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Biomedical subjects

A Lombardo

Publications and source records attributed to A Lombardo.

At least 55 records · Page 3Linked to original sources
PubMed1994

The esters of p-hydroxy-benzoate (parabens) inhibit the release of lysosomal enzymes by mitogen-stimulated peripheral human lymphocytes in culture.

An in vitro test was set up to assess the release of lysosomal enzymes from cells and the effect on this process of the commonly used preservatives, parabens. Human peripheral lymphocytes, cultivated in vitro for 24 h in the presence or absence of phytohaemagglutinin (PHA; 5 mg/l), were used. After 1 day of incubation, PHA treatment caused an increased release (from 220 to 500%) of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-L-fucosidase and alpha-D-galactosidase. This enhancement was analytically reliable, and detectable with 1-5 micrograms of cell protein. Leakage of lactate dehydrogenase (LDH) underwent only a 20% increase on PHA treatment, indicating that the increased release of lysosomal enzymes was presumably due to secretion, not to cell damage. In PHA-stimulated lymphocytes, methyl-, ethyl-, propyl- and butyl-parabens caused a concentration-dependent diminution of the secretion of lysosomal enzymes. Butyl-paraben appeared to be the most potent inhibitor, causing a 45-50% inhibition at 0.06 mmol/l. With the other parabens, the inhibitory effect became statistically significant at about 0.25 mmol/l for alpha-L-fucosidase and alpha-D-galactosidase, and at 0.5 mmol/l for N-acetyl-beta-D-glucosaminidase and beta-D-glucuronidase. At 1 mmol/l inhibition was greater than 50% for all the enzymes and was more marked with the propyl derivative. Parabens did not influence the release of LDH, suggesting that they affected particularly the secretion of lysosomal enzymes. This supports the hypothesis that parabens are capable of affecting cellular function at concentrations which are likely to be reached in blood or tissues under conditions of common use.

Acetylglucosaminidase↗
PubMed1994

Color Doppler study of mitral regurgitation during percutaneous transluminal coronary angioplasty.

Mitral regurgitation (MR) was evaluated by color Doppler echocardiography during percutaneous transluminal coronary angioplasty (PTCA) in 28 patients with one-vessel artery disease (left anterior descending artery in 11, right coronary artery in 8, and circumflex artery in 9) and normal left ventricular function. In all three groups, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) decreased significantly during artery occlusion in comparison with baseline values (no differences among various groups). Anterior and inferior akinesia/dyskinesia was observed in all patients during left anterior descending and right coronary artery occlusion, respectively. Lateral akinesia/dyskinesia was induced by occlusion of the circumflex artery in six patients (all with proximal lesions [p < 0.05 vs the other two groups]) and the right coronary artery in one. Only the six patients with circumflex artery occlusion showed PTCA-related MR (> 2+ in two). LVEF and WMSI were similar during artery occlusion in patients with and without MR. Neither mitral leaflet prolapse nor anulus dilation occurred during PTCA in any of the patients. Our data show that during brief occlusion of the proximal circumflex artery, functional MR (usually mild) frequently occurs in relation to specific lateral akinesia/dyskinesia.

Acute Disease↗
PubMed1994

Doppler analysis of pulmonary venous flow in left atrial myxoma.

In a patient with obstructive left atrial myxoma, we analyzed by pulsed Doppler echocardiography the flow pattern through the mitral valve and in the pulmonary veins. Two mitral flow patterns were observed: the first was present near the medial commissure and along the anterior leaflet and was characterized by the absence of mid-to-late diastolic filling flow; the second was found near the lateral commissure and was characterized by the obstruction of mid-to-late diastolic filling flow, mimicking mitral stenosis. The pulmonary vein flow showed brief and rapidly decelerating anterograde diastolic flow wave and an early systolic retrograde flow wave. These waves were respectively related to the diastolic forward and the systolic backward movement of the tumor. This case report shows that pulmonary vein flow analysis may give new insights into left atrial filling and emptying dynamics in left atrial myxoma.

Aged↗
PubMed1993

The lysosomal N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes in plasma: study of distribution in a general population by a simple routine chromatofocusing procedure.

We have adapted for routine analysis a pre-existing method for separating the three major N-acetyl-beta-D-glucosaminidase (NAG) isoenzyme forms--A, B+I1 and I2--by chromatofocusing followed by fluorimetric assay of the enzyme activity. This method combines good resolution, accurate quantification of the different isoenzymes and high reproducibility with an acceptable degree of analytical precision. We have applied it to studying the isoenzyme levels in the plasma of a general population of 417 subjects and have analysed these enzyme activities as functions of age, sex, body mass and declared alcohol consumption. Unlike the levels of unfractionated enzyme, levels of all the isoenzymes were higher in men than in women at all ages except in the 20-29 year group. Isoenzyme I2 showed the greatest sex difference. On the whole, with increasing age, both sexes showed more or less regular increases in plasma levels of all the isoenzymes. We also found significant correlations for the population as a whole with age and with body mass index. The only significant correlation with alcohol consumption was for B+I1 in men.

Acetylglucosaminidase↗
PubMed1993

Enzymes of lysosomal origin in plasma of twin neonates.

The levels of some enzymes of lysosomal origin were assayed during days 2 and 5 of life in plasma from 11 sets of twin neonates and from 25 neonates from single pregnancies (13 of weight appropriate for gestational age and 12 small for their gestational age) as controls. The plasma enzyme levels were also determined in the correspondent twin and control mothers 2 days after delivery. N-Acetyl-beta-D-glucosaminidase isoenzymes were assayed after chromatofocusing separation. All the plasma enzyme levels were higher in the group of twin neonates and of their mothers than in the respective control groups with differences highly statistically significant for two enzymes, beta-D-galactosidase and alpha-D-glucosidase. In neonate plasma lysosomal enzymes are increased at the fifth day of life with respect to the second day. Full term control neonates showed the same enzyme trend. For the N-acetyl-beta-D-glucosaminidase the more significant differences concerned the isoenzyme I2-P (pregnancy). The pattern of the lysosomal enzymes in the twins resembled that of neonates of diabetic mothers who had had no insulin therapy. Since lysosomal enzymes are considered to be particularly sensitive indicators of carbohydrate metabolism abnormalities, we conclude that twin pregnancies are more at risk for these abnormalities than single ones.

Female↗
PubMed1993

Enzymes of lysosomal origin in the cerebrospinal fluid and plasma of patients with multiple sclerosis.

Several lysosomal enzymes were determined in 47 and 62 samples of CSF and plasma, respectively, obtained from MS patients. CSF levels of most enzymes considered were significantly lower in patients when compared to those of the controls, whereas the plasma levels vary little and appeared to be influenced by the course of the disease. The most interesting result is the one concerning the beta-D-glucuronidase in the plasma: in relapsing-remitting patients in the still untreated acute phase, the levels remain noticeably diminished in comparison to controls. The data suggest the potential of using this enzyme to monitor the progression of the disease.

Adolescent↗
PubMed1993

Doppler analysis of portal vein flow in tricuspid regurgitation.

Portal and hepatic vein flow-velocity profiles were examined by pulsed Doppler in 66 patients with tricuspid regurgitation (color Doppler grading: severe: 37, moderate: 18; mild: 11) and 20 normal subjects to determine if portal vein flow analysis is useful in the evaluation of tricuspid regurgitation. Portal vein flow was defined as one of the following categories: subcontinuous (dependent on respiration), pulsatile systolic (not inverted), inverted after systole, and continuous (not dependent on respiration). An index of portal vein flow pulsatility was also calculated. Standard classification of hepatic vein flow pattern was performed. Portal vein flow was pulsatile in 20% of normals subjects, and in 27.3% 44.5% and 51.3% of patients with respectively mild, moderate and severe tricuspid regurgitation; portal vein flow was inverted after systole in further 32.4% of patients with severe tricuspid regurgitation. Portal vein pulsatility index correlated with color Doppler grading of tricuspid regurgitation (r:0.63; p < 0.001) and right ventricle-atrium pressure gradient (r:0.39; p < 0.01). However, when compared with hepatic vein flow, both sensitivity and specificity of quantitative portal vein flow analysis was less reliable in diagnosing and grading tricuspid regurgitation. In particular, in patients with severe tricuspid regurgitation, the portal vein flow pattern was quite variable (pulsatile in 19 patients, inverted after systole in 12, and continuous in six). Liver biopsy was performed in nine patients, four of them with severe tricuspid regurgitation and continuous portal vein flow. Histology showed severe liver fibrosis in all four.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Abnormal intraventricular flow patterns in left ventricular dysfunction determined by color Doppler study.

We examined the relation between left ventricular (LV) flow dynamics measured by color Doppler, and either global or regional LV function in 19 normal subjects (group 1), in 55 patients with old myocardial infarction (MI) (29 without [group 2] and 26 with LV aneurysm [group 3]), and in 16 with idiopathic dilated cardiomyopathy (group 4). We calculated by M-mode color Doppler a flow persistence index (FPI) (duration of flow directed in systole toward the apex/LV ejection time). Contrast echocardiography was performed as a control method in 14 patients of the four groups. In normal subjects, rapid systolic inversion of flow toward the aorta was evident (FPI: 0.11 +/- 0.16). In all but one patient in group 2, a similar LV flow pattern was observed, but FPI was greater (0.32 +/- 0.26). In groups 3 and 4, a paradoxical antegrade LV flow pattern was evident during the entire period of systole (FPI: 1.13 +/- 0.42 and 1.28 +/- 0.36, respectively). LV flow patterns were reproduced in echo-contrast studies. FPI was related to LV end-diastolic volume (r = 0.77), end-systolic volume (r = 0.82), and ejection fraction (r = -0.84). However, when data were analyzed separately in the different groups, these correlations were significant only in groups 2 and 3. Paradoxical flow pattern is not peculiar to regional LV dysfunction; it also occurs in global LV dysfunction. This LV flow abnormality may develop after MI even in the absence of severe LV dyssynergy or dilation, and is quantitatively related to the degree of LV dysfunction.

Adult↗
PubMed1992

Control of mRNA turnover as a mechanism of glucose repression in Saccharomyces cerevisiae.

We have examined the expression of the gene encoding the iron-protein subunit (Ip) of succinate dehydrogenase in Saccharomyces cerevisiae. The gene had been cloned by us and shown to be subject to glucose regulation (A. Lombardo, K. Carine, and I. E. Scheffler, J. Biol. Chem. 265:10419-10423, 1990). We discovered that a significant part of the regulation of the Ip mRNA levels by glucose involves the regulation of the turnover rate of this mRNA. In the presence of glucose, the half-life appears to be less than 5 min, while in glycerol medium, the half-life is greater than 60 min. The gene is also regulated transcriptionally by glucose. The upstream promoter sequence appeared to have four regulatory elements with consensus sequences shown to be responsible for the interaction with the HAP2/3/4 regulatory complex. A deletion analysis has shown that the two distal elements are redundant. These measurements were carried out by Northern (RNA) analyses of Ip mRNA transcripts as well as by assays of beta-galactosidase activity in cells carrying constructs of the Ip promoter linked to the lacZ coding sequence. These observations on the regulation of mRNA stability were also extended to the mRNA of the flavoprotein subunit of succinate dehydrogenase and in some experiments of iso-1-cytochrome c.

Cloning, Molecular↗
PubMed1992

Acromegalic cardiomyopathy. Left ventricular filling and hypertrophy in active and surgically treated disease.

Myocardial hypertrophy and interstitial fibrosis are common in acromegalic hearts and may induce left ventricular (LV) dysfunction. The transmitral flow pattern was examined by pulsed-wave Doppler in 20 patients with active acromegaly and nine with acromegaly cured by pituitary microsurgery. Control groups consisted of 25 normal subjects and 13 patients with systemic hypertension. We related Doppler indices of LV filling (E and A peak velocities and E/A ratio) to the duration of acromegalic disease, the GH plasma levels and LV mass. The LV mass/BSA was significantly greater in active acromegaly (187 +/- 53 g/sq m) and systemic hypertension groups (161 +/- 48 g/sq m) than in cured acromegaly (125 +/- 35 g/sq m) and the normal control group (109 +/- 36 g/sq m) (p < 0.01 for both). No differences were found in the E peak velocity, A peak velocity, and E/A ratio in the groups with active acromegaly (E/A: 0.9 +/- 0.2), cured acromegaly (E/A: 0.9 +/- 0.3), and systemic hypertension (E/A: 0.8 +/- 0.5). An E/A ratio < 1 was found in 13 patients with active and four with cured acromegaly; (p = NS). In the active acromegaly group, the E/A ratio was related to either LV mass or the duration of disease (r:-0.45 and -0.47, respectively; p < 0.05). In the cured acromegaly group, the E/A ratio was related to the duration of disease before surgery (r:-0.70; p < 0.05) and not to LV mass (r:0.12). In conclusion, an impairment in LV filling may be present not only in the patients with active acromegaly but also in those successfully treated by surgery after a long duration of the disease, despite normal LV mass. These LV filling abnormalities may be in part determined by nonreversible myocardial changes, such as interstitial tissue fibrosis.

Acromegaly↗
PubMed1992

Preparation of a stable liquid material for calibration and quality control for lysosomal enzymes in plasma. Assay of enzymes of lysosomal origin in plasma, I.

Several lysosomal enzymes present in human plasma (N-acetyl-beta-glucosaminidase, beta-glucuronidase, beta-galactosidase, alpha-galactosidase, alpha-L-fucosidase, alpha-mannosidase, beta-glucosidase) were maintained in a fully active state for at least 8 months by the addition of ethylene glycol (300 milligrams final concentration) to freshly prepared plasma and storage at -20 degrees C. Pools of human plasma from healthy humans, stabilized and stored as above, and containing a low, medium or high content of the above enzymes, were used to establish the analytical imprecision (within-run, day-to-day and total imprecision) of the fluorimetric assay. Ten replicates in ten different analytical series, covering a period of two months, were performed. The total imprecision (expressed as coefficient of variation) was in general lower than 10%; in a few cases, particularly plasma samples with a low enzyme content, the total imprecision was 18%. The isozymes A, B, I1, and I2 of N-acetyl-beta-glucosaminidase displayed the same stability upon storage as the unfractionated enzyme. It is concluded that pools of human plasma containing known amounts of lysosomal enzymes, stabilized by the addition of 300 micrograms ethylene glycol and stored at -20 degrees C, are suitable liquid materials for calibration and quality control for the assay of the same enzymes.

Acetylglucosaminidase↗
PubMed1991

[The prevention of deep venous thrombosis in patients undergoing an internal arteriovenous fistula intervention].

Twenty patients, submitted to internal arteriovenous fistula procedure, were randomly assigned to one of the following treatments: defibrotide 400 mg b.i.d. IM (starting the day before surgery and continuing for the following 7 days); calcium heparin 5,000 IU t.i.d. SC (since the day of surgery and for the following 7 days). No deep venous thrombosis or thrombosis of the fistula were noticed during both treatments and no side effects were observed. In the defibrotide group, ELT showed a significant decrease (-40%) attesting an improvement of fibrinolysis without a plasminogen abatement. These findings indicate that defibrotide represent an effective alternative to calcium heparin for antithrombotic prophylaxis of A-V fistula in uremic patients.

Arteriovenous Shunt, Surgical↗
PubMed1990

Cloning and characterization of the iron-sulfur subunit gene of succinate dehydrogenase from Saccharomyces cerevisiae.

We describe the cloning and characterization of the complete gene for the iron-sulfur protein subunit of succinate dehydrogenase (EC 1.3.99.1) from Saccharomyces cerevisiae. The promoter and coding sequence have been cloned into an Escherichia coli-yeast shuttle vector. The cloned gene complements the defect in a succinate dehydrogenase-deficient yeast mutant isolated by us, and gene expression is fully responsive to induction by glucose deprivation, indicating that the promoter is intact.

Amino Acid Sequence↗
PubMed1989

Isolation and characterization of a Saccharomyces cerevisiae mutant with a disrupted gene for the IP subunit of succinate dehydrogenase.

A partial cDNA clone corresponding to the iron-sulfur protein of succinate dehydrogenase (EC 1.3.99.1) has been isolated by an application of the polymerase chain reaction (Gould, S. J., Subramani, S., and Scheffler, I. E. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 1934-1938). We used this clone for targeted gene disruption to isolate clones of Saccharomyces cerevisiae which were totally defective in this enzyme. The disruption of the gene was verified by Southern analysis. A Northern analysis revealed the existence of a new transcript which includes the 5' end of the mRNA for the IP subunit, but extends into the vector sequence disrupting the gene. A Western analysis suggests that the large flavoprotein subunit (FP) is still made in the mutant and imported into the mitochondria, but at significantly lower levels.

Blotting, Northern↗
PubMed1989

Doppler study of precordial musical murmurs.

Using phonocardiography, continuous- and pulsed-wave Doppler, 51 patients with precordial "musical" murmurs (49 with cardiac abnormalities) and 21 patients with noisy murmurs were examined. With M-mode echocardiography, fine fluttering of the structure generating the murmur was evident in 23 patients with musical murmurs and in 5 with noisy murmurs. A continuous-wave Doppler spectral signal characterized by parallel harmonics (Doppler musical signal) was evident in all patients with musical murmurs and in none with a noisy murmur. With pulsed-wave Doppler, the musical signal had less defined spectral features because of range ambiguity. Such a signal was experimentally reproduced by activating a diapason bathed in saline solution. The source of the musical murmur was established in all 51 patients by Doppler. The musical signal was associated with a valvular regurgitation signal in 36 patients and with a ventricular septal defect in 1 patient. The musical signal always disappeared when the pulsed-wave Doppler sample volume was placed 2 cm away from the generating structure. In 11 patients with musical murmur examined by color Doppler, no abnormal bidirectional flow signal was observed in the structures generating the signal. In 6 of the patients without valvular regurgitation, no flow disturbance was found. In conclusion, Doppler is valuable in determining the source of musical murmurs, and musical murmurs are caused by a vibrating structure even in the absence of flow turbulence.

Aortic Valve Insufficiency↗