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Biomedical subjects

M Marin

Publications and source records attributed to M Marin.

At least 37 records · Page 2Linked to original sources

Volatile release from aqueous solutions under dynamic headspace dilution conditions.

Static equilibrium was established between the gas phase (headspace) and an unstirred aqueous phase in a sealed vessel. The headspace was then diluted with air to mimic the situation when a container of food is opened and the volatiles are diluted by the surrounding air. Because this first volatile signal can influence overall flavor perception, the parameters controlling volatile release under these conditions are of interest. A mechanistic model was developed and validated experimentally. Release of compounds depended on the air-water partition coefficient (K(aw)) and the mass transport in both phases. For compounds with K(aw) values <10(-)(3), K(aw) was the factor determining release rate. When K(aw) was >10(-)(3), mass transport in the gas phase became significant and the Reynolds number played a role. Because release from packaged foods occurs at low Reynolds numbers, whereas most experiments are conducted at medium to high Reynolds numbers, the experimentally defined profile may not reflect the real situation.

Food Handling↗

Epidemiology and cost analysis of varicella in Italy: results of a sentinel study in the pediatric practice. Italian Sentinel Group on Pediatric Infectious Diseases.

BACKGROUND: Describing the epidemiology of varicella is relevant to the development of specific prevention strategies and to building up of economic models evaluating the cost:efficiency ratios of these strategies. AIM: Our study was designed to describe the epidemiology of chickenpox among Italian children and to assess the resulting economic and health burden on the country. METHODS: Thirty-nine Italian pediatricians participated in a sentinel network on pediatric infectious diseases representing a total pediatric population of 30 168 children. Each case of varicella observed from January through December, 1997, was recorded. Economic analysis was conducted from the societal point of view. All costs were broken down into two groups: direct and indirect costs. RESULTS: A total of 1599 cases of varicella were reported among children 0 to 14 years old. There were 1266 primary cases (mean age, 4.5 +/- 2 years) and 333 secondary cases (mean age, 3.6 +/- 3.2 years). The global incidence of chickenpox was 51.01/1000/year. Complications were seen in 56 cases (3.5%). Drugs were prescribed in 672 cases. A group of adults (364 susceptible and 193 with uncertain status) were exposed to primary cases. Seventy (12.5%) were eventually infected among whom there were 4 pregnant women. For pediatric patients an average cost of $146.90 (250 400 lire) was estimated; this is largely accounted for by indirect costs. CONCLUSIONS: The epidemiology of varicella in Italy is consistent with that found in previous studies in industrialized countries. Severe complications did not occur in our population. We believe that the health arguments in favor of universal vaccination of children > 18 months of age do not differ in our own country from those of other industrialized nations. Our data could now be incorporated into pharmacoeconomic models to establish cost-efficient strategies for Italy.

Adolescent↗

Pseudomonas aeruginosa: a survey of resistance in 136 hospitals in Spain. The Spanish Pseudomonas aeruginosa Study Group.

We carried out a nationwide study with all of the isolates of Pseudomonas aeruginosa collected in a week in 136 hospitals in Spain. The data on 1,014 isolates included resistance to the following antimicrobials: piperacillin-tazobactam, 7%; meropenem, 8%; amikacin, 9%; tobramycin, 10%; piperacillin, 10%; ticarcillin, 13%; imipenem, 14%; ceftazidime, 15%; cefepime, 17%; ciprofloxacin, 23%; aztreonam, 23%; ofloxacin, 30%; gentamicin, 31%. The most frequent serotypes were O:1 (25.1%), O:4 (21.6%), and O:11 (11.3%).

Anti-Bacterial Agents↗

Polymorphisms of the cell surface receptor control mouse susceptibilities to xenotropic and polytropic leukemia viruses.

The differential susceptibilities of mouse strains to xenotropic and polytropic murine leukemia viruses (X-MLVs and P-MLVs, respectively) are poorly understood but may involve multiple mechanisms. Recent evidence has demonstrated that these viruses use a common cell surface receptor (the X-receptor) for infection of human cells. We describe the properties of X-receptor cDNAs with distinct sequences cloned from five laboratory and wild strains of mice and from hamsters and minks. Expression of these cDNAs in resistant cells conferred susceptibilities to the same viruses that naturally infect the animals from which the cDNAs were derived. Thus, a laboratory mouse (NIH Swiss) X-receptor conferred susceptibility to P-MLVs but not to X-MLVs, whereas those from humans, minks, and several wild mice (Mus dunni, SC-1 cells, and Mus spretus) mediated infections by both X-MLVs and P-MLVs. In contrast, X-receptors from the resistant mouse strain Mus castaneus and from hamsters were inactive as viral receptors. These results suggest that X-receptor polymorphisms are a primary cause of resistances of mice to members of the X-MLV/P-MLV family of retroviruses and are responsible for the xenotropism of X-MLVs in laboratory mice. By site-directed mutagenesis, we substituted sequences between the X-receptors of M. dunni and NIH Swiss mice. The NIH Swiss protein contains two key differences (K500E in presumptive extracellular loop 3 [ECL 3] and a T582 deletion in ECL 4) that are both required to block X-MLV infections. Accordingly, a single inverse mutation in the NIH Swiss protein conferred X-MLV susceptibility. Furthermore, expression of an X-MLV envelope glycoprotein in Chinese hamster ovary cells interfered efficiently with X-MLV and P-MLV infections mediated by X-receptors that contained K500 and/or T582 but had no effect on P-MLV infections mediated by X-receptors that lacked these amino acids. In contrast, moderate expression of a P-MLV (MCF247) envelope glycoprotein did not cause substantial interference, suggesting that X-MLV and P-MLV glycoproteins interfere nonreciprocally with X-receptor-mediated infections. We conclude that P-MLVs have become adapted to utilize X-receptors that lack K500 and T582. A penalty for this adaptation is a reduced ability to interfere with superinfection. Because failure of interference is a hallmark of several exceptionally pathogenic retroviruses, we propose that it contributes to P-MLV-induced diseases.

Amino Acid Sequence↗

Aortic root dilatation in young men with normally functioning bicuspid aortic valves.

OBJECTIVE: To evaluate the dimensions of the aortic root in a selected population of young males with isolated normally functioning bicuspid aortic valve. DESIGN AND SETTING: Echocardiographic and Doppler evaluation of conscripts with bicuspid aortic valve at the time of military pre-enrolment screening in two military hospitals. SUBJECTS AND METHODS: 66 consecutive young men with a normally functioning bicuspid aortic valve were studied to assess aortic size at four aortic levels: annulus, sinuses of Valsalva, supra-aortic ridge, and proximal ascending aorta; 70 consecutive normal young subjects, matched for age and body surface area, were used as controls. RESULTS: In men with a bicuspid aortic valve, the diameter of the aortic root was significantly larger than in controls at the sinuses (3.16 (0.37) v 2.87 (0.31) cm, p < 0.001), at the supra-aortic ridge (2.64 (0.46) v 2.47 (0.28) cm, p = 0.01), and at the level of the proximal ascending aorta (3.12 (0.48) v 2.69 (0.28) cm, p < 0.001). The prevalence of aortic root dilatation was 7.5% at the annulus (5/66), 19.6% at the sinuses (13/66), 15% at the supra-aortic ridge (10/66), and 43.9% at the ascending aorta (29/66); 32 subjects (48%) had aortic root dimensions comparable with controls, while 34 (52%) had definitely abnormal aortic root dimensions. CONCLUSIONS: Aortic root enlargement in people with a bicuspid aortic valve occurs independently of haemodynamic abnormalities, age, and body size. However, there appear to be different subgroups of young adults with bicuspid aortic valves, one of which is characterised by aortic dilatation, possibly caused by a congenital abnormality of the aortic wall.

Adolescent↗

Genetically engineered antibodies in gene transfer and gene therapy.

Our ability to produce and engineer human monoclonal antibodies provides a basis for the development of novel therapeutical strategies against a variety of diseases. These strategies not only include improved passive immunotherapy but also more sophisticated antibody-based gene therapies involving gene transfer approaches. Four of the major applications of antibody gene engineering in the field of gene therapy are reviewed here. These are (1) the redefinition of viral vector tropism of infection for better transduction of cells of therapeutical interest, (2) the grafting of new cell recognition activities to effector cells of the immune system to kill cancer and pathogen-infected cells, (3) the inhibition of cellular and viral functions through intracellular expression of antibody-derived molecules, and (4) the systemic delivery of therapeutic monoclonal antibodies by non-B cells in living organisms.

Antibodies, Monoclonal↗

Postextrasystolic potentiation echocardiography in predicting reversible myocardial dysfunction by surgical coronary revascularization.

Sustained inotropic stimulation, such as dobutamine infusion, has the potential to cause an additional contractile deterioration in viable but chronically hypoperfused and dysfunctioning myocardium, by inducing ischemia. Postextrasystolic potentiation (PESP) represents a potent inotropic stimulus without risk of provoking ischemia, as it is instantaneous. In this study, we assessed the role of PESP-echocardiographic examination in predicting the recovery of regional contractility after coronary revascularization. We examined 105 consecutive patients with multivessel coronary artery disease who were candidates for bypass surgery; 79 were included in this prospective study. Preoperative reversibility of contractile dysfunction in asynergic myocardial regions was determined by PESP, with a coupling interval of 500 msec decreasing to 300 msec, with a progressive decrease by 10 msec. The examination was accompanied by continuous 2-dimensional (2D) echocardiographic monitoring. The assessed sensitivity and specificity were 92% and 87%, respectively; the predictive accuracy was 90%. These results demonstrated that PESP echocardiography is a useful and cost-effective method for identifying viable myocardium in patients undergoing myocardial revascularization.

Adult↗

Affinity of recombinant antibody and antibody fragment binding to human thyroglobulin: potential applications in gene therapy.

Recombinant antibodies and antibody fragments are currently being produced. They can be used in vitro for the structural study of antigen-antibody interactions for instance, but their in vivo production may have applications for gene therapy of certain cancers and severe viral diseases and in developing new animal models of autoimmune disease. We report here these two types of applications using a recombinant antihuman thyroglobulin (hTg) antibody.

Animals↗

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

3-Iodobenzylguanidine↗

Cell targeting by murine retroviral vectors.

Gene therapy involves the transfer of new genetic material to cells of individuals with the aim of conferring a therapeutical benefit. Theoretically, gene therapy can be used to treat a variety of life-threatening disorders, such as inherited genetic diseases, cancer, chronic viral infections as well as a number of other severe diseases which are not treatable at present. To this aim, both efficient gene delivery techniques and controlled gene expression systems are required. Engineered murine retroviruses are the most widely used vectors for stable clinical gene transfer because of their ability to integrate--along with the transgenes they are engineered to carry--into the genome of infected cells. However, this technology still suffers from a number of drawbacks and limitations. Particularly, the ability to target cells of therapeutic interest together with the controlled expression of transferred genes would improve both the efficiency and the safety of retroviral vectors. Such improvements would additionally allow the development of new animal models of human diseases as well as enable more fundamental investigations in the fields of oncogenesis and developmental biology.

Animals↗

Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells.

Implantation of capsules containing antibody-producing cells into patients would potentially permit systemic long-term delivery of antibodies and might, thus, be useful in the development of surveillance treatments for cancers and severe viral diseases. We show that cellulose sulphate (CS) capsules containing hybridoma cells, when implanted subcutaneously or in the intraperitoneal cavity, can be used for delivering monoclonal antibodies into the blood-stream of immunocompetent mice for at least several months. In contrast to capsules implanted into the intraperitoneal cavity, which remain mobile and nonvascularized, capsules implanted under the skin form neo-organs which become vascularized within days. This may explain the higher blood concentration of the antibody we have observed in the latter case. Importantly, neither an isolating fibrosis nor an obvious inflammatory response was detected at the capsule implantation sites during observation periods as long as 10 months. Finally, no anti-idiotypic immune response against the ectopically delivered antibody was shown to occur. This rules out any potent adjuvant effect of the cellulose sulphate matrix that might have stimulated a neutralizing humoral response. Taken together, our data indicate that encapsulation of antibody-producing cells into CS might be used in antibody-based gene/cell therapy approaches.

Animals↗

Subcoracoid dislocation of the distal end of the clavicle. A case report.

Subcoracoid dislocation of the outer end of the clavicle in association with an acromial fracture is a rare injury usually produced by high energy trauma that moves the clavicle posterior to the conjoined tendon and inferior to the coracoid process. To restore the acromioclavicular joint, open reduction is needed. After the reduction is accomplished, the clavicle has to be stabilized with a coracoclavicular screw. The acromial fracture can be reduced and held with nonabsorbable sutures placed through the bone. To avoid osteolysis of the distal end of the clavicle and to be able to repair the torn ligaments, treatment should not be delayed.

Accidents, Traffic↗

[Endovascular treatment of dural arteriovenous fistulas with medullary venous drainage. Experience with 18 patients].

INTRODUCTION AND OBJECTIVE: The authors report a series of 18 patients with myelopathy who were diagnosed of dural arteriovenous fistulas with venous medullary drainage (DFVMd). Purpose was to assess the effectiveness, initial and long term, of embolization, as the initial treatment, using polyvinyl alcohol particles (PVA) and liquid adhesives. N-butyl-cyanoacrylate (NBCA). MATERIAL AND METHODS: Magnetic resonance images were obtained in all patients showing spinal cord tissue changes consistent with an isquemic process secondary to venous hypertension. All 18 patients showed initially an improvement in clinical symptoms, demonstrating previous MR images resolution. RESULTS: The neurological status of 8 patients subsequently deteriorated with angiographically proven recurrences of their DFVMd. These patients underwent a second successful embolization procedure using NBVA. PVA embolization is long term ineffective and is not without risk. Endovascular treatment is less invasive than surgery, its morbidity is less, and it ensures earlier recovery for the patients. If embolization has failed, surgery can still be done. CONCLUSIONS: We recommend that NBVA embolization be the initial treatment of choice for DFVMd if referring the patient to an experienced interventional Neuroradiology unit is available. Careful clinical and neurologic examination is necessary to establish the diagnosis of DFVMd. Finally, we strongly recommend that patients be followed closely and aggressively. Periodic clinical and radiologic assessments, including MR and spinal angiography, are essential to achieve complete cure.

Aged↗

Postextrasystolic potentiation and dobutamine echocardiography in predicting recovery of myocardial function after coronary bypass revascularization.

BACKGROUND: Identification of viable but hibernating myocardium remains a relevant issue in the current era of myocardial revascularization. Echocardiography can be helpful in detecting reversible contractile dysfunction and optimizing the selection of patients for coronary bypass surgery. METHODS AND RESULTS: Eighty-four consecutive candidates for bypass surgery with chronic multivessel coronary artery disease were screened, and 60 were included in this prospective study. Preoperative evaluation of a reversible contractile dysfunction in asynergic myocardial regions was performed by dobutamine infusion at 5 (low dose) and 10 (intermediate dose) microg x kg(-1) x min(-1) with each stage lasting at least 5 minutes; postextrasystolic potentiation (PESP), with a coupling interval ranging from 500 to 300 ms with a progressive 10-ms decrease; or a combination of both dobutamine infusion and PESP. Sensitivity (92% versus 86%) and predictive accuracy (89% versus 84%) were higher with PESP than dobutamine (P=.009 and P=.001, respectively), but the combination did not improve sensitivity or accuracy. Dobutamine induced ischemic dysfunction in 15% of patients at the intermediate dose; however, the low dose resulted in loss of sensitivity. CONCLUSIONS: PESP echocardiography is a useful and cost-effective method to identify viable myocardium in patients with multivessel coronary disease undergoing revascularization and is more sensitive and accurate than dobutamine infusion.

Adult↗

In vitro and in vivo secretion of cloned antibodies by genetically modified myogenic cells.

In vivo production of recombinant antibodies by engineered cells may have applications for gene therapy of certain cancers and of certain severe viral diseases. It would also permit the development of new animal models of autoimmune diseases and new approaches for in vivo ablation of specific cell types for fundamental purposes. Using gene transfer of an anti-human thyroglobulin monoclonal antibody, we show here that several cell types permitting autologous grafting of genetically engineered cells are efficiently able to secrete antibodies in vitro. Those cells include skin fibroblasts, hepatocytes, and myogenic cells. We also show that the secreted antibodies display an affinity for the antigen close to that of the parental antibody, with, however, slight differences varying according to the cell type. This indicates that the foldings of antigen combining sites of antibodies produced in B cell- and non-B cell contexts are very similar. Finally, we report that, when implanted in the forelimb of a mouse, genetically modified myogenic cells are able to secrete antibodies for at least 4 months. Taken together, our observations point to the notion that genetic modification of patient cells may be used for long-term antibody-based gene therapies.

Animals↗

Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation.

Transcription factor Sp1 has been implicated in the expression of many genes. Moreover, it has been suggested that Sp1 is linked to the maintenance of methylation-free CpG islands, the cell cycle, and the formation of active chromatin structures. We have inactivated the mouse Sp1 gene. Sp1-/- embryos are retarded in development, show a broad range of abnormalities, and die around day 11 of gestation. In Sp1-/- embryos, the expression of many putative target genes, including cell cycle-regulated genes, is not affected, CpG islands remain methylation free, and active chromatin is formed at the globin loci. However, the expression of the methyl-CpG-binding protein MeCP2 is greatly reduced in Sp1-/- embryos. MeCP2 is thought to be required for the maintenance of differentiated cells. We suggest that Sp1 is an important regulator of this process.

Animals↗