Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the efficacy of HTK solution for cardioplegia in the continuous 120-minute cross-clamping method in comparison with the conventional GIK method. In an experimental model, the efficacy of ketoglutarate and tryptophan in recovering cardiac function after 6 hours' preservation was evaluated. In Group A, in which ketoglutarate was excluded from the HTK solution, percent developed pressure was significantly decreased (p<0.01) and the released enzyme (CK-MB) was significantly increased, but coronary flow was not significantly changed. In Group B, in which tryptophan was excluded from the HTK solution, a significant decrease in percent developed pressure and coronary flow was seen (p<0.01). This indicated that ketoglutarate and tryptophan were effective in protecting the myocardium during the ischemia. In the clinical study, 54 open heart operations were performed with cardioplegic solution, using either HTK solution or GIK solution. In the HTK Group, the heart was exposed to 120 minutes' of ischemia after the infusion of HTK solution (3L). In the GIK group, intermittent GIK perfusion was performed every 30 minutes in association with continuous cold blood perfusion. Percent fraction shortening and cardiac index were not significantly different. However, CK-MB and HBDH were increased in the GIK group, postoperatively. Histological findings showed deterioration of the mitochondria and myocytes during ischemia in the GIK group. These data suggest that the effect of the cardioplegias in heart preservation was satisfactory in both groups, although the interval of intermittent perfusion was prolonged to 120 minutes in the HTK solution.
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PMID:Effect of HTK solution for myocardial preservation. 869 63

Activation of cardiac actomyosin ATPase requires the occupation of the single low-affinity Ca(2+)-binding site of troponin C (cTnC). Previously, we demonstrated pronounced differences between mammals and cold-water salmonid fish in the Ca2+ sensitivity of cardiac preparations, particularly in relation to temperature [Churcotte, C., Moyes, C. D., Baldwin, K., Bressler, B., & Tibbits, G. F. (1994) Am. J. Physiol. 267, R62-R70]. In this study, we examine the extent to which cTnC structure could account for the observed differences in myofibrillar Ca2+ sensitivity. Salmonid (Oncorhynchus mykiss) cTnC was cloned, sequenced, and expressed in Escherichia coli as a maltose-binding protein fusion. The coding region has 87% homology with human cTnC cDNA and differs in 13 of 161 amino acid residues from the human/bovine/porcine isoform. The sequence corresponding to the single regulatory Ca(2+)-binding site II is completely homologous to that of mammals. The protein expressed exhibits optical properties similar (circular dichroism, intrinsic fluorescence) to those of cTnC purified from salmonid (Salmo salar) and bovine ventricle. A single tryptophan residue was introduced into the inactive Ca(2+)-binding site I (ScTnC-FW27) to facilitate Ca2+ titration. The Ca(2+)-binding constant (K1/2 = 5.33 pCa units) was within the range reported for the low-affinity sites of mammalian cTnC. Although differences in TnC primary structure are striking, Ca2+ affinity of intact cardiac myofibrils is likely influenced by interactions with other troponin proteins.
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PMID:Cloning and expression of salmon cardiac troponin C: titration of the low-affinity Ca(2+)-binding site using a tryptophan mutant. 879 56

Investigations were carried out by means of an autologous, heterotopic model for kidney transplantation applied to dogs. Duration of cold ischemia was 48 h. Four experimental groups were arranged. During the first 20 min following revitalization of the transplanted kidney, group 1 (HTK solution/80 cm perfusion height) showed a significant glomerular and tubular malfunction. In group 2 (HTK solution/120 cm perfusion height), only four urinary proteins with molecular weights of 25 kDa, 67 kDa, 100 kDa and > 100 kDa were found. The excretion of higher molecular proteins receded over the 20-min period of observation. In both group 3 (HTK/aspartate solution) and group 4 (HTK/tryptophan solution) the quantity of excreted glomerular and tubular protein was well above that of group 2. As opposed to the "Tryptophan" group, a complete restoration of renal function was observed in the "Aspartate" group after 4 weeks. In general, the "standard" HTK protective solution delivered with 120 cm perfusion pressure gave the most favorable results, with the lowest levels of proteinuria and a satisfactory recovery of renal function after revitalization.
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PMID:Effects of various HTK solution regimens on proteinuria after renal transplantation in dogs. 883 94

Ex situ protection of donor organs for transplantation with initial cold perfusion is routinely used. The superiority of histidine-tryptophan-ketoglutarate solution (HTK) has been demonstrated in animal models and clinical use, however. On the other hand, nephron-sparing surgery for surgical or functional solitary kidneys has been an established procedure for many years. Owing to wide use of ultrasound and computerized tomography, the detection of small renal tumors has increased. New concepts in conservative renal surgery are therefore gaining in importance. In this study we report on 11 patients with renal masses in a surgical or functional solitary kidney. For the first time, all enucleations were performed with continuous in situ perfusion with HTK solution. Despite extensive tumors with central extension, complete in situ tumor resection and kidney reconstruction were possible. There were no intraoperative complications. Postoperatively one kidney was lost secondary to renal artery embolism. Urine production started within 1 h postoperatively in all other cases. No further patients needed hemodialysis. Apart from temporary elevation of serum creatinine, postoperative renal function was unimpaired. There were no changes in serum electrolytes and no disorders of cardiac conduction. The indications, the surgical procedure and the first clinical results of continuous in situ perfusion with HTK solution for conservative renal surgery are presented.
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PMID:[Continuous in situ cold perfusion with HTK solution in conservative surgery of kidney tumor]. 884 55

In this study, the short-term outcome of renal transplants from non-heart-beating donors (NHBD) preserved by machine perfusion (MP) is evaluated and compared to preservation by cold storage (CS). Twenty-two NHBD kidneys were procured during 1993 and 1994 after in situ perfusion with histidine-tryptophan ketoglutarate and preserved by continuous perfusion using University of Wisconsin organ preservation solution for MP as a perfusate. Between 1980 and 1992, 57 NHBD kidneys were procured and preserved by CS. Donors in the MP group sustained increased first warm ischemia times (WIT1) (P < 0.1) and recipients in the MP group suffered longer anastomosis time, worse HLA-DR mismatch, and more initial use of cyclosporin as immunosuppressant; all these factors are known to be deleterious to short-term outcome. Despite these unfavorable conditions, delayed function (DF) rate was decreased in the MP group, although not significantly. However, when considering only kidneys with WIT1 > or = 45 min, short-term outcome was significantly better in the MP group (P < 0.05). We conclude that MP is superior for the preservation of NHBD kidneys, especially after prolonged warm ischemia.
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PMID:Short-term outcome of kidney transplants from non-heart-beating donors after preservation by machine perfusion. 895 96

Characterization of preservation injury in endothelial cells has been primarily accomplished by measurement of cell viability. To analyze early events and cellular mechanisms of preservation-reoxygenation injury, we developed high-resolution respirometry for the study of mitochondrial function in endothelial cells, to provide a quantitative marker for sublethal stress. Cultured human umbilical vein endothelial cells were stored for 4 and 8 hr at 4 degrees C under an atmosphere of 95% N2 and 5% CO2 in University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions. Respiration of suspended cells, measured after reoxygenation in growth medium at 37 degrees C, was significantly reduced in all treatments in comparison to controls not subjected to cold preservation. In contrast, trypan blue staining was unchanged after 4 hr of preservation and was significant only after 8 hr. After 8 hr of cold storage in UW and HTK solutions, respiration was 64+/-5% and 49+/-6%, respectively, of controls (46.5+/-3.3 pmol O2 x s(-1 x 10(-6) cells), indicating significantly better protection by UW solution than HTK solution. A titration regimen with substrate (succinate), uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), and inhibitors of complexes I and III (rotenone and antimycin A) resulted in identical respiratory response patterns in all treatments. The plasma membrane remained impermeable to succinate. Inner mitochondrial membrane function was preserved as indicated by a constant relative increase of respiration after uncoupling. These results demonstrate that loss of catalytic capacity for respiration constitutes an early event in preservation-reoxygenation injury, whereas membrane damage is not a primary defect. Respirometric evaluation of sublethal cell injury and localization of cell damage may provide selective guidelines for further optimization of strategies in organ preservation.
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PMID:Respiratory defect as an early event in preservation-reoxygenation injury of endothelial cells. 900 Jun 75

The hydrophobicity of the subdomain 3/4 hydrophobic loop (262-274) has been implicated to be essential for actin's function. We previously showed (Kuang, B., and Rubenstein, P. A. (1997) J. Biol. Chem. 272, 1237-1247) that a mutant yeast actin (V266G/L267G) with markedly decreased hydrophobicity in this loop conferred severe cold sensitivity to its polymerization. Here we further tested the mutational effect on the conformation and function of G-actin. This GG mutation caused no significant changes in overall secondary structure or in the microenvironment around actin's tryptophan residues, nor did it alter the dissociation constant of G-actin for ATP. However, it lowers the intrinsic ATPase activity and the melting temperature for Mg-GG actin from 51 to 33 degrees C and transforms the conformation of subdomain 2 and the central cleft of G-actin into an F-monomer-like structure. The results suggest that the hydrophobic plug may not only play a role in actin filament stabilization but also may be important for controlling the stability of G-actin and for promoting the conformational change of the monomer needed for addition to a growing actin filament.
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PMID:The effects of severely decreased hydrophobicity in a subdomain 3/4 loop on the dynamics and stability of yeast G-actin. 902 Jan 64

Three cold-sensitive mutants in phage P22 coat protein have been characterized to determine the effects of the amino acid substitutions that cause cold sensitivity on the folding pathway and the conformation of refolded coat protein. Here we find that the three cold-sensitive mutants which have the threonine residue at position 10 changed to isoleucine (T10I), the arginine residue at position 101 changed to cysteine (R101C), or the asparagine residue at position 414 changed to serine (N414S) were capable of folding from a denatured state into a soluble monomeric species, but in each case, the folded conformation was altered. Changes in the kinetics of folding were observed by both tryptophan and bisANS fluorescence. In contrast to the temperature-sensitive for folding coat protein mutants which can be rescued at nonpermissive temperatures in vivo by the overproduction of molecular chaperones GroEL and GroES [Gordon, C. L., Sather, S. K., Casjens, S., & King, J. (1994) J. Biol. Chem. 269, 27941-27951], the folding defects associated with the cold-sensitive amino acid substitutions were not recognized by GroEL and GroES.
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PMID:The folded conformation of phage P22 coat protein is affected by amino acid substitutions that lead to a cold-sensitive phenotype. 909 27

The folding and stability of maltose binding protein (MBP) have been investigated as a function of pH and temperature by intrinsic tryptophan fluorescence, far- and near-UV circular dichroism, and high-sensitivity differential scanning calorimetric measurements. MBP is a monomeric, two-domain protein containing 370 amino acids. The protein is stable in the pH range of 4-10.5 at 25 degrees C. The protein exhibits reversible, two-state, thermal and guanidine hydrochloride-mediated denaturation at neutral pH. The thermostability of MBP is maximal at pH 6, with a Tm of 64.9 degrees C and a deltaHm of 259.7 kcal mol(-1). The linear dependence of deltaHm on Tm was used to estimate a value of deltaCp of 7.9 kcal mol(-1) K(-1) or 21.3 cal (mol of residue)(-1) K(-1). These values are higher than the corresponding deltaCp's for most globular proteins studied to date. However, the extrapolated values of deltaH and deltaS (per mole of residue) at 110 degrees C are similar to those of other globular proteins. These data have been used to show that the temperature at which a protein undergoes cold denaturation depends primarily on the deltaCp (per mol of residue) and that this temperature increases with an increase in deltaCp. The predicted decrease in stability of MBP at low temperatures was experimentally confirmed by carrying out denaturant-mediated unfolding studies at neutral pH at 2 and 28 degrees C.
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PMID:Thermodynamic characterization of the reversible, two-state unfolding of maltose binding protein, a large two-domain protein. 912 24

We studied the functional effects of single amino acid substitutions in the postulated M4 transmembrane domains of Torpedo californica nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes at the single-channel level. At low ACh concentrations and cold temperatures, the replacement of wild-type alpha418Cys residues with the large, hydrophobic amino acids tryptophan or phenylalanine increased mean open times 26-fold and 3-fold, respectively. The mutation of a homologous cysteine in the beta subunit (beta447Trp) had similar but smaller effects on mean open time. Coexpression of alpha418Trp and beta447Trp had the largest effect on channel open time, increasing mean open time 58-fold. No changes in conductance or ion selectivity were detected for any of the single subunit amino acid substitutions tested. However, the coexpression of the alpha418Trp and beta447Trp mutated subunits also produced channels with at least two additional conductance levels. Block by acetylcholine was apparent in the current records from alpha418Trp mutants. Burst analysis of the alpha418Trp mutations showed an increase in the channel open probability, due to a decrease in the apparent channel closing rate and a probable increase in the effective opening rate. Our results show that modifications in the primary structure of the alpha- and beta subunit M4 domain, which are postulated to be at the lipid-protein interface, can significantly alter channel gating, and that mutations in multiple subunits act additively to increase channel open time.
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PMID:Mutations in the M4 domain of the Torpedo californica nicotinic acetylcholine receptor alter channel opening and closing. 921 18


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