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Biomedical subjects

R Palermo

Publications and source records attributed to R Palermo.

At least 19 recordsLinked to original sources
PubMed2003

Cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis with EDSS < or = 3.5.

OBJECTIVES: Previous papers have mainly demonstrated the presence and the frequency of cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis. The purpose of this study was to investigate subjects with the relapsing-remitting form of the disease and mild clinical disability (EDSS < or = 3.5), so as to quantify this deficit when the illness does not yet interfere with daily living and the ability to work. METHODS: Fifty patients and 50 healthy controls were submitted to a wide neuropsychological battery, including Wechsler Memory Scale I- (WMS), Benton Visual Retention Test D- (BVRT), Raven Coloured Progressive Matrices (RCPM), Kohs' test (KT), Judgement of Lines Orientation H- (JLO), Facial Recognition (FR) and Aachner Aphasie Test (AAT). They also underwent Clinical Depression Scale (CDQ) and State-Trait Anxiety Inventory (STAI). RESULTS: The results show the presence of significant memory impairment on both WMS (P = 0.000) and BVRT (P = 0.000) in patients compared with controls. Patients were also impaired in abstract reasoning and problem-solving deficit (KT P = 0.003; RCPM P = 0.000) and in FR (P = 0.019). Cognitive decline correlated with illness duration (r = 0.761), but was independent of EDSS (r = 0.085). CONCLUSION: Cognitive decline was present even when physical disability was not yet severe, but it was mild and did not limit patients' ability to work. The cognitive impairment outlined was of the subcortical type and correlated with illness duration. This study emphasizes the importance of cognitive examination in clinical practice. It is suggested that a complete neurological examination include tests on memory and abstract reasoning.

Adult↗
PubMed2001

Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.

The 5,5-disubstitutedpyrimidine-2,4,6-triones represent a new class of MMP inhibitors showing selectivity for the gelatinases A and B, collagenase-3, and human neutrophil collagenase. The SAR presented here is in good agreement with an X-ray structure of compound 5 bound to the catalytic domain of stromelysin-1. While of the barbiturate structural class, compound 5 did not show any toxic or sedative effects.

Animals↗
PubMed2001

X-ray structure of a novel matrix metalloproteinase inhibitor complexed to stromelysin.

A new class of matrix metalloproteinase (MMP) inhibitors has been identified by screening a collection of compounds against stromelysin. The inhibitors, 2,4,6-pyrimidine triones, have proven to be potent inhibitors of gelatinases A and B. An X-ray crystal structure of one representative compound bound to the catalytic domain of stromelysin shows that the compounds bind at the active site and ligand the active-site zinc. The pyrimidine triones mimic substrates in forming hydrogen bonds to key residues in the active site, and provide opportunities for placing appropriately chosen groups into the S1' specificity pocket of MMPS: A number of compounds have been synthesized and assayed against stromelysin, and the variations in potency are explained in terms of the binding mode revealed in the X-ray crystal structure.

Binding Sites↗
PubMed2000

Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.

Antigen Presentation↗
PubMed1999

Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease.

OBJECTIVE: To determine the prevalence of anti-ribosomal P (anti-P) proteins in several groups of patients with juvenile-onset systemic lupus erythematosus (SLE) in comparison with the prevalence in adult SLE. METHODS: Serum samples were pooled together from 3 cohorts of patients with juvenile-onset SLE in 3 different medical centers and from a miscellaneous group of juvenile-onset SLE patients whose samples were sent by regional physicians. Sera were studied for the presence of anti-P using 2 assays: Western blot with ribosomes as antigen, and an enzyme-linked immunosorbent assay with the COOH-terminal 22 amino acids of the ribosomal P protein in a multiantigenic peptide format as antigen. Sera found positive by both tests were considered positive for anti-P antibodies. Findings from similar studies involving a large cohort of patients with adult-onset SLE from Oklahoma City were used for comparison. RESULTS: The prevalence of anti-P antibodies in the pooled sample of juvenile-onset SLE sera was 45 of 108, or 42%, while in the adult cohort from Oklahoma City, 20 of 260, or 7.7%, were positive for anti-P (odds ratio [OR] 9.6, P < 10(-8) by Fisher's exact test). In addition, it was shown that 12 of 13 patients with both anti-P and anti-double-stranded DNA (anti-dsDNA) in the juvenile SLE cohort had nephritis, while only 8 of 22 patients without both antibodies were nephritic (OR 21.0, P < 10(-8)). It was also shown that in 9 illustrative cases, the levels of anti-P and anti-dsDNA antibodies usually varied together and in concordance with the clinical activity as measured by the SLE Disease Activity Index (SLEDAI). Finally, anti-P-positive and anti-P-negative patients had a similar prevalence of anti-dsDNA, anti-Ro/SSA, and anti-La/SSB antibodies, but patients with anti-P had a higher prevalence of anti-U1 RNP and anti-Sm (P = 0.041 and P = 0.0385, respectively, by Fisher's exact test). CONCLUSION: Antibodies to ribosomal P protein are more prevalent in juvenile-onset SLE than in adult-onset SLE. Levels of antibodies to ribosomal P protein vary with the clinical disease activity as measured by the SLEDAI, often in concordance with the levels of anti-dsDNA. The presence of both anti-P and anti-dsDNA antibodies was powerfully associated with nephritis in the cohort of patients for whom comprehensive clinical and serologic data were available.

Adolescent↗
PubMed1998

Protein farnesyltransferase: structure and implications for substrate binding.

The rat protein farnesyltransferase crystal structure has been solved by multiple isomorphous replacement methods at a resolution of 2.75 A. The three-dimensional structure, together with recent data on the effects of several mutations, led us to propose a model for substrate binding which differs from the model presented by Park et al. based on their independent structure determination [Park, H. -W., Boduluri, S. R., Moomaw, J. F., Casey, P. J., and Beese, L. S. (1997) Science 275, 1800-1804]. Both farnesyl diphosphate and peptide substrates can be accommodated in the hydrophobic active-site barrel, with the sole charged residue inside the barrel, Arg202 of the beta-subunit, forming a salt bridge with the negatively charged carboxy terminus of peptide substrates. Our proposals are based in part on the observation of electron density in the active site which can be modeled as bound farnesyl diphosphate carried through the enzyme purification. In addition, our model explains in structural terms the results of mutational studies which have identified several residues critical for substrate specificity and catalysis.

Alkyl and Aryl Transferases↗
PubMed1998

Cross-cultural adaptation and validation of an Argentine Spanish Version of the Stanford Childhood Health Assessment Questionnaire.

OBJECTIVES: To translate into Argentine Spanish and cross-culturally adapt the Childhood Health Assessment Questionnaire (CHAQ) and validate the adapted instrument in Argentine patients with juvenile rheumatoid arthritis (JRA). METHODS: Five bilingual Argentine pediatric rheumatologists translated into Argentine Spanish and cross-culturally adapted the United States English CHAQ. Pretesting was done in a sample of 23 parents using a probe question technique. Parents of 70 patients with JRA and 21 healthy children (controls) participated in the validation phase. All were from Argentina. RESULTS: The mean disability index (DI) scores for patients with systemic, polyarticular, or pauciarticular onset JRA were 0.64, 0.32, and 0.1, respectively. Healthy controls averaged 0.2. Intercomponent correlations were between 0.4 and 0.9, suggesting internal consistency, but also some redundancy. Test-retest reliability, studied at a 1-week interval, was moderate (mean DI 0.44 [in clinic] and 0.29 [one week later], Pearson's correlation = 0.82). We compared CHAQ scores from 15 parents with those of their children > 10 years of age. Significantly higher DI scores were given by patients than their respective parents (P > 0.019), but the pairwise scores (parent-patient) were highly correlated (r = 0.986). CONCLUSIONS: Cross-cultural adaptation of the US CHAQ to Argentina required few changes. Although DI scores for all patient subgroups were higher than for controls subjects, the scores were low, particularly for those with pauciarticular disease. Prospective studies designed to examine the sensitivity to change and predictive validity will help to assess further the usefulness of the adapted CHAQ in the Argentine population.

Activities of Daily Living↗
PubMed1996

Regression of calcinosis during diltiazem treatment in juvenile dermatomyositis.

An 8-year-old girl with juvenile dermatomyositis (DM) developed dystrophic calcifications 26 months after diagnosis. She also had severe steroid induced bone loss (osteoporosis). The calcifications turned into generalized heterotopic calcinosis with an exoskeleton-like pattern, despite successful treatment of her myopathy with methylprednisolone and immunosuppressive drugs. She was subsequently treated with oral diltiazem (5 mg/kg/day) to control calcinosis and oral pamidronate (4 mg/kg/day) in addition to calcium and vitamin D supplementation, which she had been taking for 3 years. After 21 months of treatment, clinical and radiological examination revealed dramatic regression of the calcinosis. Bone mass reached normal levels, as determined by bone absorptiometry. Diltiazem alone or in combination with other drugs could be a useful therapy in patients with juvenile DM and pronounced calcifications.

Calcinosis↗
PubMed1992

High levels of plasma atrial natriuretic factor and impaired left ventricular diastolic function in hypertensives without left ventricular hypertrophy.

OBJECTIVE: To seek possible correlations between plasma atrial natriuretic factor (ANF) and left ventricular diastolic function (LVDF) in hypertensive patients. DESIGN: Since LVDF abnormalities can be detected in patients with normal left ventricular mass, we studied a group of hypertensive patients without left ventricular hypertrophy. METHODS: Untreated hypertensive patients (n = 23) and normotensive control subjects (n = 19) were studied. LVDF indices were obtained by M-mode and pulsed Doppler echocardiography. Blood samples for plasma ANF were taken in the recumbent position from subjects on normal-sodium intake. RESULTS: Plasma ANF levels were significantly higher in hypertensive patients than in normotensive subjects. All indices for systolic function were normal in both normotensive subjects and hypertensive patients. Left atrial diameter was significantly higher for hypertensive patients than for normotensive subjects. Considering LVDF, all indices for ventricular filling were found to be altered, on average, in hypertensive patients, the only exception being peak early velocity. In addition, significant correlations were found between plasma ANF and the pulsed Doppler parameters of left ventricular filling, peak atrial velocity and the peak early:peak atrial velocity ratio. Overall correlations between plasma ANF and left atrial diameter, and between left atrial diameter and left ventricular mass index were also observed. CONCLUSIONS: The high levels of plasma ANF observed in our hypertensive patients and their correlation with the LVDF indices (which mainly reflect the atrial contribution to ventricular filling) could be the result of an increased atrial stretch due to diastolic ventricular dysfunction. This may exist in hypertensive patients before the development of ventricular hypertrophy.

Adult↗
PubMed1991

Relationship between plasma atrial natriuretic factor and urinary kallikrein excretion in essential hypertensives.

In order to seek possible relationships between renal kallikrein and atrial natriuretic factor (ANF), we measured urinary kallikrein (UK) and ANF in 84 normal subjects (NS) and in 104 uncomplicated essential hypertensives (HP). Atrial natriuretic factor was significantly higher in HP than in NS (38.5 +/- 1.3 vs 29.0 +/- 1.3 pg/mL, P less than .01), whereas UK was significantly lower in HP than in NS (11.1 +/- 0.9 v 15.3 +/- 0.6 nkatal/24 h, P less than .01). Calculating the 95% of the percentile distribution of the single values of UK in the group of NS we were able to show that 24 out of 104 HP had a UK which fell below the lowest limit (4.5 nkat/24 h) of the normal range. We therefore divided our HP into two subgroups: patients with normal kallikrein excretion (NK) (n = 80; mean UK 13.8 +/- 0.8 nkat/24 h) and patients with low kallikrein excretion (LK) (n = 24; mean UK 2.3 +/- 0.3 nkat/24 h). Normal kallikrein patients had a mean plasma ANF value of 31.9 +/- 1.2 pg/mL which was almost superimposable to that found in NS; on the contrary, the mean plasma level of ANF in LK patients (50.7 +/- 2.2 pg/mL) was significantly higher than that measured in NK patients and in NS (P less than .01 v NK patients and NS, respectively). Since a low urinary kallikrein excretion may represent a marker of an impaired production of renal kallikrein, the high levels of ANF found in the LK subgroup could be the result of a compensatory response of the atrium attempting to maintain sodium and volume homeostasis.

Atrial Natriuretic Factor↗
PubMed1990

High expression of ras p21 correlates with increased rate of abnormal mitosis in NIH3T3 cells.

The modulation of responsive genes by hormonal stimulation is an attractive in vitro model system for the study of a wide variety of biological processes. Using this methodology we have investigated the effect of the human oncogene protein p21ras on mitosis using mouse mammary tumor virus long terminal repeat (MMTV-LTR)-directed gene expression. Following the induction of p21 protein, abnormal mitotic figures were scored in metaphase and anaphase. Elevated expression of p21 was associated with marked increase in the proportion of abnormal mitoses most significantly during the metaphase. Concomitant with a three fold increase in p21 levels, abnormal mitosis rose from 14.0% to 27.25%. The increase in abnormal mitosis corresponded to a 225% increase in abnormal metaphase. The p21-induced mitotic abnormalities were exhibited as lagging chromosomes in prometaphase, 3 group metaphase and C-metaphase. In addition, high expression of p21 was accompanied by significant changes in the cell morphology and fine ultrastructure, e.g. disorganization of actin, the extensive formation of microvilli on the plasma membrane and marked dilatation of the rough endoplasmic reticulum. The mitotic and structural changes were reversible upon removal of dexamethasone and decline of p21 production to its basal levels. Our results identify an important biological effect of ras p21 during mitosis and the early stages of neoplastic transformation.

Animals↗
PubMed1990

[The use of dynamic electrocardiographic monitoring in scleroderma patients].

A comparative analysis of arrhythmias by "basal" electrocardiogram (ECG) and by continuous 24-hour Holter electrocardiogram monitoring was performed in 17 patients with systemic sclerosis (16 women and one man). Our study confirms that rhythm disturbances are better detectable using Holter monitoring. In fact, no patients had ventricular arrhythmias detected by ECG; on the contrary, Holter monitoring revealed ventricular arrhythmias in nine patients (53.3%). This method also revealed a ventricular tachycardia, not detected by ECG. In two patients ventricular repolarisation abnormalities without symptoms was revealed.

Adult↗
PubMed1990

[Cardiovascular involvement and relative risk factors in systemic sclerosis. Personal contribution].

In systemic sclerosis (SS), cardiovascular commitment was recorded in an autopsy series, in widely different percentages, from 12 to 81%. On the other hand, clinical diagnosis of cardiopathy is made in far fewer cases. In addition, the coexistence of renal and/or pulmonary commitment makes difficult separation between primary and secondary heart damage. In 22 patients (2 m, 20 f) aged between 34 and 75 (average 55 +/- 11) with SS, a study has been made of the a) prevalence of cardiovascular commitment; b) the significance of the classic risk factors; c) the erythrocyte filtration time or TF (index of microangiopathic damage). Metabolic stability, fibrinogen, haematocrit and TF (Reid et al. method) were assessed in each patient. Nine patients (40.9%) presented ischaemic cardiopathy (myocardial infarction in three and effort angina in six), one (4.5%) presented hypertensive cardiopathy. Conduction disturbances were observed in five patients (22.7%). Whereas a statistically significant increase in TF was observed in cardiopaths, no differences in plasma levels of glucose, cholesterol or fibrinogen were observed. The incidence of smoking and the familial factor were also insignificant.

Adult↗
PubMed1989

Relationship between urinary kallikrein excretion and plasma atrial natriuretic factor in essential hypertensives.

Relationships between renal kallikrein and plasma atrial natriuretic factor were investigated by measuring urinary kallikrein excretion (by spectrophotometric assay) and plasma atrial natriuretic factor (by radio-immunoassay after extraction from plasma) in 84 normal subjects and in 104 essential hypertensives with a normal renal function. The atrial natriuretic factor was significantly higher in the essential hypertensives than in the normal subjects (38.5 +/- 1.3 versus 29.0 +/- 1.3 pg/ml, P less than 0.01), whereas urinary kallikrein excretion was significantly lower in the hypertensives than in the normal subjects (11.1 +/- 0.9 versus 15.3 +/- 0.6 nkat/24 h, P less than 0.01). Taking the 95% confidence limits of urinary kallikrein excretion in the normal subjects (from 4.5 to 29.9 nkat/24 h), we divided our essential hypertensives into two subgroups, patients with a normal kallikrein excretion (n = 80; mean urinary kallikrein excretion 13.8 +/- 0.8 nkat/24 h) and patients with a low kallikrein excretion (n = 24; mean urinary kallikrein excretion 2.3 +/- 0.3 nkat/24 h) The patients with a normal kallikrein excretion had a mean plasma atrial natriuretic factor value of 31.9 +/- 1.2 pg/ml, which was similar to that found in normal subjects. In contrast, the mean plasma level of atrial natriuretic factor in the patients with a low kallikrein excretion (50.7 +/- 2.2 pg/ml) was significantly higher than that measured in the patients with a normal kallikrein excretion and in the normal subjects (P less than 0.01 versus patients with normal kallikrein excretion and normal subjects, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1988

Concomitant gonadotropin-releasing hormone agonist and menotropin treatment for the synchronized induction of multiple follicles.

In an effort to overcome possible interference by endogenous gonadotropin-ovarian hormone dynamics, desensitization of the pituitary gonadotropins by a gonadotropin-releasing hormone agonist (GnRHa) was achieved in 12 women with repeatedly failed attempts at multiple follicular stimulation. Eight women were scheduled for in vitro fertilization (IVF) and embryo transfer (ET), and 4 for gamete intrafallopian transfer (GIFT). Stimulation failure was characterized by premature luteinization, poor estradiol (E2) response, or inadequate follicular growth. The agonist was administered by nasal spray 500 to 600 micrograms/day beginning on days 21 to 23 of the menstrual cycle. A rapid desensitization occurred by 7.6 +/- 0.6 days (mean +/- standard error [SE]) following the initial dose. Gonadotropin stimulation was begun when pituitary and ovarian suppression was judged to be adequate. In response to gonadotropin stimulation, a continuous rise of E2 was observed in all patients with a mean of 989 +/- 46 pg/ml on the day of hCG. A cohort of synchronized follicles was recruited and matured. The mean number of growing follicles per patient was significantly higher (P less than 0.0001) in combined therapy than in previously failed cycles (8.0 +/- 0.3 versus 3.2 +/- 0.1). All the patients underwent oocyte retrieval and 94.3% of the harvested oocytes were preovulatory. A high fertilization rate (89.7%) of the inseminated oocytes occurred in IVF patients.

Adult↗
PubMed1988

Plasma levels of atrial natriuretic factor in mild to moderate hypertensives without signs of left ventricular hypertrophy: correlation with the known duration of hypertension.

The relationship between plasma atrial natriuretic factor (ANF), blood pressure (BP), age, plasma renin activity (PRA) and urinary sodium excretion was studied in 64 normal subjects (mean age 48.7 +/- 2.1 yrs; BP: 126.5 +/- 1.6/79.5 +/- 0.9 mmHg) and in 104 untreated uncomplicated essential hypertensives (50.8 +/- 1.1 yrs; BP: 164.7 +/- 1.6/105.2 +/- 0.6 mmHg). ANF was measured by radioimmunoassay after extraction on C18 columns. ANF was significantly higher in the hypertensives than in the normal subjects (37.1 +/- 1.2 vs 29.7 +/- 1.5 pg/ml, P less than 0.01). In normals plasma ANF was significantly correlated with age (r = 0.72, P less than 0.001), Na excretion (r = 0.42, P less than 0.001) and PRA (r = -0.71, P less than 0.001) whereas in the hypertensives ANF plasma levels correlated only with systolic (r = 0.46, P less than 0.001) and diastolic (r = 0.51, P less than 0.001) BP. In addition in hypertensive patients, by multivariate linear regression analysis, a significant correlation was found between age, known duration of hypertension and plasma ANF. The partial correlation coefficient between duration of hypertension and plasma ANF was highly significant (r = 0.80, P less than 0.001). These findings suggest that in essential hypertension the level of arterial BP is a main determinant of the ANF plasma values offsetting the ability of other physiological factors to regulate plasma ANF levels.

Aged↗