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Biomedical subjects

M A Martinez

Publications and source records attributed to M A Martinez.

At least 37 records · Page 2Linked to original sources
PubMed1997

Membranous glomerulonephritis associated with hepatitis C virus infection in renal transplant patients.

BACKGROUND: Hepatitis C virus (HCV) infection has been described in association with various types of glomerular diseases, usually type I membranoproliferative glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this article, we describe the first series of MGN exhibited in renal transplant patients and associated with HCV infection. METHODS: From January 1980 to December 1994, 2045 kidney transplantations were performed in our renal transplant units. A retrospective analysis demonstrated an overall 20% prevalence of HCV virus-positive patients; 409 transplanted patients were HCV positive (ELISA and RIBA). RESULTS: Fifteen patients developed an allograft MGN (3.66%) 24 months after renal transplantation. MGN appeared in the form of significant proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy demonstrated a thickening of the capillary wall, subepithelial electron-dense deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten cases were considered de novo, two cases were considered recurrent MGN, and three cases were considered undetermined because the primary renal disease was chronic glomerulonephritis. All patients showed negative antinuclear antibodies and cryoglobulins, normal complement, and negative rheumatoid factors. During follow-up (an average of 2 years), 12 patients developed a progressive worsening of renal function, with increased serum creatinine and persistent proteinuria; 8 of the 12 patients returned to dialysis. Of the remaining three cases, two patients showed partial remission of nephrotic syndrome after high doses of steroids, and one patient persisted with stable renal function and proteinuria (<2 g/24 h.). CONCLUSIONS: In summary, HCV is preferentially associated with MGN in renal transplant patients, rather than with membranoproliferative glomerulonephritis as in the normal adult population. MGN associated with HCV infection has a similar clinical picture and outcome to posttransplant idiopathic de novo MGN, with persistent massive proteinuria and progressive deterioration of renal function.

Adult↗
PubMed1997

Recurrent type III membranoproliferative glomerulonephritis after kidney transplantation.

The first well-documented case of recurrent type III membranoproliferative glomerulonephritis after kidney transplantation is reported in this article. A 48-year-old man was admitted to the hospital because of nephrotic syndrome and moderate renal failure. The renal biopsy showed double-contour images at light microscopy. Electron microscopy revealed electron-dense deposits in the mesangium and in both the subepithelial and subendothelial sides of the basement membrane. Subepithelial deposits were sometimes hump-like and produced an irregular disruption of the lamina densa. A diagnosis of type III membranoproliferative glomerulonephritis was suggested. The patient had a rapid decrease in renal function and received dialysis in 3 months. Three years later, he received a cadaveric kidney transplant, and subsequently recovered normal renal function. Proteinuria appeared after 13 months, and a biopsy of the graft demonstrated recurrence of the original disease. Seven years after transplantation, he returned to hemodialysis.

Biopsy↗
PubMed1997

Prenatal dexamethasone administration to premature rats exposed to prolonged hyperoxia: a new rat model of pulmonary fibrosis (bronchopulmonary dysplasia).

OBJECTIVE: To evaluate the postnatal effects of prenatal dexamethasone treatment of preterm rats and to test the hypothesis that prenatal dexamethasone treatment projects against pulmonary oxygen toxicity in the preterm rats and stimulates lung antioxidant enzyme levels in response to hyperoxia. STUDY DESIGN: We administered dexamethasone (0.4 mg/kg, intraperitoneally), or equivolume saline solution to pregnant rats at 48 and 24 hours before premature delivery at gestation day 21. Both groups of prematurely delivered rat pups were randomly assigned to other > 95% O2 or room air immediately after birth and brief resuscitation. RESULTS: The hyperoxic survival rates from day 1 through day 14 were similar in both dexamethasone-treated and control preterm O2 groups. At 7 days of hyperoxia, the preterm pups demonstrated similar lung antioxidant enzyme activity and sufactant content responses to high O2 in the dexamethasone-treated and control groups. Lung quantitative morphometry changes were similar (equal degree of inhibition of normal alveolar development) in both groups. Unexpectedly, the lungs of the preterm O2 control rats showed evidence of septal fibrosis and the pups that received dexamethasone-O2 showed even greater severity of septal fibrosis and a greater increase (+50%) of lung hydroxyproline compared with the O2 groups control rats. CONCLUSIONS: In preterm animals, prenatal dexamethasone administration does not show any of the hypothesized protective effects against hyperoxia or protective biochemical lung changes during prolonged O2 exposure. However, prenatal dexamethasone administration with prolonged exposure of the preterm rat to hyperoxia results in a pulmonary pathologic picture quite similar to bronchopulmonary dysplasia.

Animals↗
PubMed1996

Exploring the functional robustness of an enzyme by in vitro evolution.

The evolution of natural proteins is thought to have occurred by successive fixation of individual mutations. In vitro protein evolution seeks to accelerate this process. RNA hypermutagenesis, cDNA synthesis in the presence of biased dNTP concentrations, delivers elevated mutant and mutation frequencies. Here lineages of active enzymes descended from the homotetrameric 78 residue dihydrofolate reductase (DHFR) encoded by the Escherichia coli R67 plasmid were generated by iterative RNA hypermutagenesis, resulting in >20% amino acid replacement. The 22 residue N-terminus could be deleted yielding a minimum functional entity refractory to further changes, designating it as a determinant of R67 robustness. Complete substitution of the segment still allowed fixation of mutations. By the facile introduction of multiple mutations, RNA hypermutagenesis allows the generation of active proteins derived from extant genes through a mode unexplored by natural selection.

Amino Acid Sequence↗
PubMed1996

Fate of direct and inverted repeats in the RNA hypermutagenesis reaction.

RNA hypermutagenesis results from cDNA synthesis in the presence of highly biased dNTP precursor concentrations and preferentially exploits human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Such reaction conditions slow down DNA synthesis, which might be conducive to strand transfer and deletion. This has been investigated. A 6 bp inverted repeat nested between 10 bp repeats was efficiently deleted at dCTP concentrations typically used. Inter- or intramolecular strand transfer between 10 bp repeated sequences separated by runs of templated G residues occurred, but at lower concentrations. If RNA hypermutagenesis of a sequence containing direct and inverted repeats is unavoidable, avian myeloblastosis virus (AMV) reverse transcriptase could be used, as strand transfer occurs with much diminished dCTP substrate dependence.

Animals↗
PubMed1996

Toxicokinetics of deltamethrin and its 4'-HO-metabolite in the rat.

The toxicokinetics of deltamethrin and its metabolite 4'-HO-deltamethrin after single doses of 26 mg of deltamethrin/kg (oral) or 1.2 mg of deltamethrin/kg (intravenous) were studied in male Wistar rats. Serial blood samples were obtained after oral and intravenous administration. Brain, vas deferens, and anococcygeus tissue samples were also obtained after oral administration. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, vas deferens, and anococcygeus concentrations of deltamethrin and 4'-HO-deltamethrin were determined by a high-performance liquid chromatographic assay. The deltamethrin and 4'-HO-deltamethrin plasma profiles could be adequately described by a two-compartment open model. For deltamethrin and 4'-HO-deltamethrin, the elimination half-lives (t1/2 theta) from plasma were 33.0 and 25.67 hr after iv and 38.50 and 30.13 hr after po administration of deltamethrin parent compound. The apparent volume of distribution [V alpha(area)] and volume of distribution at steady state [V d(m)] for deltamethrin were 5.33 and 2.04 liters, respectively, after iv administration, suggesting a considerable diffusion of the pyrethroid into tissue. The total plasma clearance of deltamethrin was the same for both the oral and the iv routes-0.11 liter/hr. After the single oral dose, deltamethrin was rapidly absorbed with a Tmax of 1.83 hr. The maximum plasma concentrations of deltamethrin and 4'-HO-deltamethrin were 0.46 and 0.26 microgram/ml. The maximum plasma concentration of 4'-HO-deltamethrin was achieved at 3.29 hr. The oral bioavailability of deltamethrin was found to be 14.43%. The tissue concentration time data for deltamethrin and its metabolite 4'-HO-deltamethrin were found to fit a one-compartment open model. Considerable concentrations of deltamethrin and 4'-HO-deltamethrin were found in the hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, vas deferens, and anococcygeus tissues. The elimination half-lives (t1/2 el) for both deltamethrin and 4'-HO-deltamethrin were somewhat smaller for the cerebellum, frontal cortex, caudate putamen, medulla oblongata, vas deferens, and anococcygeus tissues (range, 18-33 hr for deltamethrin and 15-28 hr for 4'-HO-deltamethrin) than for plasma (t1/2 el, 38.50 and 30.13 hr, respectively). Exceptions were seen for the hypothalamus and hippocampus in which the t1/2et's for deltamethrin were 40.76 and 38.50 hr, respectively. Nervous tissue accumulation of deltamethrin and its metabolite 4'-HO-deltamethrin was evidenced by the tissue/plasma area under the concentration (AUC) versus time curve ratios. The ratios of AUCtissue/AUCplasma for deltamethrin were 2.32 in medulla oblongata, 295.30 in hypothalamus, and intermediate in other tissues.

Administration, Oral↗
PubMed1996

Induction of cytochrome P4501A1 and P4504A1 activities and peroxisomal proliferation by fumonisin B1.

The effects of repeated exposure to fumonisin B1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demethylation of erythromycin (CYP3A1) and the hepatic O-deethylation of ethoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also increased the renal O-deethylation of ethoxyresorufin. The liver, but not the kidney, was also susceptible to FB1-dependent induction of the 12- and 11-hydroxylation of lauric acid, suggesting induction of the CYP4A subfamily. Immunoblot studies employing solubilized microsomes from FB1-treated rats revealed that FB1, at the two highest doses, increased the apoprotein levels of CYP1A1 and CYP4A1. The same treatment with FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl-CoA hydratase trifunctional protein. The possible implications of these findings to the hepatocarcinogenicity of this mycotoxin are discussed.

Animals↗
PubMed1995

Effects of flumethrin on hepatic drug-metabolizing enzymes and antipyrine disposition in rats.

The effects of repeated exposure to the pyrethroid insecticide flumethrin (40 mg/kg intraperitoneally once a day for 6 days) on the activity of cytochrome P450-dependent monooxygenases and UDP-glucuronosyltransferase as well as on antipyrine disposition were investigated in male Wistar rats. Pretreatment with flumethrin decreased the activities of NADPH-cytochrome c reductase (38%), aniline hydroxylase (53%), aminopyrine N-demethylase (54%), and UDP-glucuronosyltransferase (34%), and the content of cytochrome P450 (36%) in hepatic microsomes. Total plasma clearance of antipyrine was decreased by flumethrin pretreatment (54%), while the elimination half-life at beta phase and the mean residence time of antipyrine were increased (96 and 88%, respectively). Urinary excretion of norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine was decreased by 60, 38, and 33%, respectively, in the 96 hr after flumethrin treatment. In addition, the rate constants for formation of each of these metabolites were decreased by an average of approximately 74%. These findings provide evidence that flumethrin exposure diminishes hepatic enzyme levels and catalytic activities of monooxygenase systems as well as oxidative metabolism of antipyrine.

Animals↗
PubMed1995

Identification and biotyping of Acinetobacter spp. isolated in Chilean hospitals.

Two hundred and eighty-one isolates of Acinetobacter spp. obtained from clinical specimens in hospitals from five Chilean cities were identified to species level and biotyped. Respiratory tract and wound secretions were the main sources of the isolates. Acinetobacter baumannii was the most frequent species (96.8%), followed by Acinetobacter genospecies 3 (2.8%). Twelve different biotypes of A. baumannii strains were found of which biotypes 9, 8 and 6 were the most frequent. Isolates of other biotypes were rare. These results differ from most other Latin American and European countries.

Acinetobacter↗
PubMed1995

Pharmacokinetics and tissue residues of norfloxacin and its N-desethyl- and oxo-metabolites in healthy pigs.

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight. After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a tmax of 1.46 +/- 0.06 h. The elimination half-life (t1/2 beta) and the mean residence time of norfloxacin in plasma were 4.99 +/- 0.28 and 6.05 +/- 0.22 h, respectively, after i.m. administration and 3.65 +/- 0.16 and 3.34 +/- 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 +/- 4.4%. Plasma concentrations greater than 0.2 microgram/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 +/- 0.03 micrograms/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases (t1/2 alpha, t1/2 beta) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacin and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 microgram/g on day 12 after the end of dosing.

Absorption↗
PubMed1994

Hypermutagenesis of RNA using human immunodeficiency virus type 1 reverse transcriptase and biased dNTP concentrations.

The finding of G-->A hypermutated retroviral genomes in which up to 40% of guanines may be substituted by adenines was proposed to result from the depletion of the intracellular dCTP concentration and suggested a means to hypermutagenize nucleic acids. Using a RNA/reverse transcriptase ratio of approximately 1:30, comparable to that within the retroviral replication complex, G-->A hypermutants were produced in a simple in vitro reaction using highly biased dNTP concentrations--i.e., a low ratio of [dCTP]/[dTTP]. Up to 38% of G residues could be substituted, the proportion being inversely proportional to the concentration of dCTP. As G-->A hypermutation resulted from elongation beyond multiple rG.dT mismatches, U-->C hypermutants resulting from multiple rU.dG mismatches were sought, and found, during cDNA synthesis using low [dATP] and high [dGTP]. Mixed G-->A and U-->C hypermutants could also be produced under conditions of low [dCTP] plus low [dATP] and high [dTTP] plus high [dGTP]. Hypermutagenesis should allow jumping through, and subsequent exploration of, sequence space to a greater degree than heretofore and, in conjunction with genetic screening, might be of use in the search of proteins or ribozymes with novel or enhanced properties.

Adenine↗
PubMed1994

Autoantibodies to a transfer RNA-associated protein in a murine model of chronic graft versus host disease.

We established chronic graft vs host disease (GVHD) in (C57BL/10 x DBA/2)F1 mice with an injection of lymphoid cells from the parental DBA/2 strain. In addition to Abs earlier reported, of the 20 animals studied 13 developed Abs against transfer RNA/protein particles. Ten of the 13 sera immunoprecipitated a similar-sized RNA that co-migrated in PAGE with isoleucine tRNA. In immunoblots against proteins affinity purified using anti-isoleucyl-tRNA synthetase prototype serum, 7 of the 10 sera reacted with a polypeptide of 76 kDa that was similar in size to a protein recognized by a human anti-isoleucyl-tRNA synthetase serum. Three of 10 sera significantly and specifically inhibited isoleucyl-tRNA synthetase enzyme activity and one inhibited lysyl-tRNA synthetase activity. These data suggest that the autoantibodies to tRNA-associated proteins that develop in GVHD mice may react with amino acyl-tRNA synthetases, particularly those belonging to the multienzyme complex. Such autoantibodies are associated with myositis in humans, and these mice showed evidence compatible with myositis that appeared to be a manifestation of their GVHD. No previous example of spontaneous development of antisynthetases in animals has been described. We also demonstrated the presence of Abs against the NOR:90 nucleolar Ag as a new target in chronic GVHD. We conclude that chronic GVHD in mice provides a model for the study of the autoimmune responses that characterize human diseases such as mixed connective tissue disease, scleroderma, SLE, and myositis with a wider autoantibody response than that described so far.

Animals↗
PubMed1993

Prenatal diagnosis of exencephaly.

This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post-partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly.

Adult↗
PubMed1993

Branchio-oto-renal syndrome: incidence in three generations of a family.

It is well known that the persistence of alterations in the normal embryological development of branchial arches can lead to preauricular and cervical fistulas within a family. However, until 1970, there were no reports of dysplasia affecting the branchial, otic, and renal systems (BOR syndrome) with dominant autosomic inheritance. The authors report on a family with BOR syndrome of different expressivity in three generations, and describe an unusual case of bilateral fistulas of the first and second branchial arches in a newborn.

Abnormalities, Multiple↗
PubMed1993

Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus infection: demonstration of p24 antigen in endothelial cells.

We report a case of thrombotic thrombocytopenic purpura (TTP) in a woman infected with human immunodeficiency virus (HIV) in whose endothelial cells we detected HIV p24 antigen. The patient had an excellent response to conventional therapy for TTP and remained in complete remission 12 months after diagnosis. We also present a review of the literature on the association of TTP with HIV infection and speculate on its nature. The presence of HIV p24 antigen in the endothelial cell might be indicative of a role of virus, yet to be defined, in the pathogenesis of HIV-associated TTP.

Adult↗
PubMed1993

Encrusted pyelitis and cystitis by Corynebacterium urealyticum (CDC group D2): a new and threatening complication following renal transplant.

We evaluated the pathogenic role of Corynebacterium urealyticum in the development of encrusted pyelitis (EP) and encrusted cystitis (EC), and their clinical consequences in renal transplant recipients. During a 4-year period, we studied seven renal transplant recipients with EP and two with EC. The records of 320 other renal transplant patients studied during the same period were used as a control group. C urealyticum (> or = 10(5) CFU/ml) was isolated from 4 patients with EP (urine 3, blood 1) and from 1 patient with EC (urine). Alkaline urines with struvite crystals, microscopic hematuria, and sterile conventional urine cultures were present in all our cases. All the patients with EP developed obstructive uropathy with deterioration of the renal function and pyelonephritis (4 patients) or renal abscesses (3 patients). Chronic urinary discomfort and macroscopic hematuria were present in the 2 patients with EC. Long-term vesical and ureteral catheterization were considered the most important risk factors for the development of EC and EP, respectively. Vancomycin was successfully used in 5 cases, but all the patients required a derivative procedure or a surgical resection of the incrustations to improve. We conclude that EP and EC should be investigated in renal transplant patients who develop pyelonephritis, obstructive uropathy, or chronic urinary symptoms. EP and EC could lead to the loss of their grafts. C urealyticum appears to have a pathogenic role in these entities.

Adult↗
PubMed1993

Chronic renal insufficiency after an episode of macroscopic hematuria in IgA nephropathy.

Several cases of acute renal failure associated with episodes of macroscopic hematuria (EMH) in IgA nephropathy (IgAN) have been reported; in every case renal function returned to normal. We report 2 cases with previous normal renal function that developed acute renal failure during EMH of 17 and 30 days duration, respectively. Renal biopsies showed mesangial proliferation with IgA deposits, crescents in 10-15% of glomeruli and a marked tubular necrosis with red blood cell casts obstructing the lumen in 30-45% of tubules. Although renal function improved after EMH cessation, it did not recover previous normal values. Thus, EMH can produce permanent loss of renal function in patients with IgAN.

Creatinine↗