in areas near the auditory cortex.

Adult↗

PubMed2006

Cortico-cerebellar coherence during a precision grip task in the monkey.

We studied the synchronization of single units in macaque deep cerebellar nuclei (DCN) with local field potentials (LFPs) in primary motor cortex (M1) bilaterally during performance of a precision grip task. Analysis was restricted to periods of steady holding, during which M1 oscillations are known to be strongest. Significant coherence between DCN units and M1 LFP oscillations bilaterally was seen at approximately 10-40 Hz (contralateral M1: 25/87 units; ipsilateral: 9/87 units). Averaged coherence between DCN units and contralateral M1 LFP showed a prominent approximately 17-Hz coherence peak and an average phase of approximately -pi/2 radians, implying that the DCN units fired around the time of maximal depolarization of M1 cells. The lack of a time delay between DCN and M1 activity suggests that the cerebellum and cortex may form a pair of phase coupled oscillators. Although coherence values were low (mean peak coherence, 0.018), we used a computational model to show that this probably resulted from the nonlinearity of spike generating mechanisms within the DCN. DCN unit discharge and DCN LFPs also showed significant coherence at approximately 10-40 Hz, with similarly low magnitude (mean peak coherence, 0.012). The average coherence phase was -2.5 radians for the 6- to 14-Hz range and -1.1 radians for the 17- to 41-Hz range, suggesting different frequency-specific underlying mechanisms. Finally, 4/40 pairs of simultaneously recorded DCN units showed a significant cross-correlation peak, and 16/40 pairs showed significant unit-unit coherence. The extensive oscillatory synchronization observed between cerebellum and motor cortex may have functional importance in sensorimotor processing.

Action Potentials↗

PubMed2000

Sustaining olfaction at low salinities: mapping ion flux associated with the olfactory sensilla of the blue crab Callinectes sapidus.

To test the hypothesis of a diffusion-generated, ionic/osmotic microenvironment within the olfactory sensilla (aesthetascs), flux gradients of Ca(2+) and K(+) associated with the external surfaces of these sensilla were spatially mapped using self-referencing, ion-selective microelectrodes. Blue crabs (Callinectes sapidus) acclimated to low-salinity conditions (15% sea water and fresh water) showed a net efflux of ions from the aesthetascs. The region of maximum flux associated with each aesthetasc conformed to that predicted from structural data and corresponded to the permeable region of the cuticle separating the olfactory dendrites from the external environment. Estimates of net flux from the entire tuft of aesthetascs for both Ca(2+) and K(+) fell within the predicted range on the basis of comparisons with (22)Na(+) flux measured previously and assuming a passive diffusion model of ion movement from the hemolymph to the sensillar lymph and, ultimately, to the external environment. The maximum concentrations of these ions measured deep within the tuft are discussed in the light of a potential across the aesthetascs that may limit ion efflux at low salinities.

Animals↗

PubMed2001

Melt retention and segregation beneath mid-ocean ridges.

Geochemical models of melting at mid-ocean ridges-particularly those based on trace elements and uranium-decay-series isotopes-predict that melt segregates from the matrix at very low porosities, of order 0.1%. Some of these models also require that the melt ascends rapidly. But these predictions appear to conflict with seismic data obtained by the mantle electromagnetic and tomography (MELT) experiment. These data reveal, beneath the East Pacific Rise (at 17 degrees S), a region of low velocities several hundred kilometres wide, which is best explained by the presence of 1-2% melt, distributed on a grain scale in disk-shaped geometries. Here I show that these apparently contradictory constraints can be reconciled by taking into account the geometry and resulting permeability of the intergranular network of melt, together with the changing character of the melt as it ascends. A deep, volatile-rich melt with low viscosity and density is mobile at 0.1% porosity, but basaltic melt only becomes mobile at a porosity above 1%. While the volumetric contribution of the volatile-rich melt to the erupted basalts is small, the isotopic disequilibria (except for radium) generated by porous flow of this melt are preserved if melt transport is rapid at the onset of high-productivity melting. Also, because of incomplete extraction, some melt is retained in a broad zone, consistent with the MELT observations.

Journal Article↗

PubMed2001

Detection of superficial zone protein in human and animal body fluids by cross-species monoclonal antibodies specific to superficial zone protein.

In this report we describe the purification of human superficial zone protein (SZP), the generation of cross-species monoclonal antibodies (MAbs) and the detection of this protein in human and animal body fluids. Human SZPs, used as immunizing antigens, were purified either from culture media of human cartilage organ cultures or from human synovial fluids. The immunizing antigens were mixed with RIBI adjuvant in one of three forms: nonmodified SZP, superficial zone protein-keyhole limpet hemocyanin conjugate (SZP-KLH), or a mixture of superficial zone protein and hyaluronic acid (SZP-HA). A panel of MAbs including GW4.23, S6.79, S13.52, S13.233, and S17.109 were generated and characterized. Monoclonal antibody (MAb) S6.79, an IgG2b with K(D) 3.14 x 10(-9) M from SZP-KLH immunization, is of particular interest. It reacts strongly to a large molecular weight form of SZP in both enzyme-linked immunosorbent assay (ELISA) and Western blotting. It stains the most superficial layer of articular cartilage in immunohistochemistry, whereas the middle and deep zones of cartilage are not stained. When MAb S6.79 was applied to Western blots of human body fluids, a strong 345-kDa band was detected in samples of synovial fluid and weaker bands of similar size were detected in samples of plasma and serum. MAb S6.79 also showed cross-species immunoreactivity with SZP in samples of synovial fluids harvested from bovine, dog, guinea pig, and rabbit, as demonstrated by Western blotting and antibody absorption experiments. This cross-species MAb will be a useful tool in human and animal model studies for monitoring SZP levels and tissue distribution. It may help define the roles of SZP in normal articular joints and may be of diagnostic or prognostic value for the measurement of SZP in pathological conditions such as osteoarthritis, rheumatoid arthritis, and camptodactyly-arthropathy-coxa vara-pericarditis.

Animals↗

PubMed2026

A Foundation Model Based CT Biomarker for Non-Invasive Prediction of Response to Neoadjuvant Immunochemotherapy in Non-Small Cell Lung Cancer.

Predicting pathological complete response (pCR) to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) is clinically important yet remains challenging. Here, we introduce a foundation model-derived computed tomography (CT) imaging biomarker established from a multi-center cohort of 702 patients. Specifically, we developed and validated a non-invasive baseline CT-based model for risk stratification of pathological response. To address scanner and protocol heterogeneity, we first built a 3D Vision Mamba-based CT super-resolution model trained on 2494 cases for image standardization. We then fine-tuned a lung cancer-specific CT foundation model from a pretrained 3D model (VoCo) using 6643 chest CT scans. Finally, we constructed a multi-task Swin Transformer that jointly performs risk stratification and segments tumors to generate the imaging biomarker. Across five centers, the model achieved consistently strong generalization (AUC: 0.75-0.87) for pCR prediction. Genomic analysis revealed that the biomarker was independent of tumor mutational burden but significantly associated with TP53 mutations, suggesting an association with a radiogenomic phenotype related to this alteration. Together, these results demonstrate a generalizable and biologically meaningful foundation model-based biomarker for non-invasive risk stratification of pathological response in NSCLC.

Female↗

PubMed2006

Developmental and acquired dyslexias.

Marshall (1984) highlighted potential parallels between children with developmental disorders of reading and adults who had acquired reading disorders. He advocated the use of a cognitive neuropsychological framework in the investigation of children with developmental abnormalities of cognition, including those with developmental dyslexias. Developmental phonological dyslexia has been extensively described and is a pervasive disorder. The relationship between reading difficulty and phonological difficulties evident in explicit oral phonological tasks continues to be a focus for debate. Clear cases of developmental deep dyslexia have now been described and the syndrome has also been described as characterising early reading development in Williams syndrome (WS), where there are also semantic errors in other domains, including naming and receptive vocabulary and there may be a generalised difficulty with the activation of fine grain semantic specifications. In the domain of number, highly selective reading disorders characterised by high rates of semantic errors have been documented, indicating that semantic reading errors can be domain-specific. They can occur to number words despite intact ability to read Arabic numbers and they can occur to Arabic numbers and number words despite intact ability to read words in other domains. Current models of reading written words do not allow for such material-specific dissociation. Developmental surface dyslexia has also been described in a range of countries, languages and orthographies. Descriptions of cases for whom there is no phonological impairment in reading have generated contrary evidence for theories suggesting that phonological impairment underlies all developmental dyslexia. As reading develops in Williams Syndrome, phonological reading skills may improve with over-reliance on these leading to surface dyslexia. Surface dyslexia has also been reported in cases of developmental amnesia in which there are semantic memory impairments. Hyperlexia can take several forms including broad hyperdevelopment with elevated phonological reading abilities, lexico-semantic reading abilities and reading comprehension as in Turner's syndrome (TS). This advantage has early onset in school-starters. These specific modular effects do not have pervasive impact across systems but demonstrate the limitations of functional plasticity in developmental and genetic disorders. The framework Marshall (1984) outlined has provided a foundation for the development of systematic investigation of developmental disorders.

Adolescent↗

PubMed2000

A finite element model of remote palpation of breast lesions using radiation force: factors affecting tissue displacement.

The early detection of breast cancer reduces patient mortality. The most common method of breast cancer detection is palpation. However, lesions that lie deep within the breast are difficult to palpate when they are small. Thus, a method of remote palpation, which may allow the detection of small lesions lying deep within the breast, is currently under investigation. In this method, acoustic radiation force is used to apply localized forces within tissue (to tissue volumes on the order of 2 mm3) and the resulting tissue displacements are mapped using ultrasonic correlation based methods. A volume of tissue that is stiffer than the surrounding medium (i.e., a lesion) distributes the force throughout the tissue beneath it, resulting in larger regions of displacement, and smaller maximum displacements. The resulting displacement maps may be used to image tissue stiffness. A finite-element-model (FEM) of acoustic remote palpation is presented in this paper. Using this model, a parametric analysis of the affect of varying tissue and acoustic beam characteristics on radiation force induced tissue displacements is performed. The results are used to evaluate the potential of acoustic remote palpation to provide useful diagnostic information in a clinical setting. The potential for using a single diagnostic transducer to both generate radiation force and track the resulting displacements is investigated.

Acoustics↗

PubMed1995

Quantification of sodium lauryl sulfate penetration into the skin and underlying tissue after topical application--pharmacological and toxicological implications.

Sodium lauryl sulfate (SLS) is known to penetrate skin and cause cutaneous irritation. Some of these effects have been well-defined using bioengineering techniques. In this study, the ability of SLS to penetrate skin was quantified in a hairless rat model. In addition, local deep tissue penetration and systemic exposure to SLS were also evaluated to assess the toxic potential of topically applied SLS. SLS was observed to penetrate directly to a depth of about 5-6 mm below the applied site. Systemic redistribution was predominantly responsible in determining concentrations of SLS in tissues deeper than 5-6 mm. Epidermal concentrations of SLS after application of 1% (34 mM) aqueous SLS solution for 24 h were above the threshold levels which are known to evoke typical skin irritation responses. Deeper underlying tissues including dermis, subcutaneous, and muscle may also be exposed to high levels of SLS. Topically applied SLS was also observed in blood and contralateral tissues but the observed levels were not likely to elicit any systemic side effects at these doses. Traces of SLS were observed in tissues 7 days after single 24 h application of SLS, which supports the prolonged barrier disruption data generated using conventional bioengineering techniques. Cumulative treatment of SLS significantly increased the concentration of this compound in the underlying epidermis. The known preferential affinity of SLS for skin lipids and proteins was further confirmed by both in vitro and in vivo results. However, in vitro studies failed to predict the underlying tissue toxicity of SLS under the patch site when compared to the in vivo results. Such quantitative pharmacokinetic-pharmacodynamic correlations may be useful predictors for effective use of surfactants as penetration enhancers in cosmetic, pharmaceutical, and industrial applications.

Administration, Topical↗

PubMed1997

Peptide binding to MHC class I is determined by individual pockets in the binding groove.

H-2Kb and HLA-A2 are MHC4 class I molecules with a similar overall structure. Important differences between these two class I molecules reside in the structure of the individual pockets in the antigenic-peptide-binding groove. H-2Kb, which has a deep C pocket, binds specifically peptides with a tyrosine or a phenylalanine at position 5. In contrast, HLA-A2 has a shallow C pocket, which cannot accommodate large side chains at position 5. Site-directed mutagenesis was used to generate a chimera between the murine H-2Kb and the human HLA-A2 [H-2Kb/HLA-A2(C')]. The structure of this chimera is similar to H-2Kb except for the region around the deep C pocket, where residues at positions 9, 97 and 99 were substituted with those bulkier residues from HLA-A2. Peptide binding between this chimera and H-2Kb-binding peptides [VSV (52-59), OVA (257-264), and MCMV pp89 (168-176)], revealed that the deep C pocket of H-2Kb was crucial for high-affinity binding. While a peptide, VSV (52-59), was found to bind with severalfold lower 'affinity' to H-2Kb/HLA-A2(C') than to the wild-type H-2Kb, a VSV analogue with the tyrosine in position 5 (Tyr5) substituted with an alanine was found to bind with a similar 'affinity' to both MHC class I molecules. Computer-aided modelling of the H-2Kb/HLA-A2(C') complex indicates that the VSV (52-59) peptide probably binds to the chimeric MHC molecule with the peptide side chain of anchor residue Tyr5 pointing away from the groove. These results confirm a role of the individual pockets in determining peptide-binding affinity and specificity and suggest that this may be accomplished by changes in side-chain orientation.

Animals↗

PubMed1996

Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas.

BACKGROUND: Identification of the prognosis of patients with gliomas is important for selecting and evaluating the effectiveness of treatment. The aim of this study was to evaluate the Ki-67 labeling index (LI) using the newly generated MIB-1 monoclonal antibody (MoAb) as a prognostic indicator for patients with astrocytomas. METHODS: Ki-67 immunohistochemistry was performed on paraffin sections to estimate the growth potential of 72 supratentorial astrocytomas using the MIB-1 MoAb after hydrated autoclaving treatment. Multivariate analysis using the Cox proportional hazard stepwise model was used to evaluate the influence of Ki-67 LI, as well as other prognostic factors, on the duration of survival of patients with supratentorial astrocytomas. RESULTS: The mean Ki-67 LI was 3.8% (+/- 2.7%; standard deviation [SD]) in Grade 2 gliomas (n = 19), 18.4% (+/- 9.7% SD) in Grade 3 gliomas (n = 25), and 31.6% (+/- 12.9% SD) in Grade 4 gliomas (n = 28). Multivariate survival analysis showed that histologic grade, Ki-67 LI, and Karnofsky performance status (KPS) score before and after treatment were independent, statistically significant prognostic factors for patients with all grades of astrocytomas. In high grade lesions, Ki-67 LI, tumor location (superficial vs. deep), and KPS score after treatment were significant prognostic variables, whereas histologic grade did not meet the significance level for entry into the stepwise model. CONCLUSIONS: These results indicate that the Ki-67 LI obtained using MIB-1 MoAb is an important and practical tool for estimating biologic behavior of gliomas, as well as for predicting survival.

Adolescent↗

PubMed1996

Site-directed mutants designed to test back-door hypotheses of acetylcholinesterase function.

The location of the active site of the rapid enzyme, acetylcholinesterase, near the bottom of a deep and narrow gorge indicates that alternative routes may exist for traffic of substrate, products or solute into and out of the gorge. Molecular dynamics suggest the existence of a shutter-like back door near Trp84, a key- residue in the binding site for acetylcholine, in the Torpedo californica enzyme. The homology of the omega loop, bearing Trp84, with the lid which sequesters the substrate in neutral lipases displaying structural homology with acetylcholinesterase, suggests a flap-like back door. Both possibilities were examined by site-directed mutagenesis. The shutter-like back door was tested by generating a salt bridge which might impede opening of the shutter. The flap-like back door was tested by de novo insertion of a disulfide bridge which tethered the omega loop to the body of the enzyme. Neither type of mutation produced significant changes in catalytic activity, thus failing to provide experimental support for either back door model. Molecular dynamics revealed, however, substantial mobility of the omega loop in the immediate vicinity of Trp84, even when the loop was tethered, supporting the possibility that access to the active site, involving limited movement of a segment of the loop, is indeed possible.

Acetylcholinesterase↗

PubMed2006

Area-pressure relationship of lower limb main veins in man.

BACKGROUND: The mechanical properties of human veins remain incompletely known. However they play an important part in number of physiological and pathological situations, as hemodynamic adjustment to orthostasis, deep venous thrombosis (DVP) and chronic venous insufficiency (CVI). The aim of the study was to describe the pressure/volume (area) relationship of some important conduit veins of the human's lower limb. PROBANDS AND METHODS: We investigated the area/pressure relationship of thefemoral vein (FV) at mid thigh, the great saphenous vein (GSV) at lower third of the leg, and a deep leg vein (DLV), either the peroneal or posterior tibial vein, in fifteen healthy young men. The cross section areas were measured with B-mode ultrasound while various positive and negative venous pressures were generated by body's tilting. RESULTS: Over the range of pressures investigated, the area/pressure relationship was roughly linear, the classical sigmoid relation did not emerge from our data. The relative compliance of FV, GSV and DLV was 0.0312, 0.0118, and 0.0147 mmHg(-1), respectively. CONCLUSIONS: The relative compliance of FV is more than two times higher than the relative compliance of both the DLV and the GSV.

Adult↗

PubMed2002

Pediatric physiologic pulsatile pump enhances cerebral and renal blood flow during and after cardiopulmonary bypass.

Controversy over benefits of pulsatile flow after pediatric cardiopulmonary bypass (CPB) continues. Our study objectives were to first, quantify pressure and flow waveforms in terms of hemodynamic energy, using the energy equivalent (EEP) formula, for direct comparisons, and second, investigate effects of pulsatile versus nonpulsatile flow on cerebral and renal blood flow, and cerebral vascular resistance during and after CPB with deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model. Fourteen piglets underwent perfusion with either an hydraulically driven dual-chamber physiologic pulsatile pump (P, n = 7) or a conventional nonpulsatile roller pump (NP, n = 7). The radiolabeled microsphere technique was used to determine the cerebral and renal blood flow. P produced higher hemodynamic energy (from mean arterial pressure to EEP) compared to NP during normothermic CPB (13 +/- 3% versus 1 +/- 1%, p < 0.0001), hypothermic CPB (15 +/- 4% versus 1 +/- 1%, p < 0.0001) and after rewarming (16 +/- 5% versus 1 +/- 1%, p < 0.0001). Global cerebral blood flow was higher for P compared to NP during CPB (104 +/- 12 ml/100g/min versus 70 +/- 8 ml/100g/min, p < 0.05). In the right and left hemispheres, cerebellum, basal ganglia, and brainstem, blood flow resembled the global cerebral blood flow. Cerebral vascular resistance was lower (p < 0.007) and renal blood flow was improved fourfold (p < 0.05) for P versus NP, after CPB. Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.

Age Factors↗

PubMed2005

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

Actins↗