Timed barium esophagram in achalasia types.

Relationships of timed barium esophagram (TBE) findings to achalasia types defined by high-resolution manometry (HRM) have not been elucidated. Therefore, we correlated preoperative TBE and HRM measurements in achalasia types and related these to patient symptoms and prior treatments. From 2006 to 2013, 248 achalasia patients underwent TBE and HRM before Heller myotomy. TBE height and width were recorded at 1 and 5 minutes; HRM measured lower esophageal sphincter mean basal pressure, integrated relaxation pressure (IRP), and mean esophageal body contraction amplitude. Achalasia was classified into types I (25%), II (65%), and III (9.7%). TBE height at 5 minutes was higher for I (median 8 cm; interquartile range 6-12) and II (8 cm; 8-11) than for III (1 cm; 0-7). TBE width at 5 minutes was widest (3 cm; 2-4), narrower in II (2 cm; 2-3), and narrowest in I (1 cm; 0-2), P < 0.001. Volume remaining at 1 and 5 minutes was lower in III (1 m(2) ; 0-16) than I (42 m(2) ; 17-106) and II (39 m(2) ; 15-60), highlighting poorer emptying of I and II. Increasing TBE width correlated with deteriorating morphology and function from III to II to I. Symptoms poorly correlated with TBE and HRM. Prior treatment was associated with less regurgitation, faster emptying, and lower IRP. Although TBE and HRM are correlated in many respects, the wide range of their measurements observed in this study reveals a spectrum of morphology and dysfunction in achalasia that is best characterized by the combination of these studies.

Soil Methane and Carbon Dioxide Fluxes from Cropland and Riparian Buffers in Different Hydrogeomorphic Settings.

Riparian buffers contribute to the mitigation of nutrient pollution in agricultural landscapes, but there is concern regarding their potential to be hot spots of greenhouse gas production. This study compared soil CO and CH fluxes in adjacent crop fields and riparian buffers (a flood-prone forest and a flood-protected grassland along an incised channel) and examined the impact of water table depth (WTD) and flood events on the variability of gas fluxes in riparian zones. Results showed significantly ( < 0.001) higher CO emission in riparian areas than in adjoining croplands (6.8 ± 0.6 vs. 3.6 ± 0.5 Mg CO-C ha yr; mean ± SE). Daily flux of CO and soil temperature were significantly related ( < 0.002), with Q values ranging between 1.75 and 2.53. Significant relationships ( < 0.05) were found between CH daily flux and WTD. Flood events resulted in enhanced CH emission (up to +44.5 mg CH-C m d in a swale) under warm soil conditions (>22°C), but the effect of flooding was less pronounced in early spring (emission <1.06 mg CH-C m d), probably due to low soil temperature. Although CH flux direction alternated at all sites, overall the croplands and the flood-affected riparian forest were CH sources, with annual emission averaging +0.04 ± 0.17 and +0.92 ± 1.6 kg CH-C ha, respectively. In the riparian forest, a topographic depression (<8% of the total area) accounted for 78% of the annual CH emission, underscoring the significance of landscape heterogeneity on CH dynamics in riparian buffers. The nonflooded riparian grassland, however, was a net CH sink (-1.08 ± 0.22 kg CH-C ha yr), probably due to the presence of subsurface tile drains and a dredged/incised channel at that study site. Although these hydrological alterations may have contributed to improvement in the CH sink strength of the riparian grassland, this must be weighed against the water quality maintenance functions and other ecological services provided by riparian buffers.

Comparison of radiation dose and image quality from single-energy and dual-energy CT examinations in the same patients screened for hepatocellular carcinoma.

AIM: To compare radiation dose surrogates [volume CT dose index (CTDIvol), dose-length product (DLP), size-specific dose estimate (SSDE), and effective dose] and image noise in a cohort of patients undergoing hepatocellular carcinoma screening who underwent both single-energy CT (SECT) and dual-energy CT (DECT). MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 74 adults (mean age 59.5 years) underwent 64 section SECT (120 kVp and weight-based reference mAs) and 128 section dual-source DECT (100/Sn 140 kVp and CTDIvol, adjusted to match the CDTIvol of the SECT protocol) on different occasions. Noise levels were measured in the liver, inferior vena cava (IVC), retroperitoneal (RP) fat, and aorta. Generalized linear models were constructed to compare dose and noise, adjusting for effective diameter. RESULTS: The total DLP (1371.11 mGy-cm, SD = 527.91) and effective dose (20.57 mSv, SD = 7.92) with SECT were significantly higher than the DLP (864.84 mGy-cm, SD = 322.10) and effective dose (12.97 mSv, SD = 4.83) with DECT (p < 0.001). The differences between SECT and DECT increased as the patient's effective diameter increased (p < 0.001). Noise levels in the liver (22.4 versus 21.9 HU), IVC (22.3 versus 23.4 HU), and RP fat (23.5 versus 23 HU) were similar for DECT and SECT (p > 0.05) but were significantly lower in the aorta for DECT (25.3 versus 26.4 HU; p = 0.006). CONCLUSION: DECT imaging of the abdomen can achieve noise levels comparable to those seen with SECT imaging without a dose penalty to patients.

Nitrous oxide emission from cropland and adjacent riparian buffers in contrasting hydrogeomorphic settings.

Riparian buffers are important nitrate (NO) sinks in agricultural watersheds, but limited information is available regarding the intensity and control of nitrous oxide (NO) emission from these buffers. This study monitored (December 2009-May 2011) NO fluxes at two agricultural riparian buffers in the White River watershed in Indiana to assess the impact of land use and hydrogeomorphologic (HGM) attributes on emission. The study sites included a riparian forest in a glacial outwash/alluvium setting (White River [WR]) and a grassed riparian buffer in tile-drained till plains (Leary Weber Ditch [LWD]). Adjacent corn ( L.) fields were monitored for land use assessment. Analysis of variance identified season, land use (riparian buffer vs. crop field), and site geomorphology as major drivers of NO fluxes. Strong relationships between N mineralization and NO fluxes were found at both sites, but relationships with other nutrient cycling indicators (C/N ratio, dissolved organic C, microbial biomass C) were detected only at LWD. Nitrous oxide emission showed strong seasonal variability; the largest NO peaks occurred in late spring/early summer as a result of flooding at the WR riparian buffer (up to 27.8 mg NO-N m d) and N fertilizer application to crop fields. Annual NO emission (kg NO-N ha) was higher in the crop fields (WR: 7.82; LWD: 6.37) than in the riparian areas. A significant difference ( < 0.02) in annual NO emission between the riparian buffers was detected (4.32 vs. 1.03 kg NO-N ha at WR and LWD, respectively), and this difference was attributed to site geomorphology and flooding (WR is flood prone; no flooding occurred at tile-drained LWD). The study results demonstrate the significance of landscape geomorphology and land-stream connection (i.e., flood potential) as drivers of NO emission in riparian buffers and therefore argue that an HGM-based approach should be especially suitable for determination of regional NO budget in riparian ecosystems.

Coronary angiographic profile in bangladeshi patients with metabolic syndrome and ischemic heart disease.

The metabolic syndrome, which is characterized by a constellation of fasting hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension, and/or abdominal obesity, is a risk factor for the development of coronary artery disease (CAD) and cardiovascular events. We evaluated interrelationships between angiographic CAD and the metabolic syndrome, in 478 patients who were referred for coronary angiography to evaluate suspected myocardial ischemia in the department of cardiology of BSMMU between June 2007 and May 2008. We applied the criteria for the metabolic syndrome proposed by ATP III guideline. Study populations were divided into two groups on the basis of presence or absence of metabolic syndrome. Age was similar in both groups. Body mass index (BMI) was higher (26.22 ± 1.94 vs. 22.07 ± 1.55) in metabolic syndrome group (p ≤ 0.0001). All parameters, waist circumference (103.16 ± 10.21 vs. 91.45 ± 7.61) cm, blood pressure both systolic (141.34 ± 21.49 vs. 127.94 ± 13.01) and diastolic (86.8 5 ± 8.42 vs. 79.28 ± 7.77) mm of Hg, serum triglyceride (248.32 ± 77.88 vs. 128.35 ± 19.00)mg/dl, fasting blood glucose (125.40 ± 22.86 vs. 95.65 ± 10.63)mg/dl were significantly higher in metabolic syndrome group (p value=0.0001), whereas HDL (33.10 ± 6.55 vs. 39.30 ± 6.17)mg/dl was lower (p value = 0.0001). More subjects in metabolic syndrome were having type B (55.60% vs. 31.00%) and type C (9.50% vs. 2.70%) lesion as compared to non-metabolic syndrome group. Involvement of left main artery was more (4.80% vs. 0.90%) in metabolic syndrome group. Metabolic syndrome has primary predictive ability for CAD. A metabolic profile should form part of the risk assessment in all patients with coronary disease, not just those who are obese.

Membrane transport proteins: implications of sequence comparisons.

Analyses of the sequences and structures of many transport proteins that differ in substrate specificity, direction of transport and mechanism of transport suggest that they form a family of related proteins. Their sequence similarities imply a common mechanism of action. This hypothesis provides an objective basis for examining their mechanisms of action and relationships to other transporters.

Variation of the genetic expression pattern after exposure to estradiol-17beta and 4-nonylphenol in male zebrafish (Danio rerio).

There is much concern about the increasing presence in the environment of synthetic chemicals that are able to disrupt the endocrine system. Among these compounds, 4-nonylphenol (4-NP) is one of the most studied xenoestrogens, due to its widespread accumulation in water sediment and consequent presence in fatty acid of aquatic organisms. Here, we have used a zebrafish microarray representing 16,399 genes to study the effects of 4-NP and estradiol-17beta (E2) in adult male zebrafish in order to elucidate the mechanism of action of 4-NP compared with that of E2. The microarray results showed that both 4-NP and E2 induced a strong expression of vitellogenin (VTG), the sex related precursor of the yolk proteins in oviparous vertebrates. Both treatments induced elevated protein turnover upregulating genes involved in proteolysis and those that are constituents of the ribosome. Many genes regulated by 4-NP and E2 are involved in energy metabolism, oxidative stress defense mechanisms, xenobiotic metabolism, and lipid metabolism. A different pattern of expression in the two treatments was found for genes involved in oxidative stress, since E2 seems to induce the mechanism of detoxification, while 4-NP seems to inhibit this protective mechanism of the cell. Overall, these findings demonstrate that the microarray approach can contribute significantly to the understanding of expression patterns induced by E2 and 4-NP in male zebrafish. The results also demonstrate that 4-NP is able to act through an alternative pattern to that of estradiol-17beta, modulating the expression of the same genes in a different manner.

An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn's disease.

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.

Binding of the chymotrypsin substrate, tryptophan methyl ester, by rat alpha-fetoprotein.

We studied how tryptophan methyl ester and related compounds inhibit binding of estrone to rat alpha-fetoprotein and find that: (a) like chymotrypsin, alpha-fetoprotein binds tryptophan esters with higher affinity than tryptophan or its amides; (b) the affinity of alpha-fetoprotein for tryptophan methyl ester is 3.7 . 10(-4) M, which is close to the affinity of chymotrypsin (10(-4) M); (c) alpha-fetoprotein binding of tryptophan methyl ester is stereoselective and pH dependent. All of these observations suggest that there is a specific interaction between alpha-fetoprotein and the chymotrypsin substrate, tryptophan methyl ester, and that rat alpha-fetoprotein contains a site with some structural similarities to the catalytic site in chymotrypsin. Since we also find that tryptophan methyl ester is a competitive inhibitor of estrone binding to alpha-fetoprotein, it is possible that the protease substrate binding site on alpha-fetoprotein is spatially close to the estrone binding site.

Evolution of permease diversity and energy-coupling mechanisms with special reference to the bacterial phosphotransferase system.

Different classes of apparently unrelated permeases couple different forms of energy to solute transport. While the energy coupling mechanisms utilized by the different permease classes are clearly distinct, it is proposed, based on structural comparisons, that many of these permeases possess transmembrane, hydrophobic domains which are evolutionarily related. Carriers may have arisen from transmembrane pore-forming proteins, and the protein constituents or domains which are specifically responsible for energy coupling may have had distinct origins. Thus, complex permeases may possess mosaic structures. This suggestion is substantiated by recent findings regarding the evolutionary origins of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS). Mechanistic implications of this proposal are presented.

Deletion of 12 carboxyl-terminal residues from pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase affects steroid metabolism.

Pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase (3alpha/beta,20beta-HSD) is 80-85% identical to human, rat, and mouse carbonyl reductases. However, pig 3alpha/beta,20beta-HSD contains an extra 12 amino acids at its COOH-terminus that these other mammalian carbonyl reductases lack. We constructed a pig 3alpha/beta,20beta-HSD mutant, G278opal, which lacks these amino acids and found that compared to wild-type 3alpha/beta,20beta-HSD, G278opal has a 10-fold lower catalytic efficiency for testosterone and progesterone. G278opal also has lower 3alpha- and 20beta-reductase and increased 3beta-reductase activity compared to wild-type 3alpha/beta,20beta-HSD. Binding of NADPH to G278opal was similar to that of wild-type 3alpha/beta,20beta-HSD. The recently determined three-dimensional structure of 3alpha/beta,20beta-HSD, without a steroid substrate, shows the 12 COOH-terminal amino acids in a random configuration. Our data indicate that the 12 COOH-terminal amino acids have a role in steroid metabolism suggesting that binding of steroid to wild-type 3alpha/beta,20beta-HSD induces a conformational change in which the 12 COOH-terminal amino acids interact with the steroid substrate.

Human placental 17 beta-hydroxysteroid dehydrogenase is homologous to NodG protein of Rhizobium meliloti.

The amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-steroid dehydrogenase) was found to be similar to that of the NodG protein of Rhizobium meliloti. The computer-based comparison score is 11.5 SD higher than that obtained with 2500 comparisons of randomized sequences of these proteins. The probability of getting such a score by chance is 6 x 10(-31). 17 beta-OH-steroid dehydrogenase is also similar to Klebsiella aerogenes ribitol dehydrogenase and Escherichia coli glucitol-6-phosphate dehydrogenase. We propose that the steroid recognition site on 17 beta-OH-steroid dehydrogenase evolved from an ancestral recognition site for polyols such as ribitol and glucitol-6-phosphate.

Computer-aided detection (CAD) for CT colonography: a tool to address a growing need.

Colorectal cancer is the third most common cancer in both men and women. It is estimated that in 2004, nearly 147,000 cases of colon and rectal cancer will be diagnosed in the USA, and approximately 57,000 people would die from the disease; however, only 44% of the eligible population undergoes any type of colorectal cancer screening. Many reasons have been identified for non-compliance, with key ones being patient comfort, bowel preparation and cost. Virtual colonoscopy derived from computed tomography (CT) images is gaining broader acceptance as a screening method for colorectal neoplasia. Our research suggests that computer-aided detection (CAD) as a second reader has great potential in improving polyp detection. The ColonCAD prototype presented in this paper was developed and tested on cases representative of the variability and quality in true clinical practice. Results of this study with 150 patients demonstrate that: the developed algorithm generalises well: the sensitivity for polyps > or = 6 mm is on average 90%; and the median false positive rate is a manageable 3 per volume.

Aldosterone stimulated differentiation of mouse 3T3-L1 cells into adipocytes.

We find that 1-10 nM aldosterone can induce differentiation of 3T3-L1 cells into adipose cells as evaluated by microscopic accumulation of fat droplets and quantitative measurement of triglycerides and of glycerol-3-phosphate dehydrogenase, an enzyme specific for adipocyte differentiation. Moreover, the aldosterone antagonist ZK91587 inhibits aldosterone-but not glucocorticoid-mediated differentiation of 3T3-L1 cells. Steroid binding assays with 3T3-L1 cells indicate the presence of specific binding sites for aldosterone. We conclude that there is an aldosterone receptor-mediated pathway for terminal differentiation of 3T3-L1 cells into adipose cells. Receptors for aldosterone have also been found in a variety of cells that do not function to regulate sodium and potassium transport. The aldosterone receptor may have a role in regulation expression of genes involved in differentiation of these cells.

Albumin's role in steroid hormone action and the origins of vertebrates: is albumin an essential protein?

Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and phytochemicals that bind to hormone receptors. Albumin has a low affinity for these lipophilic compounds. However, due to albumin's high concentration in serum, albumin is a major carrier of steroids and lipophilic hormones and regulator of their access to their receptors. Moreover, albumin functions as a sink for phytochemicals, which prevents their binding to hormone receptors and other cellular proteins, protecting animals from disruptive phytochemical-mediated endocrine effects. We propose that these properties of albumin were important in protochordates and vertebrates about 550 to 520 million years ago, just before and during the Cambrian. At that time, animal body sizes and exposure to phytochemicals in food were increasing, and animals in which albumin expression was high had a selective advantage in surviving and reproducing in the presence of toxic phytochemicals. This hypothesis that albumin has essential function(s) in mammalian endocrine physiology can be tested by comparing the effects of phytochemicals in Nagase rats that have 1/1000 the normal albumin concentration or in mice in which the albumin gene is knocked out with those in normal rats and mice.

Human tissue-type plasminogen activator is related to albumin and alpha-fetoprotein.

Using a computer program designed to detect evolutionary relationships between proteins, I find that residues 72-110 of the mature sequence of human tissue-type plasminogen activator (t-PA) and 39 residues at the carboxy terminus of human albumin have a comparison score that is 8.8 standard deviation units higher than that obtained with a comparison of randomized sequences of these proteins. The probability (p) of getting this score by chance is approximately 10(-18), indicating that part of t-PA and albumin are derived from a common ancestor. I also find that alpha-fetoprotein, a relative of albumin is related to t-PA. Part of this region on t-PA has been previously shown to be related to epidermal growth factor. t-PA, albumin, alpha-fetoprotein, and epidermal growth factor have diverse biological activities. The finding that these proteins are related suggests some new approaches for studying their functions.

Gossypol inhibits estrogen binding to rat alpha-fetoprotein.

We find that gossypol, a male anti-fertility compound, is a reversible competitive inhibitor of estrogen binding to rat alpha-fetoprotein (AFP). The Kd of gossypol for rat AFP is 1.75 microM, which is similar to gossypol's affinity for lactate dehydrogenase isozyme X, the putative site where gossypol exerts its anti-fertility effects. Reacting sodium cyanoborohydride with gossypol reduces its affinity for AFP, showing that intact aldehyde groups on gossypol are important for binding to rat AFP and indicating that gossypol is specifically inter-acting with a nucleophilic site on AFP that influences estrogen binding.

Location of enzymatic and DNA-binding domains on E. coli protease La.

Escherichia coli protease La is an ATP-dependent enzyme that has a DNA-binding site. The locations of the enzymatic and DNA-binding sites are not known. We report that a 75-residue segment at the carboxy-terminus of the protease La is similar to part of Bacillus licheniformis beta-lactamase, a serine enzyme. The comparison score is 8.2 standard deviations higher than that obtained with 10,000 comparisons of randomized sequences of these segments. The probability of obtaining such a score by chance is 1.2 x 10(-16). We also find that a 107-residue segment in the amino-terminus half of protease La is similar to part of the sopB protein, a DNA-binding protein of the plasmid F of E. coli. The comparison score for these segments is 8 standard deviations (P = 6 x 10(-16)). These strong amino acid sequence similarities suggest the locations of the catalytic serine and the DNA-binding domains of protease La.

Evidence that progesterone binding uteroglobin is similar to myosin alkali light chain.

Using a computer program designed to detect evolutionary relationships between proteins, I find that exon 2 of rabbit uteroglobin, a progesterone binder, and part of myosin alkali light chain have a comparison score that is 7.2 standard deviations higher than that obtained with a comparison of randomized sequences of these proteins. The probability (p) of getting this score by chance is less than 10(-12). This theoretical finding that these sequences are similar has led to the experimental finding that copper, calcium and the tranquilizer trifluoperazine, a calmodulin binding ligand, affect progesterone binding to uteroglobin.

Expansion of the mammalian 3 beta-hydroxysteroid dehydrogenase/plant dihydroflavonol reductase superfamily to include a bacterial cholesterol dehydrogenase, a bacterial UDP-galactose-4-epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus.

Mammalian 3 beta-hydroxysteroid dehydrogenase and plant dihydroflavonol reductases are descended from a common ancestor. Here we present evidence that Nocardia cholesterol dehydrogenase, E. coli UDP-galactose-4 epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus are homologous to 3 beta-hydroxysteroid dehydrogenase and dihydroflavonol reductase. Analysis of a multiple alignment of these sequences indicates that viral ORFs are most closely related to the mammalian 3 beta-hydroxysteroid dehydrogenases. The ancestral protein of this superfamily is likely to be one that metabolized sugar nucleotides. The sequence similarity between 3 beta-hydroxysteroid dehydrogenase and the viral ORFs is sufficient to suggest that these ORFs have an activity that is similar to 3 beta-hydroxysteroid dehydrogenase or cholesterol dehydrogenase, although the putative substrates are not yet known.