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Biomedical subjects

F Gentile

Publications and source records attributed to F Gentile.

At least 19 recordsLinked to original sources

Reproducibility of wall motion score and its correlation with left ventricular ejection fraction in patients with acute myocardial infarction.

The inter- and intraobserver variability, as well as the relation to left ventricular (LV) function indexes, of LV wall motion score calculated using the 16- and 11-segment models of LV segmentation were assessed in 105 patients with acute myocardial infarction who were examined at 36 +/- 7 hours from onset of symptoms. In these patients, the use of the 16-segment model of LV segmentation portends to a significantly higher inter- and intraobserver reproducibility of segmental wall motion score than the use of the 11-segment model. In addition, wall motion score assessed with the more detailed 16-segment model of LV segmentation showed a significantly higher correlation with LV ejection fraction than the wall motion score assessed using the 11-segment model.

Adult

Demonstration of the relationship between heart dimensions and QRS voltage amplitude.

This study was undertaken to elucidate the still debated question of the relationship between cardiac volume and QRS voltage amplitude. The authors studied 14 healthy men, aged 24-61 years (mean age, 41.2 +/- 12.1 years). They underwent a reduction in venous return, produced by simultaneously inflating sphygmomanometric cuffs placed around the most proximal portion of each of the four limbs. In basal conditions and 5 minutes after cuff inflation, two-dimensional and M-mode echocardiograms were recorded with vectorcardiographic loops and scalar Frank leads. The reduction of the venous return to the heart induced a significant decrease of the end-diastolic left ventricular diameter (from 52.4 +/- 4.2 to 48.5 +/- 4.6 mm, P < .001), of the R wave amplitude in leads X and Y, of the sum of the R wave amplitudes in the three leads,and of the maximal vector in the frontal and horizontal planes. No significant changes in the heart rate or arterial blood pressure were observed. These results support Brody's theory concerning the relationship between cardiac blood volume and QRS voltage.

Adult

Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old.

Left ventricular diastolic indexes are influenced by several variables. In order to evaluate the relationship of these indexes to age, heart rate, sex and to standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided into six age groups, underwent a two-dimensional colour Doppler examination. Doppler examination was performed from the apical four chamber view to evaluate transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical five chamber view. In order to obtain a sufficient number of subjects for an adequate statistical analysis, seven hospitals were involved in the study. Univariate analysis showed that age influences the peak velocity of the E (r = -0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than 70 years an inversion of the E/A wave ratio was observed. Multivariate analysis confirmed that age has an important influence on left ventricular diastolic indexes but also demonstrated that heart rate has a significant influence. Sex, ejection fraction (EF), and the dimensions of the mitral annulus and the left ventricular posterior wall had less influence on left ventricular diastolic indexes. The mean values of E and A wave acceleration, deceleration and peak velocity were used to depict left ventricular filling morphology in various age groups for three different heart rate values. The conclusions of the study, are: (1) normal left ventricular diastolic parameters were obtained as mean values at seven different hospitals (2) when evaluating left ventricular diastolic function parameters it is important to take into account age and heart rate; E/A inversion in older subjects should be considered the normal mitral flow pattern.

Adult

Dobutamine echocardiography: usefulness of digital image processing.

The present study was undertaken in order specifically to evaluate the usefulness of digital image processing so as to enhance the diagnostic power of dobutamine stress echocardiography. For this purpose 44 dobutamine echocardiographic tests, routinely performed in our echo laboratory, were analysed blindly by two observers using traditional videotape recording and digitized image acquisition. The results obtained from both observers show a trend which suggests that the traditional videotape approach provides more true-positive tests than the digitized approach (27/38 vs 23/38 and 24/38 vs 22/38 for the first and second observer, respectively). True-negative test detection was 6/6 with the videotape and 5/6 with the digitized method for both observers. As a consequence of the discrepancies observed between the two modalities, the videotape indicates that it can provide higher diagnostic accuracy than the digitized approach (72 +/- 9% vs 63 +/- 10%). The tests results concordance (positive or negative) between the two modalities of analysis was 66% for both the observers. The inter-observer agreement on the test results was 84% and 80% for the videotape analysis and the digitized analysis, respectively. On the basis of the results, we consider that digitized analysis applied to dobutamine stress echocardiography does not afford significant diagnostic advantages and should not be considered as an alternative option to traditional videotape analysis. However, it may be considered an extremely useful integrative tool since it produces the on-line image evaluation more easily and faster and allows a more practical form of stress test storage.

Adult

Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel diketopiperazine produced by Gliocladium sp.

Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation of broth of the fungal culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compounds prevented serum-stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter gene assay, with IC50 values of 1.5, 18 and 0.5 microM of 1, 2 and 3, respectively. Northern analysis revealed the exposure of cells to compound 3 causes inhibition of both phorbol ester-induced c-fos induction of serum-induced JE induction in the absence of inhibiting RNA synthesis, as measured by [3H]uridine incorporation. There results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is common to and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.

3T3 Cells

Recent progress in immunoisolated cell therapy.

Biohybrid implants represent a new class of medical device in which living cells, supported in a hydrogel matrix, and surrounded by a semipermiable membrane, produce and deliver therapeutic reagents to specific sites within a host. First proposed in the mid-1970s for diabetes, this treatment modality has progressed rapidly in the past four years and is now being investigated not just for endocrine disorders but also for alleviation of chronic pain, treatment of neurodegenerative disorders, and delivery of neurotrophic factors to sites within the blood brain barrier, and as a practical alternative to conventional ex vivo.

Alzheimer Disease

A cluster of tuberculosis among crack house contacts in San Mateo County, California.

In March 1992, a cluster of 89 persons with tuberculosis infection was identified in San Mateo County, California. Thirteen persons (15%), including 11 children, were diagnosed with active pulmonary tuberculosis. All contacts were African Americans who resided in or visited one of two houses used for crack cocaine smoking or dealing. The patient with the index case, a male infected with human immunodeficiency virus, contributed to the transmission of tuberculosis as a transient resident of several dwellings. Public health authorities applied unique intervention methods to control the outbreak, including the use of a mobile health van. Further innovative strategies will be necessary to meet the challenge of this reemerging disease.

Adolescent

Congenital hypothyroidism: etiology and pathogenesis.

Congenital hypothyroidism is a frequently occurring condition with possibly severe and irreversible consequences. Most of the cases are due to thyroid ectopia, aplasia or hypoplasia and are sporadic in occurrence. Inherited defects of thyroid hormone biosynthesis, secretion and utilization represent a minor, although not insignificant, fraction of the cases of congenital hypothyroidism. In a number of cases, transient congenital hypothyroidism can be due to such causes as maternal exposure to antithyroid drugs or excess iodine, transplacental transfer of blocking antibodies or endemic iodine deficiency. The latter is still a matter of concern in selected geographical areas. Both sporadic and familial cases of hypothalamic-pituitary hypothyroidism are quite rare. Early diagnosis of congenital hypothyroidism by mass screening programs is of the foremost importance for the prevention of long-term sequelae. The molecular defect has been elucidated in a number of inherited defects of thyroid hormone biosynthesis, secretion and utilization. These include impaired thyroidal response to thyroid-stimulating hormone (TSH) due to an altered TSH receptor, defective synthesis of thyroglobulin, defective synthesis of thyroid peroxidase, generalized resistance to thyroid hormone, and familial isolated TSH deficiency. It is anticipated that, as more mutations become available for detailed molecular analysis, further advances in our knowledge of the molecular aspects of thyroid function will ensue in the near future.

Congenital Hypothyroidism

Preferential sites of proteolytic cleavage of bovine, human and rat thyroglobulin. The use of limited proteolysis to detect solvent-exposed regions of the primary structure.

The sites and the sequence of the proteolytic cleavages of bovine, human and rat thyroglobulin, during the limited proteolysis with thermolysin and trypsin, were determined by sequencing the NH2 termini of the peptides produced and comparing them to the cDNA-derived sequences of bovine, human and rat thyroglobulin. Major cleavage sites of bovine thyroglobulin included residues 240, 502, 993, 1218, 1784 with thermolysin, and 240, 520, 1142, 1783, 2515 with trypsin. Cleavage sites of human thyroglobulin included residues 503, 982, 990, 1405, 1831 with thermolysin, and 522, 1627, 2513 with trypsin. Those of rat thyroglobulin included residues 501, 1776, 1784 with thermolysin, and 522, 1771, 1825, 2515 with trypsin (numbered as in bovine thyroglobulin). Thus, thyroglobulin from various species presents well localized and conserved regions particularly sensitive to proteolysis. The most sensitive region extended for 30 residues after residue 500. Another major cluster of cleavages was centered around residue 1800; this region was only partially sensitive in human thyroglobulin. A conserved tryptic site lay at the COOH terminus of the molecule. Most cleavage sites occurred within the inserted sequences that disrupt the Cys-rich, tandem repeats of thyroglobulin and either contain or are located near exon-intron junctions. Several cleavage sites lay in proximity of early iodinated or hormonogenic tyrosyl residues or of putative N-linked glycosylation sites. While a predominantly beta-type secondary structure and a rigid three-dimensional structure were predicted for the Cys-rich repeats, stretches of predicted alpha-helices, beta-strands and irregular structure were interspersed in the regions surrounding the cleavage sites. These data demonstrate the existence of conserved regions of thyroglobulin inherently sensitive to proteolysis, which most likely represent solvent-exposed regions of the primary structure, possibly forming loops at the surface of thyroglobulin.

Amino Acid Sequence

Trypsin-resistant regions of thyroglobulin: possible relationship with intermonomeric contact site(s).

Upon incubation of bovine thyroglobulin with trypsin at high enzyme/substrate ratio, some fragments with apparent masses between 18 and 31 kDa resisted prolonged digestion. Their NH2-terminal sequences were determined. All fragments overlapped with some of the Cys-rich repeats that compose a large part of thyroglobulin and are predicted to have a rigid structure. Among the inserts that interrupt the cysteine-rich repeats, for which several data indicate a location at the surface of thyroglobulin, the insert of repeat 1.7 was unique because of its resistance to proteolysis. This insert, although exposed at the surface of the protein, may be hidden in a region of contact between thyroglobulin monomers.

Amino Acid Sequence

A novel macrolactam-disaccharide antifungal antibiotic. Taxonomy, fermentation, isolation, physico-chemical properties, structure elucidation and biological activity.

A novel natural product (1), with antifungal activity was isolated from the culture broth of an actinomadurae. The active compound was separated from broth by n-butanol extraction and purified by silica gel and multicoil counter current chromatography. Physico-chemical data suggested the structure of this compound to be a novel macrolactam disaccharide related to Sch 38518 (3). The structure was determined by spectroscopic studies on the acetate derivative. It was active against Candida spp. (MIC's, 4 approximately 64 micrograms/ml) but less than the monosaccharide, Sch 38518 (MIC's, 1 approximately 16 micrograms/ml).

Aminoglycosides

Does aortic regurgitation affect transmitral flow? An echo-Doppler study.

Recent studies suggest that the presence of aortic regurgitation can interfere with Doppler measurement of mitral pressure half-time in patients with mitral stenosis. Amongst the factors affecting the transmitral flow in aortic regurgitation a putative role may be played by the mechanical hit of the aortic regurgitant jet impinging on the anterior mitral leaflet, as is very often seen with Doppler Color Flow examination. This study was designed to evaluate the effects of pure aortic regurgitation on the transmitral flow in patients with normal mitral valves. We studied 35 patients affected by pure chronic aortic regurgitation but with a normal mitral valve and compared them with 30 normal subjects. In all the patients the aortic regurgitant jet was directed toward the anterior mitral leaflet. In all the patients and control subjects a standard echo-Doppler examination was performed, sampling the transmitral flow at the level of the tip of the mitral leaflets. In 7 patients and 11 normal subjects the transmitral flow was also sampled at the level of the mitral annulus. Patients with aortic regurgitation showed significantly higher values of the mitral pressure half-time (61.04 +/- 15.14 vs 50.59 +/- 7.07 ms, P < 0.05) and of the time-velocity integral of the total transmitral flow, while the other parameters of transmitral flow, the mitral annulus diameter and the mitral stroke volume didn't show statistically significant differences. The comparison of the pressure half-time and time-velocity flow values measured at the level of the mitral annulus between patients and normal subjects didn't show significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Hemodynamic effects of nifedipine in patients with asymptomatic aortic regurgitation: evaluation by Doppler echocardiography.

Nineteen asymptomatic patients affected by isolated chronic aortic regurgitation received 20 mg of nifedipine sublingually: the acute hemodynamic effects of nifedipine were evaluated by combined cross-sectional and Doppler echocardiography. To assess variations in the regurgitant flow volume, the flow volume across the mitral and aortic valves was calculated as the product of velocity-time integral multiplied by the orifice valve area. Flow volume across these valves represented the total stroke volume, and forward stroke volume, respectively: the regurgitant volume was obtained by calculating the difference between total and forward stroke volume. Nifedipine induced a redistribution of the two components of the total left ventricular stroke volume: regurgitant stroke volume decreased from 57 +/- 22 ml/beat to 46 +/- 21 ml/beat (P < 0.002), while forward stroke volume increased from 83 +/- 12 to 93 +/- 15 ml/beat (P < 0.0005), as a consequence of the reduction in systemic vascular resistance from 1513 +/- 378 to 1092 +/- 307 dynes.sec.cm-5 (P < 0.0001). The reduction of regurgitant volume was due to either a 24.8% decrease of the aortic-left ventricular mean pressure gradient during diastole (P < 0.008) or a 6% decrease of the diastolic time interval (P < 0.04). The effect of these acute changes on left ventricular loading was to induce a reduction in oxygen consumption which was expressed by a decrease in the double product (from 10176 +/- 1767 to 9444 +/- 1559 mmHg.beats/min; P < 0.002), in spite of a significant increase in heart rate. This study, therefore, shows the beneficial acute hemodynamic effect induced by nifedipine in asymptomatic patients affected by chronic aortic regurgitation and shows that Doppler-echocardiography is a useful instrument for the evaluation of hemodynamic changes immediately after the administration of drugs.

Administration, Sublingual

["Incomplete closure" of the mitral valve: the relationships to valvular regurgitation and to the morphofunctional characteristics of the left ventricle].

OBJECTIVES: The present study was designed in order to evaluate the prevalence of mitral regurgitation in patients with the "incomplete mitral leaflet closure" echocardiographic pattern, to verify whether the amount of "incomplete mitral leaflet closure" is related to the severity of mitral regurgitation and, last, to verify the relation between the "incomplete mitral leaflet closure" and left ventricular morphology and function. METHODS: We studied 80 patients (14 patients with dilatative cardiomyopathy, 26 patients with coronary artery disease, and 40 patients with hypertensive heart disease or aortic valve disease) showing the "incomplete mitral leaflet closure" pattern, retrospectively selected from a population composed of 1700 consecutive patients routinely examined in our echocardiographic laboratory. In all patients we evaluated the presence and the severity of mitral regurgitation, the morphological and functional parameters of the left ventricle, the systolic diameter of the mitral annulus, the distance between the point of mitral leaflet coaptation and the annular plane, and the incomplete mitral closure area, assuming the last two parameters as indexes of the severity of incomplete closure of the mitral valve. RESULTS: We observed the presence of mitral regurgitation in 51 out of 80 patients (64%). The valvular insufficiency was considered mild in 78% of the patients. We observed no significant difference between patients with mitral regurgitation and without, as regards the diameter of the mitral annulus, the distance between the point of mitral leaflet coaptation and the annular plane, and the incomplete mitral closure area in different types of heart diseases. The incomplete mitral closure area and the diameter of the mitral annulus showed a significant, although not elevated, correlation with the severity of the mitral regurgitation (r = 0.36 and r = 0.32, respectively). The severity of mitral regurgitation showed significant correlations with all of the left ventricular morphological and functional parameters evaluated. Finally, we observed significant correlations between the incomplete mitral closure area and all of the morphological and functional parameters of the left ventricle. CONCLUSIONS: On the basis of the results obtained we can conclude that: 1) the "incomplete mitral leaflet closure" pattern does not appear to be a highly specific marker of mitral regurgitation, 2) this pattern appears to be related to the morphology and function of the left ventricle, and 3) the severity of the incomplete mitral valve closure is more easily evaluated by a parameter that takes into account the numerous factors acting on the mitral apparatus, that is the incomplete mitral closure area.

Aged

TSH-induced galactose incorporation at the NH2 terminus of thyroglobulin secreted by FRTL-5 cells.

FRTL-5 cells were cultured in media containing standard growth factors with or without TSH, plus labeled precursors of N-linked oligosaccharide chains. The thyroglobulin secreted in the medium was purified and fragmented with CNBr. Three peptides were identified by NH2-terminal sequencing, that were labeled mainly with D-[2-3H]mannose, independent of TSH. One of them, corresponding to the NH2-terminus of thyroglobulin, incorporated both more D-[2-3H]mannose and more D-[1-3H]galactose upon TSH addition. These data likely reflect a TSH-induced increment of N-linked glycosylation at the NH2-terminus of thyroglobulin, mostly with the maturation of high-mannose to complex chains.

Amino Acid Sequence

The origin of the electrophoretic doublet of thyroglobulin.

Bovine and human thyroglobulin show two closely migrating bands in reducing SDS-PAGE. Limited digestion with chymotrypsin, trypsin and thermolysin converted the slower band of the doublet into a peptide identical to the faster band, with an apparent mass of 270 kDa, in both species. The starting point of the faster band of the doublet was established at Ileu 520 with native bovine Tg and at Ser 503 with native human Tg, and at Ser 503 and Ser 504 with chymotrypsin-digested bovine and human Tg, respectively. These data explain the electrophoretic heterogeneity of thyroglobulin and unveil a region highly susceptible to proteolysis at about 500 residues from the NH2-terminus of the molecule.

Amino Acid Sequence

Macrolactams: a novel class of antifungal antibiotics produced by Actinomadura spp. SCC 1776 and SCC 1777.

Three novel antifungal antibiotics, Sch 38518, Sch 39185 and Sch 38516 were isolated from the fermentation broths of two actinomycetes identified by chemical, morphological and physiological analysis as a new species of Actinomadura. The compounds were isolated from broth by solvent extraction and purified by silica gel chromatography. Physico-chemical properties, mass spectral analysis, IR and UV suggested the compounds were similar. Sch 38518 and Sch 39185 have a molecular formula of C25H48N2O5. 1H NMR, 13C NMR and hydrolysis indicated the aglycones were identical, however the compounds differed in containing isomeric sugar moieties. Sch 38518 contains mycosamine while Sch 39185 contains 3,6-dideoxy-3-amino-L-talopyranose. Sch 38516 has a molecular formula of C24H46N2O5 and is a lower homolog of Sch 39185. The three compounds, Sch 38518 (1), Sch 39185 (2), and Sch 38516 (3) exhibit similar activity against Candida spp. with geometric mean MICs of 1.81, 2.00 and 0.91 micrograms/ml, respectively.

Actinomycetales