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Biomedical subjects

L Villa

Publications and source records attributed to L Villa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Defective proliferative response of T lymphocytes from patients with inactive systemic lupus erythematosus.

OBJECTIVE: To further define the pattern of alterations in the activation and apoptosis of T lymphocytes in patients with inactive systemic lupus erythematosus (SLE) through analysis of a large series of individuals. METHODS: We isolated CD2+ peripheral blood lymphocytes (PBL) from 41 patients with inactive SLE and analyzed their proliferative and apoptotic responses to polyclonal activation. RESULTS: In 19 of 41 (47%) patients, a low proliferative response to polyclonal mitogens was found. This defective response was inversely associated with an increased apoptotic response and increased expression of CD95 and CD45RO antigens. CONCLUSION: We found that 2 groups of patients with inactive disease can be defined according to the functional behavior of their T lymphocytes, as defined by the proliferative and apoptotic responses to mitogenic signals.

Adolescent↗
PubMed1998

Human papillomavirus DNA and p53 status in penile carcinomas.

Our study aimed at evaluating the presence of human papillomavirus (HPV) DNA in a series of 84 paraffin-embedded (PET) penile carcinomas. We have also investigated the presence of p53 mutations in these tumors by immunohistochemistry (IHC), single-stranded conformational polymorphism (SSCP) and DNA sequencing. Tissues were submitted to amplification of a 268 bp fragment from the beta-globin gene and a fragment of the E6 gene of HPV types 6, 11, 16 and 18. Twenty samples (18 fixed in Bouin's solution and 2 in buffered formalin) were found inadequate and were excluded from the analysis. In the remaining 64 tumors, HPV DNA was found in 26% of the samples. The prevalence of HPV in fresh samples of the same tumors was 56%. The most prevalent type was HPV 16 in both fresh samples and PET. Isotopic in situ hybridization was performed in all PET samples, but only 2 cases were positive, 1 for HPV 16 and 1 for HPV 18. Immunohistochemistry with anti-p53 pAb 1801 antibody showed a positive nuclear reaction over more than 5% of tumor cells in 26% of the cases. SSCP of exons 5-8 of the p53 gene was performed on 9 HPV-positive and 12 HPV-negative specimens. Abnormal mobility was found in 26% of the tumors, of which 2 were HPV-positive and 5 HPV-negative. Point mutations were detected in p53 exons 6 (1 case), 7 (1 case) and 8 (5 cases), showing that high-risk type HPVs and mutated p53 may coexist in these tumors. Our data indicate that a subset of penile carcinomas are etiologically related to HPV and that an overlapping subset may arise from mutational events in the p53 gene.

Adult↗
PubMed1998

Fetal and neonatal echocardiographic findings in twin-twin transfusion syndrome.

OBJECTIVE: The study's aim was to analyze the type of cardiac involvement in fetuses or infants with twin-twin transfusion syndrome. STUDY DESIGN: Seventeen pairs of monochorionic diamniotic twin fetuses with twin-twin transfusion syndrome underwent serial Doppler echocardiographic studies. Repeated decompressive amniocenteses were performed in all pregnancies. RESULTS: No specific cardiac involvement was seen in donor twins in utero or after birth. All recipient twin fetuses showed variable degrees of biventricular hypertrophy and dilation with tricuspid regurgitation. These features were also evident in 45% of the recipient twin neonates. The fluid unbalance resolved with serial amniocenteses in 9 cases and in a further 2 after the death of the donor twin; in all 11 of these recipient twin fetuses there was some degree of improvement of the cardiac involvement, which became normal in all surviving recipient twin infants within 40 days to 6 months after birth. CONCLUSION: Features of cardiac hypertrophy with signs of a prehydropic or hydropic state develop during fetal life in recipient twins in twin-twin transfusion syndrome; this impairment is reversible with the resolution of the fluid imbalance or after delivery.

Diseases in Twins↗
PubMed1998

4-Oxystilbene compounds are selective ligands for neuronal nicotinic alphaBungarotoxin receptors.

1. Starting from the structure of an old 4-oxystilbene derivate with ganglioplegic activity (MG624), we synthesized two further derivates (F2 and F3) and two stereoisomers of F3 (F3A and F3B), and studied their selective effect on neuronal nicotinic acetylcholine receptor (AChR) subtypes. 2. MG 624, F3, F3A and F3B inhibited of 125I-alphaBungarotoxin (alphaBgtx) binding to neuronal chick optic lobe (COL) membranes, with nM affinity, but inhibited 125I-alphaBgtx binding to TE671 cell-expressed muscle-type AChR only at much higher concentrations. 3. We immobilized the alpha7, beta2 and beta4 containing chick neuronal nicotinic AChR subtypes using anti-subunit specific antibodies. MG 624, F3, F3A and F3B inhibited 125I-alphaBgtx binding to the alpha7-containing receptors with nM affinity, but inhibited 3H-Epi binding to beta2-containing receptors only at very high concentrations (more than 35 microM); their affinity for the beta4-containing receptors was ten times more than for the beta2-containing subtype. 4. Both MG624 and F3 compounds inhibited the ACh evoked currents in homomeric oocyte-expressed chick alpha7 receptors with an IC50 of respectively 94 and 119 nM. 5. High doses of both MG 624 and F3 depressed the contractile response to vagus nerve stimulation in guinea pig nerve-stomach preparations although at different IC50s (49.4 vs 166.2 microM) The effect of MG624 on rat nerve-hemidiaphragm preparations was 33 times less potent than that of F3 (IC50 486 vs 14.5 microM). 6. In conclusion, MG624 and F3 have a high degree of antagonist selectivity for neuronal nicotinic alphaBgtx receptors containing the alpha7 subunit.

Animals↗
PubMed1998

Is videopupillography useful in the diagnosis of Alzheimer's disease?

Patients with Alzheimer's disease (AD) reportedly exhibit greater pupillary dilation than healthy subjects in response to tropicamide. By means of videopupillography, we have found that the average basal pupillary diameter was greater in AD patients than in normal controls and that there is an inverse relationship between the average pupillary diameter and the maximal dilation obtained following tropicamide application in both groups. Pupillary response to tropicamide and videopupillography do not distinguish between Alzheimer's patients and controls.

Aged↗
PubMed1997

Protection from apoptotic cell death by interleukin-4 is increased in previously treated chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) cells were cultured in a medium supplemented with 0.01-1 ng/ml interleukin-4 (IL-4) for 18 h, fixed and analyzed on a flow cytometer. The percentage of apoptotic (AP) cells with hypodiploid DNA content was determined from DNA histograms. IL-4 at 0.01 ng/ml protected from spontaneous apoptosis of cells from previously treated CLL patients, but had very little effect on apoptotic death in cultures of cells from untreated patients. The number of AP cells in the absence of IL-4 was similar in cultures from treated and untreated patients. The concentration of IL-4 which inhibited spontaneous apoptosis by 50% was less than 0.01 ng/ml for pretreated patients and close to 1 ng/ml for untreated patients. Stage of the disease had no effect on the level of spontaneous apoptosis and its sensitivity to IL-4. Protection from apoptosis by IL-4 was not accompanied by the upregulation of bcl-2 protein. The number of AP cells in methylprednisolone hemisuccinate (MP) treated cultures from previously treated patients was significantly lower than in cultures from untreated patients in the presence of 0.01-1.0 ng/ml IL-4. Treatment with the combination L-phenylalanine mustard (L-PAM)+ fludarabine induced synergistic apoptotic response. Apoptosis induced by this combination was relatively resistant to IL-4 in patients treated with chlorambucil and prednisone, but not in patients previously treated with fludarabine. Protection from cytotoxicity by IL-4 may be one of the mechanisms of acquired drug resistance in CLL.

Adult↗
PubMed1997

Hypernatremic dehydration in the elderly on admission to hospital.

Dehydration is the most common cause of fluid and electrolyte disturbances in the elderly. This condition is related to the lack of increase in water intake in the presence of an increased fluid loss. The aim of this study was to evaluate the prevalence of hypernatremic dehydration in elderly patients admitted to the hospital. We retrospectively studied 2,894 subjects admitted to the acute ward of the Geriatric Section of the Department of Medical and Surgical Disciplines of the University of Torino from January 1990 to July 1995. Among them 84 (2.9%) patients, mean age 77.3 +/- 9.8 years, had serum sodium levels and blood urea nitrogen greater than 145 mEq/L and 25 mg/dL respectively with serum creatinine below 3 mg/dL. The prevalence of hypernatremic dehydration increases with age. Only 1.6% of the subjects under 65 years old are affected by this condition, against 5.3% of those over 85 years. The mortality rate observed during hospitalization is 29.8%. Mortality is positively related to serum sodium levels. We found mortality rates of 33.3% and 71.4% respectively in subjects with serum sodium levels from 151 to 153 mEq/L and in those with values over 154 mEq/L. Both serum sodium levels and age are independent risk factors for mortality (O.R. 1.31 and 1.07 respectively).

Aged↗
PubMed1997

[Cardiac failure secondary to hypoparathyroidism. An unusual presentation].

The case of a 37 year old woman with hypoparathyroid congestive heart failure (CHF) is reported. Thyroidectomy had been performed eight years earlier and she had experienced symptoms of hypocalcemia postoperatively. CHF improved rapidly and completely with the treatment of hypocalcemia. Good prognosis is emphasized but it is necessary to think about this cause of ventricular dysfunction in a patient with CHF and a history of neck surgery in order to make an early diagnosis. Pathogenic mechanisms and differential diagnosis are discussed.

Adult↗
PubMed1997

Apoptosis in breast carcinomas detected with monoclonal antibody to single-stranded DNA: relation to bcl-2 expression, hormone receptors, and lymph node metastases.

Precise quantitation of apoptotic cells in solid tumors is necessary to determine the role of apoptosis in cancer growth, prognosis, and treatment. In this study, the intensity of apoptotic death was determined in 91 breast carcinomas with a novel cellular marker of apoptosis based on the staining of histological sections with a monoclonal antibody (MAb) to single-stranded DNA. Staining of apoptotic cells with the MAb reflected the decreased thermal stability of DNA induced by the digestion of nuclear proteins, as demonstrated by the elimination of staining in sections reconstituted with histones before heating. The high sensitivity and specificity of apoptosis analysis with the MAb is based on the central role of protease activation in the mechanism and control of apoptosis. Apoptotic indexes (AIs) in breast carcinomas ranged between 0 and 46%. Most of the carcinomas had relatively low AIs, whereas 29 cases were classified as carcinomas with intensive apoptosis (AI >/= 10%). The high level of apoptotic cell death was associated with negative immunostaining for bcl-2 protein, the loss of estrogen and progesterone receptors, high proportion of cells in S-phase, and increased risk of lymph node metastases. There was no correlation between AI and tumor size or p53 immunostaining. Lymph node metastases were detected in 59% of patients with high levels of apoptosis in primary carcinomas and in only 21% of patients with AIs below 10% in primary carcinomas. Thus, the high sensitivity of the MAb assay made it possible to identify a subset of breast carcinomas with intensive apoptosis and markers of poor prognosis. These results demonstrate that the measurement of apoptosis in breast carcinomas provides valuable prognostic information.

Adult↗
PubMed1996

Monoclonal antibody to single-stranded DNA is a specific and sensitive cellular marker of apoptosis.

The most widely used histochemical marker of apoptosis (in situ end labeling, TUNEL) detects both apoptotic and necrotic cells and evaluates only late stages of apoptosis. Hence, a specific and sensitive cellular marker of apoptosis is needed to determine the role of apoptotic death in biology and pathology. The present study describes a novel immunohistochemical procedure for the staining of apoptotic cells using a monoclonal antibody (MAb) to single-stranded DNA. This MAb stained all cells with the morphology typical of apoptosis in etoposide-treated HL-60, MOLT-4, and R9 cell cultures, in which apoptosis was accompanied by high, moderate, and low levels of internucleosomal DNA fragmentation, respectively. TUNEL stained all apoptotic cells in HL-60 cultures, nearly 60% of apoptotic cells in MOLT-4 cultures, and only 14% of apoptotic cells in R9 cultures. Apoptotic R9 cells, which progressed into secondary necrosis, retained MAb staining and became TUNEL-positive. Necrotic cells in MOLT-4 cultures treated with sodium azide were stained by TUNEL, but were negative for MAb staining. All floating cells at a late stage of apoptosis in MDA-MB-468 cultures treated with cisplatin were stained by both MAb and TUNEL. However, among adherent cells in the early stages of apoptosis, MAb stained nearly 20 times more cells than TUNEL. In histological sections of human tumor xenografts, MAb detected clusters of apoptotic cells in viable tumor tissue, but did not stain cells in areas of central ischemic necrosis. In contrast, TUNEL stained nuclei in necrotic areas. Thus, MAb to single-stranded DNA is a specific and sensitive cellular marker of apoptosis, which differentiates between apoptosis and necrosis and detects cells in the early stages of apoptosis.

Animals↗
PubMed1996

Expression of nitric oxide synthase in ulcerative colitis.

Nitric oxide (NO) is generated from L-arginine by a family of enzymes called the NO synthases. Previous investigators have proposed that the expression of this inducible enzyme (iNOS) may account for the characteristic vasodilatation, oedema and impairment of get motility seen in active ulcerative colitis. Using a specific antibody to iNOS, we have investigated the distribution of this enzyme in colonic tissue from patients with histologically proven ulcerative colitis. Eight patients with ulcerative colitis expressed calcium-independent citrulline activity (9.96 +/- 2.34 pmol citrulline mg-1 protein min-1) and showed immunoreactivity to the iNOS antibody within the inflammatory infiltrate of the lamina propria, and also within the cytoplasm of the epithelial cells lining the colon. Five age-matched controls showed no calcium-independent citrulline activity (0.2 +/- 0.08 pmol citrulline mg-1 protein min-1) and no immunoreaction to the antibody. We conclude that this enzyme is present in colonic tissue including the epithelium from patients with active colitis. Inhibition of this enzyme may provide a novel therapeutic option for patients with active ulcerative colitis.

Adult↗
PubMed1996

Human papillomavirus DNA in invasive cervical carcinomas and its association with patient survival: a nested case-control study.

This study sought to examine the association between the presence of human papillomavirus (HPV) DNA in invasive cervical cancer and prognosis. A case-control study was undertaken nested in a cohort of 208 patients with invasive cervical carcinoma in Montreal. All 40 deceased patients formed the case groups. A control group of equal size was selected by matching to each case (1:1) a patient of the same age and year of admission who had survived her disease. HPV DNA was detected by the use of a PCR protocol. The odds ratio (OR) for cervical cancer death was computed by logistic regression. Detection of HPV, particularly of types 16 and 18, was negatively correlated with disease stage and histological grade. The OR for death was 0.27 [95% confidence interval (CI), 0.1-0.8] for those whose tumors were positive for HPV DNA versus those in whom HPV DNA was not detected. After adjusting for the confounding effects of stage and grade, the prognostic effect was somewhat reduced, with an OR of 0.34 (CI, 0.1-1.1), which was no longer significant. The magnitude of the HPV-survival association was not altered when the analyses were restricted to carcinomas of stages I and II. Regardless of the mechanism for the prognostic role, detection of HPV DNA in primary tumors may play an important adjunct role in assessing prognosis of patients with invasive cervical cancer.

Adult↗
PubMed1995

Synergistic induction of apoptosis in breast cancer cells by tamoxifen and calmodulin inhibitors.

Breast cancer cells are relatively resistant to the induction of apoptosis (AP) and drug regimens which readily activate apoptotic death, may enhance the antitumor effect. Rapid and intensive induction of apoptosis was observed in estrogen receptor positive and negative breast cancer cell cultures treated with tamoxifen (TMX) combined with the calmodulin antagonists trifluoperazine (TFP) or W7. TMX (1-5 microM) alone or calmodulin antagonists alone did not induce apoptosis. Importantly, intensive apoptosis was also induced by TMX and TFP in the cells obtained from primary human breast carcinomas. Inhibition of the Ca2+ calmodulin signaling pathway is an effective way to activate apoptotic death in epithelial cells. Combination of TMX with non-toxic calmodulin inhibitors may increase the preventive and therapeutic effects of TMX.

Apoptosis↗
PubMed1995

Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic study.

Frequency of recurrence of fibroids after myomectomy has been evaluated in 145 women (median age 38 years, range 21-52) who underwent myomectomy. After surgery all women returned for follow-up visit every 12 months after surgery. Transvaginal ultrasound examination was performed routinely in every patient at 24 and 60 months and at 12, 36 and 48 months if there were any abnormal pelvic findings or suspicious symptomatology. A total of 39 (27%) women gave birth after myomectomy. For the whole series, the cumulative probability of recurrence (CPR) increased constantly during the study period reaching 51% in 5 years. The 5-year CPR decreased with parity after myomectomy, being 55% for women with no childbirth after surgery and 42% (based on 13 recurrences, P < 0.01) for those who gave birth.

Adult↗
PubMed1995

Relationships between conformational behaviour and binding affinity towards beta 1 and beta 2 adrenoceptors of some chiral phenoxypropanolamines with bulky N-substituents.

The optical isomers of a series of phenoxypropanolamine compounds with N-substituents bulkier than isopropyl have been synthesized, and their binding affinity towards beta 1 and beta 2-adrenoceptors has been determined. A computational study, including a Molecular Dynamics (MD) simulation and quenching in water and a GRID analysis provided some useful suggestions for possible interpretation patterns for the different affinity exhibited by the compounds studied.

Computer Simulation↗
PubMed1995

Protective effects of ITF 296 in the isolated rabbit heart subjected to global ischemia.

The anti-ischemic action of ITF 296 was evaluated in isovolumic, electrically driven rabbit heart preparations subjected to temporary ischemia and reperfusion. Reduction of perfusion rate from 20 to 0.2 ml/min produced a sharp decrease of peak systolic pressure, left ventricular (LV)-developed pressure, and LV dP/dt, which culminated in complete ventricular arrest within 3-4 min. Thereafter, LV end-diastolic pressure (LVEDP) progressively increased, suggesting a severe ischemic episode. Reperfusion with 20 ml Krebs solution/min after 40 min of low-flow perfusion produced only minimal recovery from the rhythm disturbances associated with cardiac mechanical activity. During reperfusion, loss of myocardial elasticity was associated with a significant increase in coronary vascular resistance, as indicated by the augmentation of coronary perfusion pressure. Injection of ITF 296 (0.3-10 microM) into the perfusion system dose-dependently inhibited the increase in LVEDP that took place during ischemia and progressively improved the recovery of a regular rhythm in the isolated heart. Isosorbide dinitrate (ISDN) at a concentration of 10 microM exerted a protective action on the myocardium similar to that obtained with ITF 296 (3 microM). Treatment with ITF 296 (1 and 10 microM) resulted in a dose-dependent increase in the rate of 6-keto-PGF1 alpha biosynthesis during both the ischemia and the reperfusion period (+157% over basal values). Similar results were obtained when hearts were pretreated with ISDN (10 microM). Infusion of a buffer containing NG-monomethyl-L-arginine (L-NMMA; NO synthase inhibitor at 10 microM) just before reduction of flow, markedly exacerbated the effects of ischemia and reperfusion on the myocardium and increased coronary perfusion pressure. The effects of L-NMMA were clearly antagonized by ITF 296 (10 microM) or L-arginine (100 microM). Mechanical activity and sinus rhythm during reperfusion were rapidly and completely restored, and coronary resistance values were close to the preischemic values. As with ISDN, ITF 296 significantly increased the rate of synthesis of 6-keto-PGF1 alpha both under basal conditions and during reperfusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Ascidian interspecific fertilization. III. Ultrastructural investigations of sperm-egg interaction.

Transmission electron microscope investigations on ascidian interspecific fertilization have been carried out on some crosses: Ascidia malaca female x Ascidiella aspersa male, Ascidia malaca female x Phallusia mammillata male, Ascidiella aspersa female x Ascidia malaca male. The morphological aspects of heterospecific sperm-egg interaction were compared with those of homospecific fertilization to complete the previous light and scanning electron microscope observations in this field. Sperm behaviour in homo- and heterospecific crosses mainly differs in the power of sperm passageway through the egg envelopes. Foreign spermatozoa, firstly interacting with the follicle cells (FCs), remain on the FC surface, leaving the interfollicular clefts empty. In homospecific fertilized eggs the initial events, also observed in hybrid crosses, are: attraction, entrapment and sperm mitochondrion translocation. But in homospecific crosses the FCs, by means of projections on their surface, facilitate the sperm path between the clefts for reaching the vitelline coat; the clefts are full of spermatozoa. These observations suggest a role of initial reproductive barrier for the FCs.

Animals↗