PubMed Health⌕ Search

Biomedical subjects

M Olivares

Publications and source records attributed to M Olivares.

At least 19 recordsLinked to original sources
PubMed1999

The L1Tc, long interspersed nucleotide element from Trypanosoma cruzi, encodes a protein with 3'-phosphatase and 3'-phosphodiesterase enzymatic activities.

The presence of a long interspersed nucleotide element, named L1Tc, which is actively transcribed in the parasite Trypanosoma cruzi, has been recently described. The open reading frame 1 of this element encodes the NL1Tc protein, which has apurinic/apyrimidinic endonuclease activity and is probably implicated in the first stage of the transposition of the element. In the present paper we show that NL1Tc effectively removes 3'-blocking groups (3'-phosphate and 3'-phosphoglycolate) from damaged DNA substrates. Thus, both 3'-phosphatase and 3'-phosphodiesterase activities are present in NL1Tc. We propose that these enzymatic activities would allow the 3'-blocking ends to function as targets for the insertion of L1Tc element, in addition to the apurinic/apyrimidinic sites previously described. The potential biological function of the NL1Tc protein has also been evidenced by its ability to repair the DNA damage induced by the methyl methanesulfonate alkylating or oxidative agents such as hydrogen peroxide and t-butyl hydroperoxide in Escherichia coli (xth and xth, nfo) mutants.

Animals↗
PubMed1999

Tumor radiosensitization by sustained intratumoral release of bromodeoxyuridine.

We have previously reported that the use of the polymer bis(p-carboxyphenoxy)propane-sebacic acid (20:80) for intratumoral delivery of cis-platinum in a mouse tumor model (RIF-1) potentiated the effects of acute and fractionated radiation. This mode of drug delivery seems particularly applicable to the administration of radiosensitizing drugs because an optimum concentration of radiosensitizer can be maintained in the tumor over the prolonged period required for fractionated radiation treatment. We have now investigated, in the same tumor model, radiosensitization by the thymidine analogue bromodeoxyuridine (BrdUrd). BrdUrd (20%, w/w) was incorporated into bis(p-carboxyphenoxy)propane-sebacic acid (20:80) and polymer rods containing the drug implanted in the RIF-1 tumor. Preliminary in vitro studies of the rate of release of BrdUrd from the polymer showed an initial rapid loss over 24 h, followed by a slower release extending over the next 5 days. In experiments in which tumor cells, which had incorporated BrdUrd in vivo from implanted polymer, were excised and a single cell suspension irradiated in vitro radiosensitization indicative of BrdUrd incorporation was associated mainly with an increase in the alpha constant for the linear quadratic model of cell survival. Radiosensitization was seen for tumor cells harvested between 5 and 10 days after polymer implant, a finding that is consistent with results of experiments in which the percentage of cells that had incorporated BrdUrd were measured by flow cytometry at various times after polymer/BrdUrd implant. The proportion of tumor cells positive for BrdUrd was 40-50% between 3 and 8 days after polymer implant. When tumors were irradiated in situ and response measured in terms of tumor growth delay (TGD), radiosensitization was not seen for an acute dose of 16.5 Gy. In contrast, significant radiosensitization was seen for fractionated treatments when polymer/BrdUrd was implanted 3 days before the first radiation dose. For a dose of 5 x 6 Gy, TGD was increased from 22 days for radiation alone to 27 days for radiation plus polymer implant. For 10 x 6 Gy fractions, TGD increased from 45-77 days for those mice in whom the tumor eventually regrew, whereas for 25% of the mice in this group the tumor volume was reduced to a point where it was no longer detectable and there was no recurrence for at least 120 days after treatment.

Animals↗
PubMed1999

Acute gastrointestinal effects of graded levels of copper in drinking water.

The objective of this study was to determine the acute gastrointestinal effects caused by the consumption of drinking water containing graded levels of added copper. Sixty healthy, adult women were randomly assigned to receive copper [Cu(II)] at four concentrations in their drinking water following a Latin-square design. Each group (n = 15) received tap water with no added copper, 1, 3, and 5 mg Cu/l of added copper sulfate for a 2-week study period, followed by 1 week of standard tap water. The subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. The average daily consumption of water was 1.64 liters per subject, regardless of the amount of copper added. Final serum copper, ceruloplasmin, and liver enzymes were measured in all subjects and were not different from baseline concentrations. Twenty-one subjects (35%) recorded gastrointestinal disturbances sometime during the study, 9 had diarrhea, some with abdominal pain and vomiting, and 12 subjects presented abdominal pain, nausea, or vomiting. There was no association between copper levels in drinking water and diarrhea. However, nausea, abdominal pain, or vomiting were significantly related to copper concentrations in water. The recorded incidence rate of these symptoms was 5, 2, 17, and 15% while ingesting water with 0, 1, 3, and 5 mg Cu/l, respectively (overall [chi]2 = 11.3, p<0.01; Cu [less than/equal to]1 mg/l versus Cu [Greater than/equal to]3 mg/l, [chi]2, p<0.01). When subjects interrupted their consumption of drinking water with added copper, most symptoms disappeared. We conclude that under the conditions of the study, there was no association between aggregate copper in drinking water within the range of 0-5 mg/l and diarrhea, but a [Greater than/equal to]3 mg Cu/l level of ionized copper was associated with nausea, abdominal pain, or vomiting. Additional studies with sufficient numbers of subjects are needed to define thresholds for specific gastrointestinal symptoms with precision and to extrapolate these results to the population at large.

Adult↗
PubMed1999

An outbreak of tinea gladiatorum in Lanzarote.

Canary Islands wrestling is a variant of the sport played exclusively in that region, and is associated with close participant contact. An outbreak of a fungal infection, so-called tinea gladiatorum, amongst such wrestlers in Lanzarote, one island in the archipelago is now described. 102 wrestlers from the eight teams on the island were examined; some of the clubs are 50 km apart; 45 wrestlers (44.1% of those examined) were noted to be affected. To our knowledge, this is the largest reported series of patients with tinea gladiatorum and the only one to demonstrate such infection in a variety of geographical locations.

Adolescent↗
PubMed1998

Essentiality of copper in humans.

The biochemical basis for the essentiality of copper, the adequacy of the dietary copper supply, factors that condition deficiency, and the special conditions of copper nutriture in early infancy are reviewed. New biochemical and crystallographic evidence define copper as being necessary for structural and catalytic properties of cuproenzymes. Mechanisms responsible for the control of cuproprotein gene expression are not known in mammals; however, studies using yeast as a eukaryote model support the existence of a copper-dependent gene regulatory element. Diets in Western countries provide copper below or in the low range of the estimated safe and adequate daily dietary intake. Copper deficiency is usually the consequence of decreased copper stores at birth, inadequate dietary copper intake, poor absorption, elevated requirements induced by rapid growth, or increased copper losses. The most frequent clinical manifestations of copper deficiency are anemia, neutropenia, and bone abnormalities. Recommendations for dietary copper intake and total copper exposure, including that from potable water, should consider that copper is an essential nutrient with potential toxicity if the load exceeds tolerance. A range of safe intakes should be defined for the general population, including a lower safe intake and an upper safe intake, to prevent deficiency as well as toxicity for most of the population.

Animals↗
PubMed1998

Copper in infant nutrition: safety of World Health Organization provisional guideline value for copper content of drinking water.

BACKGROUND: Copper is an essential nutrient for humans. Recently, a limit of 31.48 micromol/l (2 mg/l) was proposed by the World Health Organization as the provisional guideline value for copper content of drinking water. The objective of the study was to determine the tolerance of chronic exposure to drinking water with low or high copper content in infants. METHODS: Healthy infants (n = 128) were randomly assigned to receive drinking water with less than 1.57 micromol/l (<0.1 mg/l) (n = 48) or 31.48 micromol/l (2 mg/l) of copper (n = 80) from 3 to 12 months of age. At 6, 9, and 12 months of age, serum concentrations of copper, ceruloplasmin, and superoxide dismutase; erythrocyte metallothionein; bilirubin; transaminases; and gamma-glutamyl transferase were measured. RESULTS: Small differences in biochemical indexes of copper nutrition were observed between the groups, but there was no evidence of adverse or toxic effects. These findings may be explained by an adaptive response to the higher copper intake, limiting copper absorption, and increasing biliary secretion, as well as by an increase in copper storage. It is also possible that the sensitivity of the biochemical indicators employed to detect differences in copper status is limited. CONCLUSION: No acute or chronic adverse consequences of consuming water with copper content of 31.48 micromol/l (2 mg/l) were detected in infants during the first year of life. The results support the safety of the World Health Organization's provisional guideline value for copper in drinking water during infancy.

Alanine Transaminase↗
PubMed1998

High absorption of fortification iron from current infant formulas.

BACKGROUND: Estimations of iron absorption from infant formulas are based on 20-year-old data. Data about iron bioavailability from currently used infant formulas are scarce, considering that during the last decades, formulas have had modifications that could affect iron absorption. METHODS: Bioavailability of isotopically labeled iron (55Fe and 59Fe) from several infant formulas administered to contraceptive-using women between the ages of 30 to 50 years was measured. Six infant formulas and one follow-on formula were compared with a powdered, whole cow's milk, and the results were normalized to an absorption of 40% from a reference dose of iron. RESULTS: Iron bioavailability from the infant formulas was consistently higher (19%), contrasting with the low value (4%) of the unmodified cow's milk (p < 0.0001). Iron absorption of the follow-on formula was intermediate (13%). Formulas with 8 mg/l iron and one with 7 mg/l supply approximately 1 mg of absorbed iron, assuming a consumption of 750 ml/day of formula. This amount covers the iron needs of most infants during their period of greatest vulnerability. Formulas containing 12 mg/l iron would allow the absorption of approximately twice the infant iron requirements. CONCLUSIONS: Current infant formulas have a high iron bioavailability, which is an appealing argument for lowering the level of iron fortification in these products.

Absorption↗
PubMed1998

[Effect of altitude on iron absorption].

Iron bioavailability was evaluated in people living in high altitudes. Absorption was estimated from a reference dose of ferrous ascorbate and from a standard diet of wheat flour, using extrinsic tag radioisotope technique of 55Fe and 59Fe. Twenty four volunteers, healthy women, with ages ranging from 28 to 45 years, participated. Of those, eleven lived at 3450 meters above sea level (m.a.s.l.) in Huancayo city-Peru (study group), and 13 lived in Santiago de Chile at 630 m.a.s.l. (control group). Iron absorption from reference dose of ferrous ascorbate was 32.0% and 31.1% in the study and control groups respectively. The geometric mean of iron absorption from the standard diet, corrected to 40% of absorption of reference dose, was 9.0% and 6.9% in the study and control groups respectively (NS). The results suggest that altitude does not produce a high iron absorption in highlander residents.

Adult↗
PubMed1997

Long-term pancreas allograft outcome in simultaneous pancreas-kidney transplantation: a comparison of enteric and bladder drainage.

BACKGROUND: The optimal pancreatic exocrine drainage method remains controversial. Bladder drainage (BD) is widely used, but associated with a high incidence of urological complications (acidosis, dehydration, pancreatitis, and urinary tract infection). Enteric drainage (ED) avoids this morbidity, but may be associated with inferior graft survival. METHODS: We conducted a retrospective study comparing BD and ED in 71 simultaneous pancreas-kidney transplant recipients (37 BD; 34 ED) transplanted between February 1988 and June 1996. RESULTS: Five BD and five ED patients experienced early pancreas loss within 3 months after transplantation. The mean follow-up of the remaining 61 patients has been 45.7+/-3.9 and 76.0+/-3.3 months for ED and BD patients, respectively (P<0.005). Both groups had similar pretransplant demographics, co-morbidity, and nutritional and immunological status. The incidence of volume depletion (3.4% vs. 34.3%), acidosis (0% vs. 41.0%), pancreatitis (3.4% vs. 39.7%) and urinary tract infection (26.7% vs. 71%) was lower in ED patients (P<0.005 vs. BD). Of the BD group, 18.7% required conversion to ED for intractable complications. Initial length of stay was equivalent (17.7+/-9 days vs. 18.4+/-10 days) between groups. However, the number of admissions (0.79+/-0.18 vs. 1.38+/-0.14) and in-hospital days/patient/year (6.26+/-1.16 vs. 11.46+/-2.12) was less in ED patients (P<0.05 vs. BD). Actuarial patient and pancreas allograft survival up to 4 years after transplant was similar between groups. CONCLUSIONS: Compared with BD, (a) perioperative morbidity is not increased by ED, (b) ED is associated with fewer complications and hospitalizations, and (c) ED is not associated with increased long-term pancreas graft failure. These data suggest that ED is superior to BD and should be considered as the preferred technique for simultaneous pancreas-kidney transplants.

Acute Disease↗
PubMed1997

The open reading frame 1 of the L1Tc retrotransposon of Trypanosoma cruzi codes for a protein with apurinic-apyrimidinic nuclease activity.

The deduced amino acid sequence of the open reading frame 1 (ORF1) of the L1Tc non-site-specific non-long terminal repeat retrotransposon of Trypanosoma cruzi exhibits a significant homology with the consensus sequence of the class II family of the endonuclease apurinic-apyrimidinic (AP) proteins. The analysis of the activity of the 40-kDa recombinant protein, named NL1Tc, obtained from the expression of the L1Tc ORF1 in an Escherichia coli "in vitro" expression system revealed that the sequence codes for a protein with endonuclease activity specific for apurinic-apyrimidinic (AP) sites. Data are also presented showing that in vivo expression of the NL1Tc protein conferred viability by complementation to E. coli exonuclease III deletion mutants (BW286 strain). We propose that the biological function of the AP endonuclease activity of the NL1Tc protein may be connected with the introduction into the DNA of free 3' ends that could be used as primers for the integration, along the T. cruzi genome, of the L1Tc element and that the nicking could be a general mechanism for the retrotransposition of non-site-specific non-long terminal repeat retrotransposons.

Amino Acid Sequence↗
PubMed1997

Milk inhibits and ascorbic acid favors ferrous bis-glycine chelate bioavailability in humans.

The chemical properties of ferrous bis-glycine chelate allow for its use as a fortificant in fluid, high fat vehicles. This chemical form may also protect iron from the inhibitory or enhancing effects of the diet on iron absorption. Alternatively, iron bis-glycine chelate may be absorbed by a mechanism independent of an individual's iron stores. To test these hypotheses, the bioavailability of iron bis-glycine chelate added to water and milk was studied using a double-isotopic method in two groups of 14 women. Iron absorption from aqueous solutions of 0.27 mmol/L (15 mg/L) of elemental iron as either iron bis-glycine or ferrous ascorbate was not significantly different (34.6 and 29.9%, respectively). There were significant correlations between (log) iron absorption of iron bis-glycine with (log) serum ferritin (r = -0.60, P < 0.03) and with (log) iron absorption from ferrous ascorbate (r = 0.71, P < 0.006), suggesting that iron bis-glycine chelate bioavailability is indeed affected by iron stores. Iron absorption of iron bis-glycine given in milk was significantly lower (P < 0.002) than when given in water, with values of 11.1 and 46.3%, respectively (standardized to 40% absorption of the reference dose). With the addition of 0.57 mmol/L ascorbic acid (100 mg/L), iron absorption of iron bis-glycine given in milk increased significantly from 11.1 to 15.4% (P < 0.05). These findings show that milk and ascorbic acid affect iron bis-glycine chelate bioavailability and also demonstrate that iron stores may influence its bioavailability as well. The good bioavailability of iron bis-glycine makes this compound a suitable alternative to be considered in iron fortification programs.

Adult↗
PubMed1997

Clear-cell porocarcinoma: another cutaneous marker of diabetes mellitus.

The relationship between clear-cell syringoma and diabetes mellitus is well established. We present a case of clear-cell porocarcinoma in a diabetic patient. The lesion consisted of a 5-cm nodule on the lateral aspect of the left leg. Histopathologically, the neoplasm was composed of irregular aggregations of neoplastic cells with striking clear-cell appearance, showing features of ductal differentiation. The clear-cell appearance of neoplastic cells was due to glycogen accumulation within their cytoplasm. Immunohistochemistry and ultrastructural studies also supported the diagnosis of a neoplasm with sweat ductal differentiation. Enzyme histochemical reactions for phosphorylase immunoreactivity on fresh, unfixed sections of the neoplasm demonstrated that this immunoreactivity was remarkably decreased. Some adnexal neoplasms of the skin mostly composed of clear cells may be cutaneous markers of diabetes mellitus. Phosphorylase activity deficiency in diabetic patients may be responsible for glycogen accumulation in neoplastic cells resulting in clear-cell appearance of these neoplasms.

Acrospiroma↗
PubMed1997

Iron, anemia, and infection.

The data on the relationship between iron deficiency and infection are conflicting. Some researchers conclude that mild iron deficiency is beneficial for immunity, whereas others contend that any deficit is not good for immunity. Additionally, infection or inflammation generate anemia and profound changes in iron metabolism mediated by cytokines. These changes are important confounders to consider in assessments of iron status.

Anemia, Iron-Deficiency↗
PubMed1997

Genetic and transcriptional analysis of flgB flagellar operon constituents in the oral spirochete Treponema denticola and their heterologous expression in enteric bacteria.

Oral spirochetes possess many potential virulence factors, including the capacity for tissue invasion and persistence despite a vigorous host immune response. In an attempt to identify treponemal immunoreactive components, sera derived from individuals with advanced periodontal disease were used as a reagent to isolate recombinant bacteriophage lambda clones expressing antigens of the oral spirochete Treponema denticola ATCC 35405. Nucleotide sequence analysis of a clone expressing three immunoreactive products has revealed seven T. denticola genes which appear to encode homologs of flagellar basal body constituents, FlgB, FlgC, FliE, and FliF, a flagellar switch component, FliG, and the putative flagellar export proteins, FliH and FliI, initially characterized in Salmonella typhimurium. Also identified was a gene resembling fliJ. Primer extension analysis identified a transcriptional start site 5' to the treponemal flgB gene. Appropriately spaced with respect to this start site was a sigma28 binding motif. The absence of additional identifiable sigma factor binding motifs within the treponemal sequence and the proximity of adjacent genes suggested operonic arrangement, and reverse transcriptase PCR provided evidence of cotranscription. Supporting the identification of these genes as flagellar components, heterologous expression in enteric bacteria of the putative switch basal body genes from T. denticola interfered with motility. Specifically, the presence of a plasmid expressing treponemal fliG reduced swarming motility in S. typhimurium, while in Escherichia coli, this plasmid conferred a nonmotile phenotype and a reduction in flagellar number. Thus, while spirochetal flagella are subject to unique synthetic and functional constraints, the organization of flagellar genes and the presence of sigma28-like elements are reminiscent of the flagellar systems of other bacteria, and there appears to be sufficient conservation of constituent proteins to allow interaction between T. denticola switch-basal body proteins and the flagellar machinery of gram-negative bacteria.

Amino Acid Sequence↗
PubMed1996

Cutaneous metastases from prostatic carcinoma.

Cutaneous metastasis from carcinoma of the prostate is a rare phenomenon. When it occurs, metastases usually appear as multiple nodules involving the suprapubic area and the anterior aspect of the thighs. We report on two cases of cutaneous metastases from prostatic carcinoma, one of them presenting the stereotypical clinical and histopathological findings, whereas in the other one cutaneous metastasis consisted of a morphea-like plaque on the chest. Histopathologically, the later case revealed accumulations of neoplastic cells distributed in a folliculotropic pattern. In both examples immunohistochemical study with prostatic specific antigen (PSA) confirmed the prostatic origin of the metastases. We review the literature on this subject.

Aged↗
PubMed1996

Copper as an essential nutrient.

Animal and human studies have shown that copper is involved in the function of several enzymes. Studies have also shown that copper is required for infant growth, host defense mechanisms, bone strength, red and white cell maturation, iron transport, cholesterol and glucose metabolism, myocardial contractility, and brain development. Copper deficiency can result in the expression of an inherited defect such as Menkes syndrome or in an acquired condition. Acquired deficiency is mainly a pathology of infants; however, it has been diagnosed also in children and adults. Most cases of copper deficiency have been described in malnourished children. The most constant clinical manifestations of acquired copper deficiency are anemia, neutropenia, and bone abnormalities. Other, less frequent manifestations are hypopigmentation of the hair, hypotonia, impaired growth, increased incidence of infections, alterations of phagocytic capacity of the neutrophils, abnormalities of cholesterol and glucose metabolism, and cardiovascular alterations. Measurements of serum copper and ceruloplasmin concentrations are currently used to evaluate copper status. These indexes are diminished in severe to moderate copper deficiency; however, they are less sensitive to marginal copper deficiency. Erythrocyte superoxide dismutase and platelet cytochrome c activities may be more promising indexes for evaluating marginal copper deficiency.

Anemia↗