Relationship between early postoperative C-reactive protein elevation and long-term postoperative major adverse cardiovascular and cerebral events in patients undergoing off-pump coronary artery bypass graft surgery: a retrospective study.

BACKGROUND: Inflammation plays a key role in the pathogenesis of vascular occlusive diseases, such as myocardial infarction and stroke. Additionally, these conditions are predicted by C-reactive protein (CRP), a general inflammation marker. We hypothesized that the inflammation induced by surgery itself augments vascular occlusive disease. We retrospectively evaluated the relationship between postoperative CRP elevation and postoperative major adverse cardiovascular and cerebral events (MACCE) in patients undergoing off-pump coronary artery bypass surgery (OPCAB). METHODS: The electronic medical records of 1046 patients who underwent OPCAB were reviewed retrospectively. The relationship between postoperative serum CRP and long-term postoperative MACCE (median follow-up 28 months) was investigated. RESULTS: Patients were divided into quartiles according to maximum postoperative CRP levels (<18, 18-22, 22-27, ≥27 mg dl(-1)). The adjusted hazard ratios (HRs) were 2.15, 2.45, and 2.81, respectively (P=0.004), compared with the lowest quartile (<18 mg dl(-1)). In the multivariate analysis, the postoperative CRP quartile (HR 2.81; P=0.004), postoperative non-use of statins (HR 1.86; P=0.003), and postoperative maximum troponin I (HR 1.02; P<0.001) independently predicted postoperative MACCE, while preoperative CRP did not (P=0.203). Several parameters were correlated with postoperative maximum CRP level: body temperature (P=0.001) and heart rate (P<0.001) at the end of surgery; intraoperative last lactate (P<0.001) and base excess (P<0.001); and red blood cell transfusion (P=0.019). CONCLUSIONS: Postoperative CRP elevation was associated with long-term postoperative MACCE in OPCAB patients. This was mitigated by postoperative statin medication. Furthermore, postoperative CRP elevation was associated with intraoperative parameters reflecting hypoperfusion and inflammation.

Strongly spin-orbit coupled two-dimensional electron gas emerging near the surface of polar semiconductors.

We investigate the two-dimensional highly spin-polarized electron accumulation layers commonly appearing near the surface of n-type polar semiconductors BiTeX (X=I, Br, and Cl) by angular-resolved photoemission spectroscopy. Because of the polarity and the strong spin-orbit interaction built in the bulk atomic configurations, the quantized conduction-band subbands show giant Rashba-type spin splitting. The characteristic 2D confinement effect is clearly observed also in the valence bands down to the binding energy of 4 eV. The X-dependent Rashba spin-orbit coupling is directly estimated from the observed spin-split subbands, which roughly scales with the inverse of the band-gap size in BiTeX.

Intramyocardial transfer of hepatocyte growth factor as an adjunct to CABG: phase I clinical study.

The purpose of this phase I clinical trial was to evaluate the safety, tolerability and potential efficacy of VM202, naked DNA expressing two isoforms of hepatocyte growth factor, as an adjunct therapy to coronary artery bypass grafting (CABG) in patients with ischemic heart disease (IHD). Nine patients were assigned to receive increasing doses (0.5 to 2.0 mg) of VM202 injected into the right coronary artery (RCA) territory following completion of CABG for the left coronary artery territory. Patients were evaluated for safety and tolerability, and changes in myocardial functions were monitored via echocardiography, cardiac magnetic resonance imaging and myocardial single photon emission computed tomography throughout 6-month follow-up period. No serious complication related to VM202 was observed throughout the 6-month follow-up period. Global myocardial functions (wall motion score index, P=0.0084; stress perfusion, P=0.0002) improved during the follow-up period. In the RCA region, there was an increase in the stress perfusion (baseline vs 3-month, P=0.024; baseline vs 6-month, P=0.024) and also in the wall thickness of the diastolic and systolic phases. Intramyocardial injection of VM202 can be safely used in IHD patients with the tolerable dose of 2.0 mg. In addition, VM202 might appear to have improved regional myocardial perfusion and wall thickness in the injected region.

Subband structure of a two-dimensional electron gas formed at the polar surface of the strong spin-orbit perovskite KTaO3.

We demonstrate the formation of a two-dimensional electron gas (2DEG) at the (100) surface of the 5d transition-metal oxide KTaO3. From angle-resolved photoemission, we find that quantum confinement lifts the orbital degeneracy of the bulk band structure and leads to a 2DEG composed of ladders of subband states of both light and heavy carriers. Despite the strong spin-orbit coupling, our measurements provide a direct upper bound for the potential Rashba spin splitting of only Δk(parallel)}~0.02 Å(-1) at the Fermi level. The polar nature of the KTaO3(100) surface appears to help mediate the formation of the 2DEG as compared to nonpolar SrTiO3(100).

A high-mobility electron gas at the LaAlO3/SrTiO3 heterointerface.

Polarity discontinuities at the interfaces between different crystalline materials (heterointerfaces) can lead to nontrivial local atomic and electronic structure, owing to the presence of dangling bonds and incomplete atomic coordinations. These discontinuities often arise in naturally layered oxide structures, such as the superconducting copper oxides and ferroelectric titanates, as well as in artificial thin film oxide heterostructures such as manganite tunnel junctions. If polarity discontinuities can be atomically controlled, unusual charge states that are inaccessible in bulk materials could be realized. Here we have examined a model interface between two insulating perovskite oxides--LaAlO3 and SrTiO3--in which we control the termination layer at the interface on an atomic scale. In the simple ionic limit, this interface presents an extra half electron or hole per two-dimensional unit cell, depending on the structure of the interface. The hole-doped interface is found to be insulating, whereas the electron-doped interface is conducting, with extremely high carrier mobility exceeding 10,000 cm2 V(-1) s(-1). At low temperature, dramatic magnetoresistance oscillations periodic with the inverse magnetic field are observed, indicating quantum transport. These results present a broad opportunity to tailor low-dimensional charge states by atomically engineered oxide heteroepitaxy.

Effect of hormone replacement therapy on nitric oxide bioactivity and monocyte chemoattractant protein-1 levels.

BACKGROUND: Vascular inflammation plays an important role in the pathogenesis of atherosclerosis. We investigated the effect of hormone replacement therapy (HRT) on vasomotor function and monocyte chemoattractant protein (MCP)-1 levels, an important serological marker of inflammation. METHODS: We administered micronized progesterone (MP) 200 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and remaining 5 days off cyclically during 2 months to 20 healthy postmenopausal women (PMW). We measured NO bioactivity and plasma levels of MCP-1 before and after HRT in 20 PMW. And we measured plasma levels of MCP-1 in each 20 subjects of premenopausal women, men <50, and men >50 years, respectively. RESULTS: MP combined with CEE significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P<0.001). PMW receiving HRT had lower levels of MCP-1 than those not receiving HRT (121+/-38 versus 146+/-44 pg/ml, P<0.001). In all comparisons, subjects with high estrogen status had significantly lower MCP-1 levels than subjects with low estrogen status (P<0.001 by ANOVA). Premenopausal women had lower levels of MCP-1 than men of a similar age (106+/-14 versus 164+/-40 pg/ml, P<0.001). PMW not receiving HRT had similar levels of MCP-1 compared with men of a similar age (146+/-44 versus 143+/-29 pg/ml, P=0.816). Premenopausal women had markedly lower levels of MCP-1 than PMW not receiving HRT (106+/-14 versus 146+/-44 pg/ml, P=0.001). PMW receiving HRT had similar levels of MCP-1 compared with premenopausal women (121+/-38 versus 106+/-14 pg/ml, P=0.323). CONCLUSION: These findings might provide at least a partial explanation for the protection against cardiovascular disease experienced by premenopausal women, and the loss of that protection following menopause.

CT findings of portal vein aneurysm caused by gastric adenocarcinoma invading the portal vein.

The known causes of acquired origin portal vein aneurysm are portal hypertension, pancreatitis and trauma. We describe the CT findings of an additional cause of acquired origin portal vein aneurysm, namely gastric adenocarcinoma invading the portal venous system.

Expression of recombinant human granulocyte macrophage-colony stimulating factor (hGM-CSF) in mouse urine.

We have generated transgenic mice expressing human granulocyte macrophage-colony stimulating factor (hGM-CSF) in urine. In particular, the expression plasmid DNA containing mouse uroplakin II promoter was used to direct uroepithelium-specific transcription of transgene. In this study, hGM-CSF transcript was detected only in bladder uroepithelium as determined by northern blot analysis. Furthermore, hGM-CSF protein was detected in the suprabasal layer of the uroepithelium and ureter by immunohistochemistry. The hGM-CSF was secreted into urine at high level (up to 180 ng/ml), and enhanced proliferation of hGM-CSF-dependent human acute monocyte leukemic cells, suggesting that transgenic urine-derived hGM-CSF was bioactive. This is the first case of demonstrating biological activity of a cytokine produced in the urine of a transgenic animal. Our results demonstrate that bladder can be used as a bioreactor to produce biologically important substances. In addition, it suggests a potential application of bladder expression system to livestock for high-yield production of pharmaceuticals.

Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women.

BACKGROUND: Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. METHODS AND RESULTS: In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). CONCLUSIONS: CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

SQV-7, a protein involved in Caenorhabditis elegans epithelial invagination and early embryogenesis, transports UDP-glucuronic acid, UDP-N- acetylgalactosamine, and UDP-galactose.

Caenorhabditis elegans sqv mutants are defective in vulval epithelial invagination and have a severe reduction in hermaphrodite fertility. The gene sqv-7 encodes a multitransmembrane hydrophobic protein resembling nucleotide sugar transporters of the Golgi membrane. A Golgi vesicle enriched fraction of Saccharomyces cerevisiae expressing SQV-7 transported UDP-glucuronic acid, UDP-N-acetylgalactosamine, and UDP-galactose (Gal) in a temperature-dependent and saturable manner. These nucleotide sugars are competitive, alternate, noncooperative substrates. The two mutant sqv-7 missense alleles resulted in a severe reduction of these three transport activities. SQV-7 did not transport CMP-sialic acid, GDP-fucose, UDP-N-acetylglucosamine, UDP-glucose, or GDP-mannose. SQV-7 is able to transport UDP-Gal in vivo, as shown by its ability to complement the phenotype of Madin-Darby canine kidney ricin resistant cells, a mammalian cell line deficient in UDP-Gal transport into the Golgi. These results demonstrate that unlike most nucleotide sugar transporters, SQV-7 can transport multiple distinct nucleotide sugars. We propose that SQV-7 translocates multiple nucleotide sugars into the Golgi lumen for the biosynthesis of glycoconjugates that play a pivotal role in development.

Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.

Methionine synthase (MS) catalyses the methylation of homocysteine to methionine and requires the vitamin B12 derivative, methylcobalamin, as cofactor. We and others have recently cloned cDNAs for MS and described mutations associated with the cblG complementation group that correspond to MS deficiency. A subset of cblG, known as "cblG variant," shows no detectable MS activity and failure of [57Co]CN cobalamin to incorporate into MS in patient fibroblasts. We report the mutations responsible for three cblG-variant patients, two of them siblings, who presented with neonatal seizures, severe developmental delay, and elevated plasma homocysteine. Cell lines from all three patients were negative by northern blotting, though trace MS mRNA could be detected by means of phosphorimage analysis. Reverse transcriptase-PCR, SSCP, and nucleotide sequence analysis revealed four mutations. All were functionally null, creating either a frameshift with a downstream stop codon or an insert containing an internal stop codon. Of the two mutations found in the siblings, one of them, intervening sequence (IVS)-166A-->G, generates a cryptic donor splice site at position -166 of an intron beginning after Leu113, resulting in a 165-bp insertion of intronic sequence at junction 339/340. The second is a 2-bp deletion, 2112delTC. Mutations in the third patient include a G-->A substitution, well within the intron after Lys203, which results in intronic inserts of 128 or 78 bp in the mRNA. The second mutation is a 1-bp insertion, 3378insA. We conclude that the absence of MS protein in these cblG variants is due to mutations causing premature translation termination and consequent mRNA instability.

Genetic analysis of purine metabolism in Leishmania donovani.

To dissect the contributions of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase (APRT), and adenosine kinase (AK) to purine salvage in Leishmania donovani, null mutants genetically deficient in HGPRT and/or APRT were generated by targeted gene replacement in wild type cells and preexisting mutant strains lacking either APRT or AK activity. These knockouts were obtained either by double targeted gene replacement or by single gene replacement followed by negative selection for loss-of-heterozygosity. Genotypes were confirmed by Southern blotting and the resultant phenotypes evaluated by enzymatic assay, resistance to cytotoxic drugs, ability to incorporate radiolabeled purine bases, and growth on various purine sources. All mutant strains could propagate in defined growth medium containing any single purine source and could metabolize exogenous [3H]hypoxanthine to the nucleotide level. The surprising ability of mutant L. donovani lacking HGPRT, APRT, and/or AK to incorporate and grow in hypoxanthine could be attributed to the ability of the parasite xanthine phosphoribosyltransferase enzyme to salvage hypoxanthine. These genetic studies indicate that HGPRT, APRT, and AK, individually or in any combination, are not essential for the survival and growth of the promastigote stage of L. donovani and intimate an important, if not crucial, role for xanthine phosphoribosyltransferase in purine salvage.

Cloning and expression of the hypoxanthine-guanine phosphoribosyltransferase from Leishmania donovani.

The gene encoding the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme from Leishmania donovani has been cloned and sequenced. The hgprt open reading frame encoded a polypeptide of 211 amino acids that exhibited 3 regions of significant homology with other eukaryotic HGPRTs and a C-terminal tripeptide compatible with a glycosomal targeting signal. Northern blot analysis of L. donovani RNA revealed two hgprt transcripts, a 1.9-kb mRNA and a 1.7-kb transcript. The expression of the 1.7-kb hgprt mRNA and the activity of HGPRT enzyme were both augmented approx. 5-fold in parasites incubated in the absence of purines. Southern blots of genomic DNA indicated only a single hgprt locus within the L. donovani genome. Overexpression of L. donovani hgprt in E. coli complemented genetic deficiencies in hypoxanthine and guanine phosphoribosylating activities and yielded abundant quantities of enzymatically active HGPRT. The recombinant HGPRT was purified to homogeneity and recognized hypoxanthine, guanine and allopurinol, but not adenine or xanthine, as substrates. The hgprt clone and pure HGPRT protein provide essential reagents for validating HGPRT as a therapeutic target for the treatment of leishmaniasis and other diseases of parasitic origin.

Calcified gastric carcinoma: CT findings.

The computed tomographic (CT) findings of 13 cases of calcified gastric carcinoma were analyzed retrospectively. Eleven cases were confirmed as a mucinous adenocarcinoma by surgery (three cases), or endoscopic biopsy (eight cases). Two cases were diagnosed as adenocarcinoma by endoscopic biopsy. In all cases the calcifications were of the punctate or miliary shape and the size varied from 1-3 mm in diameter. The calcifications were located in the thickened gastric wall in all cases, and were seen in metastatic lesions such as lymph nodes and the liver in two cases. In 10 cases, some tumor portions showed lower attenuation number than that of the muscle on CT scans, and corresponded to mucin pool in tumor portions histologically. Twelve cases were in inoperable advanced stage.

Uterine metastasis from stomach cancer: radiological findings.

The uterus is an unusual site for metastasis from an extrapelvic neoplasm. We report a case of uterine metastasis with extensive calcification. Plain radiography, ultrasonography and CT showed diffuse calcification within the uterine wall and T2-weighted MR images showed abnormally high signal intensity of the entire myometrium.

Nutrient reabsorption of intestine in vitro: effects of ethanol and caffeine.

We studied the effect of ethanol and caffeine on the intestinal reabsorption (jejunum from SD rats) of glucose (Glu) and amino acids. Since most of the studies on the effect of ethanol utilized high concentration, we first characterized the effect of 8% (approximately 1.4 M) ethanol on the activity of Na(+)-coupled nutrient transport. Consistent with previous reports, ethanol (greater than 1 M) was found to inhibit the uptake rates of glucose and its non-metabolizable analogue 3-O-methyl-glucose (3-OMG) by 30%, while leucine (Leu) uptake was inhibited by 60%. Phloridzin, a specific inhibitor for Na(+)-coupled sugar transport, at 1 mM concentration could inhibit Glu and 3-OMG uptake by more than 60% without affecting Leu uptake. We then compared the effects of various concentrations of ethanol on about 20 intestinal segments taken from the same animal. We consistently observed transport inhibition at high concentration of ethanol but at low concentrations (up to 200 mM), there was no consistent effect, while phloridzin or low-Na media (86% of Na replaced by choline) significantly reduced the rate of nutrient uptake in the same experiment. Thus, it appeared that low concentrations of ethanol had no significant effect on Na(+)-coupled nutrient uptake. We also determined the effect of caffeine on intestinal 3-OMG uptake. At concentration of 0.05 mM, caffeine inhibited 3-OMG uptake by about 15% (p less than 0.05). The level of inhibition was not significantly different at 0.5 mM, but a slightly higher level of inhibition (20%) was reached at 5 mM. The action of caffeine could be mimicked by dibutyryl cAMP (1 mM).

Methods of vascular pedicle coverage.

Based on our clinical experience, various methods of donor or recipient vascular pedicle coverage for an arterialized or free flap are reported. The vascular pedicle may be placed in the subcutaneous space either by incising the skin along the full length of the vascular route or by passing it through a subcutaneous tunnel. It has been our experience that the vascular pedicle can also be covered by either a local flap or a free skin graft. On rare occasions, a narrow skin flap strip including the vascular pedicle can be lifted en bloc and rotated toward the base of the area transferred.