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PubMed2000

[The difference of thrombin-induced TF/uPAR mRNAs expressions in cultured endothelial cells and U937 cell line].

OBJECTIVE: To compare the effects of thrombin on the expression of the tissue factor (TF) and urokinase-type plasminogen activator receptor (uPAR) mRNA in the cultured vascular endothelial cells (VEC) and U937 cell line. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of TF and uPAR genes in the cultured cells under stimulation of thrombin, inactivated thrombin (DFP-T), or at the presence of the inducers and anti-thrombin receptor antibody (ATR-Ab). RESULTS: In U937 cells, the TF and uPAR mRNA expression induced by thrombin could be fully quenched with the ATR-Ab, but in VEC, even at the presence of ATR-Ab, there still was a little stimulative effect of thrombin revealed. DFP-T had no effect on the expression of TF and uPAR mRNA in U937 cells, but could elicit a faint reaction in VEC. CONCLUSION: The induction effects on TF and uPAR mRNA expression in both of the cultured cells by thrombin were mainly dependent on the TR activation, which may not be the unique pathway for thrombin to induce TF and uPAR mRNA expression in VEC.

Cells, Cultured↗

PubMed2002

Ku affects the ataxia and Rad 3-related/CHK1-dependent S phase checkpoint response after camptothecin treatment.

Camptothecin (CPT) that targets DNA topoisomerase I is one of the most promising broad-spectrum anticancer drugs in development today. The cytotoxicity of CPT is S phase (S)-specific because the collision of advancing replication forks with CPT-topoisomerase I-DNA complexes results in DNA damage. After DNA damage, proliferating cells could actively slow down the DNA replication through an S checkpoint to provide time for repair. We report now that there is an activated S checkpoint response in CPT-treated mammalian cells. This response is regulated by Ataxia and Rad3-related (ATR)/CHK1 pathway. Compared with their wild-type counterparts, CPT-treated Ku80-/- cells showed stronger inhibition of DNA replication. This stronger inhibition had no relationship with DNA-dependent protein kinase (DNA-PK) activity but correlated with the higher activities of ATR and the higher activities of CHK1 in such cells. Not only caffeine, the nonspecific inhibitor of ATR, or UCN-01, the nonspecific inhibitor of CHK1, but also the specific CHK1 antisense oligonucleotide abolished the stronger inhibition of DNA replication in CPT-treated Ku80-/- cells. These results in aggregate indicated that the stronger S checkpoint in CPT-treated Ku80-/- cells is regulated through the highly activated ATR/CHK1 pathway.

Animals↗

PubMed2002

Expression of antisense thrombin receptor gene inhibits intimal hyperplasia of rat carotid artery after balloon injury.

OBJECTIVE: To study the mechanism of restenosis after angioplasty and to clarify the effect of thrombin and its receptor on restenosis development. METHODS: Balloon catheter-induced injury was adopted to induce intimal hyperplasia of the carotid arteries in rats. Antisense thrombin receptor (ATR) cDNA was transfected by perfusing recombinant LXSN ATR plasmid/nanoparticle complex into the segment of the injured carotid artery. RESULTS: PCR result showed integration of the recombined gene. Dot blot showed the expression of antisense TR mediated by recombinant LXSN ATR plasmid/nanoparticle complex in the wall of common carotid arteries of the experimental group rats, which enabled to inhibit TR gene expression and intimal hyperplasia of the injured arteries. CONCLUSIONS: Thrombin and its receptor play an important role in the formation of neointima after the injury, which provides a potential clue in developing a new approach for prevention and treatment of restenosis after angioplasty.

Animals↗

PubMed2006

[Characteristics of adenine nucleotide translocator in mitochondria of rat cerebral cortex during hypobaric hypoxia exposure].

The purpose of the present study was to explore the effects of hypoxic exposure on mitochondrial adenine nucleotide translocator (ANT) activity and its characteristics. Male Wistar rats were exposed to hypoxia in a hypobaric chamber simulating high altitude at 5 000 m for 1, 5, 15 and 30 d. Control rats were fed outside the hypobaric chamber. Rats were sacrificed by decapitation and mitochondria from the cerebral cortex were isolated by differential centrifugation at each time point. The ANT activity was detected by the atractyloside (ATR)-inhibitor stop technique. Mitochondria was initiated by addition of (3)H-ADP and terminated after 12 s by quick addition of ATR. The radioactivity was measured in a liquid scintillation counter. Nonspecific binding of (3)H-ADP to mitochondria was estimated by incubation of mitochondrial samples with ATR prior to the addition of (3)H-ADP. This blank was substracted from the measured radioactivities. The activity of ANT was expressed as nanomoles (3)H-ADP per minute per milligram protein. The ANT density was determined by titrating the rate of state 3 respiration with increasing concentrations of carboxyatractyloside (CAT). Mitochondria were pre-incubated with CAT in a respiratory medium before ADP addition to initiate state 3 respiration. Plots of O2 consumption versus CAT appeared biphasic with an increasing inhibitory segment followed by a steady respiration, indicating that state 3 respiration was completely inhibited. The density of ANT was determined by the amount of CAT required to completely inhibit state 3 respiration, assuming a 1:1 binding stoichiometry, which was expressed as ANT density per milligram mitochondria protein. (ATP+ADP) in mitochondria was measured by high performance liquid chromatography (HPLC). The results showed that there was an obvious decrease in the ANT activity during hypoxic exposure. The lowest ANT activity was seen in 5 d group. Partial recovery of ANT activity was observed in 15 and 30 d groups, but ANT activity was still lower than that in the control group (P<0.01). Compared with that in normoxic control group, no change of ANT density in mitochondria was observed in hypoxia group (P>0.05). The turnover number of ANT in control, 1, 5, 15, 30 d groups were 16.67, 1.90, 0.40, 1.81, 4.73 pmol ADP/(min.pmol ANT), respectively. However, (ATP+ADP) in mitochondria in 1, 5, 15, 30 d groups were 63.37%, 48.44%, 52.73%, 60.16% of control group respectively. Therefore, the turnover number of energy production and expenditure were reduced. These observations suggest that the change of ANT activity may be one of the mechanisms of cellular oxidative phosphorylation dysfunction during hypoxic exposure.

Altitude↗

PubMedDate not supplied

Direct determination of lycopene content in tomatoes (Lycopersicon esculentum) by attenuated total reflectance infrared spectroscopy and multivariate analysis.

Lycopene is a potent antioxidant that has been shown to play critical roles in disease prevention. Efficient assays for detection and quantification of lycopene are desirable as alternatives to time- and labor-intensive methods. Attenuated total reflectance infrared (ATR-IR) spectroscopy was used for quantification of lycopene in tomato varieties. Calibration models were developed by partial least-squares regression (PLSR) using quantitative measures of lycopene concentration from liquid chromatography as reference method. IR spectra showed a distinct marker band at 957 cm(-1) for trans Carbon-Hydrogen (CH) deformation vibration of lycopene. PLSR models predicted the lycopene content accurately and reproducibly with a correlation coefficient (sigma) of 0.96 and standard error of cross-validation <0.80 mg/100 g. ATR-IR spectroscopy allowed for rapid, simple, and accurate determination of lycopene in tomatoes with minimal sample preparation. Results suggest that the ATR-IR method is applicable for high-throughput quantitative analysis and screening for lycopene in tomatoes.

Carotenoids↗

PubMed1990

Effects of indomethacin on neural and myogenic components in equine airway smooth muscle.

Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally antagonistic CO and lipoxygenase (LO) metabolites. The present studies were designed to assess the relative contributions of altered arachidonic acid metabolism on those respective elements. The utility of the model, in terms of distinguishing neural and myogenic components, was assessed by examining the effects of the muscarinic antagonist atropine (ATR) and the neurotoxin tetrodotoxin (TTX) on the stimulus-response (SR) relationship. The observations that TTX and ATR produced similar rightward (but not downward) shifts of the SR curve and that D-600 inhibited the TTX-insensitive responses are consistent with a selective activation of the muscle by the nerves at lower voltages and a direct stimulation of the muscle at higher voltages. INDO potentiated both the neural and myogenic components of the SR curve, effects which were sensitive to ATR and 5,8,11,14-eicosatetraynoic acid, an inhibitor of LO, and reversed by PGE2. The finding that PGE2 at low doses (10(-8) M) inhibited responses at lower voltages and that at higher concentration (10(-7) M) it shifted the SR curve right and downward suggested that neurotransmitter release is more sensitive to PGE2 inhibition than is muscle response.(ABSTRACT TRUNCATED AT 250 WORDS)

5,8,11,14-Eicosatetraynoic Acid↗

PubMedDate not supplied

Effects of atropine and mecamylamine given locally into periaqueductal gray on bioelectrical activity of chosen brain structures of the rabbit.

Atropine (Atr) or mecamylamine (MeC) were administered locally into the periaqueductal gray (PAG) of rabbits with chronically implanted electrodes into the motor-sensory cortex (MSC) ventro-posterolateral thalamic nuclei (NVPL), PAG and midbrain reticular formation (MRF). Bioelectrical responses in the cortex and subcortical structures were analyzed automatically by means of Fast Fourier Transform and Autoregressive Method. Both Atr and Mec modified the activity in PAG, Atr had also the influence in MRF and MSC.

Animals↗

PubMed1989

Prevalence and variation of astigmatism in a military population.

Astigmatism is a common refractive anomaly. Observations on 1112 consecutive patients from a military optometric clinical population were taken to establish the prevalence of astigmatism and the incidence of its different variations. Astigmatism was found to exist in about 63% of the eyes. It was found that with-the-rule (WTR) and against-the-rule (ATR) astigmatism were the predominant types of astigmatism, and that approximately 70% of astigmatism found required 1.00D of correcting cylinder power or less. One objective of the study was to discover if a statistically significant difference existed between right and left eyes when comparing the mean correcting minus cylinder axes for WTR, ATR, and oblique types of astigmatism. This was shown to exist for WTR and ATR astigmatism. Further studies to determine the etiology of this difference are indicated.

Adult↗

PubMed1979

[Quantitative measurement of the tendon reflexes. A study on Achilles tendon reflex (author's transl)].

Quantitative analyses of tendon reflexes were performed for the purpose of clinical application. Tendon tap was marked with a WNS-5D semiconductor load cell inserted in the hammer to measure tapping force. Achilles tendon reflex (ATR) was measured with a LAS-0.1 displacement transducer in kneeling position on the chair. In ATR, six factors, i.e. duration of reaction time, the height of the wave, the time from the hammer tap to the top of the wave, the maximum speed of contraction, the time from the hammer tap to the maximum speed and half relaxation time, were analyzed. Correlation between these six factors were discussed. From the analyses of these factors, half relaxation time may serve as the best indicator of clinical status among the factors obtained by analysis of ATR.

Achilles Tendon↗

PubMed1982

Changes of triiodothyronine and thyroxine in patients with thyrocardiac disease and their relationship to systolic time intervals.

The relationship between the ejection time from the left ventricle (LVET), the pre-ejection period (PEP) of the left ventricle, the Q-Kd interval, the course of the Achilles tendon reflex (ATR) and the thyroxine (T4) and triiodothyronine (T3) serum level in 184 patients with different grades of thyroid function was investigated. Some of these patients suffered from cardiac affection caused by thyrotoxicosis or ischemic heart disease. The significant inverse correlations between the T3 level and the duration of PEP, LVET, the Q-Kd interval and the ATR was revealed. An inverse relationship with T4 level was found only in the Q-Kd interval and ATR. In those instances, where there was a correlation with T4 and T3, higher values of correlation coefficients were observed in the correlation with T3. T4 concentration was higher in patients with cardiac affection. In thyrocardiacs was an increase in the quotient T4:T3, while in thyrotoxic patients without cardiac affection this quotient was rather decreased. The significance of disturbed T4 metabolism in development of cardiac affection in thyrotoxicosis is discussed with respect to ageing processes.

Achilles Tendon↗

PubMed1980

[The specificity of pharmacological responses in Ascaris muscle (author's transl)].

To investigate the pharmacological properties of Ascaris muscle, comparative studies were undertaken on the actions of various drugs on Ascaris muscle, guinea pig isolated ileum and frog isolated rectus preparations. In Ascaris muscle and frog isolated rectus preparations, the contractile activities with acetylcholine (ACh, 10(-5) g/ml in Ascaris and 10(-6) g/ml in frog rectus) and 1, 1-dimethyl-4-phenylpiperazinium (DMPP, 10(-6) g/ml) were inhibited significantly and reversely by d-tubocurarine (d-Tc, 10(-5) g/ml) and mecamylamine (Meca, 10(-5) g/ml), and slightly by atropine (Atr, 10(-4) g/ml) and hexamethonium (C6, 10(-4) g/ml). In guinea pig isolated ileum preparation, the contractile activity with ACh (10(-6) g/ml) was inhibited markedly and reversely but Atr (10(-6) g/ml), while the activity with DMPP (10(-6) g/ml) was similarly inhibited by Meca (10(-6) g/ml), C6 (10(-6) g/ml) and Atr (10(-6) g/ml). Although frog isolated rectus preparation was contracted with 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium (McN-A-343, 10(-5) g/ml) but not with pilocarpine (10(-4) g/ml), Ascaris muscle preparation was not affected by these agonists. Frog isolated rectus preparation was contracted with 5-hydroxytryptamine (5 HT, 10(-4) g/ml) but was not affected by histamine (His, 10(-3) g/ml) and gamma-aminobutyric acid (GABA, 10(-4) g/ml), whereas Ascaris muscle was contracted with His (10(-3) g/ml) and relaxed with 5-HT (10(-4) g/ml) and GABA (10(-5) g/ml). These results suggest that Ascaris muscle as well as skeletal muscle have nicotinic receptors and that the Ascaris muscle has properties which differ specifically from skeletal muscle.

Acetylcholine↗

PubMed1995

Fluorescence polarization from isomers of tetramethylrhodamine at SH-1 in rabbit psoas muscle fibers.

We have used fluorescence polarization to examine orientational changes of the 5- and 6-isomers of acetamidotetramethylrhodamine (ATR) covalently bound to SH-1 (Cys-707 of the myosin heavy chain) in single, skinned fibers from rabbit psoas muscle after rapid length steps or photolysis of caged nucleotides. Similar results were obtained with both the 5- and 6-isomers of ATR. After the photolysis of caged ATP, large and rapid changes in the fluorescence polarization signals were observed and were complete well before appreciable force had been generated. Changes in the fluorescence polarization signals after the photolysis of caged ADP were similar to those after the photolysis of caged ATP, despite an almost negligible change in force. The fluorescence polarization signals remained almost constant after rapid length steps in both rigor and active muscle fibers. These results suggest that structural changes at SH-1 monitored by 5- or 6-ATR are not associated directly with the force-generating event of muscle contraction, but may be involved in the communication pathway between the nucleotide and actin-binding sites of myosin.

Adenosine Triphosphate↗

PubMed1994

Radial suture stabilized by fibrin glue to correct preoperative against-the-rule astigmatism during cataract surgery.

We evaluated the efficacy of using a modified wound-closure technique in cataract surgery to reduce presurgical against-the-rule (ATR) astigmatism. Seventy-seven eyes received a radial 10-0 nylon suture in the axis of the preexisting ATR cylinder, combined with an application of fibrin glue to stabilize the wound. A control group of 76 patients with comparable preoperative ATR astigmatism was operated on in the same manner, but only fibrin glue and no suture was used for wound closure. The mean induced astigmatism in these two groups differed by 0.42 diopters, a significant difference (P < .05). In the cases with preoperative astigmatism greater than 1.00 D, the difference between the two groups, again a significant one, was 0.73 (P < .05).

Aged↗

PubMed1993

Postoperative astigmatism following phacoemulsification with sutured vs. unsutured wounds.

A total of 293 cases of phacoemulsification cataract surgery with a 5.0- or 6.0-mm frown incision were analysed retrospectively to compare postoperative astigmatism between cases with sutured wounds and those with unsutured wounds. Astigmatic analysis was done with a simplified method (keratometric readings with steep meridians between 46 degrees and 134 degrees were considered "with-the-rule" [WTR], and those with steep meridians less than 46 degrees and greater than 134 degrees, "against-the-rule" [ATR]). Among patients with WTR astigmatism preoperatively, the mean keratometric cylinder in the sutureless group (n = 53) was significantly lower at 1 day and at 4 to 6 months postoperatively than before surgery (p < or = 0.001); in the suture group (n = 120) the mean cylinder was significantly higher at 1 day and significantly lower at 4 to 6 months than before surgery (p < 0.05). Among patients with ATR astigmatism preoperatively, the mean keratometric cylinder in the sutureless group (n = 22) was significantly higher at 1 day than before surgery (p < 0.01); in the suture group (n = 98) the mean cylinder was significantly lower at 1 day than before surgery (p < 0.001), and the difference at 4 to 6 months almost reached statistical significance (p = 0.052). Vector analysis showed that surgically induced cylinders in the suture and sutureless groups were similar. Our findings suggest that in the short term patients with preoperative WTR astigmatism may benefit from unsutured wounds, and those with preoperative ATR astigmatism may benefit from sutured wounds if the incision is placed in the vertical meridian.

Astigmatism↗

PubMed1996

Cardiopulmonary actions of muscarinic receptor subtypes in the newborn dog.

We addressed the role of muscarinic receptor subtypes in neurally mediated bronchoconstriction in vivo and airway smooth muscle contraction in vitro in the newborn dog. The in vivo dose-response effects of "selective" muscarinic antagonists on changes in lung resistance (RL) and heart rate (HR) in response to electrical stimulation of the vagus nerves were obtained in four groups of newborns. Each group was exposed to a different muscarinic antagonist: M1-selective pirenzepine (pir), M2-selective AF-DX 116 (11-[2-[(diethylamino)methyl]-1-piperidinyl]acetyl-5,11-dihydro-6H-pyrid o- [2,3-b]-[1,4]-benzodiazepine-6-one), M3-selective p-F-HHSiD (p-fluoro-hexahydro-sila-difenidol), and nonselective atropine (atr). In vitro concentration-response effects of pir and AF-DX 116 were obtained for neurally induced contractions of tracheal smooth muscle, elicited by electrical field stimulation. In a separate series of experiments we measured the bronchoconstrictor response to the muscarinic agonist acetylcholine delivered by right heart injection. Muscarinic antagonists reduced RL and HR responses to vagal stimulation in a dose-dependant fashion; however, ED50 values and selectivity for airway and cardiac responses (HR/RL ED50 ratio) were significantly different between antagonists. The rank order of potencies for inhibition of the increase in RL was atr > pir, M1 > p-F-HHSiD, M3 > AF-DX 116, M2, while that for HR was atr > AF-DX 116 > pir > p-F-HHSiD. AF-DX 116 preferentially inhibited the HR response, as reflected by the lowest HR/RL ED50 ratio (p < 0.001). The remaining antagonists preferentially inhibited RL, with the highest HR/RL ED50 ratio seen for p-F-HHSiD. These data suggest that muscarinic receptor subtypes are differentiated at birth and mediate cardiac and airway responses to vagal stimulation. We did not find autoinhibitory actions of airway M2 receptors on either the in vivo bronchoconstrictor response or the in vitro contractile response to electrical field stimulation. This suggests that neonatal airway M2 receptors, but not myocardial M2 receptors, are reduced in number or weakly coupled to muscarinic signal transduction mechanisms. Direct activation of airway smooth muscle by acetylcholine caused dose-dependent increases in RL that reached a plateau at approximately 200% at 100 micrograms, similar to values reported for vagal stimulation.

Airway Resistance↗

PubMed1977

Effect of sojourn at 3200-m altitude on spinal reflexes in young adult males.

Studies of the H reflex and the Achilles tendon reflex (ATR) were performed in 12 healthy males under six conditions: 1) sea level control, 2) during the first 1-3 h at altitude while normoxic conditions were maintained, 3-5) at 6, 24 and 72 h of hypoxia, and 6) after Ve acclimatization at altitude in 5-14 d. After altitude acclimatization, the peak-to-peak amplitude of the H reflex and the ATR response was significantly elevated over control. A trend toward decreased amplitudes of both the ATR and the H reflex was observed at 6 h after the onset of hypoxia. There was no significant alteration in latency of the H reflex under any test condition. These findings suggest that sojourn at altitude by sea level residents induces changes in spinal motor reflexes. These changes are most probably mediated by altered high central modulation of the cord.

Acclimatization↗

PubMed1997

Diagnostic value of certain mastitis markers in following up the clinical and bacteriological changes in pharmacotherapeutic studies.

Trends of certain mastitis markers were studied in udder quarters (n = 201) showing clinical symptoms of acute mastitis. Besides the clinical examination, before the first treatment (baseline sample), and about 3 weeks later, 17 to 24 days following the last treatment (control sample) milk samples were collected for bacteriological identification of the mastitis pathogens and for the determination of certain inflammatory markers: somatic cell count (SCC), N-acetyl-beta-D-glucosaminidase (NAGase) and alpha 1-antitrypsin (ATR) activities, as well as bovine serum albumin (BSA) and chloride (Cl-) concentrations. Based upon the clinical and bacteriological status as well as the SCC recorded at the control investigations, 6 groups were established (recovered, latently infected, subclinical mastitis: bacteriologically positive and negative, as well as clinical mastitis: bacteriologically positive and negative). As compared to the baseline samples, all parameters decreased in the case of recovered udder quarters, as well as in those with abated latent infection or subclinical mastitis at the time of control examination. Comparing the control samples of the different categories, characteristic differences were found in NAGase activity, indicating the grade of cytodamaging effect of mastitis. Of the other markers, ATR and Cl- proved to be more adequate for the differentiation than BSA. It can be concluded that, in addition to SCC, first of all NAGase can be recommended for use as an inflammatory parameter in pharmacodynamic studies. Besides these two parameters, ATR and Cl- can also be chosen as a possible third marker.

Acetylglucosaminidase↗

PubMed2026

Heterozygous germline deletion in Hif3a exacerbates esophageal squamous cell carcinoma development.

Germline variations contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. We identified a germline deletion (exons 7-8) in HIF3A in an ESCC family and investigated its functional impact using CRISPR/Cas9-engineered cells and Hif3a-eKO1 mice (heterozygous for exons 7-8 deletion). Multi-omics analysis of Hif3a-eKO1 and WT mice revealed dysregulated pathways in normal esophagus and during 4NQO-induced carcinogenesis, with key biomarkers validated by immunohistochemistry. Hif3a deficiency enhanced ESCC cell proliferation and invasion in vitro and accelerated 4NQO-induced tumorigenesis in vivo, with Hif3a-eKO1 mice developing more and larger neoplastic lesions. Multi-omics analysis revealed downregulation of cytokeratin-related genes (notably Krt17) and γδ T cells in normal esophagus of Hif3a-eKO1 compared with WT. Consistently reduced Krt17 expression in Hif3a-eKO1 was confirmed by both esophageal immunohistochemistry and cellular Western blot analyses. During 4NQO-induced carcinogenesis, Hif3a deficiency upregulated DNA damage response markers, including Krüppel-like factor 4 (Klf4) and ATR serine/threonine kinase (Atr). Notably, epithelial cells with abundant γH2AX foci lacked Krt17 expression, while Krt17-positive cells showed minimal γH2AX foci. Heterozygous germline Hif3a deletion (exons 7-8) may promote ESCC by disrupting esophageal barrier function-impairing Krt17-mediated epithelial integrity and reducing γδ T cells-while exacerbating genomic instability. These findings reveal ESCC predisposition mechanisms and therapeutic targets. © 2026 The Pathological Society of Great Britain and Ireland.

HIF3A↗