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P Fernandez

Publications and source records attributed to P Fernandez.

At least 73 records · Page 4Linked to original sources
PubMed1995

Substrate specificity of small-intestinal lactase: study of the steric effects and hydrogen bonds involved in enzyme-substrate interaction.

Milk lactose is hydrolysed to D-galactose and D-glucose in the small intestine of mammals by the lactase-phlorizin hydrolase complex (LPH, EC 3.2.1.23-62). Lactase activity has broad substrate selectivity and several glycosides are substrates. Recently, using the monodeoxy derivatives of methyl beta-lactoside (1), we have shown the importance of each hydroxyl group in the substrate molecule concerning the interaction with the enzyme. Now we have studied the corresponding O-methyl derivatives, as well as some of the halo derivatives of 1. We have found that the enzyme presents steric restrictions to the recognition of substrates modified in the galactose moiety. In contrast, the binding site for the aglycon part of the substrate is looser. On the other hand, we have previously shown that HO-3' and HO-6 were important for the recognition of the substrate by the enzyme. Now we have found that the corresponding fluorine derivatives are not, or very poorly, recognized. This suggests that the HO-3' and HO-6 participate, as donors, in hydrogen bonds in the interaction with the enzyme.

Animals↗
PubMed1995

Bioassay-directed chemical analysis of genotoxic components in urban airborne particulate matter from Barcelona (Spain).

Organic extracts of airborne particulate matter, collected in the city of Barcelona, were subjected to three-level, bioassay-directed, chemical fractionation, including gel permeation chromatography (GPC) and normal-phase (NP) and reversed-phase (RP) liquid chromatography (LC). The chemical characterization, directed by the Salmonella microsome mutagenicity assay (TA98, TA98NR and TA98/1,8DNP6 +/- S9), was carried out by capillary GC (CGC) coupled to selective detection systems, and by GC-MS techniques. The results obtained with the nitroreductase deficient strains show the important contribution of nitroaromatic compounds. Detailed chemical analysis of the mutagenic fractions led to the identification of 82 aromatic compounds and revealed the large contribution of chemical classes that are more polar than polycyclic aromatic hydrocarbons such as aromatic ketones, quinones and aldehydes.

Air Pollutants↗
PubMed1995

Prognostic factors influencing the outcome in pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Studies attempting to identify the prognostic factors that influence the outcome of Pneumocystis carinii pneumonia (PCP) in patients with AIDS using a multivariate analysis are few. In order to identify those prognostic factors amenable to medical intervention, univariate and multivariate analyses were performed on 102 patients with AIDS suffering a first episode of PCP. METHODS: One hundred and two consecutive patients with AIDS (51% drug abusers, 45% homosexuals, and 4% with other HIV risk factors) admitted to our institution between 1986 and 1989 whose respiratory infection was diagnosed by bronchoalveolar lavage were studied prospectively. RESULTS: The overall mortality was 28%, rising to 79% in those patients who required mechanical ventilation. According to univariate analysis the following variables were related to a poor prognosis: age > 35 years; risk factor for HIV infection other than drug abuse; and AIDS diagnosis confirmed before 1988; PaO2 < 8 kPa at admission; severe acute respiratory failure on admission (PaO2/FIO2 < 20 kPa); mechanical ventilation; antibiotic therapy for PCP other than trimethoprim-sulphamethoxazole; multiple microbial pulmonary infection; serum lactate dehydrogenase (LDH) > 22.5 mukat/l on admission; serum albumin level < 30 g/l. Multivariate analysis showed that only mechanical ventilation was independently associated with a poor outcome. CONCLUSIONS: The mortality of AIDS patients presenting with a first episode of PCP before 1990 was high (28%). The main prognostic factor associated with poor outcome was the requirement for mechanical ventilation due to severe acute respiratory failure.

AIDS-Related Opportunistic Infections↗
PubMed1994

Effect of fat feeding on human intestinal apolipoprotein B mRNA levels and editing.

Our purpose was to assess the effect of a fat-rich meal on intestinal apolipoprotein B (apoB) mRNA levels and editing. We obtained jejunal biopsies from eight healthy adults in the fasting state and 3 h after a meal containing 1 g/kg of fat. In the fasting state, 93% of the apoB mRNA contained the editing sequence resulting in apoB-48 production. Feeding induced no significant changes in apoB mRNA levels or editing. Our data are consistent with the concept that the significant increase in apoB-48 within triglyceride-rich lipoproteins in postprandial plasma is not due to alterations in apoB gene expression or editing.

Apolipoproteins B↗
PubMed1994

High passage T47D human breast cancer cells: altered endocrine and 2,3,7,8-tetrachlorodibenzo-p-dioxin responsiveness.

Low passage (L) T47D cells cultured for up to 12 months in media containing fetal bovine serum, fetal bovine serum plus 1 nM 17 beta-estradiol and estrogen-deficient media gave high passage cells denoted H, H(E+) and H(E-) cells, respectively, which exhibited differential responsiveness to 17 beta-estradiol, various growth factors, tamoxifen, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and their combinations. Moreover, the altered mitogen/antimitogen responsiveness was paralleled by changes in hormone receptor levels, cellular architecture and ploidy. Estrogen receptor binding levels in the H, L and H(E+) cells varied from 36 to 155 fmol/mg protein; in contrast, the estrogen receptor binding in H(E-) cells exhibited a time-dependent increase from 81 to 1229 fmol/mg after culturing in estrogen-deficient media for approximately 12 months. Gel mobility shift assays of the nuclear estrogen receptor extracts from high and low passage cells with 32P-labeled estrogen responsive element showed that levels of the estrogen receptor-estrogen responsive element retarded band were lower in all the high passage cells compared to the low passage cells. These studies further illustrate the genetic instability of the T47D human breast cancer cell line and the resulting changes in mitogen and antimitogen responsiveness. In addition, the high passage H(E-) cells which express high estrogen receptor but low estrogen responsive element binding represent a unique model system for investigating the cellular and molecular biology of breast cancer cells which appear to be estrogen receptor-positive but are insensitive to antiestrogens.

Base Sequence↗
PubMed1994

Future evaluation of antiarrhythmic therapy.

The expansion of antiarrhythmic therapy beyond pharmacologic agents to include surgery, devices, and ablation procedures, plus the reaffirmation by the Cardiac Arrhythmia Suppression Trial (CAST) of the need for concurrent placebo-controlled trials to establish a mortality benefit, have resulted in the need to consider the requirements for evaluating therapy. Pharmacologic therapy may be used in three ways: (1) primary; (2) alternative; and (3) adjunctive. To accurately identify a mortality benefit from primary therapy, a placebo-controlled study is necessary. In contrast, control of symptoms may be identified without the same rigorous demands. Current data are limited by the absence of true negative controls for most interventions that claim a possible mortality benefit. Alternative therapy provides a choice between equally effective therapies, neither of which has necessarily been documented to have a mortality benefit. Adjunctive therapy is that which is used for control of symptoms, whereas another therapy is used to provide a presumed or proved mortality benefit. For any of these approaches, therapy must be further evaluated in terms of four modifying variables: (1) impact of therapy on the basis of both its efficacy and efficiency; (2) interpretation of outcome data based on analysis of competing risks; (3) measurement of efficacy in terms of extension of life; and (4) analysis of outcome as the equilibrium between antiarrhythmic benefit and proarrhythmic risk. With these approaches a rational analysis of the effect of therapy and its cost-based benefit can be achieved.

Anti-Arrhythmia Agents↗
PubMed1993

Pleural pressure measured in the zone of apposition of diaphragm to rib cage in rabbits.

In 10 anesthetized adult rabbits, we studied the effect of spontaneous breathing and positive pressure ventilation on pleural pressure on the costal lung surface (Ppl) and in the zone of apposition of the rib cage to the diaphragm (Papp). Ppl and Papp were measured by rib capsules installed in the 5th or 6th rib and 11th or 12th rib, respectively. Esophageal (Pes) and gastric (Pga) pressures were measured with air-filled balloons. At end expiration (functional residual capacity), Ppl was subatmospheric (-2.5 +/- 1.4 cm H2O), decreased during spontaneous inspiration, and was in phase with Pes. In contrast, Papp was above atmospheric pressure (2.1 +/- 1.8 cm H2O), increased during inspiration, and was in phase with Pga. Papp lagged Ppl by 180 degrees during spontaneous inspiration but was in phase with Ppl during mechanical ventilation. Changes in Ppl (delta Ppl) during inspiration were greater in magnitude than either delta Papp or delta Pga. Changes in transdiaphragmatic pressure in the zone of apposition (delta Pga-delta Papp) were near zero (-0.4 +/- 0.3 cm H2O), much smaller in magnitude than those (delta Pga-delta Ppl) associated with the lung (3.0 +/- 1.5 cm H2O). These results are consistent with the concept that during breathing, abdominal pressure is transmitted to the zone of apposition of the rib cage to the abdomen. During spontaneous breathing at rest, the pleural space in the zone of apposition is mechanically independent of the pleural space associated with the lung.

Animals↗
PubMed1993

Osteomyelitis associated with chronic periodontitis in a patient with end-stage renal disease: a case report.

The end-stage renal patient undergoing dialysis is susceptible to a number of infections. We report a case of localized suppurative osteomyelitis of the jaws, secondary to periodontitis, in a patient with chronic renal failure, with review of the physiologic and biochemical changes associated with renal failure. The clinical, radiographic, histologic, and microbiologic findings are presented with a discussion of the differential diagnosis and treatment provided.

Aged↗
PubMed1992

Growth inhibitory and antimitogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in T47D human breast cancer cells.

The T47D human breast cancer cells used in this study express relative high levels of the progesterone receptor (637 +/- 118 fmol/mg protein) and lower levels of the estrogen and aryl hydrocarbon (Ah) receptors (81 +/- 3.4 and 55 +/- 8.2 fmol/mg protein, respectively). Treatment of these cells with 0.1, 1.0 and 10 nM concentrations of 17 beta-estradiol, transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) resulted in concentration-dependent increase in cell proliferation and the ratios of mitogen-treated/control cell numbers were 2.46, 2.00 and 1.90, respectively. In contrast, insulin did not significantly stimulate T47D cell proliferation and insulin-like growth factor-I (IGF-I) was active only at a concentration of 10 nM. In parallel studies, the proliferative agents also stimulated the uptake of [3H]thymidine into cellular DNA. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) did not affect T47D cell growth at concentrations of 0.1 and 1.0 nM, whereas at a concentration of 10 nM a 44% decrease in cell numbers was observed. In cells cotreated with TCDD plus 100 ng/ml insulin or 10 nM 17 beta-estradiol, EGF, TGF-alpha and IGF-I, TCDD caused a concentration-dependent decrease in cell proliferation and [3H]thymidine uptake. For example, at a 10 nM concentration of TCDD there was a 32, 45, 29, 25 and 32% decrease in the 17 beta-estradiol, TGF-alpha, EGF, IGF-I and insulin-induced cell growth, respectively. These results confirm the antiproliferative activity of TCDD in T47D cells and this was similar to results previously reported in MCF-7 human breast cancer cells for the interaction of TCDD and 17 beta-estradiol. In addition, the data also show that TCDD inhibits the growth stimulatory effects of other polypeptide growth factors in T47D cells.

Breast Neoplasms↗
PubMed1992

[Cholelithiasis in childhood. Proposals based on a multicentric study].

Fifty six cases of cholelithiasis in patients aged two months to 15 years (mean age 7.65 years) concerning to 11 hospitals are reviewed. The study protocol followed was the same in all medical records, although own criterions were considered on management performed in each center. From the cases, it follows: 1. Male/female rate is 1/1.5. 2. Symptomatology in infancy is relatively poor and pain localization is not orientative. 3. It was an incidentally finding in 41 per 100 of the cases. 4. Ultrasonography is the best examination procedure rendering diagnosis in the 51 cases it was underwent. 5. Hematologic study was abnormal in six of 46 cases. 6. Medical treatment was not performed in any hospital. 7. Existence of "lithogenic families" seems to be demonstrated. 8. The presence of four patients with Down syndrome in this series must be pointed out. 9. Among total 56 cases, 21 underwent surgical treatment, 29 were conservatively treated, two have died and four patients had spontaneous stone resolution. 10. In the face of these, we propose: A) Surgical treatment in symptomatic cases, porcelain gallbladder and nonfunctionating gallbladder. B) Expectant management and sonographic monitoring in asymptomatic cases. C) Carefully evaluation in patients with predisposing factors and patients with recurrent abdominal pain.

Adolescent↗
PubMed1991

Usefulness of the automatic implantable cardioverter defibrillator in improving survival of patients with severely depressed left ventricular function associated with coronary artery disease.

Clinical outcome was analyzed among a group of 39 consecutive patients with coronary artery disease, left ventricular (LV) ejection fractions less than 30% and arrhythmias that required an automatic implantable cardioverter defibrillator (AICD) in an attempt to better define the role of the device in patients with severely depressed LV function. Twenty-nine (74%) were survivors of out-of-hospital cardiac arrest and 10 (26%) had ventricular tachycardia that was refractory to electrophysiologically guided antiarrhythmic therapy. The study group had the following demographic characteristics: 90% were men, mean age was 64 years (range 41 to 79) and mean LV ejection fraction was 21 +/- 4%. Concomitant pharmacotherapy included antiarrhythmic drugs 31 (79%), vasodilators in 22 (56%) and digoxin in 20 (51%). There was no statistical difference in baseline characteristics between survivors and nonsurvivors. Patients were followed for a mean of 24 months (range 2 to 72) from implantation. The difference between actuarial survival--77% at 1 year and 72% at 2 years--and projected survival without the AICD (patients who survive without appropriate device discharge)--30% at 1 year and 21% at 2 years--was significant (p less than 0.01 and less than 0.05 at 1 and 2 years, respectively). This study suggests that the AICD improves survival in patients with coronary artery disease despite severely depressed LV function.

Adult↗
PubMed1991

A fatal case of parenteral paraquat poisoning.

The chief clinical and analytical aspects of the suicide of a 21-year-old male with psychiatric problems by parenteral administration of a 200 g/l aqueous solution of paraquat are described. Paraquat levels were determined in plasma, urine, kidney, liver and lung after autopsy. Tissue damage was studied by electron microscopy. The death ensued from pulmonary dysfunction 15 days after hospital admission.

Adult↗
PubMed1991

The implantable cardioverter-defibrillator: clinical results.

To evaluate the effectiveness of the automatic implantable cardioverter-defibrillator (AICD), a 7-year experience, from 1983-1990, was reviewed. A total of 111 patients received an AICD device. Their ages ranged between 8 and 83 years. Mean age was 63.9 years. There were 91 men and 20 women. Eighty of the patients received the AICD following an out-of-hospital cardiac arrest, while 31 were suffering from intermittent symptomatic ventricular tachycardia. The underlying etiology in 97 patients (87%) was ischemic coronary artery disease, in 11 patients (10%) dilated cardiomyopathy, and in 3 patients (3%) idiopathic ventricular fibrillation. Mean ejection fraction was 33.2%. Implantation of the AICD was performed via a left thoracotomy in 39 patients, median sternotomy in 49 patients and subxiphoid-subcostal approach in 23 patients. In-hospital mortality occurred in one patient who suffered an acute myocardial infarction 4 hours postoperatively. Out-of-hospital mortality was observed in 19 patients. There were two arrhythmic deaths. Follow-up was available for 107 patients. Mean follow-up was 33.1 months. Sixty-six patients (62%) had AICD shocks. The initial appropriate shocks occurred during the first postimplantation year in 91% of the patients. In 53 of the survivors, initial AICD shocks took place within 4.4 +/- 4.7 months from implantation. Thirteen of the 20 patients who died had received appropriate AICD shocks. In these patients, the time between implantation and first shock was 2.7 +/- 3.6 months whereas the time between implantation and death was 11.3 +/- 10.3 months (NS). We conclude that the AICD is effective in converting ventricular tachyarrhythmias and prolongs survival.

Electric Countershock↗