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Biomedical subjects

F Suarez

Publications and source records attributed to F Suarez.

At least 37 records · Page 2Linked to original sources

Cytomegalovirus colitis mimicking a colonic neoplasm or ischemic colitis 4 years after heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) colitis is a polymorphous disease presenting in immunodepressed patients in a variety of clinical forms that can delay diagnosis and therapy. We report the case of a patient who presented with abdominal pain 4 years after heart transplantation; clinical and x-ray findings were suggestive of a neoplastic or ischemic stenosis, and histopathological examination likewise initially suggested an ischemic etiology. METHODS: Tissue samples were fixed in 10% formaldehyde, embedded in paraffin, cut, and stained with hematoxylin/eosin and periodic acid-Schiff-Alcian Blue. Immunohistochemistry with monoclonal antibodies was performed using an indirect immunoperoxidase method. RESULTS: CMV colitis was eventually diagnosed and resolved with surgery and specific anti-CMV therapy. CONCLUSIONS: CMV colitis should be suspected in any heart transplant patient with signs or symptoms of abdominal pathology, even without classical signs or symptoms of CMV infection. If stenotic lesions are present, surgery may be required not only to remove the obstruction but also to rule out malignancy.

Cardiomyopathy, Dilated↗

Production and elimination of sulfur-containing gases in the rat colon.

Highly toxic sulfur-containing gases have been pathogenetically implicated in ulcerative colitis. Utilizing a rat model, we studied the production and elimination of sulfur-containing gases within the unperturbed colon. The major sulfur-containing gases were hydrogen sulfide (H2S), methanethiol, and dimethyl sulfide with cecal accumulation rates of 2.6, 0.096, and 0.046 microliter/min, respectively. The dependence of H2S production on dietary components was demonstrated via a sixfold reduction with fasting and a fivefold increase with carrageenan (a nonabsorbable, sulfur compound) feeding. Zinc acetate reduced cecal H2S by fivefold, indicating the importance of H2S binding by divalent cations. During passage from the cecum to the rectum, > 90% of the sulfur gases were absorbed or metabolized. An H2 35S turnover of 97%/min was observed in the isolated cecum. Thus mucosal exposure is > 10 times the measured accumulation rate. Cecal mucosal tissue very rapidly metabolized H2S and methanethiol via a nonmethylating reaction.

Animals↗

Interactive effect of estradiol and vitamin D receptor gene polymorphisms as a possible determinant of growth in male and female infants.

An association between vitamin D receptor (VDR) gene polymorphism and body size has been observed in infants. We hypothesized that the estradiol receptor (ER) gene is another determinant of infant growth and that the effects of the VDR and ER genotypes may interact with each other. The ER genotype (PvuII and XbaI sites), VDR genotype (BsmI site), and body size during the first 2 yr of life were analyzed in 161 healthy Caucasian full-term babies homozygous for the BsmI polymorphism of the VDR gene (BB or bb). There was no significant association between ER polymorphism and 1) body weight in boys and girls, 2) body length in girls, or 3) body length in boys with a bb genotype. In contrast, ER polymorphism and body length were significantly associated in BB boys. Boys with the BBpp genotype were shorter at birth (P < 0.005) and at 10 months of age (P < 0.001) than boys with other genotypes. They were even shorter than girls with the same genotype. These results indicate some degree of interaction between the effects of the VDR and ER genes, leading to significant variations in body growth during infancy, especially in boys.

Anthropometry↗

Absence of gaseous symptoms during ingestion of commercial fibre preparations.

BACKGROUND: While fibre is believed to cause gaseous symptoms, a study in healthy volunteers showed no increase in flatulence when the diet was supplemented with fermentable (psyllium) or non-fermentable (methylcellulose) fibre. However, extrapolation of this observation to subjects who use fibre is arguable since these individuals may have a propensity to gaseousness. In the present study, gaseous complaints during fibre ingestion were assessed in subjects who believed that a previous exposure to fibre induced gas. METHODS: In a double-blind protocol, subjects were randomized to one of four treatment periods, during which the regular diet was supplemented for 1-week periods with two daily doses of: placebo 10 g, psyllium 3.4 g, methylcellulose 2 g or lactulose 5 g. A symptom diary was maintained for 1-week periods on or off treatment. RESULTS: During treatment, the lactulose group passed gas significantly more often than did the psyllium or the methylcellulose group (P = 0.01). No other symptom was significantly different among the treatment groups. CONCLUSIONS: (1) psyllium and methylcellulose did not cause greater gaseous symptomatology than did placebo in subjects who believed that these preparations caused gas; and (2) subjects commonly misidentify dietary components that cause gaseous symptoms.

Adolescent↗

Insights into human colonic physiology obtained from the study of flatus composition.

To better understand the physiology of colonic gas production, each flatus passage of 16 subjects over a 4-h period was analyzed by gas chromatography for N2, O2, H2, CO2, CH4, and for odoriferous sulfur-containing gases. Appreciable intraindividual and enormous interindividual variability was observed, indicating that each gas passage reflected the interaction of highly variable liberation and/or removal mechanisms. The predominant flatus gas was CO2, H2, and N2 in seven, six, and three subjects, respectively. Gases produced intraluminally (H2, CO2, and CH4) comprised approximately 74% of flatus, and rapid CO2 and H2 productions were responsible for high passage rates. A positive correlation between flatus H2 and CO2 suggested that CO2, like H2, mainly was a bacterial product. Whereas methanogens and H2S-producing bacteria usually are mutually exclusive in feces, CH4 and H2S did not negatively correlate, indicating coexistence of both organisms in the colon. We conclude that analysis of flatus composition provides a novel means of assessing colonic physiology, particularly ongoing bacterial metabolism throughout the unperturbed colon.

Adolescent↗

Association between vitamin D receptor gene polymorphism and sex-dependent growth during the first two years of life.

An association between vitamin D receptor (VDR) gene polymorphisms and bone mass variance has been observed in adult populations. To analyze possible association between VDR genotype and growth, we studied 589 healthy infants who were homogeneous for age, diet, and vitamin D status. The Bsm I, TaqI, and ApaI alleles' frequencies and genotypes were similar to those reported for Caucasian populations. Variations in Bsm I polymorphism were not associated with calcium intakes nor with serum levels of calcium, 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D, or alkaline phosphatase activity. But, they were associated with differences in body size. At 2 yr, homozygote BB (BsmI site absent) girls had higher length, weight and body surface area, and inversely, BB boys had lower weight, body mass index and body surface area, than their respective bb counterparts. As a result, gender-related differences were observed in Bb and bb, but not in BB populations. This VDR genotypic effect was observed also at birth and at 10 months in the longitudinal analysis of 145 selected full-term babies homozygous for the Bsm I polymorphism. These findings provide support for the hypothesis that VDR genotype influences intrauterine and early postnatal growth, directly or via interactions with gender-related growth regulators.

Alleles↗

Expression and modulation of the parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acid in skin fibroblasts from patients with type Ib pseudohypoparathyroidism.

To explore the possibility that defects in the regulation of expression of the messenger ribonucleic acid (mRNA) coding for the PTH receptor could be involved in pseudohypoparathyroidism type Ib (PHP-Ib), PTH-induced cAMP production and PTH/PTH-related peptide (PTH-rp) receptor mRNA expression, measured using a ribonuclease protection assay, were compared in untreated and dexamethasone (dexa)-pretreated (5 x 10(-7) mol/L; 7 days) cultured skin fibroblasts from controls (n = 4) and patients with PHP-Ib (n = 6). In control fibroblasts, stimulation of cAMP production by PTH and expression of PTH/PTH-rp receptor mRNA were easily detectable and were not significantly affected by dexa pretreatment. In fibroblasts from three PHP-Ib patients demonstrating reduced PTH-induced cAMP production that was reversed by dexa, the level of basal PTH/PTH-rp receptor mRNA was also reduced, but increased to levels similar to those in control cells after dexa pretreatment. In fibroblasts from a patient with resistance to PTH not reversed by dexa, PTH/PTH-rp receptor mRNA expression was also significantly lower than that in control cells (18 +/- 13%; P < 0.001) and remained only 30 +/- 15% of that observed in control cells after dexa pretreatment (P < 0.001). In fibroblasts from two PHP-Ib patients expressing normal cAMP responsiveness to PTH before and after dexa treatment, the level of PTH/PTH-rp receptor mRNA was not different from that in control cells before or after dexa treatment. Thus, in all conditions where PTH-induced cAMP production by PHP-Ib fibroblasts was reduced, the abnormality could be explained by the reduced level of PTH/PTH-rp receptor mRNA in these cells. These results suggest that defects in the regulation of expression of the PTH/PTH-rp receptor mRNA, not structural defects in the receptor itself, explain the PTH resistance in PHP-Ib in the patients evaluated, but several different defects must exist.

Amino Acid Isomerases↗

Use of sentinel pigs to monitor environmental Taenia solium contamination. The Cysticercosis Working Group in Peru (CWG).

We tested a novel approach to assay Taenia solium prevalence using the enzyme-linked immunoelectrotransfer blot assay in sentinel piglets to determine environmental contamination with T. solium eggs in a disease-endemic zone in Peru. Twelve sentinel piglets from an area where the disease is not present were tested at two months of age, moved to an area where the disease is endemic, and retested at the of age nine months. Sentinel piglets native from this T. solium-endemic area were also tested concurrently at two and nine months of age. Of the non-native pigs, 33% (4 of 12) acquired new infection. Of the 28 native pigs tested, 64% (18 of 28) acquired the infection. In a subset of the native piglets from seronegative sows, 44% (4 of 9) were infected at five months of age. Serodiagnosis of sentinel piglets is a practical method to detect T. solium eggs in the environment. Furthermore, it permits indirect assessment of human risk, which may be useful for monitoring the efficacy of intervention programs.

Animals↗

Expression of annexin I, II, V, and VI by rat osteoblasts in primary culture: stimulation of annexin I expression by dexamethasone.

To determine whether rat osteoblasts synthesize proteins of the annexin family and to evaluate the extent to which glucocorticoids modulate the expression of annexins by these cells, osteoblasts were grown in primary cultures in the absence or presence of dexamethasone, and the expression of annexins was evaluated by immunoblotting using polyclonal antibodies against human annexins. Four different annexins (I, II, V, and VI) were found to be expressed by rat osteoblasts. The expression of annexin I, but not the other annexins studied, was increased in osteoblasts cultured in the presence of dexamethasone (173 +/- 33% increase comparing untreated cells and cells treated for 10 days with 5 x 10(-7) M dexamethasone). Increased expression of annexin I was observed after the third day of exposure to dexamethasone and rose thereafter until day 10; annexin I expression increased with dexamethasone concentrations above 10(-10) M throughout the range of concentrations studied. The increase in annexin I protein was associated with an increase in annexin I mRNA and was completely blocked by the concomitant addition of the glucocorticoid receptor antagonist RU 38486. The increase in annexin I content following dexamethasone treatment was associated with an increase in alkaline phosphatase activity and PTH-induced cAMP stimulation, whereas phospholipase A2 activity in the culture medium was reduced to undetectable levels. The finding that four annexins are expressed in rat osteoblasts in primary culture raises the possibility that these proteins could play an important role in bone formation by virtue of their ability to bind calcium and phospholipids, serve as Ca2+ channels, interact with cytoskeletal elements, and/or regulate phospholipase A2 activity. In addition, the dexamethasone-induced increase in annexin I may represent a mechanism by which glucocorticoids modify osteoblast function.

Alkaline Phosphatase↗

Effect of parathyroid hormone on arachidonic acid metabolism in mouse osteoblasts: permissive action of dexamethasone.

We examined the regulation of arachidonic acid (AA) metabolism in primary cultures of mouse osteoblasts under steady state and after acute stimulation by PTH. Both dexamethasone-treated and untreated cells were evaluated, as glucocorticoids are known to modulate some actions of PTH in osteoblasts and to affect arachidonic acid metabolism in cells in general. Cells were labeled with [3H]AA for 3 h, followed by a 20-h equilibrium period, then exposed to 10(-8) M PTH for different time periods ranging from 2-60 min. The results showed that although osteoblasts maintained in vitro in the absence of dexamethasone were responsive to PTH, as measured by cAMP production (50-fold increase), PTH had no effect on the distribution of AA in phospholipids and did not induce the release of free AA from phospholipid pools. After 7-day treatment of the cells with 4 x 10(-7) M dexamethasone, 15-min PTH stimulation resulted in a significant increase in free AA within the cells (mean +/- SE, +142 +/- 11%; n = 9) and a short-lived change in the distribution of AA within cellular phospholipids (phosphatidylethanolamine, -63 +/- 3%; phosphatidylinositol, +168 +/- 7%; phosphatidylserine, +296 +/- 50%; sphingomyelin, +220 +/- 20%; lysophosphatidylcholine, +634 +/- 31%; mean +/- SE; n = 3), despite the fact that no changes in PTH-induced cAMP production were observed. Because the release of free AA is an essential step in the production of eicosanoid metabolites that could act as second messengers, these findings suggest that corticosteroid treatment may activate signal transduction pathways for PTH which are latent in untreated cells, and thereby explain at least in part the profound effects of corticosteroids on osteoblast function.

Analysis of Variance↗

The resistance to parathyroid hormone of fibroblasts from some patients with type Ib pseudohypoparathyroidism is reversible with dexamethasone.

Skin fibroblasts from some patients with pseudohypoparathyroidism type Ib (PHP-Ib) are resistant to PTH. To characterize the defect producing PTH resistance in these cells and determine whether the abnormality is potentially reversible, we evaluated the ability of fibroblasts from patients with PHP-Ib to produce cAMP in response to PTH both before and after exposure to dexamethasone, an agent known to increase PTH responsiveness in other cell types. Before dexamethasone treatment, fibroblasts from five of eight patients with PTH-Ib produced reduced amounts of cAMP in response to PTH (but not prostaglandin E1 and forskolin) compared to that of control cells (6.3 +/- 1.0 and 37.3 +/- 6.3 pmol cAMP/100 micrograms protein, respectively). Whereas dexamethasone pretreatment had no effect on cAMP production by control or PTH-responsive PHP-Ib fibroblasts, it resulted in a dose-dependent increase in PTH-induced cAMP production by PTH-resistant fibroblasts to normal levels in four of five cases. Studies evaluating the binding of radiolabeled PTH did not permit quantification of the small number of high affinity PTH receptors present on these cells. We conclude that PTH resistance in PHP-Ib patients with PTH-resistant fibroblasts results from an abnormality in the expression of or coupling to cyclase of high affinity PTH-receptor complexes. Because it is expressed in only some tissues and is reversible, the defect could be regulatory in nature.

Adult↗

Bilio-pancreatic common channel in children. Clinical, biological and radiological findings in 12 children.

Twelve patients (11 girls and 1 boy) with dilated bile ducts and anomalous junction between the common bile duct and pancreatic duct are reported. All patients underwent preoperative opacification of the bile ducts either by transhepatic cholangiography or percutaneous cholecystography. Abdominal pain and jaundice were the main clinical symptoms. Reflux of pancreatic enzymes in the bile duct was proven by measuring amylase and lipase activity in the biliary system after IV injection of 1 IU/kg of cholecystokinin. All patients were operated upon. Bile ducts size returned to normal in all patients who are clinical well with a follow-up from 1 to 6 years.

Adolescent↗

Detection, rescue, and mapping of mutations in the adenovirus DNA binding protein gene.

r(ts107)202 was isolated in HeLa cells as a temperature-independent revertant of H5ts107, an adenovirus mutant that maps in the structural gene of the viral DNA-binding protein. r(ts107)202 is a host-range temperature-conditional mutant: it is temperature independent for growth in HeLa cells but temperature sensitive for growth in 293 cells, a type 5 adenovirus-transformed human cell line. Marker rescue experiments using H5ts107 DNA and restriction enzyme fragments from r(ts107)202 DNA demonstrated that the mutations causing the r(ts107)202 phenotype were localized in HindIII fragment A containing the entire DNA-binding protein gene. To obtain a fine structure map of the r(ts107)202 mutations, overlap recombination between EcoRI fragment A (0-75.9 map units) from either Ad5wt or r(ts107)202 and BamHI fragment B (59.5-100 map units) from either Ad5wt or r(ts107)202 was performed. Segregation of the H5ts107 primary-site mutation away from the accompanying reversion mutation could be demonstrated in 5 of 200 plaques when r(ts107)202 EcoRI fragment A was crossed with the Ad5wt BamHI fragment. In the reciprocal cross, none of 200 plaques contained the H5ts107 mutant. These results permitted a determination of the order of the primary-site mutation (H5ts107) and secondary-site mutation in r(ts107)202, and the frequency of recombination predicted a distance of 50-340 base pairs between these two mutations. This experimental result agrees with the nucleotide sequence of the r(ts107)202 mutant which shows that 182 base pairs separate the primary-site and secondary-site mutations in r(ts107)202.

Adenoviruses, Human↗