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The Triage area is within the decontamination area, both of which are in the outer contaminated area. Triage will include an assessment of injuries, medical problems, and radiation injury.
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Chart 1. Conversion of S and 6-MP nbonucleoside-35 5 to 6-MeMP ribonucleotide in H. Ep. No. 2 cells in culture as a function of time. MeMPRP, 6-MeMP ribonucleotide. The experimental conditions and procedures were the same as those described in Table 2, except that the cells were harvested at various times after addition of the labeled compound. The labeled compounds were the same as those described in Table 2; for the plots, the dpm have been adjusted for the differences in specific activities of the precursors. A bscissae, hr after addition of the compounds. "., MeMP ribonucleoside 5 ~-monophosphate from.
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Before reaching extracellular compartment. Thus, based on our experimental data, we propose that serum LDH activity is more indicative of necrotic processes in vivo, whereas the release of cytochrome c characterizes apoptotic events. So far, it has only been described that cytochrome c is released from the mitochondria to the cytosol. The exact mechanism of this key event is not understood. Several models including rupture of the outer mitochondrial membrane and permeability transition15 and the escape of cytochrome c through megachannels or pores formed by proapoptotic Bcl-2 family members have been proposed.7, 9, 10 It is possible that related mechanisms of externalization may be responsible for the release of cytochrome c into the extracellular medium. However, it is unlikely that cytochrome c is released by a nonspecific mechanism such as cell lysis, because a release of LDH occurred at later time points Figure 2 ; . It has been reported that the tripeptide glutathione is specifically extruded during apoptosis, 23 although it is unlikely that cytochrome c, a 14.5-kd protein, is externalized by a related mechanism. In addition, there are several examples of proteins, such as HIV-Tat, thioredoxin, interleukin 1 and basic fibroblast growth factor, which lack a signal peptide and are exported by alternative pathways.24 For most of these proteins the mechanism of export is unclear. In some cases, proteins lacking a signal peptide can be released by exocytosis of preterminal endocytic vesicles and an ABC-related transport mechanism.24, 25 It has been also found that death ligands, such as CD95L and TRAIL, are stored in microvesicles that may be released on cell activation and apopto.
To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-1062, USA. E-mail: msoloff utmb.
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CF animal modeling. One aspect of chloride channel activation demonstrating no species specificity was cAMP-inducibility which was present in all species of ALI cultures. However, given that tracheas and ALI tracheal cultures from CF mice are known to express cAMP-inducible chloride channels 4, 35 ; , such a finding cannot be interpreted as specific evidence for CFTR function. In addition to examining standard electrophysiologic parameters of tracheal epithelia, our study has also attempted to address the pharmacologic profile of DIDS-insensitive, cAMP-inducible chloride currents, with the hypothesis that similarities between a given species and human might reflect the potential for that species to suitably model human CF lung disease. Mouse served as a negative control for this hypothesis, given that tracheal airway epithelia from this species is known to express cAMPinducible non-CFTR channels that are thought to compensate for the lack of CFTR 4, 35 ; . Results from this analysis demonstrated considerable species-specific variability in the pharmacologic profiles of the four chloride channel blockers evaluated two non-selective CFTR blockers and two CFTRspecific blockers ; . Although all of the blockers significantly inhibited cAMP-inducible chloride currents in human ALI cultures, glibenclamide and CFTRinh-172 produced a significantly lower level of inhibition in pig ALI cultures as compared to human. Recent studies evaluating nasal potential differences in pig have demonstrated similar findings that both glibenclamide and CFTRinh-172 were ineffective at blocking cAMP-mediated changes in nasal PD 34 ; . Similarly, this same study demonstrated that ALI cultures of pig airway epithelium required significantly higher doses of CFTRinh-172 to inhibit cAMP-induced Isc under chloride secretory conditions in comparison to mouse. Our study demonstrating that CFTRinh-172 effectively inhibits cAMP-induced chloride current in mouse ALI cultures confirms the latter result. Notably, the newer CFTR-specific inhibitor CFTRinhGlyH101 was effective at inhibiting cAMP-induced Isc in pig but not mouse ALI cultures. If indeed both CFTRinh-172 and CFTRinh-GlyH101 are specific for mouse and pig CFTR, then one must conclude that the structure function of CFTR is significantly different in these two species. Ferret ALI cultures also demonstrated a unique anion channel-blocker pharmacologic profile. Of the four blockers evaluated, only CFTRinh-172 exhibited a reduced ability to inhibit cAMP-induced Isc in ferret airway epithelia as compared to human. These results again emphasize the potential for unique CFTR structure function between species and or differing levels of DIDS-insensitive alternative non-CFTR ; chloride channels that are also uniquely susceptible to these inhibitors. Several biological parameters could potentially affect CFTR-dependent biology in the airway of the four species studied here. These include a species-specific distribution of airway cell types and cell type-specific chloride channel composition. For example, in mouse tracheal airway epithelia the 15.
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Biotechnology Working Party: The CPMP adopted a Position Paper for Production of Tallow Derivatives for Use in Pharmaceuticals CPMP 1163 97 ; . The first joint workshop between the Biotechnology Working Party, the European Plasma Fractionation Association EPFA ; and the European Association of the Plasma Products Industry EAPPI ; on plasma-derived medicinal products was hosted by the EMEA on 8 December 1997. The objective of the workshop was to share scientific information and views with the aim of reaching a common understanding. The topics addressed included issues related to: Plasma source material. Inactivation removal of viruses, with a focus on removal of viruses by filtration. Consideration of potential effects of viral inactivation or removal processes on biological activity of plasma-derived medicinal products. A more detailed report of the meeting is being prepared and will be made available in early 1998 and filgrastim.
Staggering. The cost to treat CVD, infections, and related hospitalizations associated with CKD is estimated at billion, 9 and treating CKD is projected to cost the Medicare system more than billion in 2010, an increase from billion in 1998.10 Several treatment options are available to slow the progression of CKD. A component of CKD care often overlooked and undertreated by both the primary care physician and the nephrologist is the management of SHPT, which can lead to CVD and ROD if untreated. Since kidney disease is often diagnosed comparatively late in many patients, the staging at diagnosis is often stage 3 or 4, the same time that these extrarenal complications begin to appear.11-14 Thus, many patients who acquire the CKD diagnosis often have had chronic exposure to reductions in vitamin D and serum calcium, and elevations in PTH and phosphorus, and may manifest significant skeletal and or cardiovascular sequelae. This review focuses on the complications of elevated parathyroid hormone level and their prevalence, evaluates current avenues of treatment, and introduces the subject of the economic impact of different treatments. Parathyroid Hormone Regulation The parathyroid glands are responsible for maintaining calcium homeostasis through the actions of PTH, a polypeptide hormone. Fluctuations in serum calcium concentration are detected by calcium receptors CaRs ; --G-protein-coupled receptors located on the chief cells of the parathyroid gland that mediate the secretion of PTH.15 Stimulated by low serum calcium levels, PTH secretion increases and up-regulates the expression of 1-hydroxylase in the kidney. This enzyme is responsible for the production of vitamin D 1, 25-dihydroxyvitamin D3 or calcitriol ; .16 Under hypocalcemic conditions, PTH stimulates the synthesis of calcitriol, correcting the calcium imbalance by 1 ; increasing absorption of calcium from the gastrointestinal tract, 2 ; conserving calcium that would ordinarily be excreted by the kidneys, and 3 ; releasing calcium from bone see Figure ; .17 It has been suggested that PTH levels and the serum phosphorus equilibrium are also linked. Patients with advanced CKD who were administered a low-phosphorus diet showed reductions in serum PTH levels independent of calcium and calcitriol concentrations.18 Recent studies have elaborated on the role of phosphorus in PTH regulation. Animal models have shown that dietary phosphorus can alter PTH mRNA expression and, moreover, phosphorus has been shown to directly stimulate PTH secretion from parathyroid cells.19-21 Calcitriol and PTH are both capable of directly regulating serum mineral levels, as shown in the Figure. The effects of PTH on the intestine are accomplished indirectly through the actions of calcitriol. Acting to increase calcium absorption, calcitriol has been shown to up-regulate the expression of calcium channel and transporter proteins, correcting hypocalcemia at the transcriptional level.22 The effects of elevated PTH levels on the skeleton include the stimulation of calcium mobilization from bone and the direct.
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L361L373. Nathan C, Xie Q, Halbwachs-Mecarelli L, Jin WW. Albumin inhibits neutrophil spreading and hydrogen peroxide release by blocking the shedding of CD43 sialophorin, leukosialin ; . J Cell Biol 1993; 122: 243256. Remold-O'Donnell E, Parent D. Two proteolytic pathways for downregulation of the barrier molecule CD43 of human neutrophils. J Immunol 1994; 152: 35953605. Nahori M-A, Renesto P, Vargaftig BB, Chignard M. Activation and damage of cultured airway epithelial cells by human elastase and cathepsin G. Eur J Pharmacol Environ Toxicol Pharmacol 1992; 228: 213218. Kercsmar CM, Davis PB. Resistance of human tracheal epithelial cells to killing by neutrophils, neutrophil elastase, and Pseudomonas elastase. J Respir Cell Mol Biol 1993; 8: 5662. Chung Y, Kercsmar CM, Davis PB. Ferret tracheal epithelial cells grown in vitro are resistant to lethal injury by activated neutrophils. J Respir Cell Mol Biol 1991; 5: 125132. Rickard KA, Taylor J, Rennard SI. Observations of development of resistance to detachment of cultured bovine bronchial epithelial cells in response to protease treatment. J Respir Cell Mol Biol 1992; 6: 414 Lee T-C, Wu R, Brody AR, Barrett JC, Nettesheim P. Growth and differentiation of hamster tracheal epithelial cells in culture. Exp Lung Res 1984; 6: 2745. Devalia JL, Sapsford RJ, Wells CW, Richman P, Davies RJ. Culture and comparison of human bronchial and nasal epithelial cells in vitro. Respir Med 1990; 84: 303312. Janoff A. Elastase in tissue injury. Ann Rev Med 1985; 36: 207216. Bieth JG. Elastases: catalytic and biological properties. In: Mecham RP, ed. Regulation of Matrix Accumulation. Orlando, Academic Press, 1986; pp. 217320. Amitani R, Wilson R, Rutman A, et al. Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. J Respir Cell Mol Biol 1991; 4: 2632. Fujisawa T, Kephart GM, Gray BH, Gleich GJ. The neutrophil and chronic allergic inflammation: immunochemical localization of neutrophil elastase. Rev Respir Dis 1990; 141: 689697 and flax.
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Using recordings of extracellular potentials Schroeder et al. 1995 ; . When the median nerve representation in primates is deafferented, there is an increase in the size of the response to radial nerve stimulation in deafferented cortex Schroeder et al. 1997 ; . Moreover, the sequence of activation reflects direct input from radial nerve-linked thalamocortical afferents to middle layers of the median nerve representation Schroeder et al. 1997 ; . Several investigators have found evidence that after a median or ulnar nerve lesion, the radial nerve becomes a dominant nerve input and that its preexisting fringe inputs into both ulnar and median nerve cortical territory can effectively drive the neurons of this region, perhaps as a result of release from tonic inhibition Alloway et al. 1989, Schroeder et al. 1997, Schwark 1996, Wall et al. 1992a ; . Our data are consistent with a dominance by superficial radial nerve after ulnar nerve lesions. In normal ferret forelimb, our peripheral nerve recordings clearly demonstrate that radial nerve innervates the dorsum of all the forepaw digits and overlaps the ulnar nerve innervation to digits 4 and 5. It is expected, therefore that the dorsum of digits 4 and 5 could gain dominance over the deafferented cortex. Neural origin of components N1 and P2 The neural origin of somatosensory-evoked components has been examined in the somatosensory cortex of several species using intracortical recordings, cortical ablations, and pharmacological manipulations Allison et al. 1990; Legatt et al. 1986a, b; McLaughlin and Kelly 1993 ; . In human somatosensory cortex, the typical early response to median nerve stimulation consists of four reproducible components that originate in specific layers. An early negativity is linked to neural activity in the middle layers of primary somatosensory cortex followed in 10 ms its upper layer counterpart McLaughlin and Kelly 1993 ; . A number of studies on cats, using a diversity of recording arrangements and stimulation conditions, found response latencies for initial cortical activation to be in the range of 10 15 Allison and Hume 1981; Heninger and Sheard 1976; Iragui-Madoz and Wiederholt 1977a, b; Iwayama et al. 1987 ; . The onset latencies of the earliest components recorded here in ferret are within the expected range based on extrapolation from the feline data. Our initial prominent, prolonged negativity N1, therefore likely reflects the onset of activity in the recipient layers of somatosensory cortex. Iwayama et al. 1987 ; noted that the initial response in cortex reversed in the middle layers and showed its highest amplitude near the level of the inversion. The ensuing component is largest in the superficial layers and has an opposite-polarity counterpart in the deep layers. This suggests that the initial cortical response N1 ; is related to middle layer processing whereas the longer latency peak P2 ; is associated with upper layer processing. We interpret component N1 as a manifestation of direct, short-latency, excitatory activity in neurons in the middle layers of deafferented cortex to stimulation of superficial radial nerve. Nerve transections in younger animals lead to substantial changes in the distribution and peak latency of N1, whereas lesions in older juveniles and adults exert much less influence on initial cortical activity. Later activity, P2, is more heavily affected by lesions in adult animals, and presumably reflects and flecainide.
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7 A study of learning and automatic motion generation with emotional factors, Yasuhito . Imai, Yoshikazu Yano, Shinji Doki, Shigeru Okuma Invited.
Bleeding from lung cancer lesions were described in several patients although a spontaneous bleeding due to disease progression could not be excluded. Therefore these side effects may be inherent to blockade of VEGF signaling. Another side effect needs to be mentioned, namely fatigue. However, it is difficult to evaluate this effect in a severely ill population such as patients with refractory AML. But fatigue has also been observed in several phase 1-2 studies of SU11248 in patients with solid tumors. This potential drug effect needs further attention in ongoing phase 2 studies with SU11248. A two-week wash-out period was chosen between cycles for safety reasons. In animal models of chronic dosing, histological changes occurred in organs such as adrenal and pancreas. In this trial, this interruption led to almost complete elimination of SU11248 and SU12662. This was accompanied by an increase in blast counts in 4 of responding patients during the end of the treatment-free interval. After reinstitution of therapy, blast counts dropped again. In patients where samples were analyzed for Flt3 phosphorylation, Flt3 was phosphorylated on rebounding blasts. These data suggest that SU11248 decreased proliferation but did not elicit a complete cytotoxic effect. Therefore the protocol was amended to include a cohort with a one-week wash-out period between cycles with the goal to keep the drug concentration at a therapeutic level for a greater period of time. One patient received three cycles of therapy with a reduced rest period. No increase in blast counts was observed during the pause, therapy was well tolerated and no accumulation of SU11248 was seen during repeated cycles. Therefore, in fast proliferating malignancies, such as AML, a reduced wash-out period may be necessary to prevent re-growth of malignant cells and flexeril.
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Some single trace labscopes are able to display ignition waveforms. You must connect both the Cylinder #1 Trigger Ferret 951 ; , and the Ferret 950 to the input channel by stacking the banana jacks. Since the Trigger is on the same channel as the Ferret 950, Cylinder #1 will have a very high spike. Set the trigger to pickup just the top portion of the spike. This will synchronize the display to #1 Cylinder. To analyze Cylinder #1, move the Ferret 951 Cylinder #1 Trigger to another cylinder and ferret.
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Broadband transducers 2.0 to 4.0 MHz ; were used on a Vivid 7 GE Ultrasound, Horten, Norway ; and a Sequoia C-256 ultrasound system Siemens AG, Munich, Germany ; . Images were obtained from an anteriorly modified 4-chamber apical view through either a subxifoid abdominal incision animals ; or a transthoracic approach humans ; . Care was taken to align the M-mode cursor with the RV filling flow as visualized by 2-dimensional color Doppler. Pulse repetition frequency was adjusted to visualize the low-velocity flow of RV filling with maximum sensitivity. Animal images were taken during transient disconnection to the ventilator; clinical images were taken during end-expiration apnea. The method used for digital image processing of color M-mode Doppler echocardiograms has been described.1113 Briefly, if the M-mode cursor closely approximates a flow streamline, the spatiotemporal velocity distribution of a discrete blood sample is provided by the value of its corresponding pixel color: v s, t ; , where v represents velocity, s represents the linear dimension of the streamline, and t is time. Thus, the color M-mode Doppler recording provides the data necessary to solve Euler's momentum equation: 1 ; p s
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There can be significant refractive unpredictability following penetrating keratoplasty PK ; . Current options for correction include astigmatic keratotomy, regraft, lensectomy with toric IOL implantation and LASIK. Advantages and disadvantages exist for each. Advantages for LASIK include: expanded range of treatable refractive errors, predictability, potential for enhancement, and low risk of scarring. Concerns include: potential weakening of the wound, induction of graft rejection, and uncertain predictability. 33 eyes underwent LASIK following PK. 76% were keratoconus patients. Mean number of months from PK to LASIK was 62 months. Mean refractive error preLASIK was 6.2D and mean cylindrical refractive error was 6.0D. Mean % reduction in sphere following LASIK was 81% and mean reduction in cylinder following LASIK was 65%. Complications included 3 cases of diffuse lamellar keratitis DLK ; , 1 buttonhole flap, and 1 slipped flap. There were no graft rejections. LASIK following PK is a safe and effective procedure for reducing refractive errors and feverfew.
Background: Nicotine and alcohol dependence often occur together. We examined data from male twin pairs to determine whether there are genetic or environmental influences common to nicotine and alcohol dependence, and, if so, to estimate the magnitude and correlation of these influences. Methods: Subjects were 3356 male-male twin-pair mem and fludarabine.
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