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Biomedical subjects

A Villa

Publications and source records attributed to A Villa.

At least 163 records · Page 9Linked to original sources
PubMed1996

P-selectin is expressed on the oolemma of human and hamster oocytes following sperm adhesion and is also detected on the equatorial region of acrosome-reacted human spermatozoa.

Selectins are a family of adhesive molecules, involved in the interactions between leukocytes and endothelium and in platelet adhesion. P-selectin, one of the members of this family, is stored in alpha-granules and dense granules of platelets as well as in Weibel-Palade bodies of endothelial cells, and it is rapidly redistributed to the cell surface after activation. It recognizes carbohydrate structures as ligands, in particular sialyl-Lewis(x), which is part of the CD15 antigen. In this work we studied P-selectin expression on gametes. While zona-free human and hamster oocytes did not react with a monoclonal antibody directed against P-selectin, oocytes from both species displayed a reactivity with this antibody following their contact with human spermatozoa, as demonstrated both by covasphere binding and indirect immunofluorescence. Artificial activation of zona-intact human oocytes by means of the calcium lonophore A23187 induced the expression on the oolemma of a moiety reacting with anti-P-selectin antibody as well. P-selectin also appeared to be expressed on the sperm surface following the acrosome reaction, as demonstrated by a flow cytometric study of reactivity of spermatozoa with the anti-P-selectin antibody, using the expression of CD46 as a marker of the acrosome reaction. The localization of the P-selectin moiety on the equatorial region of the plasma membrane of acrosome reacted spermatozoa was confirmed by transmission electron microscopy using immunogold labelling. We suggest that P-selectin might be involved in gamete interactions.

Acrosome↗
PubMed1996

Uterine myomas and smoking. Results from an Italian study.

OBJECTIVE: To evaluate the relationship between smoking and uterine myomas requiring surgery. STUDY DESIGN: We conducted a case-control study in Milan between 1986 and 1992. Cases were 476 patients under 55 years of age with histologically confirmed myomas. Controls were 1,283 women admitted to the hospital for a spectrum of acute, other-than-gynecologic, hormonal or neoplastic conditions (30% trauma, 25% nontraumatic orthopedic conditions, 25% surgical, 20% other miscellaneous). RESULTS: Cases were less frequently current smokers (22%) than controls (32%). In comparison with never smokers, the multivariate relative risk (RR) for myomas was 0.5 (95% confidence interval [CI], 0.4-0.7) in smokers. Ex-smokers were 10% of cases versus 7% of controls (RR 1.2, 95% CI 0.9-1.8). No clear trend in risk was observed with the number of cigarettes smoked per day or duration of smoking and risk of fibroids. The estimated RRs were largely consistent when separate analyses were performed in strata of age and other selected covariates, including indices of body weight. CONCLUSION: Current smoking seems to reduce the risk of myomas.

Adult↗
PubMed1996

Synthesis and microbiological evaluations of (N-heteroaryl) arylmethanamines and their Schiff bases.

The synthesis as well as the antimicrobial and antiviral activities of new (N-heteroaryl)arylmethanamines and their Schiff bases are reported. None of the tested compounds shown activity against Herpes simplex virus type 2 and against Gram positive and Gram negative bacteria. Weak or moderate activity on poliovirus Sabin type 1, on reverse transcriptase and against Cryptococcus neoformans was shown by some of the tested compounds. Viceversa several synthesized compounds exhibited a moderate or good activity against strains of Candida albicans, while only some of the tested compounds were found moderately active against strains of Candida sp. Instead numerous new compounds 3 or 4 were active as control against isolates of plant pathogenic fungi. The obtained results are discussed on the basis of structure-activity relationships.

Amines↗
PubMed1996

Partial regression, yet incomplete eradication of mammary tumors in transgenic mice by retrovirally mediated HSVtk transfer 'in vivo'.

Mice transgenic for the activated rat neu oncogene under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) (neu+ mice), develop breast tumors in 100% of cases. We have previously reported that double transgenic mice obtained from crossing neu+ mice with mice transgenic for the herpes simplex virus thymidine kinase (HSVtk) gene can be used as a suitable model to test the 'suicide gene' strategy for mammary tumor gene therapy in vivo. In the present study, we evaluated the efficacy of the HSVtk/ganciclovir (GCV) system in the neu+ mice by inoculating cells producing a retroviral vector bearing the HSVtk gene in the mammary tumors on one side of the animals, and comparing their weight with that of the contralateral tumors, after systemic GCV administration. A statistically significant effect of this therapy was clearly seen (P < 0.001) but complete eradication of the tumors could not be achieved. This was not due to the inefficient delivery of GCV, as no HSVtk expression was detected in the residual tumors, but could be related to the low transduction efficiency (< 10%) and to inability of the 'bystander effect' (probably due to the absence of functional gap-junctions among mammary tumor cells) to kill nontransduced neoplastic cells. These data suggest that results obtained by in vivo models using transplanted tumor cell lines as targets for gene therapy might not be immediately transferable to spontaneously arising tumors in animals or humans.

Adenocarcinoma↗
PubMed1995

The N-terminal domain of human DNA ligase I contains the nuclear localization signal and directs the enzyme to sites of DNA replication.

DNA replication in mammalian cells occurs in discrete nuclear foci called 'replication factories'. Here we show that DNA ligase I, the main DNA ligase activity in proliferating cells, associates with the factories during S phase but displays a diffuse nucleoplasmic distribution in non-S phase nuclei. Immunolocalization analysis of both chloramphenicol acetyltransferase (CAT)-DNA ligase I fusion proteins and epitope tagged DNA ligase I mutants allowed the identification of a 13 amino acid functional nuclear localization signal (NLS) located in the N-terminal regulatory domain of the protein. Furthermore, the NLS is immediately preceded by a 115 amino acid region required for the association of the enzyme with the replication factories. We propose that in vivo the activity of DNA ligase I could be modulated through the control of its sub-nuclear compartmentalization.

3T3 Cells↗
PubMed1995

Distal deletion of chromosome 13 in a child with the "opitz" GBBB syndrome.

We describe a patient who had craniofacial and genitourinary abnormalities, swallowing difficulties, esophageal dysfunction, hypotonia and moderate developmental delay, and who also had a terminal deletion of chromosome 13 (q32.3qter). This MCA pattern strongly suggests the Opitz GBBB syndrome. The deletion of chromosome 13 was interpreted as terminal with a breakpoint at 12q32.3. Coagulation factors VII and X located in 13q34, were markedly reduced in the propositus. Although there is some clinical overlap between patients with terminal deletion of 13q and those with the Opitz GBBB syndrome, our patient manifests a whole pattern of abnormalities characteristics of the latter disorder. The concurrence of the Opitz GBBB syndrome and the chromosome abnormality in our patient could be due to chance or, be because a gene for the Opitz GBBB syndrome is located at the tip of 13q.

Abnormalities, Multiple↗
PubMed1995

Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).

Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma c), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID). The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the gamma c-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T- B+ SCID. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.

B-Lymphocytes↗
PubMed1995

The genomic organization of the human transcription factor 3 (TFE3) gene.

We have determined the exon-intron structure of the human TFE3 gene located on Xp11.22-23. By designing PCR primers, we were able to amplify various segments of the TFE3 genomic region, thus establishing that this gene is composed of seven exons, the first six of which are small (from 56 to 159 nt). The 5' UT region is contained entirely in the first exon, while the 3' UT region is contained in the seventh exon. The comparison of the genomic and the published cDNA versions revealed that the deduced amino acid sequence of TFE3 in the C-terminus region is 125 amino acids shorter than previously reported. This eliminates most of the putative proline- and arginine-rich domain and makes the human sequence more similar to its mouse homolog. The activation domain at the N-terminus is contained in exon 2, as has been described for the mouse. The basic helix-loop-helix (BHLH) motif is spread over exons 4 to 6, while the leucine zipper (LZ) is almost all contained in the last portion of exon 6. This split BHLH is different from other BHLH-LZ genes whose genomic structures have been determined up to now.

Animals↗
PubMed1995

Presynaptic component of long-term potentiation visualized at individual hippocampal synapses.

Long-term potentiation has previously been studied with electrophysiological techniques that do not readily separate presynaptic and postsynaptic contributions. Changes in exocytotic-endocytotic cycling have now been monitored at synapses between cultured rat hippocampal neurons by measuring the differential uptake of antibodies that recognize the intraluminal domain of the synaptic vesicle protein synaptotagmin. Vesicular cycling increased markedly during glutamate-induced long-term potentiation. The degree of potentiation was heterogeneous, appearing greater at synapses at which the initial extent of vesicular turnover was low. Thus, changes in presynaptic activity were visualized directly and the spatial distribution of potentiation could be determined at the level of single synaptic boutons.

Amino Acid Sequence↗
PubMed1995

De novo interstitial deletion q16.2q21 on chromosome 6.

A de novo interstitial deletion of 6q16.2q21 was observed in a 23-month-old boy with mental and psychomotor delay, obese appearance, minor craniofacial anomalies, and brain anomalies. We compare clinical manifestations of this patient with those observed in previously reported cases with similar 6q interstitial deletions. It is interesting to note the clinical similarities between some patients with interstitial deletions of 6q16 or q21 bands and patients with Prader-Willi syndrome (PWS) and it may help to keep in mind cytogenetic studies of patients with some PWS findings.

Abnormalities, Multiple↗
PubMed1995

Antifungal agents, Part 11. Biphenyl analogues of naftifine: synthesis and antifungal activities.

A series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram-positive and Gram-negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c, and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.

Allylamine↗
PubMed1995

Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection.

Autonomic neuropathy has been reported in human immunodeficiency virus positive (HIV+) patients. Since alterations in cardiac innervation may determine QT interval prolongation, this interval was studied in a group of HIV+ subjects to evaluate if it is prolonged and to compare this measurement with other diagnostic tests for autonomic neuropathy. Fifty-seven HIV+ and 23 human immunodeficiency virus negative (HIV-) subjects were studied. Autonomic function was tested by noninvasive cardiovascular reflex tests, and the QT interval on the electrocardiogram was measured at rest, at maximum tachycardia during Valsalva manoeuvre, and afterwards at maximum bradycardia. QT intervals were corrected for heart rate according to Bazzett's formula (QTc). Autonomic neuropathy was found in 37 HIV+ subjects: 25 had moderate autonomic neuropathy (HIV+/mAN) and twelve had severe autonomic neuropathy (HIV+/sAN). The 23 HIV- and 20 HIV+ (HIV+/AN-) patients did not have autonomic neuropathy. QTc intervals were significantly longer in HIV+/sAN and HIV+/mAN than in HIV- at rest; in HIV+/sAN than in HIV- at maximum tachycardia; in HIV+/sAN and HIV+/mAN than in HIV+, in HIV+/sAN and HIV+/mAN than in HIV+/AN- and in HIV+/sAN than in HIV+/mAN at maximum bradycardia. QTc was > or = 440 ms in 24 out of 37 (64.8%) patients with autonomic neuropathy and in five out of 20 (25%) HIV+/AN- patients (sensitivity 65%, specificity 75%). A significant correlation was observed between scores of autonomic involvement and QTc interval prolongation. This study confirms that the QTc measurement is a reliable parameter indicating the presence of autonomic neuropathy. Since QT prolongation may determine ventricular arrhythmias, such patients must be followed because they may be at increased risk of sudden death.

Adult↗
PubMed1995

Risk factors for benign ovarian teratomas.

Risk factors for benign ovarian teratomas have been analysed in a case-control study conducted in Milan. Cases were women aged less than 65 years with a histologically confirmed diagnosis of benign ovarian teratoma who were admitted to a network of Obstetrics and Gynecology Departments in Milan. A total of 77 women aged 16-64 years were interviewed. Controls were women admitted to hospital for acute, non-gynaecological, non-hormonal and non-neoplastic diseases; 231 controls were interviewed (age range 15-64 years). Cases tended to be more educated: in comparison with women with less than 7 years of education, the estimated relative risk (RR) of ovarian benign teratoma was 1.6 and 2.5 respectively in women with 7-11 and 12 or more years of schooling, the trend in risk being statistically significant (chi 2(1) trend 5.39, P < 0.01). Four of the 77 cases (5.2%) and two of the 231 controls (0.9%) reported a history of infertility, with a corresponding RR of 8.3 (95% confidence interval 1.3-54.0). There was no clear relation between parity and risk of ovarian benign teratomas: in comparison with nulliparae, the estimated RRs were 1.1 and 0.7 respectively in women reporting one or two or more births (chi 2(1) trend 0.53, P = not significant). No relation emerged between marital status, age at menarche, menstrual cycle pattern, menopausal status, abortions, age at first pregnancy, oral contraceptive use and risk of ovarian benign teratomas.

Adolescent↗
PubMed1995

X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.

X-linked thrombocytopenia (XLT) is a rare recessive hereditary disorder characterized by isolated thrombocytopenia with small-sized platelets. The XLT locus has been located to chromosome Xp11 by linkage analysis, which is also where the recently cloned Wiskott-Aldrich syndrome (WAS) gene, maps. The relationship between XLT and WAS has long been debated; they might be due to different mutations of the same gene or to mutations in different genes. We now show that mutations in the WAS gene, different from those found in WAS patients, are present in three unrelated male patients with isolated thrombocytopenia and small-sized platelets. Our results demonstrate that XLT and WAS are allelic forms of the same disease, but the causes of the differences need to be further investigated.

Alleles↗
PubMed1995

Differential localization and functional role of calsequestrin in growing and differentiated myoblasts.

Calsequestrin (CSQ) is the low affinity, high capacity Ca(2+)-binding protein concentrated within specialized areas of the muscle fiber sarcoplasmic reticulum (a part of the ER) where it is believed to buffer large amounts of Ca2+. Upon activation of intracellular channels this Ca2+ pool is released, giving rise to the [Ca2+]i increases that sustain contraction. In order to investigate the ER retention and the functional role of the protein, L6 rat myoblasts were infected with a viral vector with or without the cDNA of chicken CSQ, and stable clones were investigated before and after differentiation to myotubes. In the undifferentiated L6 cells, expression of considerable amounts of heterologous CSQ occurred with no major changes of other ER components. Ca2+ release from the ER, induced by the peptide hormone vasopressin, remained however unchanged, and the same occurred when other treatments were given in sequence to deplete the ER and other intracellular stores: with the Ca2+ pump blocker, thapsigargin; and with the Ca2+ ionophore, ionomycin, followed by the Na+/H+ ionophore, monensin. The lack of effect of CSQ expression on the vasopressin-induced [Ca2+]i responses was explained by immunocytochemistry showing the heterologous protein to be localized not in the ER but in large vacuoles of acidic content, positive also for the lysosomal enzyme, cathepsin D, corresponding to a lysosomal subpopulation. After differentiation, all L6 cells expressed small amounts of homologous CSQ. In the infected cells the heterologous protein progressively decreased, yet the [Ca2+]i responses to vasopressin were now larger with respect to both control and undifferentiated cells. This change correlated with the drop of the vacuoles and with the accumulation of CSQ within the ER lumen, where a clustered distribution was observed as recently shown in developing muscle fibers. These results provide direct evidence for the contribution of CSQ, when appropriately retained, to the Ca2+ capacity of the rapidly exchanging, ER-located Ca2+ stores; and for the existence of specific mechanism(s) (that in L6 cells develop in the course of differentiation) for the ER retention of the protein. In the growing L6 myoblasts the Ca(2+)-binding protein appears in contrast to travel along the exocytic pathway, down to post-Golgi, lysosome-related vacuoles which, based on the lack of [Ca2+]i response to ionomycin-monensin, appear to be incompetent for Ca2+ accumulation.

Animals↗