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Biomedical subjects

M Moreno

Publications and source records attributed to M Moreno.

At least 91 records · Page 5Linked to original sources

Peroxisomal proliferation induced by treatment with clofibrate in a patient with a peroxisomal disease.

The induction of peroxisomal proliferation in liver parenchymal cells of rats fed a diet containing clofibrate, a hypolipidemic drug, is a well-established event. However, the available data on human hepatocytes in vivo and in vitro indicate that agents that induce peroxisomal proliferation in rats and mice have no effect on human liver cells. The authors are reporting the case of a patient with clinical and laboratory diagnosis of X-linked-adrenoleukodystrophy. In an initial liver biopsy, a reduced volume fraction of peroxisomes was found (Vv. = .012) after a morphometric analysis, initiating treatment with clofibrate at a dose of 1.5 g/d. The administration of clofibrate was maintained for 7 yr. Liver biopsies were taken after 2, 4, and 7 yr, to follow the peroxisomal response. Results demonstrated a 500% increase in peroxisomal Vv. (.060) after 2 yr of treatment, compared with the pretreatment Vv. In subsequent biopsies, the peroxisomal Vv. value was maintained at 225 and 183% increases above the pretreatment biopsy (.027 and .022, respectively).

Adolescent↗

Molecular epidemiology of group A rotavirus causing acute diarrhea in infants and young children hospitalized in Rio de Janeiro, Brazil, 1995-1996.

During 1995-1996, an epidemiological survey was conducted at Fernandes Figueira Institute (Rio de Janeiro, DC) on group A rotavirus strains causing acute diarrhea in infants and young children. Rotaviruses were detected in 15.7% of examined specimens. Among the rotavirus strains tested for dsRNA by PAGE, 70% belonged to the long pattern and 30% to the short pattern. A long pattern classified as LA was the prevalent electropherotype among all of the types, and the prevalent short pattern was a unique SA type. Fifteen years ago, LA type was prevalent in the city among long patterns, and a SB type among short patterns, showing a substitution of circulating electropherotypes. The long pattern occurred throughout the period studied and in all age ranges studied (0-5 years old), but the short pattern occurred only in young children (age range 0-11 months) in May 1995, and September 1996. The data demonstrate epidemiologic differences between long and short electropherotypes incidence; the long electropherotype strains circulate throughout the community and the short electropherotype strains appear only in young children. Rotavirus was observed throughout the period studied but there were peaks of infection in the months of May and September.

Acute Disease↗

Regulation of sigma S degradation in Salmonella enterica var typhimurium: in vivo interactions between sigma S, the response regulator MviA(RssB) and ClpX.

The alternate sigma factor sigmaS plays an important role in the survival of Salmonella typhimurium following sudden encounters with a variety of stress conditions. The level of sigmaS is very low in rapidly growing cells but dramatically increases as those cells encounter environmental stress or enter into stationary phase. This increase is due in large measure to the stabilization of sigmaS protein against degradation by the ClpXP protease. The MviA protein, also known as RssB or SprE in Escherichia coli, is a putative member of a two component signal transduction system that plays a central role in facilitating sigmaS degradation by ClpXP. In contrast to most two-component systems, MviA does not appear to regulate gene expression but is believed to interact directly with sigmaS and somehow facilitate degradation. We now provide evidence that MviA(RssB) directly interacts both with sigmaS and ClpX in vivo, presumably enabling presentation of sigmaS to the ClpP protease. Interactions were demonstrated using a bacterial two-hybrid system in which sigmaS, MviA, and ClpX were fused to separate moieties of Bordetella pertussis CyaA (adenylate cyclase). Paired hybrid plasmids containing Cya'-MviA/RpoS-'Cya or Cya'-MviA/ClpX-'Cya successfully reconstituted adenylate cyclase activity in both S. typhimurium and E. coli. However, no direct interactions were detected between ClpX and RpoS. A second series of experiments has indicated that the interaction between MviA and sigmaS requires the N-terminus but not the C-terminus of MviA. Cellular levels of MviA appear to be very low in the cell based on lacZ fusion, Western blot and Northern blot analyses suggesting a catalytic role for MviA in sigmaS degradation. Mutagenesis of MviA residue D58, a canonical residue subject to phosphorylation in many two-component systems, decreased the ability of MviA to facilitate sigmaS turnover in vivo confirming that phosphorylation of MviA increases MviA activity.

ATPases Associated with Diverse Cellular Activitie↗

[Change in metabolic risk factors in obese patients in treatment].

BACKGROUND: Obesity is a threat to health due to its association with cardiovascular risk factors. AIM: To assess the change in metabolic risk factors after weight reduction in obese patients. PATIENTS AND METHODS: A retrospective analysis of 277 obese patients (198 female) aged 39.5 +/- 12 years old, that completed a six month treatment period, consisting in a calorie restricted diet (800-1200 Kcal/day), physical activity, education and group psychological counseling. At the beginning and at the end of the program, weight, waist circumference, resting energy expenditure (REE), serum lipid profile, plasma glucose and plasma insulin levels were measured. RESULTS: During the treatment period, body mass index decreased from 38 +/- 7 to 33.2 +/- 6.4 kg/m2 with a weight loss of 11.7 kg, waist circumference decreased from 106.6 +/- 14.6 to 93.9 +/- 13.5 cm, REE decreased from 1774 +/- 383 to 1585 +/- 267 Kcal/day, blood glucose fell by 5.8%, plasma insulin fell by 40.4%, total cholesterol fell by 7.5%, LDL cholesterol fell by 8.7%, triglycerides fell by 26.6%, and total cholesterol/HDL ratio fell by 12.2%. CONCLUSIONS: Weight loss was associated with improvement in metabolic cardiovascular risk factors in obese patients.

Adolescent↗

Fatal injuries in adolescents.

Injuries are a major cause of morbidity and mortality among adolescents. Adolescents routinely experiment with high-risk behaviors, increasing their risk of injury. Major modes of injury in adolescents include motor vehicle collisions, drowning, suicide and homicide. This article reviews the risk factors for fatal injuries in adolescents and discusses current prevention strategies. Previous research identifies many risk factors associated with adolescent injuries. Practitioners can help prevent teen injuries by screening all adolescent patients and identifying those at high risk of injury. Patients at high risk need preventive counseling and evaluation for possible referral to other services. Current strategies are useful in preventing many injuries; however, further research is needed to evaluate these strategies and to design new prevention programs.

Accidents, Traffic↗

[Humoral rejection in heart transplantation. Report of 2 cases].

Heart transplantation is a therapeutic alternative for selected patients with refractory heart failure. Acute allograft rejection is one of the main causes of early death after transplantation. The cellular rejection is characterized by cellular infiltrates with or without myocyte necrosis. However, some patients develop left ventricular dysfunction due to rejection without evidence of cellular infiltration. In these patients, the rejection is mediated by antibodies and complement. Humoral rejection is a relative rare but potentially fatal form of acute allograft rejection. We report two patients with left ventricular dysfunction secondary to humoral rejection, shortly after cardiac transplantation. Both patients were treated with methylprednisolone, and azathioprine was substituted by cyclophosphamide. One patient underwent plasmapheresis. The clinical outcome was satisfactory and the left ventricular function returned to normal in both cases. The diagnostic and therapeutic strategies for the management of humoral rejection are reviewed.

Antibody Formation↗

Action of thyroid hormones at the cellular level: the mitochondrial target.

Thyroid hormones exert profound effects on the energy metabolism. An inspection of the early and more recent literature shows that several targets at the cellular level have been identified. Since their effects on the nuclear signalling pathway have already been well-defined and extensively reviewed, this article focuses on the regulation of mitochondrial activity by thyroid hormones. Mitochondria, by virtue of their biochemical functions, are a natural candidate as a direct target for the calorigenic effects of thyroid hormones. To judge from results coming from various laboratories, it is quite conceivable that mitochondrial activities are regulated both directly and indirectly. Not only triiodo-L-thyronine, but also diiodothyronines are active in regulating the energy metabolism. They influence the resting metabolism in rats with 3,5-diiodo-L-thyronine seeming to show a clearer effect.

Animals↗

Infectious virus in transgenic plants inoculated with a nonviable, P1-proteinase defective mutant of a potyvirus.

A mutant (P1-616) of the tobacco vein mottling potyvirus that contains a four-codon insertion in the P1 protein coding region of the viral RNA is unable to infect the normal host plant of the virus. Processing of the P1/HC-Pro cleavage site does not occur during in vitro translation of the mutant viral RNA. When plants transformed with the P1/HC-Pro/P3 coding region of tobacco vein mottling potyvirus RNA were inoculated with P1-616, some of them became infected, although there was a delay in the production of disease symptoms. Virus isolated from these plants was able to infect nontransgenic plants. Two variants of the recovered, infectious virus contained single-nucleotide alterations in the four-codon insertion in the P1-616 genome. In vitro translation of the variant genomic RNAs resulted in partial processing of the P1/HC-Pro cleavage site, although serological analysis of infected tissue showed complete processing in vivo. These results indicate that limited complementation of P1-616 occurs in the transgenic plants and that eventually there arises one or more variants of the mutant sequence that can effect P1/HC-Pro processing and therefore be replicated.

Mutagenesis, Insertional↗

Expression of uncoupling protein-3 and mitochondrial activity in the transition from hypothyroid to hyperthyroid state in rat skeletal muscle.

We sought a correlation between rat skeletal muscle triiodothyronine (T3)-mediated regulation of uncoupling protein-3 (UCP3) expression and mitochondrial activity. UCP3 mRNA expression increased strongly during the hypothyroid-hyperthyroid transition. The rank order of mitochondrial State 3 and State 4 respiration rates was hypothyroid < euthyroid < hyperthyroid. The State 4 increase may have been due to the increased UCP3 expression, as the proton leak kinetic was stimulated in the hypothyroid-hyperthyroid transition and a good correlation exists between the State 4 and UCP3 mRNA level. As a significant proportion of an organism's resting oxygen consumption is dedicated to opposing the proton leak, skeletal muscle mitochondrial UCP3 may mediate part of T3's effect on energy metabolism.

Animals↗

Inducible acid tolerance mechanisms in enteric bacteria.

Enteric micro-organisms have developed several inducible mechanisms for surviving transient periods of extreme acid stress. Salmonella typhimurium possesses an acid tolerance response (ATR) induced in minimal medium by short exposures to mild acid stress. More than 50 acid shock proteins (ASPs) are induced during adaptation. Eight ASPs are regulated by the major iron regulatory protein, Fur, in an unusual iron-independent manner. The two-component regulator, PhoP, is an autoinduced ASP that controls the induction of three additional ASPs. The stress sigma factor sigma S is an ASP that regulates induction of eight ASPs. Acid induction of sigma S is due to its decreased proteolytic turnover via the ClpXP protease in conjunction with the two-component-type response regulator MviA (RssB in Escherichia coli). Mutations in any of these three regulators leads to a defective ATR. Repair of pH stress-induced DNA damage appears to require the Ada protein (O6-methylguanine methyltransferase) since an ada mutant is both acid and alkaline sensitive. In contrast to S. typhimurium, E. coli and Shigella have acid resistance systems induced in complex media that include a glucose-repressed system protective at pH 2.5 without amino acid supplementation, a glutamate decarboxylase system that requires glutamate and an arginine decarboxylase system unique to E. coli.

Acids↗

[The Doppler color detection of internal mammary artery anastomoses and a functional assessment of their patency].

BACKGROUND: Left internal mammary artery coronary graft patency is usually evaluated invasively by cardiac catheterization. The objective of this study was to assess the ability of a high-frequency transthoracic Doppler echocardiographic system in the evaluation of patency and flow velocities changes in left internal mammary artery. METHODS: Twenty-two patients (63 +/- 9 years, 17 male) who had previously undergone left internal mammary artery to left anterior descending artery were evaluated by transthoracic echocardiography, with an Acuson Sequoia C256 equipment (Acuson, Mountain view, USA), placing the transducer (5 MHz) in the second-third left intercostal space. Left internal mammary artery flow was considered to be found in the presence of one systolic/diastolic biphasic blood flow. Dipiridamol 0.5 mg/kg was administered in absence of contraindications in order to evaluate the flow reserve. RESULTS: In 16 patients (73%), a biphasic systolic-diastolic flow was visualized. Peak velocity of systolic and diastolic waves was 38 +/- 13 and 37 +/- 15 cm/s, respectively. Eleven patients received i.v. dipiridamol 0.5 mg/kg. After dipiridamol, systolic and diastolic velocities rose from 32 +/- 8 to 43 +/- 14 cm/s (p = 0.0429) and from 25 +/- 8 to 50 +/- 17 cm/s (p = 0.0002), respectively (an increasing of 33 +/- 22% and 103 +/- 46% over the baseline, respectively). CONCLUSION: This descriptive study shows that a non-invasive functional evaluation of left internal mammary artery grafts by a transthoracic approach with a high-frequency echocardiographic equipment is possible.

Aged↗

Non-random distribution of the pericentromeric heterochromatin in meiotic prophase nuclei of mammalian spermatocytes.

The central or peripheral distribution of condensed chromatin (CC) was studied in pachytene spermatocyte nuclei in Mus domesticus, 2n = 40; Pudu puda, 2n = 70; Ctenomys opimus, 2n = 26 and Octodon degus, 2n = 58. Species were chosen according to the morphological characteristics of their chromosomal complements and in particular, the terminal or medial chromosomal localisation of the pericentromeric constitutive heterochromatin. Counts were made by defining the areas corresponding to peripheral and central location in each nuclear section from a series. The null hypothesis (i.e. random distribution of CC) was rejected. In the nuclear sections of Mus domesticus and Pudu puda, 69% and 74% of CC, respectively, was found in the peripheral nuclear space, while in those of Octodon degus and Ctenomys opimus, 69% and 65% of CC, respectively, was found in the central nuclear space. We estimate that if the CC measured in spermatocyte nuclei corresponds mainly to pericentromeric constitutive heterochromatin, the distribution found is consistent with that expected in accordance with the nuclear architecture model for meiocytes (Fernández-Donoso, 1982; Fernández-Donoso & Berrios, 1985). This model proposes a peripheral nuclear localisation for pericentromeric heterochromatin of telocentric bivalents and a relatively central nuclear localisation for pericentromeric heterochromatin of metacentric bivalents. We also discuss some of the biological consequences that could arise from the conservation of such distributions.

Animals↗

Effects of DksA and ClpP protease on sigma S production and virulence in Salmonella typhimurium.

Salmonella typhimurium responds to a variety of environmental stresses by accumulating the alternative sigma factor sigmaS. The repertoire of sigmaS -dependent genes that are subsequently expressed confers tolerance to a variety of potentially lethal conditions including low pH and stationary phase. The mechanism(s) responsible for triggering sigmaS accumulation are of considerable interest, because they help to ensure survival of the organism during encounters with suboptimal environments. Two genes associated with regulating sigmaS levels in S. typhimurium have been identified. The first is clpP, encoding the protease known to be responsible for degrading sigmaS in Escherichia coli. The second is dksA, encoding a protein of unknown function not previously associated with regulating sigmaS levels. As predicted, clpP mutants accumulated large amounts of sigmaS even in log phase. However, dksA mutants failed to accumulate sigmaS in stationary phase and exhibited lower accumulation during acid shock in log phase. DksA appears to be required for the optimal translation of rpoS based upon dksA mutant effects on rpoS transcriptional and translational lacZ fusions. The region of rpoS mRNA between codons 8 and 73 is required to see the effects of dksA mutations. This distinguishes the role of DksA from that of HF-I (hfq ) in rpoS translation, as the HF-I target area occurs well upstream of the rpoS start codon. DksA appears to be involved in the expression of several genes in addition to rpoS based on two-dimensional SDS-PAGE analysis of whole-cell proteins. As a result of their effects on gene expression, mutations in clpP and dksA decreased the virulence of S. typhimurium in mice, consistent with a role for sigmaS in pathogenesis.

Adenosine Triphosphatases↗

Pulmonary venous flow in hypertrophic cardiomyopathy as assessed by the transoesophageal approach. The additive value of pulmonary venous flow and left atrial size variables in estimating the mitral inflow pattern in hypertrophic cardiomyopathy.

AIMS: This study was conducted to assess the characteristics of the pattern of pulmonary venous flow and to document the interaction of this flow and left atrial function with the pattern of mitral inflow in hypertrophic cardiomyopathy. METHODS AND RESULTS: Pulmonary venous and mitral flows were evaluated by the transoesophageal approach in 80 patients with hypertrophic cardiomyopathy. Left atrial size and function were measured by the transthoracic approach. Their values were compared with those obtained from 35 normal controls. Twelve patients showed significant (> 2+) mitral regurgitation. As a group, hypertrophic cardiomyopathy patients showed increased atrial reversal flow and longer deceleration time of the diastolic wave, but a wide variability of pulmonary venous flow patterns were observed. Thirty patients (37.5%) had pseudonormal mitral flow patterns. Stepwise multilinear regression analysis identified the ratio of systolic to diastolic pulmonary venous flow velocity, the ratio of velocity-time integrals of both flow waves at atrial contraction, the left atrial minimal volume and the systolic fraction as independent predictive variables of the mitral E/A wave velocity ratio (r = 0.82). By logistic regression, the former three variables were selected as independent predictive covariates of a pseudonormal mitral flow pattern (sensitivity: 83%, specificity: 90%). The ratio of velocity-time integrals of both atrial waves was the most important predictive variable in both analyses. CONCLUSIONS: The observed variability in the configuration of pulmonary venous flow velocity waveform is related to what occurs in transmitral flow in patients with hypertrophic cardiomyopathy. Significant mitral regurgitation is not an independent correlate of pseudonormal mitral inflow patterns in these patients. Our results further emphasize the complementary, additive value of the pulmonary venous flow velocity pattern and left atrial size in the interpretation of the mitral flow velocity pattern, and indirectly suggest the underlying increased left ventricular filling pressures of patients with hypertrophic cardiomyopathy and pseudonormal mitral flow patterns.

Adult↗

Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging.

AIMS: The aim of this study was to determine the utility of pulsed wave Doppler tissue imaging in the evaluation of regional left ventricular diastolic function in patients with ischaemic heart disease. METHODS AND RESULTS: In 30 normal subjects and 43 patients with ischaemic heart disease, Doppler tissue imaging was performed in each of the 16 segments of the myocardium. The following diastolic pulsed wave Doppler tissue imaging parameters were obtained for each segment: (1) regional early diastolic peak velocity (regional e wave cm.s-1); (2) regional late diastolic peak velocity (regional a wave cm.s-1); (3) regional diastolic e/a velocity ratio; and (4) the regional isovolumic relaxation time, defined as the time interval from the second heart sound to the onset of the diastolic E wave. In patients with ischaemic heart disease, each of these parameters was evaluated and compared in ischaemic and normally perfused segments, based on the presence or absence of obstructive lesions of the supplying coronary artery. In patients with coronary artery disease, several differences were observed between diseased and normal wall segments: the mean segmental peak early diastolic velocity (e wave) was reduced (mean +/- SD: 6.4 +/- 2.1 cm.s-1 vs 8.5 +/- 2.8 cm.s-1; P < 0.01); the e/a diastolic velocity ratio was decreased (0.95 +/- 0.3 vs 1.5 +/- 0.6, respectively; P < 0.01) and the regional isovolumic relaxation time was prolonged (104 +/- 36.7 ms vs 69.6 +/- 30 ms; P < 0.01. No differences were observed in any of these parameters between the normally perfused segments of ischaemic patients and normal subjects. Patients with a normal transmitral diastolic Doppler inflow pattern had a mean of 3.7 +/- 2.7 myocardial segments with a local e/a pulsed wave Doppler tissue imaging velocity ratio < 1, fewer than those with an inverted diastolic transmitral Doppler inflow pattern (10.3 +/- 3 segments; P < 0.001). Overall sensitivity and specificity for an inverted local e/a ratio and a local isovolumetric relaxation time > or = 85 ms were of 62% and 72% and 69% and 80%, respectively. CONCLUSION: Regional diastolic wall motion is impaired at baseline in ischaemic myocardial segments, even when systolic contraction is preserved. Pulsed wave Doppler tissue imaging is a useful non-invasive technique which allows the assessment of regional diastolic performance and dynamics of the left ventricular myocardium. Further studies are required to define this role in the evaluation of coronary heart disease.

Blood Flow Velocity↗

Snakin-1, a peptide from potato that is active against plant pathogens.

A new type of antimicrobial peptide, snakin-1 (SN1), has been isolated from potato tubers and found to be active, at concentrations < 10 microM, against bacterial and fungal pathogens from potato and other plant species. The action of SN1 and potato defensin PTH1 was synergistic against the bacterium Clavibacter michiganensis subsp. sepedonicus and additive against the fungus Botrytis cinerea. Snakin-1 causes aggregation of both gram-positive and gram-negative bacteria. The peptide has 63 amino acid residues (M(r) 6,922), 12 of which are cysteines, and is unrelated to any previously isolated protein, although it is homologous to amino acid sequences deduced from cloned cDNAs that encode gibberellin-inducible mRNAs and has some sequence motifs in common with kistrin and other hemotoxic snake venoms. A degenerate oligonucleotide probe based on the internal sequence CCEECKC has been used to clone an SN1 cDNA. With the cDNA used as probe, one copy of the StSN1 gene per haploid genome has been estimated and expression of the gene has been detected in tubers, stems, axillary buds, and young floral buds. Expression levels in petals and carpels from fully developed flowers were much higher than in sepals and stamens. The expression pattern of gene StSN1 suggests that protein SN1 may be a component of constitutive defense barriers, especially those of storage and reproductive plant organs.

Amino Acid Sequence↗

Multiple sclerosis: association to HLA DQalpha in a tropical population.

Studies performed in subtropical populations have found significant association between the phenotype multiple sclerosis (MS) and the major histocompatibility complex (MHC). We present the results of a case-control study conducted on a tropical population (Antioquia, Colombia) in order to detect a possible association between MS and HLA DQalpha (HLA DQA1*) alleles. Forty chromosomes belonging to MS patients were compared to two sets of controls (40 and 910 chromosomes, respectively). The HLA DQA1*0101 and DQA1*0102 alleles were found in a significantly higher proportion among the cases than among the controls, whereas the HLA DQA1*0103 allele was found in a significantly lower proportion of the cases. These results suggest that the association of HLA DQA1*0101, DQA1*0102 and DQA1*0103 to the MS phenotype found in Caucasian subtropical populations remains in individuals with MS inhabiting the tropics. This finding could mean that the major genetic component associated to the MHC in subtropical populations is the same in the tropics.

Adult↗