Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For 227 episodes of Pneumocystis carinii pneumonia (PCP) treated at St Mary's between 1983 and 1989, factors predictive of fatal outcome were age, haemoglobin levels, peripheral lymphocyte count and alveolar-arterial oxygen gradient. Case fatality for the 47 empirically-treated episodes was significantly higher compared with the 180 cytologically proven episodes (55% vs 18%, chi 2 = 25.7, P less than 0.0001). Case fatality for episodes which could not be bronchoscoped was significantly higher compared with bronchoscopy negative cases (66% vs 25%, chi 2 = 4.5, P less than 0.05). Predictive factors for fatal outcome differed significantly for cases which could not be bronchoscoped and cytologically proven cases: haemoglobin level (10.7 g/dl vs 12.0 g/dl, P less than 0.001), lymphocyte count (0.64 x 10(9)/l vs 0.87 x 10(9)/l, P = 0.05) and oxygen gradient (77.7 mmHg vs 58.9 mmHg, P less than 0.02). Such differences were not observed between bronchoscopy negative and cytologically proven cases. Case fatality decreased significantly over time (b = -0.39, SE = 0.14, P less than 0.05). Total and non-fatal first time episodes displayed an inverse relationship between oxygen gradient and time (r = -0.22, P less than 0.006 and r = -0.24, P less than 0.01, respectively). Mean oxygen gradient of fatal episodes for sequential years increased significantly from 73 mmHg in 1983 to 102 mmHg in 1989 (r = 0.92, P less than 0.01). This suggests that medical intervention as well as presentation with less severe disease both contributed to improved case fatality over time.
Int J STD AIDS
PMID:Empirically treated Pneumocystis carinii pneumonia in London, 1983-1989. 150 62

Nitroimidazoles are good quenchers of triplet state porphyrins in chemical systems, thereby inhibiting singlet oxygen formation and type II photodynamic reactions. Photobiological studies were performed with EMT-6 tumor cells in vitro utilizing Photofrin II (PII) in combination with etanidazole (ETAN), misonidazole (MISO), and trifluoromisonidazole (TF-MISO). After short-term (1 h) exposure of cells to PII, 5 mM ETAN and MISO had no effect on photoinactivation while 5 mM TF-MISO had a small but significant protective effect. When the intracellular oxygen level was equilibrated with 0.3% oxygen in the gas phase, all three nitroimidazoles produced significant photoprotection at concentrations as low as 0.3 microM. After long-term (24 h) exposure of cells to PII, all three nitroimidazoles demonstrated large photoprotective effects under both aerobic and 0.3% oxygen conditions. At equal concentrations of nitroimidazole, photoprotection was greatest for the most lipophilic compound (TF-MISO) and least effective for the most hydrophilic compound (ETAN). These studies suggest that nitroimidazoles can quench triplet state porphyrins (within cells) to reduce intracellular concentrations of singlet oxygen, the putative toxin in PII photoinactivation. In addition, after long-term exposures to PII when porphyrins have partitioned into cellular membranes and lipid environments, the lipophilicity of this class of photoprotector correlates with effectiveness in these mammalian cells.
 ...
PMID:Protection against light-activated photofrin II killing of tumor cells by nitroimidazoles. 153 56

The purpose of this study was to assess the physiologic training effects of functional electrical stimulation leg cycle ergometer (FES-LCE) exercise in persons with spinal cord injury (SCI) who were previously untrained in this activity. Ten persons with quadriplegia (C5 to C7) and eight with paraplegia (T4 to T11) performed FES-LCE training on an ERGYS I ergometer 10 to 30 minutes per day, 2 or 3 days per week for 12 to 16 weeks (36 total sessions). Training session power output (PO) ranged from 0.0W (no external resistance) to 30.6W. Each subject completed discontinuous graded FES-LCE and arm crank ergometer (ACE) tests before and after training for determinations of peak lower and upper extremity metabolic, pulmonary, and hemodynamic responses. Compared with pretraining, this SCI group exhibited significantly (p less than or equal to .05) higher posttraining peak PO (+45%), oxygen uptake ([O2], + 23%), pulmonary ventilation (+27%), heart rate (+11%), cardiac output ([Qt], + 13%) and significantly lower total peripheral resistance ([TPR], - 14%) during FES-LCE posttests. There were no significant changes in peak stroke volume (+6%), mean arterial pressure ([MAP], - 5%), or arteriovenous oxygen difference ([a-vO2diff], + 10%) during posttraining FES-LCE tests. In addition, no significant differences were noted for the peak level of any monitored variable during ACE posttests after FES-LCE training. The rise in total vascular conductance, implied by the significant decrease in posttraining TPR during FES-LCE tests, denotes that a peripheral circulatory adaptation developed in the persons with SCI during FES-LCE exercise training.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Physiologic effects of electrical stimulation leg cycle exercise training in spinal cord injured persons. 158 Jul 76

Eight male Japanese Brazilians (20-32 yrs) and 11 male Japanese (22-24 yrs) volunteered for this study. The Brazilians had been staying for about 2-21 weeks in Japan. Their physical characteristics are not significantly different from those of the Japanese. Each one of them sat on a chair for 45 min at 40 degrees C (R.H. 50%) in a climatic chamber. Then, they exercised using a bicycle ergometer in a semi-reclining position for 45 min at 40% of maximal oxygen uptake. Forearm blood flow (FBF), oxygen uptake (VO2), heart rate (HR), skin temperature (Tsk), sweat rate (SR) at chest region and body weight loss (delta Wt) were measured. Thermal sensation and thermal comfort were also measured. Thermal and comfort sensation confirmed that Japanese Brazilians felt cooler and more comfortable in 40 degrees C environment than the Japanese. VO2, SR and delta Wt for both groups were not significantly different. FBF and HR for Brazilians were significantly lower than those for Japanese. Tsk at chest region for Brazilians was found to be significantly higher than that for Japanese. Thus the thermoregulatory responses observed in Japanese Brazilians may be largely attributed to the climate in their native places located on the Tropic of Capricorn.
 ...
PMID:Comparative studies on thermoregulatory responses to heat between Japanese Brazilians and Japanese. 159 Aug 76

During exercise in a hot climate, children have been reported to have a less effective temperature regulation capability, compared with adults. It is likely that the transition from a child-like to an adult-like response occurs during puberty. To assess the association between the thermoregulatory response and physical maturation, three groups of circum-pubertal boys cycled at 50% VO2max (three 20-min bouts with 10-min rests), in a climatic chamber (42 degrees C, 20% relative humidity). Based on Tanner staging (pubic hair), 10 were classified as prepubertal (PP), 13 as midpubertal (MP), and eight as late pubertal (LP). Measurements included rectal and skin temperatures (Tre, Tsk), heart rate (HR), sweating rate (SR), oxygen consumption (VO2), and forearm blood flow (FBF). Tre, Tsk, and HR increased with time, with no significant difference among groups. Relative VO2 (ml O2.kg-1) was similar among groups. FBF was consistently higher in PP compared with LP. In spite of the higher SR (PP = 4.9 +/- 0.2, MP = 5.7 +/- 0.3, LP = 6.6 +/- 0.4 ml.min-1.m-2) (mean +/- SEM) among LP compared with PP, the rate of heat storage (PP = 5.5 +/- 0.4, MP = 5.3 +/- 0.4, LP = 6.8 +/- 0.3, kJ.h-1.kg-1) was also significantly higher among those in the LP group. Three of eight LP did not complete the session due to high Tre, while two of the 10 PP were unable to complete the session even though the physiologic heat strain was not high. The results suggest that the transition from a child-like to an adult-like thermoregulatory effectiveness in a hot, dry climate may occur at a somewhat later stage, but not during puberty.
 ...
PMID:Thermoregulatory responses of pre-, mid-, and late-pubertal boys to exercise in dry heat. 160 41

Factors determining the outcome of an episode of Pneumocystis carinii pneumonia (PCP) in 149 AIDS patients treated at St Mary's Hospital were identified and their importance on improved survival evaluated between 1984 and 1989. The proportion of fatal episodes of PCP decreased over time. Fatal compared with nonfatal episodes had lower mean alveolar-arterial oxygen gradient (82.5 mmHg vs 53.8 mmHg, P less than 0.001), mean haemoglobin level (11.2 g/dl vs 12.1 g/dl, P = 0.01), mean lymphocyte count (0.68 x 10(9)/l vs 0.92 x 10(9)/l, P = 0.05) and more coinfections (31% vs 5%, P less than 0.001). Over time, the most significant change which occurred was a reduction in alveolar-arterial oxygen gradient at time of first presentation with PCP (r = -0.37, P less than 0.001). Mean alveolar-arterial oxygen gradient declined from 79.9 mmHg in 1984 to 45.3 mmHg in 1989 (r = -0.88, P = 0.02), independently of zidovudine therapy or PCP prophylaxis. Patients were being treated at an earlier stage in their disease course as indicated by their reduced alveolar arterial oxygen gradient. This is due either to earlier patient presentation, earlier medical diagnosis or both. The widespread introduction of zidovudine and PCP prophylaxis may further contribute to improve morbidity and mortality patterns in the future.
Int J STD AIDS
PMID:Improved outcome of Pneumocystis carinii pneumonia in AIDS patients: a multifactorial treatment effect. 161 64

Conscious guinea pigs were either microinjected intrapreoptically (iPO) with various doses of norepinephrine (NE) bilaterally or microdialyzed with pyrogen-free saline (PFS) or 10 micrograms/microliters NE unilaterally immediately and unilaterally or bilaterally 2 days after probe insertion. Core temperature (Tco), skin temperature (Tsk), and rate of oxygen consumption (VO2) were monitored continuously. The microinjection of low doses of NE induced Tco rises, whereas that of the highest dose (10 micrograms/microliters) caused an initial Tco fall followed by a rise. The microdialysis of PFS or NE immediately after probe insertion caused Tco rises; the former was abolished and the latter was converted into a fall by indomethacin (Indo, a prostaglandin synthase inhibitor) pretreatment. Two days later, PFS evoked no thermal response whereas NE induced a Tco fall; neither response was affected by Indo pretreatment. The falls in Tco produced by NE microdialyzed uni- or bilaterally were similar. The microdialysis of NE induced a 15% reduction in metabolic rate but no change in Tsk. These results indicate that the Tco rise induced by NE microinjected iPO is a methodological artifact mediated by PGE2, whereas the Tco fall observed in its microdialysis appears to represent the authentic physiological action of this transmitter effected by a reduction in metabolic rate.
 ...
PMID:Validation of the hypothermic action of preoptic norepinephrine in guinea pigs. 161 36

This study determined the metabolic and hemodynamic responses in eight spinal cord injured (SCI) quadriplegics (C5-C8/T1) performing subpeak arm crank exercise (ACE) alone, subpeak functional electrical stimulation leg cycle exercise (FES-LCE) alone, and subpeak FES-LCE concurrent with subpeak ACE (hybrid exercise). Subjects completed 10 minutes of each exercise mode during which steady-state oxygen uptake (VO2), pulmonary ventilation (VE), heart rate (HR), cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), arteriovenous oxygen difference (a-v O2 diff), and total peripheral resistance (TPR) were determined. Although mean VO2 for both ACE alone and FES-LCE alone was matched at 0.66 l/mi, individualized power outputs ranged from 0-30 W (mean = 19.4 +/- 1.3) and 0-12.2 W (mean = 2.3 +/- 0.6), respectively. Hybrid exercise elicited significantly higher VO2 (by 54 percent), VE (by 39-53 percent), HR (by 19-33 percent), and CO (by 33-47 percent), and significantly lower TPR (by 21-34 percent) than ACE or FES-LCE performed alone (P less than or equal to 0.05). Stroke volume was similar between hybrid exercise and FES-LCE alone, and these two exercise modes evoked a significantly higher SV (by 41-56 percent) than during ACE alone. These data clearly demonstrate that hybrid exercise creates a higher aerobic metabolic demand and cardiac-volume load in SCI quadriplegics than either subpeak levels of ACE or FES-LCE performed separately. Therefore, hybrid exercise may provide more advantageous central cardiovascular training effects in quadriplegics than either ACE or FES-LCE alone.
 ...
PMID:Metabolic and hemodynamic responses to concurrent voluntary arm crank and electrical stimulation leg cycle exercise in quadriplegics. 164 Mar 77

Asynchronous populations of mouse EMT-6 tumor cells were treated with Photofrin II and exposed to various doses of 630 nm light in slowly stirred suspensions which had been equilibrated with various concentrations of oxygen. Survival curves were generated with cells exposed to 20 micrograms/ml Photofrin II in tissue culture medium for 1 h, a procedure which made it possible to remove more than 50% of the drug by washing. It is expected that under these conditions the drug would be loosely bound to cell surface and plasma membranes and in the cellular cytosol. Survival curves were also generated with cells exposed to 5 micrograms/ml Photofrin II for 20-24 h, a procedure which resulted in greater than 90% of the drug being tightly bound within cells, presumably to cellular lipids and membranes. Oxygen was obligatory for killing cells which had been exposed for both "short term" and "long term" to Photofrin II. After 30-40 min of pregassing cells with nitrogen gas which contained precise levels of oxygen, the concentration required to reduce rates of cell killing to 50% of maximum was approximately 0.5% O2 (gas phase) for short-term drug exposures and less than or equal to 0.05% O2 for long-term drug exposures. Even after pregassing times of 90-120 min prior to light administration, a Km of approximately equal to 0.1% O2 was observed for cells exposed to the drug for the longer time. When the same cells were exposed to 137Cs gamma rays in this irradiation chamber, no change in radiation sensitivity was observed after 30 min of pregassing cells with all oxygen concentrations studied.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Oxygen dependency of tumor cell killing in vitro by light-activated Photofrin II. 182 59

In six male subjects the sweating thresholds, heart rate (fc), as well as the metabolic responses to exercise of different intensities [40%, 60% and 80% maximal oxygen uptake (VO2max)], were compared at ambient temperatures (Ta) of 5 degrees C (LT) and 24 degrees C (MT). Each period of exercise was preceded by a rest period at the same temperature. In LT experiments, the subjects rested until shivering occurred and in MT experiments the rest period was made to be of exactly equivalent length. Oxygen uptake (VO2) at the end of each rest period was higher in LT than MT (P less than 0.05). During 20-min exercise at 40% VO2max performed in the cold no sweating was recorded, while at higher exercise intensities sweating occurred at similar rectal temperatures (Tre) but at lower mean skin (Tsk) and mean body temperatures (Tb) in LT than MT experiments (P less than 0.001). The exercise induced VO2 increase was greater only at the end of the light (40% VO2max) exercise in the cold in comparison with MT (P less than 0.001). Both fc and blood lactate concentration [1a]b were lower at the end of LT than MT for moderate (60% VO2max) and heavy (80% VO2max) exercises. It was concluded that the sweating threshold during exercise in the cold environment had shifted towards lower Tb and Tsk. It was also found that subjects exposed to cold possessed a potentially greater ability to exercise at moderate and high intensities than those at 24 degrees C since the increases in Tre, fc and [1a]b were lower at the lower Ta.
 ...
PMID:Comparison in men of physiological responses to exercise of increasing intensity at low and moderate ambient temperatures. 187 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>