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Biomedical subjects

M Rivera

Publications and source records attributed to M Rivera.

At least 19 recordsLinked to original sources
PubMed2001

Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features.

Myelodysplastic syndrome (MDS) and T-cell large granular lymphocytic disease (T-LGL) are bone marrow failure disorders. Successful use of immunosuppressive agents to treat cytopenia in MDS and LGL suggests a common pathophysiology for the two conditions. Of 100 patients with initial diagnoses of either MDS or T-LGL referred to the National Institutes of Health for immunosuppressive treatment of cytopenia, nine had characteristics of both T-LGL and MDS (T-LGL/MDS). Fifteen patients with T-LGL received cyclosporin (CSA) (10 responses). Eight out of nine patients with T-LGL/MDS received CSA (two responses) and one patient received ATG (one response). Of 76 patients with MDS, eight received CSA (one response) and 68 received ATG (21 responses). The response to immunosuppression was significantly lower in patients with T-LGL/MDS and MDS than in patients with T-LGL disease alone (28% vs. 66%, P = 0.01). The proportion of T-helper cells and T-suppressor cells with an activated phenotype (HLA-DR(+)) was increased in patients with T-LGL, T-LGL/MDS and MDS, but the increase in activated T-suppressor cells in patients with T-LGL/MDS was not statistically significant. Autoreactive T cells may suppress haematopoiesis and contribute to the cytopenia in T-LGL and some patients with MDS, leading to T-LGL/MDS. The lower response rate of MDS or T-LGL/MDS to immunosuppression, compared with T-LGL alone, may reflect the older age and intrinsic stem cell abnormalities in MDS and T-LGL/MDS patients.

Adult↗
PubMed2000

Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8(+) T-cell responses in vivo.

Liposomes have been proposed as a vehicle to deliver proteins to antigen-presenting cells (APC), such as dendritic cells (DC), to stimulate strong T cell-mediated immune responses. Unfortunately, because of their instability in vivo and their rapid uptake by cells of the mononuclear phagocyte system on intravenous administration, most types of conventional liposomes lack clinical applicability. In contrast, sterically stabilized liposomes (SL) have increased in vivo stability. It is shown that both immature and mature DC take up SL into neutral or mildly acidic compartments distinct from endocytic vacuoles. These DC presented SL-encapsulated protein to both CD4(+) and CD8(+) T cells in vitro. Although CD4(+) T-cell responses were comparable to those induced by soluble protein, CD8(+) T-cell proliferation was up to 300-fold stronger when DC had been pulsed with SL-encapsulated ovalbumin. DC processed SL-encapsulated antigen through a TAP-dependent mechanism. Immunization of mice with SL-encapsulated ovalbumin led to antigen presentation by DC in vivo and stimulated greater CD8(+) T-cell responses than immunization with soluble protein or with conventional or positively charged liposomes carrying ovalbumin. Therefore, the application of SL-encapsulated antigens offers a novel effective, safe vaccine approach if a combination of CD8(+) and CD4(+) T-cell responses is desired (ie, in anti-viral or anti-tumor immunity).

Adoptive Transfer↗
PubMed2000

External dissipation in driven two-dimensional turbulence

Turbulence in a freely suspended soap film is created by electromagnetic forcing and measured by particle tracking. The velocity fluctuations are shown to be adequately described by the forced Navier-Stokes equation for an incompressible two-dimensional fluid with a linear drag term to model the frictional coupling to the surrounding air. Using this equation, the energy dissipation rates due to air friction and the film's internal viscosity are measured, as is the rate of energy injection from the electromagnetic forcing. Comparison of these rates demonstrates that the air friction is a significant energy dissipation mechanism in the system.

Journal Article↗
PubMed2000

Hemin is kinetically trapped in cytochrome b(5) from rat outer mitochondrial membrane.

Cytochrome b(5) from the outer mitochondrial membrane of rat liver (OM cyt b(5)) is substantially more stable to thermal and chemical denaturation than cytochrome b(5) from the endoplasmic reticulum of bovine liver (microsomal, or Mc cyt b(5)). In contrast, the corresponding apoproteins have similar stability, suggesting stronger interactions between hemin and the polypeptide in OM cyt b(5). Whereas complete transfer of hemin from bovine Mc cyt b(5) to apomyoglobin at pH 5.2 takes less than 1 h, hemin transfer from OM cyt b(5) is unmeasurably slow. Coupled with the previously reported 1:1 ratio of hemin orientational isomers in OM cyt b(5), this finding suggests that the cofactor is kinetically trapped under physiologically relevant conditions. This conclusion is confirmed by (1)H NMR studies which show that the hemin isomeric ratio changes when the protein is incubated for several hours at 68 degrees C. Interestingly, the orientational isomer favored in OM cyt b(5) is the form less favored in all other known cytochromes b(5).

Animals↗
PubMed2000

Endothelial dysfunction in arterial hypertension.

Systemic arterial pressure is a dynamic and reactive physiological parameter depending on a great many factors. The endothelial cells of the vascular system are responsible for many biochemical reactions maintaining vascular homeostasis and therefore arterial pressure. Arterial hypertension, atherosclerosis and endothelial dysfunction constitute risk factors increasing morbidity and mortality of cardiovascular origin. These three elements are closely related and frequently act simultaneously damaging different organs. In this paper we review the physiology of the endothelium and the probable consequences of endothelial dysfunction on the pathophysiology of arterial pressure.

Arteries↗
PubMed2000

Diabetes and hypertension physiopathology and therapeutics.

Diabetes mellitus by itself, is a frequent and increasing public health problem. The prevalence in most Western countries varies between 2 to 5% and it is rapidly increasing in Asiatic countries due to changes in dietary habits during the last years. The association between diabetes mellitus and hypertension has been described in 60 to 65% of diabetics. In hypertension we find insulin resistance mainly in skeletal muscle involving the conversion of glucose to glycogen independently of blood flow. The degree of resistance is related to the severity of hypertension and varies between races. States of hyperinsulinaemia and insulin-resistance have been postulated as causes and/or consequences of hypertension. Regardless of the type of diabetes, hypertension is two to three times more common among diabetics compared with non-diabetics. In this paper we propose to review the essential physiopathological mechanisms involved in this association that causes high morbidity and mortality rates and increases disability among the population involved.

Antihypertensive Agents↗
PubMed2000

Modulation of redox potential in electron transfer proteins: effects of complex formation on the active site microenvironment of cytochrome b5.

The reduction potential of cytochrome b5 is modulated via the formation of a complex with polylysine at the electrode surface (Rivera et al., Biochemistry, 1998, 37, 1485). This modulation is thought to originate from the neutralization of a solvent exposed heme propionate and from dehydration of the complex interface. Although direct evidence demonstrating that neutralization of the charge on the heme propionate contributes to the modulation of the redox potential of cytochrome b5 has been obtained, evidence demonstrating that water exclusion from the complex interface plays a similar role has not been conclusive. Herein we report the preparation of the V45I/V61I double mutant of rat liver outer mitochondrial membrane (OM) cytochrome b5. This mutant has been engineered with the aim of restricting water accessibility to the exposed heme edge of cytochrome b5. The X-ray crystal structure of the V45I/V61I mutant revealed that the side chain of Ile at positions 45 and 61 restricts water accessibility to the interior of the heme cavity and protects a large section of the heme edge from the aqueous environment. Electrochemical studies performed with the V45I/V61I mutant of cytochrome b5, and with a derivative in which the heme propionates have been converted into the corresponding dimethyl ester groups, clearly demonstrate that dehydration of the heme edge contributes to the modulation of the reduction potential of cytochrome b5. In fact, these studies showed that exclusion of water from the complex interface exerts an effect (approximately 40 mV shift) that is comparable, if not larger, than the one originating from neutralization of the charge on the solvent exposed heme propionate (approximately 30 mV shift).

Binding Sites↗
PubMed2000

Clinical and laboratory evidence for a trilineage haematopoietic defect in patients with refractory Diamond-Blackfan anaemia.

Diamond-Blackfan anaemia (DBA) is a constitutional pure red cell aplasia presenting in early childhood. In some patients, neutropenia and/or thrombocytopenia have also been observed during the course of the disease. We have followed 28 patients with steroid-refractory DBA for up to 13 years with serial peripheral blood counts and bone marrow (BM) aspirates and biopsies. In 21/28 (75%) patients, moderate to severe generalized BM hypoplasia developed, with overall cellularities ranging from 0% to 30%. Marrow hypoplasia correlated with the development of neutropenia (9/21; 43%) and/or thrombocytopenia (6/21; 29%) in many patients. No patient had either cytogenetic abnormalities or progressed to acute leukaemia, although one 13-year-old developed marked marrow fibrosis and trilineage dysplasia. We used the in vitro long-term culture-initiating cell (LTC-IC) assay to quantify multilineage, primitive haematopoietic progenitors in a representative subset of these patients. LTC-IC assays showed equivalent frequencies of cobblestone area-forming cells (CAFCs) with a mean of 5.42/10(5) cells +/- 1.9 SD and 6.13/10(5) cells +/- 2.6 SD in nine patients and six normal controls respectively. The average clonogenic cell output per LTC-IC, however, was significantly lower in DBA patients (mean 2.16 +/- 1.2 SD vs. 7. 36 +/- 2.7 SD in normal controls, P = 0.0008). Our results suggest that the underlying defect in patients with severe refractory DBA may not be limited to the erythroid lineage, as was evidenced by the development of pancytopenia, bone marrow hypoplasia and reduced clonogenic cell output in LTC-IC assays.

Adolescent↗
PubMed2000

Airway disorders and pulmonary function in snorers. A population-based study.

The aim of our study was to determine the relationship between snoring, airway disorders and pulmonary function in the general population. We performed a stratified random sampling from the population (n = 92,364). Four hundred subjects agreed to participate and were invited to the clinic, where a detailed medical history, physical examination, spirometric test and maximal respiratory pressures measurements were carried out. Snoring was reported by 152 subjects (38%). Nasal obstruction and the presence of abnormal pharynx exploration were more frequent in subjects with snoring. Age, body mass index and neck circumference were significantly higher in the snorer group. In addition, we found that the non-snoring group had a significantly higher frequency of tonsillectomy during infancy and adolescence than the snorer group. We did not detect any significant difference in spirometric test values or in maximal respiratory pressure values between snorer group and non-snorer group. In conclusion, in the general population snoring is associated with nasal obstruction and abnormal pharynx exploration. Furthermore, snoring appears not to be associated with modifications in spirometric or in maximal respiratory pressure tests.

Adult↗
PubMed2000

Ileal perforation secondary to histoplasmosis in AIDS.

Our patient presented with abdominal pain, weight loss, and fever with evidence of oral thrush and pelvic inflammatory disease on exam. Radiographs demonstrated a small bowel obstruction with free air. An exploratory laparotomy demonstrated 2 perforations of the distal ileum. Pathologic exam revealed features consistent with histoplasmosis. We discuss gastrointestinal involvement of histoplasmosis in AIDS and its treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Self-exciting chaos as a dynamic model for irregular neural spiking

We introduce a nonlinear dynamical system with self-exciting chaotic dynamics. Its interspike interval return map shows a noisy Poisson-like distribution. Spike sequences from different initial conditions are unrelated but possess the same mean frequency. In the presence of noisy perturbations, sequences started from different initial conditions synchronize. The features of the model are compared with experimental results for irregular spike sequences in neurons. Self-exciting chaos offers a mechanism for temporal coding of complex input signals.

Journal Article↗
PubMed2000

Differences between blood flow as indicated by the hemodialysis blood roller pump and blood flow measured by an ultrasonic sensor.

BACKGROUND/AIM: The ultrasonic transit time is currently the best method for measuring the blood flow rate in the extracorporeal hemodialysis circuit. The purpose of this study was to analyze the differences between blood flow as indicated by the hemodialysis blood roller pump (prescribed blood flow) and by an ultrasonic flowmeter (delivered blood flow). METHODS: The ultrasonic blood flow was measured in 20 patients on chronic hemodialysis who were dialyzed through an arteriovenous fistula. During each dialysis session the ultrasonic blood flow was measured at three different blood roller pump flow rates (300, 350, and 400 ml/min). In order to analyze the influence of inflow and outflow pressures on blood flow, this study was conducted during nine consecutive dialysis sessions during which needles of different sizes were used. RESULTS: The ultrasonic flow was always lower than indicated by the blood roller pump: 265+/-12, 304+/-15, and 341+/- 19 ml/min for blood roller pump flow rates of 300, 350, and 400 ml/min, respectively (variability: -11.6, -13.1, and -14.8%, respectively). An univariate regression analysis showed that the reduction in flow recorded ultrasonically correlated with both venous blood line pressure (r = -0.2679, p<0.001) and negative arterial blood line pressure (r = 0. 6773, p<0.001). By multivariate analysis, only the arterial blood line pressure has a predictive value. When all measurements were grouped by arterial blood line pressure ranges, the variability between ultrasonic blood flow and blood roller pump flow was found to be similar in those groups with the same arterial blood line pressure, regardless of the blood roller pump flow rate. CONCLUSIONS: The blood flow indicated by the dialysis blood roller pump is always greater than the delivered blood flow, and this difference is in turn conditioned by the negative pressure induced by the blood roller pump in the arterial blood line.

Blood Flow Velocity↗
PubMed2000

Patterns of sulfadiazine acute nephrotoxicity.

Sulfadiazine acute nephrotoxicity is reviving specially because of its use in toxoplasmosis in HIV-positive patients. We report 4 cases, one of them in a previously healthy person. Under treatment with sulfadiazine they developed oliguria, abdominal pain, renal failure and showed multiple radiolucent renal calculi in echography. All patients recovered their previous normal renal function after adequate hydration and alcalinization. A nephrostomy tube had to be placed in one of the patients for ureteral lithiasis in a single functional kidney. None of them needed dialysis or a renal biopsy because of a typical benign course. Treatment with sulfadiazine requires exquisite control of renal function, an increase in water ingestion and possibly the alcalinization of the urine. We communicate a case in a previously healthy person, a fact not found in the recent literature. Probably many more cases are not detected. We think that a prospective study would be useful.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Treatment of hyperthyroidism with radioiodine: effects of administered dose on complications and thyroid function].

BACKGROUND: Radio-iodine is a definite therapy for Graves disease hyperthyroidism. However, the optimal dosage is still debatable. AIM: To assess the effects of different radioiodine doses on thyroid function and complications in patients with hyperthyroidism. MATERIAL AND METHODS: A retrospective analysis of 139 patients with hyperthyroidism, treated with ratio-iodine between 1988 and 1998. Radio iodine dose used was classified as low (< 10 mCi), intermediate (10-14.9 mCi) or high (> or = 15 mCi). RESULTS: Thirty-five patients were treated with low doses, 33 with intermediate doses and 71 with high doses. There were no differences between these patients in age, disease severity, frequency of post treatment euthyroidism or complications. Patients treated with low doses had a higher frequency of persistent hyperthyroidism than patients treated with high doses (25.7 and 4.2% respectively, p < 0.001). Likewise, the frequency of subsequent hypothyroidism was 60% in patients treated with low doses and 84.5% of those with high doses, in whom it also appeared earlier. Associated complications were clinically irrelevant. In seven patients, Graves ophthalmopathy progressed after treatment, but this progression was not associated with the dose used. CONCLUSIONS: Radio iodine in high doses is useful, safe and effective for the treatment of Graves hyperthyroidism.

Adolescent↗
PubMed1999

Complete isomer-specific 1H and 13C NMR assignments of the heme resonances of rat liver outer mitochondrial membrane cytochrome b5.

Singly and doubly labeled delta-aminolevulinic acid derivatives were used to prepare rat liver outer mitochondrial membrane (OM) cytochrome b5 containing a 13C-labeled heme active site. A variety of NMR experiments, including HMBC and INADEQUATE in conjunction with the more commonly used HMQC, NOESY, and COSY, were conducted to make unambiguous assignments of protonated carbons and the quaternary pyrrole-alpha and -beta carbons in both isomeric forms of the paramagnetic active center of OM cytochrome b5. Because the long interpulse delays in the HMBC experiment have a detrimental effect on the detectability of fast relaxing paramagnetically affected resonances. INADEQUATE is proposed as the experiment of choice for assigning quaternary carbons in paramagnetic hemes with carefully chosen macrocycle labeling patterns. Furthermore, the applicability of the INADEQUATE experiment to paramagnetic heme active sites should be facilitated greatly by the availability of biosynthetic methods for producing isotopically labeled b-hemes and, more recently, isotopically labeled c-hemes.

Aminolevulinic Acid↗
PubMed1999

An electrochemical study of the factors responsible for modulating the reduction potential of putidaredoxin.

The gene coding for putidaredoxin has been synthesized using a combination of chemical and enzymatic methods and subsequently expressed in Escherichia coli. The recombinant protein characterized by electronic spectroscopy, mass spectrometry, and electrochemistry was found to be identical to putidaredoxin obtained from Pseudomonas putida. Polylysine was found to promote the fast and reversible electrochemistry of putidaredoxin at negatively charged electrodes such as indium-doped tin oxide or gold surfaces modified with mercaptoalkanoate groups. The value of the heterogeneous electron transfer rate constant obtained from solutions containing a mixture of putidaredoxin and polylysine (k(s) = 1.3 x 10(-3) cm/s) is one order of magnitude larger than the values reported previously at gold electrodes modified with mercaptoethylamine or at antimony-doped tin oxide semiconductor electrodes. It was observed that when the reduction potential of putidaredoxin is measured by cyclic voltammetry, the resultant value is consistently more positive (64 mV) than the reduction potential measured with potentiometric titrations. A comparison between the electrochemical responses of putidaredoxin and spinach ferredoxin, combined with the examination of their corresponding three-dimensional structures, indicates that the positive shift in the reduction potential of putidaredoxin originates from the formation of a transient complex between putidaredoxin and polylysine at the electrode surface. The formation of this transient complex modulates the reduction potential of putidaredoxin by lowering the value of the dielectric constant around its iron-sulfur cluster microenvironment, specifically by neutralizing negative charges surrounding the active site and by excluding water from the solvent exposed iron sulfur cluster. The observed positive shift in E degrees ', which is induced by complexation with polylysine at the electrode-surface, suggests that similar factors are likely to contribute to the anodic shift in the E degrees ' of cytochrome P450(cam)-bound putidaredoxin (+44 mV) with respect to the E degrees ' measured for free putidaredoxin.

Amino Acid Sequence↗