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Biomedical subjects

A Merino

Publications and source records attributed to A Merino.

At least 55 records · Page 3Linked to original sources

Isolation of microfilariae from blood by gravitational field-flow fractionation.

Over 100 million persons suffer from diseases caused by filariae infestation, and one billion are at risk. A simple isolation method for both analytical and preparative separation is presented. Based on the simplest field-flow fractionation technique, the gravitational one, effective isolation of microfilariae is achieved. Microfilariae are eluted in the void volume of the channel without pollution by red blood cells. The red blood cell elution peak shows a total absence of microfilariae, as demonstrated after fraction collection and microscopic investigation. The elution mode of microfilariae and red blood cells appears to be a steric one, as confirmed by a reinjection experiment. The simplicity, low cost and the relatively short time required for this separation (10 min) indicate that gravitational field-flow fractionation could become a new separation tool for screening of microfilariae. With both live and dead microfilariae, the high recovery (66-80%) allows preparative fractionation for diagnostic purposes or fundamental research.

Animals↗

Clinical and angiographic characteristics and outcome of patients with rest-unstable angina occurring during regular aspirin use.

Today many patients admitted with an acute coronary syndrome are already taking aspirin. Because they have symptoms despite antithrombotic therapy, these patients are presumed to be at higher risk for subsequent clinical events. In a pilot trial of antithrombotic therapy in patients with unstable angina at rest or non-Q wave infarction, 93 patients admitted within 48 h of pain were prospectively followed up for 12 weeks. On admission, 29 patients (31%) were already taking daily aspirin; 64 (68%) were receiving no antiplatelet agent. After enrollment all patients received antithrombotic therapy with either aspirin or heparin according to protocol regardless of prior aspirin use. The two groups (prior users versus nonusers of aspirin) were similar with regard to age, gender, coronary risk factors, prior antianginal medication, duration of symptomatic coronary disease, presentation with non-Q wave infarction and extent of electrocardiographic changes on admission. Quantitative analysis of coronary arteriograms (on a 0 to 10 scale) showed similar myocardium-in-jeopardy scores (JS). Follow-up events (recurrent ischemia [Isch], infarction [MI] and revascularization [Revasc]) were: (formula: see text) Aspirin users experiencing rest angina are similar to other patients with ischemic rest pain. The "resistant to aspirin" group does not constitute a subgroup that is at higher risk for cardiac events or revascularization.

Adult↗

Occurrence of hereditary leaky red cell syndrome and partial coagulation factor VII deficiency in a Spanish family.

A Spanish family was found to have the coexistence of a hereditary haemolytic syndrome associated with excessively leaky RBC membrane to sodium (Na+) and potassium (K+) cations and a partial coagulation factor VII deficiency. Haemolysis was mild in the propositus and the RBC membrane leak included a marked increase in passive permeability to Na+ and K+. This was associated with an increase in active Na+,K(+)-pump activity and in the ouabain-resistant fluxes: Na+, K(+)-cotransport and Na+, Li(+)-countertransport. Factor VII deficiency was of 50% and no clinical expression of the coagulation deficiency was observed. The family study revealed slightly abnormal RBC membrane cationic fluxes only in the father and decreased coagulation factor VII activity of 67% in the mother. Both parents were clinically and haematologically normal. It is suggested that the propositus has inherited the abnormal gene for leaky RBC syndrome from the father and the partial coagulation factor VII deficiency from the mother.

Anemia, Hemolytic, Congenital↗

The value of exercise testing in patients with coronary artery spasm.

To analyze the usefulness of a single exercise test to predict the presence of fixed obstructive coronary artery disease in patients with active coronary spasm, 91 consecutive patients with angiographically proven symptomatic coronary artery spasm who had performed a symptom-limited exercise test within the week before diagnostic coronary angiography were studied. Coronary angiography revealed significant coronary obstructions in 61 patients (67%). According to the type of angina, the prevalence of significant coronary stenosis was 53% for patients with angina at rest, 68% for those with effort angina, and 92% for those with mixed angina. Exercise-induced ST segment elevation was present in eight patients (9%), ST segment depression was seen in 37 patients (41%), and no ST abnormalities in 46 (50%). There was not a significant relationship between the ST segment response to exercise and the clinical variables assessed except for coronary anatomy. Abnormal exercise test results were significantly more frequent in patients with significant coronary obstructions than in those without significant coronary occlusions (62% versus 23%; p less than 0.01). ST elevation was not useful to predict the presence of fixed coronary lesions. However, ST depression strongly suggested the presence of underlying coronary lesions with a sensitivity of 54%, a specificity of 87%, and a positive predictive value of 89%. Using this criterion, 65% of the patients were correctly classified. The results indicate that despite the functional component of ischemia in patients with coronary spasm, ST segment depression with exercise is still a highly specific sign with a high positive predictive value for the presence of significant coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phosphorylation of cellular proteins regulates their binding to the cAMP response element.

We have studied the protein factors that promote transcription via binding to the cAMP response element (CRE) present in the adenovirus early region III (EIII) and early region IV (EIV) promoters. Three sets of CRE-binding phosphoproteins, ranging in molecular mass from 65-72, 38-43, and 31-37 kDa, were identified in vivo from HeLa cells. Western blot analysis revealed that all three sets of proteins identified were immunologically related to the transcription factor AP1. We found that binding of these proteins to the CRE could be regulated by phosphorylation in vitro. EivF, a 65-72-kDa protein was found to bind specifically to the adenovirus EIV promoter. We have also shown that the smaller molecular mass proteins of 31-37 and 38-43 kDa were able to bind to the CRE present in the adenovirus EIV promoter, as well as to two related DNA elements present in the adenovirus EIII promoter, the ATF and AP1 sites. Phosphorylation of these proteins with the cAMP-dependent protein kinase, affected their transcriptional activity and binding affinity to the three sites. Furthermore, the binding specificity of the 31-37-kDa polypeptides was mediated by cAMP-dependent protein kinase in vitro. Our data suggests that phosphorylation of factors that bind to the CRE may, in part, underlie the cellular response to the adenovirus-encoded Ela protein.

Adenoviridae↗

Factors involved in specific transcription by mammalian RNA polymerase II. Role of factors IID and MLTF in transcription from the adenovirus major late and IVa2 promoters.

The role of the adenovirus major late upstream transcription factor (MLTF) in transcription from the adenovirus major late and the IVa2 promoters was studied. The transcription initiation site of the IVa2 promoter is located 210 nucleotides upstream from the CAP site of the major late promoter. Transcription from these two promoters occurs on different DNA strands. Thus, this divergent transcription suggests that the same factor could simultaneously regulate the expression of two different genes. This was investigated utilizing a reconstituted transcription system in vitro. The addition of MLTF to reaction mixtures containing the purified general transcription factors and the major late promoter resulted in a 10-12-fold stimulation of transcription. This stimulation was because of an increase of the stability of the preinitiation complex. MLTF allowed DNA template molecules to undergo multiple rounds of transcription. MLTF also stimulated transcription from the adenovirus-encoded IVa2 promoter. Surprisingly, reconstitution experiments indicated that transcription from the IVa2 promoter which does not have a TATA sequence required all the previously described general transcription factors, including TFIID, the TATA binding protein. The requirement for TFIID was demonstrated by reconstitution experiments as well as by oligonucleotide competition experiments. The implications of this observation are discussed.

Adenoviruses, Human↗

Chronic nonspherocytic hemolytic anemia (CNSHA) and glucose 6 phosphate dehydrogenase (G6PD) deficiency in a patient with familial amyloidotic polyneuropathy (FAP). Molecular study of a new variant (G6PD Clinic) with markedly acidic pH optimum.

A new glucose-6-phosphate dehydrogenase (G6PD) variant with severe erythrocytic G6PD deficiency and a unique pH optimum is described in a young patient with chronic nonspherocytic hemolytic anemia (CNSHA) and familial amyloidotic polyneuropathy (FAP). Chronic hemolysis was present in the absence of infections, oxidant drugs or ingestion of faba beans. Residual enzyme activity was about 2.6% and 63% of normal activity in erythrocytes and leucocytes, respectively. A molecular study using standard methods showed G6PD in the patient to have normal electrophoretic mobility (at pH 7.0, 8.0 and 8.8), normal apparent affinity for substrates (Km, G6P and NADP) and a slightly abnormal utilization of substrate analogues (decreased deamino-NADP and increased 2-deoxyglucose-6-phosphate utilization). Heat stability was found to be markedly decreased (8% of residual activity after 20 min of incubation at 46 degrees C) and a particular characteristic of this enzyme was a biphasic pH curve with a greatly increased activity at low pH. Although molecular characteristics of this variant closely resemble those of G6PD Bangkok and G6PD Duarte, it can be distinguished from these and all other previously reported variants by virtue of its unusual pH curve. Therefore the present variant has been designated G6PD Clinic to distinguish it from other G6PD variants previously described.

Adult↗

Complementary mechanisms of atenolol and diltiazem in the clinical improvement of patients with stable angina.

The combination of atenolol with diltiazem has been shown to be useful in the treatment of patients with coronary artery disease. Eighteen patients with proven coronary artery disease, stable angina, and no previous myocardial infarction were studied before and after treatment with atenolol (100 mg/day) (9 patients) or diltiazem (180 mg/day) (9 patients). Ischemic threshold at stress test, pressure-rate product at ischemic threshold, direct oxygen consumption at ischemic threshold, and exercise ejection fraction were determined. There was a slight increase in the duration of exercise, maximal oxygen consumption, and ischemic threshold after treatment with each drug. Double product at ischemic threshold decreased from 20.9 to 19.8 (p = NS) with atenolol but increased from 20.1 to 21.9 (p = NS) with diltiazem. Conversely oxygen consumption at ischemic threshold increased with atenolol to nearly significant values from 17.2 to 23.6 (p = 0.067) but not with diltiazem (16.2 to 22.3; p = 0.16). Before treatment, exercise ejection fraction increased less than 10% or decreased from its resting values in all patients but 1 with atenolol and 1 with diltiazem, but exercise ejection fraction increased significantly after treatment with atenolol (60.6 to 67.5; p = 0.02) but not with diltiazem. This improvement was due to a significant reduction in end systolic volume (103.8 to 78.6; p = 0.019), despite a similar increase in heart rate and blood pressure in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stress testing in patients with coronary spasm: comparison of those with and without fixed coronary artery disease.

Stress testing is one of the preferred noninvasive methods of identifying patients with coronary artery disease (CAD). Its value in patients with coronary artery spasm (CAS) is, however, difficult to ascertain. The authors studied 91 consecutive patients with angiographically documented CAS. All patients underwent a symptom-limited bicycle exercise test before coronary angiography. Eight patients (8.8%) showed ST-segment elevation during exercise; 37 (40.7%), ST-segment depression; and 46 (50.5%), no changes. Thirty patients had normal coronary arteries; 19, one-vessel disease; 19, two-vessel disease; and 23, three-vessel disease. Stress testing yielded abnormal results in 7 of 30 patients (23%) with no CAD and in 38 of 61 (62%) with fixed CAD (p less than 0.01). ST-segment response to exercise did not correlate with most clinical findings such as age, type of angina, duration of pain episodes, or the degree of disease activity. However, a significant correlation was found with the extent and severity of CAD. Absence of ST changes or ST-segment elevation did not differentiate those patients with or without CAD, but only 4 of 37 patients with ST-segment depression had no significant fixed lesions. In conclusion, half of the patients with CAS had a normal stress test. ST-segment elevation is an uncommon finding in these patients and does not reliably differentiate those with and without fixed CAD. The only relevant finding of stress testing in CAS patients is ST-segment depression, which strongly suggests the presence of underlying CAD.

Angiography↗

[Value of the stress test in patients with coronary spasm].

UNLABELLED: Ninety-one consecutive patients with angiographically documented spasm who performed a bicycle stress test within one week before diagnostic coronary angiography are studied. Stress test induced ST elevation in 8 patients (9%), ST depression in 37 (41%) and no ST shifts in 46 (50%). ST response to exercise did not correlate with any of the clinical variables assessed except for coronary anatomy. ST depression was a highly specific sign of underlying coronary lesions, with a high positive predictive value (89%). Patients were stratified according to the type of angina and their post-test probability of significant coronary disease was calculated following Bayes' theorem. The post-test likelihoods of significant coronary stenosis (positive and negative test, respectively) were: 82 and 37% for patients with angina at rest; 90 and 53% for those with effort angina, and 98 and 85% for those with mixed angina. IN CONCLUSION: 1) stress testing in patients with coronary spasm correlates well with coronary anatomy; 2) ST depression strongly suggests the presence of underlying coronary stenosis; 3) stress testing is especially useful in patients with angina exclusively at rest.

Adult↗

Influence of age on left ventricular contractility.

Controversy exists about whether left ventricular (LV) function is affected by aging. Therefore, peak systolic pressure to end-systolic diameter, peak systolic pressure to end-systolic volume, systolic wall stress to fractional shortening and systolic wall stress to end-systolic diameter relations were calculated in the left ventricle of 10 healthy subjects greater than 65 years old (age 70 +/- 4 years) (group B). They were compared with a control group composed by 10 healthy subjects (group A, age 22 +/- 1 years). LV measurements were obtained with M-mode echocardiography and an automatic cuff was used to determine blood pressure. Changes in the load conditions were obtained by 15 mg sublingual isosorbide dinitrate. There were no differences in resting end-systolic diameter, end-systolic volume, end-diastolic diameter, end-diastolic volume, fractional shortening, ejection fraction or systolic wall stress. Older subjects had higher values of resting peak systolic pressure (p less than 0.05) and lower heart rates (p less than 0.05). Young subjects had a steeper peak systolic pressure to end-systolic diameter slope (92 +/- 11 vs 51 +/- 11 mm Hg/cm; p less than 0.001) and peak systolic pressure to end-systolic volume slope (3.4 +/- 0.7 vs 1.9 +/- 0.6 mm Hg/ml; p less than 0.001). There was a slight difference in systolic wall stress to fractional shortening slopes between both groups (group A -0.215 vs group B -0.49%/10(3) dynes/cm2, p = 0.02) but not between systolic wall stress to end-systolic diameter slopes (group A 0.013 vs group B 0.019 cm/10(3) dynes/cm2, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Effect of age on long-term prognosis of patients with myocardial infarction.

We studied 181 patients aged under 65 years and 129 patients over 65 with acute myocardial infarction. There were no major differences in the prevalence of coronary risk factors, angina or previous myocardial infarction. A larger percentage of elderly patients had congestive heart failure (51.4% vs 32.6%, P less than 0.001) and complete heart block (17.1% vs 7.2%, P less than 0.01) during the acute phase. In-hospital mortality was significantly higher in the elderly patients (34% vs 16%, P less than 0.01). Late mortality rates correlated in both groups with the Killip class at the time of infarction and with the occurrence of reinfarction. In the elderly group, it was also associated with complete heart block during the acute phase. Five-year survival was 80% in the older and 72% in the younger patients (P = 0.1). Age did not affect survival of Killip class I patients (85% vs 86%, P = 0.83), but life expectancy was significantly reduced in elderly patients in Killip class greater than II (39% vs 60%, P less than 0.05). In conclusion, elderly patients cannot be considered a homogeneous group of high-risk patients. Clinical variables at the time of infarction can identify low- and high-risk subsets among them. Age constitutes an independent prognostic factor for late mortality when any degree of heart failure is present.

Adult↗

EivF, a factor required for transcription of the adenovirus EIV promoter, binds to an element involved in EIa-dependent activation and cAMP induction.

The isolation of a cellular factor that was specifically required for transcription from the promoter of the adenovirus early gene iv, an EIa-activated promoter, is described. This factor (EivF) was purified from HeLa cells using a functional transcription assay and identified as a 72,000- to 65,000-dalton protein. DNase I footprinting experiments demonstrated that purified EivF bound to the sequence 5'-GT(G/T)ACGT-3' present two times upstream of the Eiv TATA box. Nuclear extracts prepared from HeLa cells contained more than one factor capable of binding to the EivF recognition site. Previous studies have indicated that a sequence similar to the EivF-binding site was recognized by a 43,000-dalton protein and participated in the cAMP response of the somatostatin promoter. The purified and transcriptionally active EivF also bound to DNA sequence elements present in the somatostatin and alpha-gonadotropin promoters shown previously to be responsive to cAMP.

Adenoviridae↗

Syndrome of coronary artery spasm of normal coronary arteries. Clinical and angiographic features.

To define the clinical and angiographic features of the syndrome of spasm of angiographically normal coronary arteries, 77 patients with spasm and fixed angiographically normal coronary arteries, 77 patients with spasm and fixed coronary stenosis equal to or greater than 50% (group A) were compared with 35 patients with spasm and normal or minimally diseased coronary arteries (group B). Statistically significant differences between groups A and B were as follows: the incidence of rest angina (50.6% vs 85.7%; p less than 0.01) and mixed angina (32.5% vs 5.7%; p less than 0.01); the appearance of ST segment depression (53.3% vs 16%; p less than 0.01) and no electrocardiographic changes during stress test (35.6% vs 76%; p less than 0.01); and the tendency for arteriographically documented spasm to be focal (87.5% vs 71.4%; p less than 0.05) and to affect only one vessel (76.6% vs 57.1%; p less than 0.05). No differences were found between groups A and B in major coronary risk factors, history of previous myocardial infarction, electrocardiographic abnormalities at rest or during pain episodes, or arteries affected by spasm. Thus, angina appearing exclusively at rest is the main clinical feature of spasm of normal coronary arteries. The electrocardiogram, whether at rest or during pain episodes, has no value for predicting the existence of underlying coronary lesions, whereas stress testing does. Spasm of normal arteries tends to be more diffuse than that superimposed on organic lesions and to affect more than one artery, suggesting different mechanisms in the genesis of both types of spasm.

Adult↗