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Biomedical subjects

G D'Angelo

Publications and source records attributed to G D'Angelo.

At least 73 records · Page 4Linked to original sources

[Clinical significance of the determination of lactate dehydrogenase in acute leukemia and non-Hodgkin's lymphoma].

The serum concentration of LDH increases in various cancers and its increase can represent a prognostic marker of the disease and a good indicator of the tumoral mass's degree of growth. In patients with acute leukaemia, LDH can show a moderate increase only in some cases of acute non-lymphoblastic leukaemia with FAB M4 and M5 cytotype, whereas in acute lymphoblastic leukaemia LDH almost always increases, an event related to the number of white cells during remission or a relapse of the disease. In non-Hodgkin lymphomas, measurement of total LDH is not on its own a useful aid for monitoring the therapeutic response and the course of the disease. In such cases it is right to also evaluate LDH isoenzymes because they pinpoint the persistence of residual lymphomatous foci which do not affect the level of total LDH and have not clinical evidence.

Clinical Enzyme Tests↗

[Apical hypertrophic cardiomyopathy: variability of bidimensional echocardiographic and electrocardiographic expression].

Apical hypertrophic cardiomyopathy is characterized by primary hypertrophy of the myocardium which is localized exclusively at the apex of the left ventricle. Previous studies have indicated that apical hypertrophic cardiomyopathy is characterized by a unique combination of cross-sectional echocardiographic and ECG findings ("giant" T wave inversion and high R wave voltage in the precordial leads). The aim of this study was to evaluate the possible relation between apical hypertrophy, quantitatively defined by cross-sectional echocardiography, and ECG findings in patients with apical hypertrophic cardiomyopathy. We studied 13 pts with apical hypertrophic cardiomyopathy, 10 men and 3 women (aged between 11 and 73 years, mean age 47). Apical hypertrophy was assessed quantitatively by determinating the muscle cross-sectional area in the apical region. From the end-diastolic apical 4 chamber view, endocardial and epicardial contours were digitized in order to obtain the muscle cross-sectional area of the left ventricle. The walls of the left ventricle were then divided into 3 regions (basal, mid-ventricular, apical). Final values of planimetered muscle areas are given as the average of the calculations obtained blindly and independently by 4 observers. The comparison between cross-sectional echocardiographic and electrocardiographic findings showed that patients with giant T wave inversion (T wave greater than 10 mm) and high R wave voltages (R greater than wave 25 mm) had a more severe degree of apical hypertrophy. However there was no complete agreement between cross-sectional echocardiographic and electrocardiographic findings. This study in fact demonstrates a wide variation in the degree of severity of apical hypertrophy among patients with apical hypertrophic cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Complete amino acid sequence of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

The complete amino acid sequence of 6-phospho-fructo-2-kinase/fructose-2,6-bisphosphatase from rat liver was determined by direct analysis of the S-carboxamidomethyl protein. A complete set of nonoverlapping peptides was produced by cleavage with a combination of cyanogen bromide and specific proteolytic enzymes. The active enzyme is a dimer of two identical polypeptide chains composed of 470 amino acids each. The NH2-terminal amino acid residue of the polypeptide chain was shown to be N-acetylserine by fast atom bombardment mass spectrometry of the purified N-terminal tetradecapeptide isolated after cleavage of the intact S-carboxamidomethylated protein with lysyl endoproteinase (Achromobacter protease I). Alignment of the set of unique peptides was accomplished by the analysis of selected overlapping peptides generated by proteolytic cleavage of the intact protein and the larger purified cyanogen bromide peptides with trypsin, Staphylococcus aureus V8 protease, and lysyl endoproteinase. Four nonoverlapping peptides were aligned by comparison with the amino acid sequence predicted from a partial cDNA clone encoding amino acid positions 166-470 of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (Colosia, A.D., Lively, M., El-Maghrabi, M. R., and Pilkis, S. J. (1987) Biochem. Biophys. Res. Commun. 143, 1092-1098). The nucleotide sequence of the cDNA corroborated the peptide sequence determined by direct methods. A search of the Protein Identification Resource protein sequence database revealed that the overall amino acid sequence appears to be unique since no obviously homologous sequences were identified. However, a 100-residue segment of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (residues 250-349), including the active site histidine residue of the bisphosphatase domain, was found to be homologous to the active site regions of yeast phosphoglycerate mutase and human bisphosphoglycerate mutase.

Amino Acid Sequence↗

Prognostic value of clonal chromosomal abnormalities in patients with primary myelodysplastic syndromes.

Chromosome analyses were carried out on bone marrow cells from 43 consecutive patients with primary myelodysplastic syndromes (MDS), classified according to the French-American-British (FAB) cooperative group criteria. The objective was to evaluate the prognostic value of clonal chromosomal abnormalities and of an excess of blasts for early death from acute nonlymphocytic leukemia (ANLL) and/or bone marrow failure (BMF). Patients were subdivided into two main groups: (1) refractory anemia without an excess of blasts (RAWEB), grouping patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS), and (2) refractory anemia with an excess of blasts (RAEB), grouping patients with refractory anemia with an excess of blasts (RAEB) and refractory anemia with an excess of blasts in transformation (RAEBt). There were 29 patients with RAWEB and 14 with RAEB. The median time of observation was 26 months for RAWEB and 12 months for RAEB. Ten RAWEB patients (34%) and 11 RAEB patients (78%) had clonal chromosomal abnormalities. Among the ten RAWEB patients with clonal abnormalities, one (10%) died from ANLL, while of 19 RAWEB patients with a normal karyotype, two (10%) died from ANLL or BMF. The median survival for patients with RAWEB and an abnormal karyotype was not reached. In contrast, eight of the 11 RAEB patients with clonal chromosomal abnormalities (74%) died from ANLL or BMF. The median survival in this sub-group was 7 months. By using a Cox proportional hazard regression analysis, it was determined that a karyotype abnormality was not a significant predictory of survival once the contribution of the RAWEB/RAEB variable was taken into account. Being in the RAEB group was associated with a relative risk of 10.6 of dying from ANLL or BMF (beta = 2.36, standard error (SE) = 0.68, P = .0001). We conclude that classifying patients according to an excess of blasts will lead to a better prediction of survival than determining karyotype abnormality.

Adult↗

cDNA sequence of rat liver fructose-1,6-bisphosphatase and evidence for down-regulation of its mRNA by insulin.

A coding-length clone of rat liver fructose-1,6-bisphosphatase (EC 3.1.3.11) was isolated by immunological screening of a cDNA library in lambda gt11. Its identity was verified by comparing the deduced amino acid sequence with that obtained by direct sequencing of a complete set of CNBr and proteolytic peptides from the purified protein. The enzyme subunit is composed of 362 amino acids and has N-acetylvaline as the amino-terminal residue. The cDNA, 1255 base pairs (bp) long, consisted of 1086 bp of coding region, 15 bp of 5' untranslated sequence, and 154 bp at the 3' untranslated end. The 3' untranslated sequence contained a polyadenylylation signal (AATAAA) followed after 30 bp by a stretch of 7 adenines at the end of the clone. The deduced amino acid sequence was identical to the primary sequence of the protein and confirmed the alignment of five nonoverlapping peptides. It also confirmed the 27-residue extension, unique to the rat liver subunit, ending with a carboxyl-terminal phenylalanine. RNA blot analyses using the radiolabeled liver cDNA as a probe revealed a single band of fructose-1,6-bisphosphatase mRNA, 1.4 kilobases long, in liver and kidney but not in nongluconeogenic tissues. Fructose-1,6-bisphosphatase mRNA was increased 10-fold in livers from diabetic rats and was reduced to control levels after 24 hr of insulin treatment, suggesting that the changes in enzyme activity observed in diabetes and after insulin treatment are due to alterations in mRNA abundance.

Amino Acid Sequence↗

[Blood platelet changes in myeloproliferative disorders].

Morphofunctional alterations to the platelets in myeloproliferative disorders (MPD), conditions featuring clonal rearrangement of the haemopoietic stem-cell, were examined. These platelet anomalies including morphological alterations, acquired storage pool disease, membrane alterations, altered arachidonic acid metabolism and structural alterations to the von Willebrand factor may cause thromboembolisms or haemorrhages that are responsible for a significant incidence of morbidity and mortality. In contrast the reduced mitogenic activity of the platelets may be of significant prognostic value since it proves the anomalous transformation of the megakaryocytic clone. The main in vivo and in vitro tests (bleeding time and the study of platelet aggregation) were investigate as indicators of platelet function. Unfortunately, these tests proved of little use for the early diagnosis of haemorrhage or thromboembolism in MPD.

Arachidonic Acid↗

[Comparison of continuous wave Doppler and heart catheterization in the determination of the mean transvalvular gradient in mitral stenosis. A simultaneous beat to beat analysis].

Continuous wave Doppler echocardiography (CWD) is widely used in the assessment of pressure gradients in patients with valvular heart disease, utilizing the simplified Bernoulli equation. However determination of non-simultaneous mean pressure gradient (MG) in mitral stenosis (MS) from CWD recordings has often been described as being unsatisfactory. Therefore, the purpose of this study was to compare the estimates of trans-mitral MG derived from CWD with gradients measured simultaneously at cardiac catheterization (beat to beat analysis). We studied 3 patients (pts) with MS (1 man and 2 women, aged 55, 55 and 62 years respectively); one patient (pt) was in sinus rhythm and 2 were in atrial fibrillation. In each pt the trans-mitral flow velocity curve was obtained simultaneously with trans-mitral gradient measured directly at cardiac catheterization (cath). In this way it was possible to obtain a beat to beat correlation between Doppler and cath in 181 beats taken from the 3 pts. These beats were selected from a total number of 321 beats because of their excellent quality for analysis (74 beats were obtained from the first pt, 38 from the second pt and 69 from the third pt). Mean diastolic velocity, defined as the mean of maximal velocities throughout diastole, was obtained for each beat by planimetring the envelope of the spectral velocity profile. MG was calculated from mean velocity by applying the simplified Bernoulli equation (delta P = 4V2).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

[Primary non-Hodgkin's lymphoma of the breast. Description of a case].

A 65 year old female was admitted to Somma Lombardo Hospital (VA) for a growing mass in the right breast. Histology revealed a diffuse lymphocytic well-differentiated lymphoma. Malignant lymphoma primarily involving the breast is unusual, and its incidence is only 0.05% to 1.1% of all breast malignancies.

Aged↗

Rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Identification of essential sulfhydryl residues in the primary sequence of the enzyme.

The kinase and sugar phosphate exchange reactions of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase were inactivated by treatment with 5'-p-fluorosulfonylbenzoyladenosine or 8-azido-ATP, but activity could be restored by the addition of dithiothreitol. This inactivation was accompanied by incorporation of 5'-p-sulfonylbenzoyl[8-14C]adenosine into the enzyme that was not released by the addition of dithiothreitol. The lack of effect of ATP analogs on the ATP/ADP exchange or on bisphosphatase activity and reversal of their effects on the kinase and sugar phosphate reactions by dithiothreitol suggest that 1) they reacted with sulfhydryl groups important for sugar phosphate binding in the kinase reaction, and 2) the inactivation of the kinase by these analogs involves a specific reaction that is not related to their general mechanism of attacking nucleotide-binding sites. In addition, alkylation of the enzymes' sulfhydryls with iodoacetamide prevented inactivation by 5'-p-fluorosulfonylbenzoyladenosine, suggesting that the same thiols were involved. o-Iodosobenzoate inactivated the kinase and sugar phosphate exchange; the inactivation was reversed by dithiothreitol; but there was no effect on the bisphosphatase or nucleotide exchange, indicating that oxidation occurred at the same sulfhydryl that are associated with sugar phosphate binding. ATP or ADP, but not fructose 6-phosphate, protected these groups from modification by 5'-p-fluorosulfonylbenzoyladenosine, 8-azido-ATP, and o-iodosobenzoate. ATP also induced dramatic changes in the circular dichroism spectrum of the enzyme, suggesting that adenine nucleotide protection of thiol groups resulted from changes in enzyme secondary structure. Analysis of cyanogen bromide fragments of 14C-carboxamidomethylated enzyme showed that all radioactivity was associated with cysteinyl residues in a single cyanogen bromide fragment. Three of these cysteinyl residues are clustered in a 38-residue region, which probably plays a role in maintaining the conformation of the kinase sugar phosphate-binding site.

Adenosine↗

A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity.

Tetracyclines (including the semi-synthetic analogues, minocycline and doxycycline) are considered useful adjuncts in periodontal therapy because they suppress Gram-negative periodontopathogens. Recently, these antibiotics were found to inhibit mammalian collagenase activity, a property which may also be of therapeutic value. It has been suggested that the anti-collagenase properties of the tetracyclines are independent of their antibiotic efficacy. To advance this hypothesis further, we chemically converted tetracycline hydrochloride to its non-antimicrobial analogue, de-dimethylaminotetracycline. This chemically-modified tetracycline (CMT), although no longer an effective antibiotic, was found to inhibit the in vitro activity of collagenase from partially purified extracts of human rheumatoid synovial tissue and rachitic rat epiphysis. In a preliminary in vivo study, pathologically-excessive collagenase in skin and gingiva was induced by rendering adult male rats diabetic, and the oral administration of CMT to these rats significantly reduced the excessive collagenase activity in both tissues. Moreover, CMT administration did not affect the severe hyperglycemia in these rats but did prevent, at least in part, the diabetes-induced loss of body weight, skin weight, and skin collagen mass; these effects suggest a lack of toxicity in this animal model. A proposed clinical advantage of CMT over conventional tetracyclines, in the treatment of diseases characterized by excessive collagenolytic activity, is the lack of development of antibiotic-resistant micro-organisms during prolonged use. However, the consideration of clinical trials to support this hypothesis must await further laboratory and extensive toxicity tests.

Animals↗

[Visualization and characterization of the transvalvular jet in mitral stenosis using color-coded Doppler].

Two-dimensional Color Doppler flow imaging is a new non-invasive technique which allows real-time visualization of intracardiac blood flow and provides informations about its direction, velocity and presence of turbulence. As a consequence the identification of jets configuration across stenotic valve orifices is now possible by Color flow imaging. This non invasive tool may be particularly helpful in patients with rheumatic mitral valve disease in whom distortion of mitral valve apparatus is often present, determining a non uniform and variable appearance of jets. Therefore the aim of this study was to describe our initial experience with color flow imaging in the visualization of transtenotic mitral jets in order to characterize different spatial configurations. We studied 45 patients with clinical and echocardiographic diagnosis of mitral stenosis. The mean age of these patients was 59 years (range from 36 to 72 years), 34 were women and 11 men. The different types of transmitral jets were characterized by real time and frame by frame analysis. The following characteristics of transmitral jets have been evaluated: A) appearance ("Candle flame", "Mushroom", "Scimitar"-shaped, "Double-jets"); B) direction (centrally directed or eccentric); C) extension into the left ventricle (basal, mid-ventricular and apical); D) persistence of turbulent flow during diastole (early-, mid-, late diastole). Mitral valve area was calculated from the velocity tracings obtained by continuous wave Doppler, applying the pressure half-time method. Color flow imaging of good quality for analysis was obtained in 41 of 45 patients (91%). In the other 4 patients the quality of color flow images was suboptimal however the direction and configuration of the jets could still be visualised.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Isolated tricuspid valve prolapse: identification using 2-dimensional and Doppler echocardiography].

Echocardiography has been already applied in previous studies to identify tricuspid valve prolapse. However this anomaly has been found more frequently to be associated with mitral valve prolapse or with other cardiac and lung diseases. Isolated primitive tricuspid prolapse appears in fact a relatively unknown anatomo-clinical entity. In this paper we describe the two-dimensional and Doppler findings of three patients with isolated tricuspid prolapse. Two-dimensional echocardiography is the appropriate technique for its detection and allows the assessment of the echogenic characteristics of the valve texture.

Adult↗

An anatomical comparison of the human and bovine thoracolumbar spine.

The bovine spine has been frequently selected as the model for in vitro mechanical studies. A comparative anatomical study has been presented describing important differences and similarities between selected areas in the adult human and calf thoracolumbar spinal segment. Differences in column length and curvature were observed. The total length of the adult bovine vertebral column was found to be on average 209 cm longer than the adult human spine. Equivalent thoracolumbar lengths were obtained by selecting 6-8 week-old dairy calves, which because of their young age had the benefit of consistent bone density. The bovine spine was found to have only a single cervical lordotic curve and a single thoracolumbar kyphotic curve (2). A quantitative comparison of selected dimensions of vertebrae T6, T12, and L3 was performed, and significant findings are discussed. The bovine spinous processes were found to be on average 111% greater in length at level T6, which contributed to a 56% greater total anterior/posterior length at this level in comparison to the vertebrae of an adult male. A 23% greater bovine intertransverse length at level L3 was also shown. The orientation of the human and bovine superior facets, while being in the same general plane and direction, varied as much as 10.5 and 107% at vertebral level L3 on the two axes measured. These significantly different measurements were considered important factors that can influence experimental results when using the bovine spine as a model.

Anatomy, Comparative↗

Noninvasive evaluation of left-to-right shunts by pulsed Doppler echocardiography.

The systemic and pulmonary blood flows and the ratio of pulmonary to systemic flow were noninvasively evaluated by pulsed Doppler echocardiography in 25 children with left-to-right shunts. Fourteen patients had atrial septal defect and 11 had ventricular septal defect. In patients with atrial septal defect, right ventricular stroke volume was obtained from the recordings of mean velocity flow and the diameter at the level of pulmonary valve in short-axis view. The left ventricular stroke volume was evaluated from the suprasternal approach by positioning the sample volume within the ascending aorta just above the valvar leaflets. In children with ventricular septal defect, the pulmonary blood flow was determined at the level of the mitral orifice, whereas the systemic blood flow was estimated from the ascending aorta. The systemic and pulmonary blood flows and their ratio determined by pulsed Doppler echocardiography in the 25 patients examined, were compared using simple linear regression analysis with the results obtained by cardiac catheterization. The ratio of pulmonary-to-systemic flow showed an excellent correlation in patients with atrial septal defect (r = 0.82) and in those with ventricular septal defect (r = 0.79). Our study validates the accuracy of cross-sectional Doppler echocardiography, especially for minimizing some possibility of errors in the presence of left-to-right shunts by employing new approaches.

Blood Circulation↗

Is the platelet phenolsulfotransferase involved in the sulfoconjugation of plasma catecholamines?

Catecholamines are predominantly present in the sulfoconjugated forms in human plasma. Phenolsulfotransferase (EC 2.8.2.1), which catalyses the sulfation of phenolic compounds, is widely distributed in human tissues. In blood, a phenolsulfotransferase, more specific for catecholamine sulfation is found exclusively in platelets. Free and sulfoconjugated catecholamines were measured in plasma and platelets of healthy volunteers and compared with those present in patients with uremia or pheochromocytoma to determine the ability of platelet phenolsulfotransferase to sulfurylate plasma catecholamines. In patients with pheochromocytoma, the rise in free and sulfoconjugated plasma catecholamines is accompanied by a simultaneous rise of these molecules in platelets. In uremia, where the level of plasma catecholamines is normal, the rise in the sulfoconjugates is not accompanied by a concomitant increase in either free or sulfoconjugated catecholamines in platelets. Platelet phenolsulfotransferase activity remains unchanged in pheochromocytoma and uremia. These data indicate that the platelet phenolsulfotransferase is involved in the sulfation of the catecholamines present in platelets, but its contribution, if any, to the high level of sulfoconjugated catecholamines found in plasma is negligible. This assertion is confirmed by our observations in thrombocytopenic patients. Indeed, despite the very low number of platelets and the absence of plasma phenolsulfotransferase activity, thrombocytopenic patients have normal plasma levels of free and sulfoconjugated catecholamines.

Adrenal Gland Neoplasms↗