Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells.

In vitro studies suggest that transforming growth factor (TGF)-beta has potent effects on gastrointestinal mucosal integrity, wound repair, and neoplasia. However, the multiplicity of actions of this peptide on many different cell types confounds efforts to define the role of TGF-beta within the intestinal epithelium in vivo. To delineate these effects selective blockade of intestinal epithelial TGF-beta activity was undertaken through targeted expression of a dominant-negative (DN) TGF-beta RII to intestinal epithelial cells in vitro and in vivo.

Tropical enteritis: nutritional consequences and connections with the riddle of cholera.

One of the important consequences of the infection-nutrition interaction is mediated by malabsorption associated with chronic inflammation in the intestine, enteritis. Studies made possible after development of the peroral intestinal biopsy technique in the 1950s indicated the wide prevalence of enteropathy, particularly in tropical developing countries with poor levels of sanitation. Some consider this so-called subclinical tropical malabsorption to be the base of an iceberg, whose tip is tropical sprue, a severe form of malabsorption leading to nutritional deficiency that had been reported in colonial expatriates in tropical countries for 200 y.

Elevated serum methylmalonic acid concentrations are common among elderly Americans.

To describe serum methylmalonic acid (MMA) concentrations of elderly Americans and examine relationships between serum MMA and other factors, we used surplus serum samples collected from elderly (n = 1145) and young-adult (n = 1026) participants in Phase 2 of the third National Health and Nutrition Examination Survey (1991-1994). In approximately 20% of participants >/=65 y old, serum MMA was >370 nmol/L, the 90th percentile of the distribution of participants aged 30-39 y. Consistent with previous reports, we observed strong, independent positive associations between serum MMA concentration and serum concentrations of creatinine and homocysteine.

Folic acid intake from fortification in United States exceeds predictions.

In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998.

Hyperhomocysteinemia in renal transplant recipients.

Renal transplantation is a commonly performed curative procedure for end-stage renal disease. With the increase in renal allograft half-lives, attention is now being focused on cardiovascular morbidity and death in the renal transplant recipient (RTR) population. Among the more novel cardiovascular disease (CVD) risk factors for which this group is at risk is hyperhomocysteinemia.

Endothelial function in healthy younger and older hyperhomocysteinemic subjects.

Objectives: To compare endothelium-dependent vasomotor response in healthy younger and older subjects without classic cardiovascular risk factors, with high and normal fasting homocysteine (tHcy) levels.

Design: We compared endothelium-dependent vasodilatation, using ultrasound, in healthy younger (aged 18-40) and older (> or =70) people with normal (<13 micromol/L) and high (>15 micromol/L) tHcy levels. Exclusion criteria were smoking, personal history of cardiovascular disease, hypertension, chronic diseases, vitamin intake, obesity, abnormal serum lipids levels, and creatinine higher than 130 micromol/L.

Plasma homocysteine and parental myocardial infarction in young adults in Jerusalem.

Background: A causal role for mildly elevated plasma homocysteine (tHcy) in cardiovascular disease remains undetermined. To address the unresolved issue of the antecedent-consequent directionality of the relationship, we assessed the familial association of tHcy with parental myocardial infarction (MI) in young Israeli men and women. We also compared tHcy concentrations in Jerusalem, where rates of coronary heart disease (CHD) are high, with the United States Third National Health and Examination Survey (NHANES III).

Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis-acting element.

Trefoil factor 2 (TFF2)/spasmolytic polypeptide (SP) is a highly stable peptide which is abundantly expressed and secreted by mucous cells of the stomach and which functions in gastric cytoprotection. Previous studies from our group have shown that TFF2 is an immediate early gene capable of regulating its own expression through activation of the TFF2 promoter. We therefore aimed to investigate the cis-acting elements mediating this response in AGS cells transfected with TFF2 promoter-reporter gene constructs, using a TFF2-expression system resembling physiologic paracrine conditions.

Spectral decomposition of intracellular complex fluorescence using multiple-wavelength phase modulation lifetime determination: technical approach and preliminary applications.

Lifetime-based spectral decomposition using a frequency-domain phase/modulation technique is developed on a microspectrofluorimeter prototype. In a fluorescent mixture with strongly overlapping components, such measurements enable us to not only obtain excited state lifetimes of each fluorescent component but also determine the specific spectral contribution of each species without the use of any model spectra. Examples of such applications are first given for complex mixtures of highly overlapping fluorescent components in solution.

A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status.

DNA methylation, an essential epigenetic feature of DNA that modulates gene expression and genomic integrity, is catalyzed by methyltransferases that use the universal methyl donor S-adenosyl-l-methionine. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate (5-methylTHF), the methyl donor for synthesis of methionine from homocysteine and precursor of S-adenosyl-l-methionine. In the present study we sought to determine the effect of folate status on genomic DNA methylation with an emphasis on the interaction with the common C677T mutation in the MTHFR gene.

Total homocysteine lowering treatment among coronary artery disease patients in the era of folic acid-fortified cereal grain flour.

The prevalence of deficient plasma folate status and elevated total plasma levels of homocysteine (tHcy), have been dramatically reduced after fortification of all enriched cereal grain flour products with folic acid at 140 microg/100 g flour. Against this new background fortification, we evaluated the tHcy-lowering efficacy of pharmacological dose, folic acid-based vitamin B supplementation among stable coronary artery disease (CAD) patients. Using a 2x2 factorial design, 131 stable CAD patients (mean age 60.

Plasma homocysteine as a risk factor for dementia and Alzheimer's disease.

Background: In cross-sectional studies, elevated plasma homocysteine levels have been associated with poor cognition and dementia. Studies of newly diagnosed dementia are required in order to establish whether the elevated homocysteine levels precede the onset of dementia or result from dementia-related nutritional and vitamin deficiencies.

Methods: A total of 1092 subjects without dementia (667 women and 425 men; mean age, 76 years) from the Framingham Study constituted our study sample.

The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine to methionine. The C677T MTHFR polymorphism is associated with mild hyperhomocysteinemia, but only in the presence of low folate status. Because MTHFR contains flavin adenine dinucleotide (FAD) as a prosthetic group, riboflavin status may also influence homocysteine metabolism.

-CH2- lengthening of the internucleotide linkage in the ApA dimer can improve its conformational compatibility with its natural polynucleotide counterpart.

The complete family of ApA phosphonate analogues with the internucleotide linkage elongated by insertion of a -CH2- group was prepared and the hybridisation and structural properties of its members in interaction with polyuridylic acid were investigated using an original 2D Raman approach. Except for the conformationally restricted A(CH)pA(2'3'endo-5') modification, all of the isopolar, non-isosteric analogues form triplex-like complexes with poly(rU) at room temperature, in which two polymer strands are bound by Watson-Crick and Hoogsteen bonds to a central pseudostrand consisting of a 'chain' of A-dimers. For all of these dimers, the overall conformation of the triplexes was found to be similar according to their extracted Raman spectra.

[Lasers in dentistry. Part B--Interaction with biological tissues and the effect on the soft tissues of the oral cavity, the hard tissues of the tooth and the dental pulp].

The interaction of laser energy with target tissue is mainly determined by two non operator-dependent factors: the specific wavelength of the laser and the optical properties of the target tissues. Power density, energy density, pulse repetition rate, pulse duration and the mode of energy transferring to the tissue are dictated by the clinician. Combination of these factors enables to control optimal response for the clinical application.

Plasma total homocysteine levels among patients undergoing nocturnal versus standard hemodialysis.

Mild hyperhomocysteinemia, a putative risk factor for arteriosclerotic outcomes, is seen in >85% of hemodialysis patients. Therapeutic strategies, including pharmacologic-dose B vitamin supplementation and "high-flux" or "super-flux" hemodialysis, have consistently failed to normalize total homocysteine (tHcy) levels in these patients. Predialysis plasma tHcy levels in 23 patients who were undergoing nocturnal hemodialysis (NHD) six or seven nights/wk were compared with those in 31 patients from the same Canadian dialysis unit who were undergoing chronic standard hemodialysis (SHD) (all <65 yr of age, undergoing thrice-weekly treatments).

Folic acid fortification increases red blood cell folate concentrations in the Framingham study.

In 1996 the Food and Drug Administration (FDA) issued a regulation to take effect in January 1998 that all enriched cereal grain products include 140 microg of folic acid/100 g. The present cross-sectional study was undertaken to assess the effect of this fortification on RBC folate concentrations in the Framingham Offspring Cohort. Among those who did not take B-vitamin supplements, we compared RBC folate in 561 individuals who were examined before implementation of the FDA mandatory folic acid fortification (not exposed) vs.

Intestinal trefoil factor induces decay-accelerating factor expression and enhances the protective activities against complement activation in intestinal epithelial cells.

Mucosal damage induces a massive influx of serum complement components into the lumen. The epithelium produces a number of factors that can potentially ameliorate injury including intestinal trefoil factor (ITF), a small protease-resistant peptide produced and secreted onto the mucosal surface by goblet cells, and decay-accelerating factor (DAF), a protein produced by columnar epithelium which protects the host tissue from autologous complement injury. However, coordination of these intrinsic defensive products has not been delineated.

Oligonucleotides with isopolar phosphonate internucleotide linkage: a new perspective for antisense compounds?

Several types of isopolar modified oligothymidylates and oligoadenylates (15 mers) with the phosphonate -O-P-CH2-O- internucleotide linkage were prepared. The modified oligonucleotides were subjected to the study of their hybridization properties, resistance against nucleases, and the ability to elicit RNase H activity.

The kidney and homocysteine metabolism.

Homocysteine (Hcy) is an intermediate of methionine metabolism that, at elevated levels, is an independent risk factor for vascular disease and atherothrombosis. Patients with renal disease, who exhibit unusually high rates of cardiovascular morbidity and death, tend to be hyperhomocysteinemic, particularly as renal function declines. This observation and the inverse relationship between Hcy levels and GFR implicate the kidney as an important participant in Hcy handling.

2'C-alkoxy and 2'-C-aryloxy derivatives of N-(2-phosphonomethoxyethyl)-purines and -pyrimidines: synthesis and biological activity.

A series of novel, unusual type of acyclic phosphonate-based nucleotide analogues related to well-known antivirals (PMEA and HPMPA) was synthesized using easily available synthon. These compounds, which are distinguished for the presence of phosphonomethyl acetal linkage, form a group of derivatives that contribute to the understanding of structure-activity relationship within the area of acyclic nucleotide analogues.

Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond.

Context: A high homocysteine level has been identified as an independent modifiable risk factor for coronary heart disease (CHD) events and death. Since January 1998, the US Food and Drug Administration has required that all enriched grain products contain 140 microg of folic acid per 100 g, a level considered to decrease homocysteine levels.

Objectives: To examine the potential effect of grain fortification with folic acid on CHD events and to estimate the cost-effectiveness of additional vitamin supplementation (folic acid and cyanocobalamin) for CHD prevention.