Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sympathetic-adrenal medullary responses to acute footshock stress were assessed in inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats by measuring plasma levels of norepinephrine (NE) and epinephrine (EPI). Ten-week-old S/JR and R/JR rats were surgically prepared with indwelling tail artery catheters which permitted direct measurements of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats/min) and remote sampling of blood. Two days after surgery, S/JR and R/JR rats were subjected to an acute stress paradigm. Blood samples were collected before and 3 minutes after transfer of rats to a shock chamber, after 1 minute of intermittent footshock, and again 5 minutes later. S/JR rats had significantly higher resting MAP's compared to R/JR rats. In contrast, baseline heart rates were similar for rats of the two strains. Basal plasma levels of NE and EPI were also similar in S/JR and R/JR rats. Upon transfer from the home cage to a shock chamber, S/JR rats exhibited significant increases in plasma levels of both catecholamines, while R/JR rats maintained circulating levels of NE and EPI that were near baseline values. However, S/JR and R/JR rats had similar increments in plasma NE and EPI following acute footshock stress. Five minutes after footshock, levels of NE and EPI returned toward baseline values for R/JR's, but remained significantly elevated above baseline in hypertensive S/JR rats. These data suggest that S/JR rats are more responsive than R/JR controls to the mild stress of transfer, but exhibit comparable responses to the more intense stress of inescapable footshock.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sympathetic-adrenal medullary responses to acute stress in Dahl hypertensive (S/JR) rats. 272 39

Haloperidol (HPD: 0.4 mg/kg, sc) completely abolished not only the ambulatory stimulation by methamphetamine (MAP: 2 mg/kg, sc) but also the induction and expression of MAP sensitization in the combined administration schedule. HPD also significantly reduced the induction of MAP sensitization when the mice were treated with HPD at 1/12, 1/4, 1, 2, 3, 4 or 5 hr but not at 1/2 hr or later than 6 hr, after each administration of MAP. The inhibition by the 3-hr post-treatment with HPD was as strong as that by the combined administration. On the other hand, a restraint of abulation for 3 hr (putting the mouse in a small jar) significantly inhibited the induction of MAP sensitization when it was started at 0/4 hr, but not at 1/2-6 hr, after each MAP administration. The inhibitory effects of restraint, starting at 0-1/4 hr, were almost equivalent to those of the post-treatments with HPD at the same times. The post treatments with HPD + restraint showed similar inhibitory effects on MAP sensitization to those of HPD alone. The repeated administration of saline together with post-treatment with either HPD, restraint or HPD + restraint did not change MAP sensitivity. These results suggest that a couple of free movement in the activity cage and stimulation of dopamine receptors for longer than 1/2 hr immediately after administration of MAP, and an agonistic effect on dopamine receptors during 1-5 hr after MAP are responsible for perfect induction of the MAP sensitization in terms of ambulation in mice.
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PMID:Haloperidol and restraint differently inhibit the induction of sensitization to the ambulation-increasing effect of methamphetamine in mice. 758 19

Cross-fostering of litters was used to determine the timing of preweanling maternal influences on the development of high blood pressure in spontaneously hypertensive (SHR) rats. The SHR litters were either reared by their natural mothers or reciprocally cross-fostered to normotensive Wistar-Kyoto (WKY) mothers for postnatal days 1-7, 1-14, 1-21, 8-21, or 15-21. All SHR litters were weaned at 21 days of age and males were housed in groups of two to three per cage until physiological measures were obtained at 100 days of age. At 100 days of age, all rats were surgically prepared with tail artery catheters and, on the day after surgery, direct measures of mean arterial pressure (MAP, mmHg) and heart rate (HR, bpm) were obtained while rats were resting and undisturbed in their individual home cages. Our findings indicate that cross-fostering SHR pups to WKY foster mothers was attended by significant effects on body weights at weaning and on adult MAPs. Compared to control SHRs, cross-fostered SHRs, with the exception of the 15-21-day group, were significantly heavier at weaning. By 100 days of age, body weights of SHRs were similar across treatment groups. Basal MAPs of SHRs cross-fostered for days 1-7, 1-14, 1-21, and 8-21, but not days 15-21, were reduced significantly compared to SHR controls reared by their natural mothers. In contrast, basal HRs were not affected in any of the cross-fostered SHR groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Timing of preweanling maternal effects on development of hypertension in SHR rats. 802 3

Mice given five repeated administrations of methamphetamine (MAP: 2 mg/kg SC) or cocaine (COC: 20 mg/kg SC) at 3-day intervals in a round tilting-type activity cage (20 cm in diameter) showed sensitization to the ambulation-increasing effect of each drug. The mean 3- or 2-h overall activity count at the fifth administration of MAP or COC, respectively, was 2.3-2.5 times higher than that at the first administration. Mice given MAP or COC 4 times in round spaces (15-30 cm in diameter), where the floor did not tilt, exhibited sensitization as strong as that demonstrated by mice given each drug in the activity cages, when the mice were given the fifth administration in the activity cages. In contrast, mice repeatedly given the drugs in spaces 4-9 cm in diameter never, and those in space 12 cm in diameter only partially, exhibited sensitization to MAP and COC. Furthermore, mice given MAP or COC 4 times in their home cages (25D x 20W x 15H cm, with ten mice in each cage) showed partial sensitization. Repeated administration of saline to mice in activity cages, in the spaces 4-30 cm in diameter, or in the home cages did not cause significant change in the sensitivity to either MAP or COC. These results suggest that repeated experience of the stimulant effect of drug and the resultant ambulation is required for induction of sensitization to MAP and COC in terms of ambulation in mice. It is also suggested that spaces larger than 12 cm in diameter, which correspond to 2-2.5 times as long as the body length without tail, and no interference from other mice are required for induction of strong sensitization to both MAP and COC.
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PMID:Importance of post-drug environmental factors for induction of sensitization to the ambulation-increasing effects of methamphetamine and cocaine in mice. 887 45

Peptides with high affinities and specificities for numerous proteins and nucleic acids have been previously identified from random peptide bacteriophage display libraries. Here, random peptide bacteriophage display libraries were used to identify sequences that bound the cancer-associated Thomsen-Friedenreich glycoantigen (T antigen). The T antigen, present on most malignant cells, contains an immunodominant Gal beta1 --> 3GalNAc alpha disaccharide unmasked on the surfaces of most carcinomas. This antigen has been postulated to be involved in tumor cell aggregation and metastasis. Two 15 amino acid random peptide bacteriophage display libraries were affinity selected with glycoproteins displaying T antigen on their surfaces. Sequence analysis revealed that many of the peptides shared homology with sugar recognition sites in several carbohydrate-binding proteins. A comparison of affinity selected sequences from both libraries yielded a common motif (W-Y-A-W/F-S-P) rich in aromatic amino acids. Four peptides, corresponding to the affinity selected sequences, were chemically synthesized and characterized for their carbohydrate recognition properties. The synthetic peptides exhibited high specificities and affinities to T antigen displayed on asialofetuin or conjugated to bovine serum albumin (Kd = 5 nM for MAP-P30 binding to asialofetuin) as well as free T-antigen disaccharide in solution (Kd = 10 microM for MAP-P30, 20 microM for P10). Two peptides, P30 and P10, demonstrated high affinities and specificities for both asialofetuin and T antigen in solution. Iodination of a lone tyrosine residue in each sequence dramatically reduced their abilities to bind T antigen, suggesting that the tyrosine residue plays an important role in carbohydrate recognition. That these peptides are of functional significance is evidenced by the ability of both P30 and P10 to inhibit asialofetuin-mediated melanoma cell aggregation in vitro and to compete with peanut lectin for binding to T antigen displayed on the surface of MDA-MB-435 breast carcinoma cells in situ.
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PMID:Characterization of peptides that bind the tumor-associated Thomsen-Friedenreich antigen selected from bacteriophage display libraries. 923 4

This study describes a technique for the direct daily measurement of arterial blood pressure, sampling of arterial blood, and continuous intravenous infusion in free-moving, conscious, Swiss-Webster mice. Catheters were chronically implanted in the femoral artery and vein, tunneled subcutaneously, exteriorized at the back of the neck in a lightweight tethering spring, and attached to a swivel device at the top of the cage. Time-control experiments (n = 8) demonstrated stable values of mean arterial pressure (MAP, 116 +/- 1 mmHg) and heart rate (HR, 627 +/- 21 beats/min) for up to 35 days after catheter implantation. It was further observed that restraining mice (n = 7) increased MAP by 10 +/- 3 mmHg and HR by 78 +/- 8 beats/min from the values observed under free-moving conditions. To demonstrate the chronic use of the venous catheter, intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME, 8.6 mg.kg-1.day-1, n = 6) for 5 days significantly increased MAP from 117 +/- 4 to 131 +/- 4 mmHg without altering HR. In a final group of mice (n = 5), oral L-arginine (2% in drinking water) increased plasma arginine concentration from 90 +/- 7 to 131 +/- 17 microM and prevented L-NAME hypertension. These experiments illustrate the feasibility of long-term intravenous infusion, direct arterial blood pressure measurements, and arterial blood sampling in conscious mice.
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PMID:Long-term measurement of arterial blood pressure in conscious mice. 948 19

Much research has demonstrated that events occurring in early life can have a profound influence on future biobehavioral responses to stressful and emotion provoking situations. The purpose of these studies was to determine the effects of an early environmental manipulation, handling (HAN) on cardiovascular (CV) reactivity, freezing behavior and corticosterone (CORT) responses to contextual fear conditioning in the borderline hypertensive rat (BHR),which is susceptible to environmental stressors. HAN subjects were separated from the nest for 15 min/day on post-natal days 1-14, while non-handled (NON-HAN) controls remained in the home cage. Adult subjects were exposed to the contextual fear conditioning procedure and returned to the chamber 24 h later for a 10 min test period. HAN subjects displayed significantly more freezing behavior compared to NON-HAN(92%+/-2.2 vs 80.7%+/-5.7, p<.05). Although resting MAP did not differ between groups, HAN subjects had increased MAP reactivity when re-exposed to the chamber. In addition, HAN subjects had significantly lower CORT levels at the end of the 10 min test period (174.2+/-9 ng/ml vs 237.2+/-12.9 ng/ml, p<.05). In the second experiment, CORT responses to 60 min of restraint stress and recovery following return to the home cage were assessed in separate groups of HAN and NON-HAN subjects. HAN subjects showed reduced CORT levels in response to acute restraint stress. These results indicate that neonatal handling can modulate biobehavioral responses to contextual fear conditioning in BHR and may suggest a useful model with which to study emotionality and susceptibility to CV disease.
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PMID:Neonatal handling increases cardiovascular reactivity to contextual fear conditioning in borderline hypertensive rats (BHR). 1853 2

The mechanisms by which mammary carcinomas acquire hormone independence are still unknown. To study the role of cancer-associated fibroblasts (CAF) in the acquisition of hormone-independence we used a hormone-dependent (HD) mouse mammary tumor and its hormone-independent (HI) variant, which grows in vivo without hormone supply. HI tumors express higher levels of FGFR-2 than HD tumors. In spite of their in vivo differences, both tumors have the same hormone requirement in primary cultures. We demonstrated that CAF from HI tumors (CAF-HI) growing in vitro, express higher levels of FGF-2 than HD counterparts (CAF-HD). FGF-2 activated the progesterone receptors (PR) in the tumor cells, thus increasing cell proliferation in both HI and HD tumors. CAF-HI induced a higher proliferative rate on the tumor cells and in PR activation than CAF-HD. The blockage of FGF-2 in the co-cultures or the genetic or pharmacological inhibition of FGFR-2 inhibited PR activation and tumor cell proliferation. Moreover, in vivo, the FGFR inhibitor decreased C4-HI tumor growth, whereas FGF-2 was able to stimulate C4-HD tumor growth as MPA. T47D human breast cancer cells were also stimulated by progestins, FGF-2 or CAF-HI, and this stimulation was abrogated by antiprogestins, suggesting that the murine C4-HI cells respond as the human T47D cells. In summary, this is the first study reporting differences between CAF from HD and HI tumors suggesting that CAF-HI actively participate in driving HI tumor growth.
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PMID:Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis. 1876 44

The importance of dietary salt in the development of hypertension has long been a source of controversy. Recent studies suggest a combination of high-salt and ANG II infusion may increase sympathetic drive; however, the effect of a change in dietary salt alone is unclear. Using telemetry, we recorded renal sympathetic nerve activity (RSNA), arterial pressure (MAP), and heart rate (HR) in seven New Zealand white rabbits before and during a 6-day period of increased salt intake (normal NaCl 0.5 g x kg(-1) x day(-1), high NaCl 2.5 g x kg(-1) x day(-1)) and a second group of seven rabbits with normal salt intake throughout. The responses to stressful stimuli encountered in the laboratory were recorded and compared with rest in control and high-salt groups. Resting MAP, HR, and RSNA were not significantly altered with high salt intake [88 +/- 5 vs. 91 +/- 6 mmHg; 251 +/- 8 vs. 244 +/- 9 beats per minute (bpm); 9.7 +/- and 1.2 vs. 10.8 +/- 1.7 normalized units (nu)] despite significant reductions in plasma renin activity (1.88 +/- 0.18 vs. 1.27 +/- 0.15 nmol ANG I x l(-1) x h(-1); P < 0.05) and ANG II (7.5 +/- 1.2 vs. 4.3 +/- 0.8 pmol/l). Increasing levels of stressful stimuli (resting in home cage, containment in box, handling, and nasopharyngeal activation) in animals on a normal salt diet caused graded increases in MAP (89 +/- 2 mmHg, 95 +/- 2 mmHg, 107 +/- 4 mmHg, and 122 +/- 5 mmHg, respectively) and RSNA (9.7 +/- 0.9 nu; 11.8 +/- 2.7 nu; 31.4 +/- 3.7 nu; 100 nu) but not HR (245 +/- 8 bpm; 234 +/- 8 bpm; 262 +/- 9 bpm; 36 +/- 5 bpm). High dietary salt did not significantly alter the responses to stress. We conclude that a 6-day period of high salt intake does not alter the level of RSNA, with non-neural mechanisms primarily responsible for the observed renin-angiotensin system suppression.
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PMID:A high-salt diet does not influence renal sympathetic nerve activity: a direct telemetric investigation. 1949 74

Y-Box protein 1 (YB-1) is a multifunctional cellular protein expressed in a range of mammalian cells, including human cancer cells. It is involved in the regulation of various genes including cancer-associated genes, but the full range of target genes and regulatory mechanisms have not been fully elucidated. To identify global mRNA expression patterns that are potentially regulated by YB-1, a previously established and well-characterized cell model derived from drug-sensitive (EPG85-257P/tetR/YB-1) and multidrug-resistant (EPG85-257RDB/tetR/YB-1) gastric carcinoma cells in which the expression of YB-1 can be inhibited by tetracycline-dependent activation of the RNA interference (RNAi) pathway, was analyzed by microarray technology. By this approach, various potentially regulated genes encoding members of important cellular pathways such as the Jak/STAT, VEGF and the MAP-kinase signaling pathways were identified. Independent validation of these findings by quantitative real-time reverse transcriptase polymerase chain reaction and Western blot did not confirm these regulatory effects. In conclusion, the findings suggest that YB-1 is not directly involved in the regulation of mRNA expression in drug-sensitive or drug-resistant gastric carcinoma cells.
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PMID:Regulation of mRNA expression in drug-sensitive and drug-resistant gastric carcinoma cells is independent of YB-1 expression. 2033 92


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