[Specific characteristic of X-ray changes in Klebsiella pneumonia ].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Jun Wu
Publications and source records attributed to Jun Wu.
[Gene therapy of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and GTP cyclohydrolase genes in rat model of Parkinson's disease].
OBJECTIVE: To detect the expression and function of enzyme genes involved in biosynthetic pathway for dopamine in vitro and assess their effect in rat model of Parkinson's disease. METHODS: Cos7 cells were transfected with separate adeno-associated virus (AAV) expressing tyrosine hydroxylase (TH) gene, aromatic L-amino acid decarboxylase (AADC) gene and GTP cyclohydrolase I (GCH-I) gene. The expression and function of the three genes were detected by methods of immunohistochemistry, in situ hybridization and high performance liquid chromatograph and electrochemical detection (HPLC-ECD). Gene engineered cells were sequentially transplanted into the striatum of 6-hydroxy-dopamine-leisioned Parkinsonian rat by stereotaxic instrastriatal injection. The asymmetric rotations of these rats after apomorphine administration were detected every week after transplantation. 10 weeks after grafting, the animals were sacrificed and the dopamine produced in the striatum was detected by HPLC-ECD. RESULTS: In vitro experiments showed that the three genes were high expressed in Cos7 cells. When Cos7 cells expressing TH, AADC and GCH-I were cocultured, they produced large amount of dopamine in the condition of existance of L-tyrosine. Furthermore, triple genes therapy resulted in greater dopamine production in the striatum of Parkinsonian rats and improved the rotational behavior of the rats more efficiently than did single gene therapy. However, the production of dopamine in the rats with triple genes therapy is no more than double genes therapy. CONCLUSION: For gene therapy in Parkinson's disease, the amount of target genes to be used should be determined by the level of doperminergic neurons damaged. In the present study, the efficiency of multiple genes therapy is significantly better than that of single gene therapy.
Animals↗
[Relationship between ATP-binding cassette transporter 1 R219K genetic variation and blood lipids].
OBJECTIVE: To investigate whether ATP-binding cassette transporter 1 (ABCA1) R219K genetic variation is correlated with blood lipids. METHOD: Specimens of peripheral blood were collected from 692 patients with cerebral apoplexy, aged 62 +/- aged 12, and 352 sex- and age-matched persons without cardio-cerebro-vascular disease. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the ABCA1 genotype: RR type (177 bp), RK type (177 bp, 107 bp, and 70 bp); and KK type (107 bp and 70 bp). The RR and KK type products were sequenced. RESULTS: The level of HDL-C showed an upward trend in the sequence of RR, RK, and KK genotypes with a significant difference between RR genotype (1.3 mmol/L +/- 0.4 mmol/L) and KK genotype (1.4 mmol/L +/- 0.4 mmol/L), especially in the males. The levels of TG tended downward in the sequence of RR, RK, and KK genotypes, however, without a significant difference between any 2 genotypes. Linear regression analysis showed that the HDL-C level was positively correlated with age in the noncarriers of ABCA1R219K genetic variation (RR genotype), and the TC level was negatively correlated with age in the carriers (RK + KK genotype). In the cohort aged </= 70 the HDL-C level was higher in carriers than in noncarriers. CONCLUSION: ABCA1R219K genetic variation results in a beneficial profile of blood lipids, more evident in males. RK + KK genotype is more pronounced in the individuals aged </= 70.
ATP Binding Cassette Transporter 1↗
Gene therapy of endothelial nitric oxide synthase and manganese superoxide dismutase restores delayed wound healing in type 1 diabetic mice.
BACKGROUND: Nitric oxide (NO) deficiency contributes to diabetic wound healing impairment. The present study tested the hypothesis that increased cutaneous superoxide (O2-) levels in type 1 diabetic mice cause NO deficiency and delayed wound healing. METHODS AND RESULTS: Wound healing was markedly delayed in streptozotocin-induced type 1 diabetic mice compared with the normal controls. There were significantly reduced levels of endothelial NO synthase (eNOS) protein and constitutive NOS activity in diabetic wounds, whereas O2- levels were markedly increased. A single regimen of cutaneous gene therapy of eNOS or manganese superoxide dismutase (MnSOD) restored such healing delay, with a concomitant suppression of wound O2- levels and augmentation of both eNOS protein and constitutive NOS activity. Gene therapy of MnSOD also increased cutaneous MnSOD activity. Cutaneous O2- levels were also increased in Ins2(Akita) diabetic mice. In vitro glucose treatment of cutaneous tissues from normal mice for 24 hours increased O2- levels in a concentration-dependent manner. The enhanced cutaneous O2- levels induced by high glucose in both normal and diabetic mice were abolished by the NADPH oxidase inhibitor apocynin and the protein kinase C inhibitor chelerythrine. Furthermore, ex vivo gene transfer of dominant-negative HA-tagged N17Rac1, which inhibits NADPH oxidase subunit Rac1, significantly inhibited cutaneous O2- formation induced by high glucose in both normal and Ins2(Akita) diabetic mice. CONCLUSIONS: These results indicate that hyperglycemia augments cutaneous O2- levels, at least in part, via NADPH oxidase and protein kinase C pathways, resulting in impaired wound healing in type 1 diabetic mice. Gene therapy strategies aimed at restoring cutaneous NO bioavailability may provide an effective means to ameliorate delayed diabetic wound healing.
Acetophenones↗
Subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity.
The Frizzled (Fz; called here Fz1) and Fz2 receptors have distinct signaling specificities activating either the canonical Wnt/beta-catenin pathway or Fz/planar cell polarity (PCP) signaling in Drosophila. The regulation of signaling specificity remains largely obscure. We show that Fz1 and Fz2 have different subcellular localizations in imaginal disc epithelia, with Fz1 localizing preferentially to apical junctional complexes, and Fz2 being evenly distributed basolaterally. The subcellular localization difference directly contributes to the signaling specificity outcome. Whereas apical localization favors Fz/PCP signaling, it interferes with canonical Wnt/beta-catenin signaling. Receptor localization is mediated by sequences in the cytoplasmic tail of Fz2 that appear to block apical accumulation. Based on these data, we propose that subcellular Fz localization, through the association with other membrane proteins, is a critical aspect in regulating the signaling specificity within the Wnt/Fz signaling pathways.
Animals↗
Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from mucosa and enhances the sphingomyelinase activity.
Sphingomyelin (SM) hydrolysis in the gut has implications in colonic tumorigenesis and cholesterol absorption. It is triggered by intestinal alkaline sphingomyelinase (Alk-SMase) that is present in the intestinal mucosa and content. The mechanism by which the enzyme is released into the lumen is not clear. We studied whether trypsin can dissociate Alk-SMase from the mucosa and affect its activity. During luminal perfusion of rat intestine, addition of trypsin to the buffer increased Alk-SMase activity in the perfusate output by about threefold. Treating COS-7 cells transfected with Alk-SMase cDNA with trypsin increased the SMase activity in the medium and reduced that in the cell lysate dose dependently. The appearance of Alk-SMase in the perfusate and culture medium was confirmed by Western blot analysis. The effect of trypsin was blocked by trypsin inhibitor, and neither chymotrypsin nor elastase had a similar effect. We also expressed the full length and COOH-terminal truncated Alk-SMase in COS-7 cells and found that the activity of the full-length enzyme is mainly in the cells, whereas that of the truncated form is mainly in the medium. Both forms were active, but only the activity of the full-length Alk-SMase was enhanced by trypsin. By linking a poly-His tag to the constructed cDNA, we found that the first tryptic site Arg440 upstream of the signal anchor was attacked by trypsin. In conclusion, trypsin cleaves the Alk-SMase at the COOH terminal, releases it from mucosa, and meanwhile enhances its activity. The findings indicate a physiological role of trypsin in SM digestion.
Alkalies↗
Defining the binding site of homotetrameric R67 dihydrofolate reductase and correlating binding enthalpy with catalysis.
R67 dihydrofolate reductase (DHFR) is a novel protein that possesses 222 symmetry. A single active site pore traverses the length of the homotetramer. Although the 222 symmetry implies that four symmetry-related binding sites should exist for each substrate as well as each cofactor, isothermal titration calorimetry (ITC) studies indicate only two molecules bind. Three possible combinations include two dihydrofolate molecules, two NADPH molecules, or one substrate with one cofactor. The latter is the productive ternary complex. To evaluate the roles of A36, Y46, T51, G64, and V66 residues in binding and catalysis, a site-directed mutagenesis approach was employed. One mutation per gene produces four mutations per active site pore, which often result in large cumulative effects. Conservative mutations at these positions either eliminate the ability of the gene to confer trimethoprim resistance or have no effect on catalysis. This result, in conjunction with previous mutagenesis studies on K32, K33, S65, Q67, I68, and Y69 [Strader, M. B., et al. (2001) Biochemistry 40, 11344-11352; Hicks, S. N., et al. (2003) Biochemistry 42, 10569-10578; Park, H., et al. (1997) Protein Eng. 10, 1415-1424], allows mapping of the active site surface. Residues for which conservative mutations have large effects on binding and catalysis include K32, Q67, I68, and Y69. These residues form a stripe that establishes the ligand binding surface. Residues that accommodate conservative mutations that do not greatly affect catalysis include K33, Y46, T51, S65, and V66. Isothermal titration calorimetry studies were also conducted on many of the mutants described above to determine the enthalpy of folate binding to the R67 DHFR.NADPH complex. A linear correlation between this DeltaH value and log k(cat)/K(m) is observed. Since structural tightness appears to be correlated with the exothermicity of the binding interaction, this leads to the hypothesis that enthalpy-driven formation of the ternary complex in these R67 DHFR variants plays a strong role in catalysis. Use of the alternate cofactor, NADH, extends this correlation, indicating preorganization of the ternary complex determines the efficiency of the reaction. This hypothesis is consistent with data suggesting R67 DHFR uses an endo transition state (where the nicotinamide ring of cofactor overlaps the more bulky side of the substrate's pteridine ring).
Amino Acids↗
A novel role for p21-activated protein kinase 2 in T cell activation.
To identify novel components of the TCR signaling pathway, a large-scale retroviral-based functional screen was performed using CD69 expression as a marker for T cell activation. In addition to known regulators, two truncated forms of p21-activated kinase 2 (PAK2), PAK2DeltaL(1-224) and PAK2DeltaS(1-113), both lacking the kinase domain, were isolated in the T cell screen. The PAK2 truncation, PAK2DeltaL, blocked Ag receptor-induced NFAT activation and TCR-mediated calcium flux in Jurkat T cells. However, it had minimal effect on PMA/ionomycin-induced CD69 up-regulation in Jurkat cells, on anti-IgM-mediated CD69 up-regulation in B cells, or on the migratory responses of resting T cells to chemoattractants. We show that PAK2 kinase activity is increased in response to TCR stimulation. Furthermore, a full-length kinase-inactive form of PAK2 blocked both TCR-induced CD69 up-regulation and NFAT activity in Jurkat cells, demonstrating that kinase activity is required for PAK2 function downstream of the TCR. We also generated a GFP-fused PAK2 truncation lacking the Cdc42/Rac interactive binding region domain, GFP-PAK2(83-149). We show that this construct binds directly to the kinase domain of PAK2 and inhibits anti-TCR-stimulated T cell activation. Finally, we demonstrate that, in primary T cells, dominant-negative PAK2 prevented anti-CD3/CD28-induced IL-2 production, and TCR-induced CD40 ligand expression, both key functions of activated T cells. Taken together, these results suggest a novel role for PAK2 as a positive regulator of T cell activation.
Antigens, CD↗
Serum level of TSGF, CA242 and CA19-9 in pancreatic cancer.
AIM: To establish a method to detect the expression of the tumor specific growth factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of pancreatic cancer. METHODS: ELISA and Biochemical colorimetric assay were used to detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52 pancreatitis patients and 96 pancreatic cancer patients. RESULTS: The positive likelihood ratios of TSGF, CA242 and CA19-9 were 5.4, 12.6 and 6.3, respectively, and their negative likelihood ratios were 0.10, 0.19 and 0.17, respectively. With single tumor marker diagnosed pancreatic cancer, the highest sensitivity and specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when all of them were positive, the sensitivity changed to 77.0% and the specificity and the positive predictive value were 100%. The levels of TSGF and CA242 were significantly higher in the patients with pancreatic cancer of head than those in the patients with pancreatic cancer of body, tail and whole pancreas, but the expression of CA19-9 had no correlation with the positions of the pancreatic cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly higher than CA242 and CA19-9. CONCLUSION: The combined use of TSGF, CA242 and CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis. And it shows that it plays an important role to differentiate positions and tissue typing. It is a forepart diagnosis for the pancreatic cancer by combination checking. There is very important correlation between the three markers and the pancreatic cancer.
Adult↗
Xyloccensins O and P, unique 8,9,30-phragmalin ortho esters from Xylocarpus granatum.
Two unique 8,9,30-phragmalin ortho esters, xyloccensins O (1) and P (2), were isolated from the mangrove plant Xylocarpus granatum. They are a new type of ortho ester of phragmalin. The structures were determined by spectroscopic and single-crystal X-ray diffraction techniques. The biogenetic pathway to these new phragmalins was also proposed. [structure: see text]
Crystallography, X-Ray↗
Binding of Cd2+ to self-assembled bilayers bearing pyridine terminal groups: attenuated total reflection Fourier transform infrared spectroscopic studies.
Various aspects of the adsorption of Cd2+ on self-assembled monolayers (SAMs) of 4-heptadecylpyridine (HDpy) and 7-tridecyl-4-methyl-1,10-bipyridine (TMbipy) supported on an octadecylsilane (ODS)-modified Ge prism have been examined both ex situ (dry) and in situ (in the presence of aqueous solutions) using attenuated total reflection Fourier transform infrared spectroscopy. In direct analogy with the behavior found for a variety of genuine pyridine (py) and bipyridine (bipy) metal ion complexes, Cd2+ binding to both SAMs led to shifts in the skeletal vibrational modes of the corresponding uncoordinated ligands in the region 1650-1400 cm(-1), toward higher energies. Analysis of spectra acquired ex situ for HDpy/ODS/Ge and TMbipy/ODS/Ge before and after exposure to 0.1 mM [Cd2+] yielded values for the fraction of uncoordinated py, theta(py(un)), and uncoordinated bipy, theta(bipy(un)), of about 0.5 and about 0.1, respectively. The features attributed to the py(un) groups for spectra collected for HDpy/ODS/Ge in situ and ex situ were found to be virtually identical, making it possible to isolate by graphical means the most prominent band of py(co) centered at about 1615 cm(-l) for HDpy/ODS/Ge collected in situ. The resulting bands for pure py(co) and pyun in situ were then used to deconvolute spectra recorded in situ for HPpy/ODS/Ge in contact with Cd2+containing solutions in the range 10 nM < [Cd2+] < 0.1 mM, from which information regarding the adsorption isotherm was obtained.
Journal Article↗
Identification of one exon deletion of intestinal alkaline sphingomyelinase in colon cancer HT-29 cells and a differentiation-related expression of the wild-type enzyme in Caco-2 cells.
Sphingomyelin (SM) metabolism in the gut has been implicated in colonic tumorigenesis. Intestinal alkaline sphingomyelinase (alk-SMase) hydrolyses SM in the intestinal content and at the brush border. The enzyme activity is decreased in the tissues of human colorectal tumours. This study examines whether site or chain-mutation of alk-SMase occurs in colon cancer HT-29 cells and Caco-2 cells. Total RNA was isolated and the cDNA of alk-SMase was amplified by RT-PCR. The size of the cDNA from HT-29 cells was smaller than that of the wild-type cDNA. DNA sequencing identified a deletion of exon 4 in alk-SMase cDNA in HT-29 cells. No mutation in genomic alk-SMase DNA from exon 3 to 5 was identified. The exon 4 deletion was caused by a shift of RNA splice site in chromosome 17q25. In Caco-2 cells, no mutation of alk-SMase cDNA was identified. Transient expression in COS-7 cells showed that the enzyme from the cDNA in HT-29 cells had little alk-SMase activity whereas that in Caco-2 cells was as active as the wild-type alk-SMase. The deleted region included residue His353, which is predicted to form a substrate-binding site of alk-SMase. H353A substitution resulted in a protein with no alk-SMase activity. In monolayer cultured Caco-2 cells and HT-29 cells the alk-SMase activities were low. However, to culture the cells under polarizing conditions increased alk-SMase activity and reduced SM level in Caco-2 cells. The alk-SMase activity varied in parallel with alkaline phosphatase activity. In conclusion, we identified an inactive deletion in alk-SMase in HT-29 cells, and a differentiation-related expression of the enzyme in Caco-2 cells. The results provide a molecular mechanism related to previous findings of reduced alk-SMase activity in human colon cancers.
Alkaline Phosphatase↗
Effects of Zhaoyangwan on chronic hepatitis B and posthepatic cirrhosis.
AIM: To study the therapeutic effects of zhaoyangwan (ZYW) on chronic hepatitis B and hepatic cirrhosis and the anti-virus, anti-fibrosis and immunoregulatory mechanisms of ZYW. METHODS: Fifty cases of chronic hepatitis B and posthepatic cirrhosis with positive serum HBsAg, HBeAg, anti-Hbc and HBV-DNA were divided randomly and single-blindly into the treatment group (treated with ZYW) and the control group (treated with interferon). After 3 month treatment, the effects of the treatment group and the control group were evaluated. RESULTS: The serum ALT normalization was 83.3% (30/36) in the treatment group and 85.7% (12/14) in the control group, with no significant difference (chi2=0.043, P>0.05). After the course, the negative expression rates of the serum HBV-DNA and HBeAg were 44.4% (16/36) and 50% (18/36) in the treatment group, and 50% (7/14) and 50% (7/14) in the control group, respectively, with no significant difference (chi2=0.125, chi2=0.00, both P>0.05). Negative HBsAg and positive HBsAb appeared in 4 cases of the treatment group and 1 case of the control group. Serum anti-HBc turned negative in 6 cases of the treatment group and 1 case of the control group, respectively. After the ZYW treatment, serum CD3+, CD4+, CD8+, CD4+/CD8+ and NK cell activation were significantly increased. Only serum CD3+ and NK cell activation were significantly increased in the control group with a significant difference between the two groups. The serum C4, C1q, C3, B and C9 were significantly increased in the treatment group. In the control group only the serum C4 was increased. The concentration of serum interferon had no change after treatment with ZYW, while it was significantly increased in the control group after treatment with interferon. The ultrastructure of the liver restored, which helped effectively to reduce the degeneration and necrosis of hepatic cells,infiltration of inflammatory cells and hepatic cirrhosis. CONCLUSION: ZYW is a pure Chinese herbal medicine. It can exert potent therapeutic effects on chronic hepatitis B and posthepatic cirrhosis. ZYW has similar therapeutic effects to those of interferon. It is cheap and easily administered with no obvious side-effects. It can be widely used in clinical practice.
Adolescent↗
Complete assignments of 1H and 13C NMR data for 10 phenylethanoid glycosides.
Ten phenylethanoid glycosides, including two new ones, isolated from the aerial parts of the mangrove plant Acanthus ilicifolius were identified. The first complete assignments of the 1H and 13C NMR chemical shifts for these glycosides were achieved by means of 2D NMR techniques, including 1H-1H COSY, TOCSY, HSQC and HMBC spectra.
Acanthaceae↗
A SISO mixed H2/l1 optimal control problem and its solution.
Study of the SISO mixed H(2)/l(1) problem for discrete time systems showed that there exists a unique optimal solution which can be approximated within any prescribed missing error bound in l(2) norm with solvable suboptimal solutions and solvable superoptimal solutions.
Algorithms↗
Effect of tracheal occlusion on peripheric pulmonary vessel muscularization in a fetal rabbit model for congenital diaphragmatic hernia.
OBJECTIVE: This study was undertaken to evaluate the effects on peripheric pulmonary vessel muscularization by tracheal occlusion (TO) performed at different gestational ages in fetal rabbits with surgically induced diaphragmatic hernia. STUDY DESIGN: In 23 New Zealand white does, both ovarian end fetuses underwent surgical creation of diaphragmatic hernia at 23 days of gestation (pseudoglandular phase). At 26, 27, or 28 days 1 fetus underwent TO, the contralateral one underwent a sham operation for a total of 46 fetuses. At 30 days (alveolar phase), fetuses were harvested together with 1 nonoperated internal control. Lungs were processed for vascular morphometry. Proportionate medial thickness and muscularization of intra-acinar vessels were evaluated. RESULTS: Late TO (day 28; saccular phase) normalizes the lung-to-body weight ratio and causes significant medial thinning in vessels up to 35 microm diameter. CONCLUSION: Tracheal occlusion decreases muscularization of intra-acinar pulmonary vessels in a gestational age-dependent fashion, with maximal effect when TO is performed at 28 days.
Actins↗
St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole.
OBJECTIVE: St John's wort, an extract of the medicinal plant Hypericum perforatum, is widely used as an herbal antidepressant. Although the ability of St John's wort to induce cytochrome P450 (CYP) 3A4-mediated reaction has been well established, the effect on CYP2C19 is still not determined. Thus the objective of this study was to determine the impact of St John's wort on the pharmacokinetic profiles of omeprazole and its metabolites. METHODS: Twelve healthy adult men (6 CYP2C19*1/CYP2C19*1, 4 CYP2C19*2/CYP2C19*2 and 2 CYP2C19*2/CYP2C19*3) were enrolled in a 2-phase randomized crossover design. In each phase the volunteers received placebo or a 300-mg St John's wort tablet 3 times daily for 14 days. Then all subjects took a 20-mg omeprazole capsule orally. Blood samples were collected up to 12 hours after omeprazole administration. Omeprazole and its metabolites were quantified by use of HPLC with ultraviolet detection. RESULTS: Omeprazole and its metabolites all exhibit CYP2C19 genotype-dependent pharmacokinetic profiles. After a 14-day treatment with St John's wort, substantial decreases in plasma concentrations of omeprazole were observed. The peak plasma concentration (C(max)) significantly decreased by 37.5% +/- 13.3% (P =.001) in CYP2C19*2/CYP2C19*2 or *3 and by 49.6% +/- 20.7% (P =.017) in CYP2C19*1/CYP2C19*1; the area under the concentration-time curve extrapolated to infinity [AUC(0- infinity )] decreased by 37.9% +/- 21.3% (P =.014) and 43.9% +/- 23.7% (P =.011) in CYP2C19 mutant and wild genotypes, respectively. Moreover, the C(max) and AUC(0- infinity ) of omeprazole sulfone increased by 160.3% +/- 45.5% (P =.001) and by 136.6% +/- 84.6% (P =.014), 155.5% +/- 58.8% (P =.001), and 158.7% +/- 101.4% (P =.017) in mutant and wild genotypes, respectively. St John's wort increased the C(max) of 5-hydroxyomeprazole by 38.1% +/- 30.5% (P =.028) and the AUC(0- infinity ) by 37.2% +/- 26% (P =.005) in CYP2C19 wild-type subjects, whereas it did not produce any significant alterations to the corresponding pharmacokinetic parameters in subjects with variant genotypes. CONCLUSION: St John's wort induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole and enormously decreases the plasma concentrations of omeprazole. Clinically relevant interactions with other drugs may occur and must be taken into account when St John's wort is being taken.
Adolescent↗
Improved vitrification solutions based on the predictability of vitrification solution toxicity.
Long-term preservation of complex engineered tissues and organs at cryogenic temperatures in the absence of ice has been prevented to date by the difficulty of discovering combinations of cryoprotectants that are both sufficiently non-toxic and sufficiently stable to allow viability to be maintained and ice formation to be avoided during slow cooling to the glass transition temperature and subsequent slow rewarming. A new theory of the origin of non-specific cryoprotectant toxicity was shown to account, in a rabbit renal cortical slice model, for the toxicities of 20 vitrification solutions and to permit the design of new solutions that are dramatically less toxic than previously known solutions for diverse biological systems. Unfertilized mouse ova vitrified with one of the new solutions were successfully fertilized and regained 80% of the absolute control (untreated) rate of development to blastocysts, whereas ova vitrified in VSDP, the best previous solution, developed to blastocysts at a rate only 30% of that of controls. Whole rabbit kidneys perfused at -3 degrees C with another new solution at a concentration of cryoprotectant (8.4M) that was previously 100% lethal at this temperature exhibited no damage after transplantation and immediate contralateral nephrectomy. It appears that cryoprotectant solutions that are composed to be at the minimum concentrations needed for vitrification at moderate cooling rates are toxic in direct proportion to the average strength of water hydrogen bonding by the polar groups on the permeating cryoprotectants in the solution. Vitrification solutions that are based on minimal perturbation of intracellular water appear to be superior and provide new hope that the successful vitrification of natural organs as well as tissue engineered or clonally produced organ and tissue replacements can be achieved.
Animals↗