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Biomedical subjects

M Davila

Publications and source records attributed to M Davila.

At least 19 recordsLinked to original sources
PubMed2001

A role for secondary V(D)J recombination in oncogenic chromosomal translocations?

Chromosomal translocations are hallmarks of certain lymphoproliferative disorders. Indeed, in many leukemias and lymphomas, translocations are the transforming event that brings about malignancy. Recurrence of the immunoglobulin (Ig) and T-cell receptor (Tcr) loci at the breakpoints of oncogenic chromosomal translocations has led to speculation that the lymphocyte-specific process of V(D)J rearrangement, which is necessary for the generation of functional Ig and TCR antigen receptors on B and T lymphocytes, mediates translocation. Recent studies have led to a fuller understanding of the molecular mechanisms of V(D)J rearrangement and have revealed that the V(D)J recombinase possesses latent transposase activity. These studies have led to plausible models of illegitimate V(D)J recombination producing chromosomal translocations consistent with those present in lymphomas and leukemias. Errors of V(D)J recombination may even generate lymphomas with the phenotypes of mature cells. For example, follicular and Burkitt's lymphomas have been classified by phenotype and somatic genotype as malignant germinal center (GC) B or post-GC B cells. The GC is a site of affinity maturation where B cells undergo V(D)J hypermutation and Ig class switch; in addition, much evidence has accumulated to suggest that GC B cells may also support secondary V(D)J recombination. Interestingly, all three of these elements, genomic plasticity, mutation, and translocation breakpoints near switch sites or recombinational elements, are characteristic of certain lymphomas. The high frequency of lymphomas carrying these GC markers suggests that the GC reaction may play a significant role in lymphomagenesis.

Amino Acid Motifs↗
PubMed2000

Health profile preferences of hepatitis C patients.

The side effects of interferon-alpha for chronic hepatitis C are well-known. Patients may differ with respect to their tolerance of these side effects and also with respect to their individual preferences. We administered a brief questionnaire to 67 outpatients with hepatitis C virus infection. Patients were asked to make hypothetical choices between six-month profiles of health. The results were as follows: (1) patients preferred to expedite rather than postpone intervals of poor health; (2) preferences of patients with low quality-of-life were quite similar to preferences of healthier patients; (3) patients' choices satisfied transitivity; (4) patients' choices satisfied preferential independence; and (5) patients gave a variety of reasons for their choices. These results corroborate other investigations of health preferences, and serve to introduce the field of preference elicitation to gastroenterologists.

Antiviral Agents↗
PubMed2000

Effect of atorvastatin on blood lipid levels in the first 2 weeks of treatment: a randomized, placebo-controlled study.

BACKGROUND: The rate and degree of LDL cholesterol reduction, in the first 2 weeks of therapy, may relate to the early benefit of hydroxymethyl glutaryl coenzyme A reductase inhibitor therapy. In patients with similar baseline LDL cholesterol levels as in the Cholesterol and Recurrent Events (CARE) trial, we report the results of a 2-week placebo-controlled, double-blind investigation of 10 mg/day atorvastatin. METHODS AND RESULTS: The 22 participants were non-Hispanic whites younger than age 72 (average age 47 years) who were modestly overweight and had normal blood pressure. There were no significant baseline lipid and lipoprotein differences. By day 5, there were significant (P <.01) reductions in total cholesterol and LDL levels. The total cholesterol level fell by 25% (226 mg/dL to 169 mg/dL) and LDL cholesterol fell 35% by day 14 (P <.001). Triglyceride levels declined by 24% (from 137 mg/dL to 104 mg/dL) by day 14, but this was not statistically significant. There was no significant difference in HDL cholesterol. The total/HDL level dropped from 4.54 (day 0) to 3.32 (day 14), and the LDL/HDL level dropped from 2.92 to 1.88; both results were highly significant (P <. 001). CONCLUSION: The rapid lipid reduction observed with atorvastatin may benefit the vascular endothelium.

Adult↗
PubMed1997

Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial.

BACKGROUND: Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency. OBJECTIVE: To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices. DESIGN: Randomized, controlled clinical trial. SETTING: Three teaching hospitals. PATIENTS: 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS. INTERVENTION: Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein. MEASUREMENTS: Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs. RESULTS: Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). CONCLUSIONS: In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.

Adult↗
PubMed1996

Phosphatidylethanol stimulates the plasma-membrane calcium pump from human erythrocytes.

Phosphatidylethanol is formed by "transphosphatidylation' of phospholipids with ethanol catalysed by phospholipase D and can be accumulated in the plasma membrane of mammalian cells after treatment of animals with ethanol. In the present work we show that phosphatidylalcohols, such as phosphatidylethanol and phosphatidylbutanol, produced a twofold stimulation of the Ca(2+)-ATPase activity of human erythrocytes. This stimulation occurs with the purified, solubilized enzyme as well as with ghost preparations, where the enzyme is in its natural lipidic environment and is different to that obtained with other acidic phospholipids such as phosphatidylserine. Addition of either phosphatidylserine, phosphatidylethanol or phosphatidylbutanol to the purified Ca(2+)-ATPase, or to ghosts preparations, increased the affinity of the enzyme for Ca2+ and the maximal velocity of the reaction as compared with controls in the absence of acidic phospholipids. However, in contrast with what occurs with phosphatidylserine, simultaneous addition of phosphatidyl-alcohols and calmodulin increased the affinity of the enzyme for Ca2+ to a greater extent than each added separately. When ethanol was added to either the purified erythrocyte Ca(2+)-ATPase or to erythrocyte-ghost preparations in the presence of acidic phospholipids, an additive effect was observed. There was an increase in the affinity for Ca2+ and in the maximal velocity of the reaction, well above the values obtained with ethanol or with the acidic phospholipids tested separately. These findings could have pharmacological importance. It is conceivable that the decrease in the intracellular Ca(2+) concentration that has been reported in erythrocytes as a result of ethanol intoxication could be due to the stimulation of the Ca(2+)-ATPase by the accumulated phosphatidylethanol, to a direct effect of ethanol on the enzyme or to an additive combination of both.

Calcium-Transporting ATPases↗
PubMed1988

Iron deficiency, inflammatory processes and humoral immunity in children.

Indicators of iron status, markers of inflammatory processes, serum immunoglobulins and C3 and C4 components of complement were assessed in 142 children 10-months old. All the iron parameters and most of the indicators of humoral immunity were correlated with markers of inflammation. Sixty-two children presented biochemical indications of inflammation (high CRP or orosomucoid level, or hyperleukocytosis), while 80 children were free of it. In the latter group, the use of a combination of iron indicators enabled separation of iron-sufficient children from those with different degrees of iron deficiency, ranging from iron depletion to iron-deficiency anemia. Serum IgG and IgA were significantly lower only in the group of iron-depleted children. Serum ferritin was significantly positively correlated with IgA, IgM and C4. Iron depletion may be responsible for a decrease humoral immunity. This effect was not visible at more advanced stages of iron deficiency.

Anemia, Hypochromic↗
PubMed1987

Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue.

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.

Adipose Tissue↗
PubMed1987

Iron status in Ecuadorian pregnant women living at 2,800 m altitude: relationship with infant iron status.

An evaluation of iron status was performed in 84 pregnant women at delivery (and in cord blood from their newborn) and in a control group of 32 menstruating women living in Quito (2800 m altitude). Anemia as defined according to the WHO references adjusted to altitude was observed in 46% of pregnant women. Iron deficiency was defined as the combination of a low serum ferritin level (12 micrograms/l or less) and a low transferrin saturation percentage (less than 16%). A moderate elevation in the serum ferritin concentration (between 13 and 50 micrograms/l) associated with low transferrin saturation indicated iron deficiency in an inflammatory context. Iron deficiency was present in 46% of pregnant women. Anemia was associated with iron deficiency in 59% of cases. A correlation between maternal and cord blood hemoglobin was found and some iron parameters in cord blood were related to maternal iron status, and especially to maternal iron stores assessed by serum ferritin concentration.

Altitude↗
PubMed1984

Structures of the oligosaccharide chains in swine trachea mucin glycoproteins.

The structures of large O-glycosidically linked oligosaccharides derived from swine trachea mucin glycoprotein were established. Reduced oligosaccharides released by treatment with alkaline borohydride were separated by gel filtration on Bio-Gel P-6 and the neutral oligosaccharides were isolated by chromatography on DEAE-cellulose. Eight oligosaccharides (DIa to BII), ranging in length from 8 to 15 sugar units, were isolated. On the basis of carbohydrate composition and analytical data from sequential treatment with exoglycosidases and permethylation analysis, the following structures were assigned to these oligosaccharides: (Formula: see text).

Animals↗
PubMed1984

Purification and properties of alpha-D-mannose:beta-1,2-N-acetylglucosaminyl-transferases and alpha-D-mannosidases from human adenocarcinoma.

Two specific N-acetylglucosaminyltransferases, alpha-1,3-mannoside:beta-2-N-acetylglucosaminyltransferase (transferase I) and alpha-1,6-mannoside:beta-2-N-acetylglucosaminyltransferase (transferase II), which catalyze the transfer of N-acetylglucosamine (GlcNAc) from uridine diphospho-GlcNAc to terminal branched alpha-mannosyl (Man) residues, were purified from liver metastases of human colon adenocarcinoma. Transferase I was assayed with Man alpha 1,6(Man alpha 1,3)Man alpha 1,6(Man alpha 1,3)Man beta 1,4GlcNAc beta 1, 4GlcNAc-Asn (Km 0.35 mM), and transferase II was assayed with Man alpha 1,6(GlcNAc beta 1,2Man alpha 1,3)Man beta 1,4GlcNAc beta 1,4-Glc-NAc-Asn (Km 1.0 mM), in which Asn is asparagine. The Km of transferase I for Man alpha 1,6(Man alpha 1,3)Man beta 1,4GlcNAc-beta 1,4)-(Fuc alpha 1,6)GlcNAc-Asn was 1 mM. The specificity of the interaction of transferase I with ovalbumin, ovomucoid, the modified heavy chain of porcine immunoglobulin G and glycopeptides prepared from these glycoproteins was examined by kinetic and structural analysis. The best macromolecular substrates for transferase I were ovalbumin devoid of terminal GlcNAc and some mannose, a solubilized preparation of the heavy chain of porcine immunoglobulin G, devoid of sialic acid, galactose, and terminal GlcNAc, and untreated ovomucoid. The apparent KmS were 45, 19, and 390 microM for ovalbumin, the modified heavy chain of immunoglobulin G, and untreated ovomucoid, respectively. The apparent Km of the enzyme for uridine diphospho-GlcNAc was not significantly influenced by the nature of the glycoprotein acceptor, and it varied between 14 and 20 microM for the different glycoproteins. The structures of the oligosaccharide chains in these glycoproteins which acted as acceptors for the purified enzyme were determined. A major glycopeptide product with the structure Man alpha 1,3(Man alpha 1,6)Man alpha 1,6(14C-GlcNAc beta 1,2Man-alpha 1,3)Man beta 1,4GlcNAc-beta 1,4-GlcNAc-Asn was isolated from both ovalbumin and ovomucoid following incubation with transferase I. The specificity of the enzyme for terminal branched mannosyl residues attached to a beta-linked mannose unit greatly restricts the action of this transferase to this juncture in the synthesis of complex-type oligosaccharide chains of N-asparagine-linked glycoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1984

Structures of the oligosaccharide chains of two forms of alpha 1-acid glycoprotein purified from liver metastases of lung, colon, and breast tumors.

Two forms of alpha 1-acid glycoprotein with common immunological determinants and almost identical amino acid compositions but different amounts of carbohydrate were isolated from liver metastases of primary colon, lung, and breast tumors by extraction with perchloric acid, gel filtration on Sepharose CL-6B and Sephadex G-200, and affinity chromatography on concanavalin A:agarose and Ricinus communis agglutinin l:agarose. Both forms of the antigen yielded single bands which stained for protein and carbohydrate when examined by disc gel electrophoresis and immunodiffusion. The molecular weights of the two forms were 45,000 and 37,000 respectively. The larger form contained about five to six oligosaccharide chains, whereas the smaller form had only three to four chains. The composition and structures of the oligosaccharide chains in the two forms of this glycoprotein were very similar. Each contained di-, tri-, and tetraantennary complex-type oligosaccharide chains. The diantennary oligosaccharide chains caused both forms of alpha 1-acid glycoprotein to be retained by concanavalin A-agarose columns. The lower-molecular-weight form contained fewer chains and correspondingly fewer terminal galactosyl residues. This resulted in the separation of this species from the higher-molecular-weight form on columns containing R. communis agglutinin I. Three types of reduced oligosaccharides were released from the light and heavy forms of alpha 1-acid glycoprotein by treatment with alkaline borohydride or by hydrazinolysis. These chains were isolated by chromatography on concanavalin A:agarose and Bio-Gel P-6 columns. The arrangement and linkage of sugars in the purified oligosaccharides were determined by periodate oxidation, sequential hydrolysis with glycosidases, and methylation analysis. The major oligosaccharide chain, comprising 50 to 55% of the carbohydrate, had a triantennary structure as shown in the structure: (formula; see text) in which NeuNAc is N-acetylneuraminic acid, Gal is galactose, GlcNAc is N-acetylglucosamine, Man is mannose, GlcNAcol is N-acetylglucosaminitol, and Fuc is fucose. Tetraantennary chains comprised about 25 to 30% of the carbohydrate, and the additional outer chain was attached to the alpha 1,6-mannosyl residue through a beta 1,6-linked GlcNAc unit. The remaining 15 to 20% of the oligosaccharide chains had a diantennary structure. The extent of sialylation of these chains varied in samples isolated from tumors of the same histological type from different individuals. However, a relatively constant proportion of the three types of chains was present in different forms of the glycoprotein isolated from liver metastases.

Amino Acids↗
PubMed1981

Isolation and properties of alpha-D-mannose:beta-1,2-N-acetylglucosaminyltransferase from trachea mucosa.

A beta-1,2-N-acetylglucosaminyltransferase which transfers N-acetylglucosamine from UDP-N-acetylglucosamine to the branched terminal mannosyl residues found in the complex type oligosaccharide units of N-linked glycoproteins was isolated from swine trachea mucosa. The enzyme was purified from microsomes after solubilization with 1% Triton X-100 and 1% Nonidet P-40, and it was also isolated from a soluble extract of this tissue. The enzyme was purified by chromatography on DEAE-cellulose, cellulose phosphate, and Sephacryl S300 columns and by affinity chromatography on a Sepharose 4B column containing covalently bound ovomucoid. The purified enzyme forms beta-1,2 bonds between N-acetylglucosamine and terminal-branched mannosyl residues of glycoproteins and glycopeptides. The enzyme has an absolute specificity for terminal branched mannosyl residues, and solute specificity for terminal branched mannosyl residues, and no activity is observed with mannose, p-nitrophenyl alpha-D-mannoside, p-nitrophenyl beta-O-mannoside, and glycopeptides which contain unbranched oligosaccharide chains terminating in free mannose. Evidence obtained by kinetic and structural analysis shows that the purified enzyme catalyzes the reactions shown in Scheme I.

Animals↗