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Biomedical subjects

L Arata

Publications and source records attributed to L Arata.

At least 19 recordsLinked to original sources
PubMed2001

Polymorphisms in genes involved in folate metabolism as risk factors for NTDs.

Moderate hyperhomocysteinemia in pregnant women has been associated with an increased risk of neural tube defects (NTDs). Periconceptional supplementation with multi-vitamins containing folic acid may normalize homocysteine metabolism and decrease the NTD risk. The C677 T variant of the MTHFR gene coding for a thermolabile enzyme has been described as the first genetic risk factor that accounts for a group of NTDs characterized by low maternal folate status and high homocysteine concentrations. Another common mutation of the same MTHFR gene, A1298 C, has also been described as an NTD risk factor. In addition to abnormal folate metabolism, anything that compromises the internalization of folate into the cell may be involved in the pathogenesis of NTDs. For this reason, a common polymorphism in the RFC-1 gene encoding the reduced folate carrier protein (A80 G) could also be an additional NTD risk factor. In the present study we examined the genotypic distributions and the allele frequencies of MTHFR A1298 C and RFC-1 A80 G polymorphisms in DNA samples from healthy Italian individuals and compared them to the frequencies observed in NTD cases and their parents. By means of restriction enzymatic analysis, we determined that the frequency of the mutated C allele of the A1298 C mutation was 0.25 among control individuals, which is in the range of that recently reported in other ethnic groups. However, we report that the mutant C allele frequencies are significantly higher among NTD cases and case mothers than among controls (0.39, 0.44, 0.25). Furthermore, for the RFC-1 A80 G mutation, we found that the frequency of the G allele of the RFC-1 mutation was 0.46 in the control population, suggesting that this is a common polymorphism in the Italian population. In spite of the high prevalence of the 80 G/G genotype among healthy subjects, we observed an increased frequency of the G allele in NTD-affected children, and their mothers and fathers. These preliminary results indicate that both the MTHFR and RFC-1 polymorphisms may play a role in NTD risk, at least in the Italian population. Further studies should be directed toward the evaluation of the level of risk conferred by the mutant MTHFR and RFC-1 genotypes, as well as the interaction between these genetic determinants and other nutritional and environmental factors.

Adult↗
PubMed2000

Lysyl oxidase activates the transcription activity of human collagene III promoter. Possible involvement of Ku antigen.

Lysyl oxidase is an extracellular enzyme that controls the maturation of collagen and elastin. Lysyl oxidase and collagen III often show similar expression patterns in fibrotic tissues. Therefore, we investigated the influence of lysyl oxidase overexpression on the promoter activity of human COL3A1 gene. Our results showed that when COS-7 cells overexpressed the mature form of lysyl oxidase, the activity of the human COL3A1 promoter was increased up to an average of 12 times when tested by luciferase reporter assay. The effect was specific, because other promoters were not affected. Moreover, lysyl oxidase effect was abolished by beta-aminopropionitrile, a specific inhibitor of its catalytic activity. Electrophoretic mobility shift assay showed a binding activity in the region from -101 to -77 that was significantly increased by lysyl oxidase overexpression. The binding was specifically competed by the cold probe, and the mutagenesis of this region abolished both the binding activity in gel retardation and lysyl oxidase stimulation of COL3A1 promoter in transfection experiments. We identified the binding activity as Ku antigen in its two components: Ku80 and Ku70. This study suggests a new coordinated mechanism by which lysyl oxidase might control the development of fibrosis.

Aminopropionitrile↗
PubMed1993

Segmentation of medical images through competitive learning.

In image analysis applications, segmentation of gray-level images into meaningful regions is an important low-level processing step. Various approaches to segmentation investigated in the literature, in general, use either local information of gray-level values of pixels (region growing based methods, for example) or the global information (histogram thresholding based methods, for example). Application of these approaches for segmenting medical images often does not provide satisfactory results. Medical images are usually characterized by low local contrast and noisy or faded features causing unacceptable performance of local information based segmentation methods. In addition, because of a large amount of structural information found in medical images, global information based segmentation methods yield inadequate results in region extraction. We present a novel approach to image segmentation that combines local contrast as well as global gray-level distribution information. The presented method adaptively learns useful features and regions through the use of a normalized contrast function as a measure of local information and a competitive learning based method to update region segmentation incorporating global information about the gray-level distribution of the image. In this paper, we present the framework of such a self organizing feature map, and show the results on simulated as well as real medical images.

Algorithms↗
PubMed1993

Silent ischemia in unstable angina is related to an altered cardiac norepinephrine handling.

BACKGROUND: Inferential evidence suggests that silent ischemia might be related to sympathetic activity. Study of [3H]norepinephrine kinetics is a suitable tool to assess the regional sympathetic activity. This method was applied to investigate whether silent myocardial ischemia in unstable angina is related to and depends on cardiac sympathetic overactivity. METHODS AND RESULTS: Patients with active unstable angina were compared with patients with inactive unstable angina, stable effort angina, and controls. Silent myocardial ischemia was evaluated by three 24-hour Holter monitoring periods on alternate days, and [3H]norepinephrine kinetics was assessed under rest conditions and following the cold pressor test. Simultaneously, catecholamine concentrations were measured in the aortic, coronary sinus, and peripheral venous blood. Different than the other groups (p = 0.0013), in patients with active unstable angina, the majority of silent ischemic episodes occurred without increase in heart rate. These patients had a positive coronary sinus-aorta norepinephrine gradient, both at rest and following the cold pressor test. [3H]Norepinephrine kinetics demonstrated an increased selective cardiac spillover, both at rest and, even more, after the cold pressor test. Reduced cardiac [3H]norepinephrine extraction also was found. A significant relation was found between the number of ischemic episodes or the overall duration of silent ischemia and norepinephrine spillover, both at rest and following cold application. CONCLUSIONS: During the acute phase of unstable angina (but not in the quiescent phase or in stable effort angina), a disorder in cardiac norepinephrine handling occurs. This results in a reflex cardiac sympathetic overactivity that plays a major role in the occurrence of silent myocardial ischemia.

Angina, Unstable↗
PubMed1992

[Early isovolumetric relaxation: correlation with the densitometric analysis of coronary stenosis].

Early relaxation is characterized by a segmental outward wall movement during isovolumic relaxation. There is still no general agreement as to its significance. Some Authors have considered the phenomenon to be a specific marker of isolated coronary narrowing, others have regarded it as a normal variation of left ventricular relaxation and still others concluded that it is a compensatory phenomenon to local ischemia in another region. We used a method of quantitative assessment of regional left ventricular function and a videodensitometric analysis of coronary stenosis. In our study we didn't observe an improved systolic function of the regions that presented early relaxation, but a slight non significant reduction. We did neither observe any correlation between early relaxation and ischemia provoked by stress test nor between early relaxation and coronary artery disease. The amplitude of early relaxation was not statistically different between patients with and without stenosis of left anterior descending artery. We conclude that early relaxation is a normal variation of left ventricular relaxation.

Constriction, Pathologic↗
PubMed1991

Assessment of severity of coronary narrowings by quantitative exercise echocardiography and comparison with quantitative arteriography.

To determine the correlation of quantitative assessment of coronary narrowings with left ventricular functional impairment induced by exercise, 57 patients with 1-vessel coronary artery disease and without evidence of collateral flow were studied. A significant relation was observed between minimal cross-sectional area, percent area stenosis, minimal lumen diameter, percent diameter stenosis and the percentage of segmental area change from rest to peak exercise in a vascular distribution territory (r = 0.76, p less than 0.001; r = -0.55, p less than 0.001; r = 0.56, p less than 0.001; r = -0.75, p less than 0.001, respectively). For minimal cross-sectional area, the best cut-off value to separate significantly patients who had a decrease in contractility at peak exercise testing from those who had a normal response was 2 mm2 (p less than 0.001); for percent cross-sectional area stenosis, it was 75% (p less than 0.001); for minimal lumen diameter, it was 0.7 mm (p less than 0.001); and, for percent diameter stenosis, it was 85% (p less than 0.001). High cut-off values for angiographic variables are necessary to separate significantly patients who have a decrease in contractility at peak exercise testing from those who have a normal response. Several patients with mild coronary stenoses may have either normal or abnormal wall motion during exercise. Thus, exercise echocardiography is a useful tool in detecting the presence of fairly severe anatomic narrowing, whereas it is of limited clinical use in the assessment of intermediate coronary atherosclerotic lesions.

Cineangiography↗
PubMed1990

Usefulness of the dipyridamole-Doppler test for diagnosis of coronary artery disease.

Two-dimensional and Doppler echocardiographic studies and a hemodynamic investigation were performed during dipyridamole testing in 42 subjects (13 control subjects and 29 patients with coronary artery disease [CAD]), to evaluate the ability of dipyridamole Doppler echocardiography in identifying patients with ischemic left ventricular dysfunction. In the control group, after dipyridamole infusion, Doppler-derived parameters increased significantly from baseline (p less than 0.001). In patients with CAD, peak flow velocity, flow velocity integral and stroke volume failed to increase after dipyridamole infusion (0.89 +/- 0.21 to 0.85 +/- 0.18 m/s, difference not significant; 14 +/- 3 to 12 +/- 4 cm, difference not significant, and 56 +/- 13 to 50 +/- 14 ml/beat, p less than 0.05, respectively). Heart rate, rate pressure product, systemic vascular resistance and mean right atrial pressure had similar variations in the 2 groups. Changes in the 3 Doppler-derived parameters are closely related to the variations of peak positive dP/dt, stroke volume (thermodilution) and left ventricular end-diastolic pressure and are closely related to the coronary angiography jeopardy score and to the appearance of wall motion abnormalities. Thus, by combining Doppler and 2-dimensional echocardiography, dipyridamole-induced myocardial ischemia may be detected in a high percentage of CAD patients, providing a sensitive tool for identifying patients with high-risk coronary artery anatomy.

Adult↗
PubMed1990

Defective coronary prostaglandin modulation in anginal patients.

In order to investigate whether coronary vasodilating prostaglandins (PGI2 and PGE2) have a role in the pathophysiology of myocardial ischemia, 26 patients with angina pectoris and 23 control subjects (nonischemic patients) were studied by assessing coronary hemodynamics and prostaglandin formation in relation to sympathetic stimulation. Following a cold pressor test (CPT), coronary prostaglandin output markedly increased (p less than 0.001) and coronary vascular resistance (CVR) decreased (p less than 0.001) in all control subjects. In contrast, in anginal patients prostaglandins in the coronary sinus were undetectable and after CPT prostaglandin output did not increase, whereas CVR paradoxically increased (p less than 0.001). In control subjects the inhibition of coronary prostaglandin formation (by ketoprofen [1 mg/kg intravenously] or by aspirin [15 mg/kg intravenously]) caused a paradoxical increase of CVR following CPT (p less than 0.001). In anginal patients the inhibition of prostaglandins further exaggerated the increase of CVR after CPT (p less than 0.001). These results indicate that coronary vasodilating prostaglandin PGI2 and PGE2 play a role in modulating coronary vascular response to sympathetic stimulation induced by CPT. Their defective production in anginal patients may be responsible for the paradoxical increase in CVR following sympathetic stimulation.

Adult↗
PubMed1990

Physiologic role of coronary PGI2 and PGE2 in modulating coronary vascular response to sympathetic stimulation.

To investigate a physiologic role of coronary prostacyclin (PGI2) and prostaglandin E2 (PGE2) 30 patients who were not affected by coronary heart disease were evaluated for coronary hemodynamics and coronary PGI2 and PGE2 production. Inhibition of coronary prostaglandin biosynthesis by ketoprofen (1 mg/kg) or aspirin (15 mg/kg) administered intravenously did not significantly change coronary hemodynamics in resting conditions. In all patients cold pressor tests induced significant increases in coronary blood flow (p less than 0.001) and decreases in coronary vascular resistance (p less than 0.001) without changes in cardiac oxygen extraction and with consequent increases in calculated myocardial oxygen consumption. Simultaneously, a marked increase in coronary PGI2 (as 6-keto-PGF1 alpha) and PGE2 formation was observed (p less than 0.001). Both ketoprofen (1 mg/kg) and aspirin (15 mg/kg) administration completely abolished PGI2 and PGE2 formation that was induced by cold pressor test and caused a paradoxical increase in coronary vascular resistance (ketoprofen: p less than 0.02; aspirin: p less than 0.05). The results of this study support a physiologic role for the coronary prostaglandins in modulating coronary vascular response to sympathetic stimulation in nonischemic patients.

Adult↗
PubMed1990

[Effect of changes of the left ventricular diastolic pressure on the coronary circulation hemodynamics].

In order to understand the effect of LVEDP changes caused by contrast injection during angiography on coronary hemodynamics we studied 15 patients (5 congestive CMP, 5 mixed angina and 5 controls). Our results do not cope with an important negative role played from LVEDP changes on coronary hemodynamics and cardiac metabolism. Actually LVEDP increase after ventriculography was balanced by coronary flow increase and impedance reduction even when the latter has been matched with LVEDP. We also observed lactate metabolism changes which are not likely to be provoked by myocardial ischemia, since there was not a definite negativization of % lactate extraction and delta A-VO2 always turned to reduction; this is apparently not in agreement with other Authors who had reported metabolic alterations suggestive for myocardial ischemia, even if they did not calculate delta A-VO2 and coronary flow. This difference could be related to the different populations studied, specially when considering the different functional meaning of coronary stenoses of the same degree at angiography. Is thus the Authors' thought that, when coronary reserve is still adequate, is it possible not to take into account LVEDP, which becomes important in patients with a more advanced coronary disease as in those cases this extravascular impedance factor to coronary flow could take his own worsening role.

Adult↗
PubMed1989

Functional study of T lymphocyte responsiveness in patients with dementia of the Alzheimer type.

The autologous mixed lymphocyte reaction (AMLR) was used to study T lymphocytes in a group of patients with dementia of the Alzheimer type (DAT) in order to confirm the observation that their T cell proliferation in AMLR was greater than in age-matched controls, and to investigate other pathways of T cell activation, searching for correlations between immunologic and clinical findings in DAT. The mean proliferative response in AMLR was increased in patients with DAT. No differences between patients and age-matched controls were detected when other pathways of T cell activation were investigated. The degree of response in the AMLR varied among patients with DAT. This fits with the suggestion that the disorder may be a heterogeneous syndrome.

Aged↗
PubMed1989

IgG paraproteinemias: a comparative CSF and serum study.

In 10 neurologic patients routine isoelectric focusing of CSF and serum revealed monoclonal IgG paraproteinemia (3 multiple myelomas and 7 benign monoclonal gammopathies). Quantitative protein study showed blood-brain barrier damage in 7 out of 10 patients; 2 patients had intrathecal synthesis of IgG measurable by Reiber's formula. Each case showed identical monoclonal IgG pattern in CSF and serum at isoelectric focusing and immunofixation. We suppose that monoclonal IgG detectable in the CSF usually derive from the serum across the intact or damaged barrier. The occurrence of quantifiable intrathecally synthesized IgG in 2 patients, both with skeletal lesions close to the subarachnoid spaces, and the identical patterns of IgG in CSF and serum suggest that tumoral plasma cells secrete monoclonal IgG into blood and CSF from the bone location.

Aged↗
PubMed1988

Oligoclonal and polyclonal synthesis of IgG in the central nervous system: an isoelectric focusing study.

The IgG pattern in isoelectric focusing (IEF) has been studied in 90 paired samples of cerebrospinal fluid (CSF) and sera obtained from patients in which intrathecal synthesis of IgG without barrier damage was detectable by Reiber's graph and formula (1980, J. Neurol. 224, 89). Thirty patients were affected by multiple sclerosis (MS), 30 by other inflammatory nervous diseases (OID), and 30 by noninflammatory nervous diseases (NID). At IEF two distinct pathological patterns of CSF IgG were detected: oligoclonal bands (OB), prevailing in the MS group (83% of cases), and a "polyclonal"--i.e., diffuse, uniform--increase of CSF IgG, prevailing in the NID (90%). The OID group was intermediate, 57% of cases with OB and 43% with polyclonal CSF IgG patterns. Overall, only 45 of 90 patients synthesizing IgG in the CNS had CSF OB. This suggests that the CNS immune response can imply either the synthesis of IgG of restricted heterogeneity (i.e., OB) or a polyclonal IgG synthesis, giving in IEF a serum-like pattern to the CSF.

Central Nervous System↗
PubMed1987

Cerebrospinal fluid and neuropathological study in Devic's syndrome. Evidence of intrathecal immune activation.

Cerebrospinal fluid (CSF) was studied in 2 cases of Devic's syndrome (DS). In one of these cases autopsy was carried out. The main CSF feature in DS is the association of blood-brain barrier damage and intrathecal IgG synthesis. These findings are in keeping with our neuropathological observation of diffuse central nervous system vasculitis and leptomeningitis. As a whole, our CSF and neuropathological findings in DS are consistently different from those in multiple sclerosis.

Albumins↗
PubMed1986

Thalamic dementia: report of a case with unusual lesion location.

Thalamic dementia usually results from a bilateral paramedian thalamic infarction. We report a case with typical clinical and neuropsychological features of thalamic dementia, but with CT evidence of an unusual and asymmetrical location of ischemic lesions. Somatosensory evoked potential recordings were consistent with a left medial thalamic infarction, associated with a contralateral lesion, possibly at lemniscal level. This case suggests that thalamic dementia may develop following a unilateral paramedian thalamic infarction.

Adult↗
PubMed1986

Evidence of T-lymphocyte functional impairment in Huntington's disease.

Huntington's Disease (HD) is a degenerative neurological disorder with autosomal dominant transmission. Although immunological defect(s) have been postulated, no confirmed laboratory evidence for this exists. In the present study we observed activated T cells in the peripheral blood of HD patients (using 4F2 monoclonal antibody), whereas the percentage of T cells bearing T-cell activation markers such as HLA-DR and MLR4 antigens was normal. We then studied T cells of HD patients in some functional assays. Since it has been suggested that autologous mixed lymphocyte reaction (AMLR) includes several immune mechanisms in which distinct cell subsets interact and perform distinct regulatory functions, it is conceivable that the remarkable deficiency of AMLR herein observed in HD patients results from some abnormal immune regulation which may contribute to the pathology of this condition. Additional experiments demonstrated a defect of AMLR in three asymptomatic young sibs of HD patients, and coculture experiments between T cells of patients (as responders) and non-T cells of their sibs (as stimulators), and vice versa, produced no proliferative response. Subnormal responsiveness in allogeneic MLR was also observed. Normal or enhanced PHA-induced production of both IL-2 and IFN-gamma in vitro was detected. These experimental data suggest a cellular branch of the immune system in HD; however, they do not indicate if this defect is primary or secondary to the disease itself.

Adult↗