[Radiotherapy induced pemphigus vulgaris].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Lis.
Explore the source record for details and available documents.
Advances in the development of highly infectious, replication-deficient recombinant retroviruses provide an efficient means of stable transfer of gene expression. Coupled with ex vivo transduction, surrogate cell populations can be readily implanted into the brain, thus serving as vehicles for delivering selected gene products into the central nervous system (CNS). Here we report that rat astrocytes can be routinely and safely isolated from brain tissue of a living donor by use of short-term gelatin sponge implants. The mature, nontransformed astrocytes were easily expanded, maintained in long-term tissue cultures and were efficiently transduced with an amphotropic retrovirus harboring a heterologous, fused transgene. In vitro retroviral infection rendered the nontransformed cells essentially 100% viable after exposure. The level of efficiency of infection (30-50% effective genome integration of provirus and expression of transgene in target cell populations) and minimal cell toxicity obviated the need to harvest large numbers of target cells. Cultured transduced astrocytes were resilient and exhibited select peptide expression for up to 1 year. Subsequently, transduced astrocytes were used in a series of experiments in which cells were transplanted intracerebrally in syngeneic animals. Post-implantation, astrocytes seeded locally and either insinuated into the surrounding parenchyma in situ or exhibited a variable degree of migration, depending on the anatomic source of astrocytes and the targeted brain implantation site. Transduced astrocytes remained viable in excess of 8 months post-transplantation and exhibited sustained transgenic peptide expression of green fluorescent protein/neomycin phosphotransferase in vivo. The sequential isolation and culture of nontransformed, mature, adult astrocytes and recombinant retrovirus-mediated transduction in vitro followed by brain reimplantation represents a safe and effective means for transferring genetic expression to the CNS. This study lays the foundation for exploring the utility of using a human autologous transplantation system as a potential gene delivery approach to treat neurological disorders. Prepared and utilized in this manner, autologous astrocytes may serve as a vehicle to deliver gene therapy to the CNS.
The effects of pertussis toxin, an uncoupler of Gi protein from adenylate cyclase, and luzindole, a competitive inhibitor of melatonin receptor binding, were examined for their ability to inhibit melatonin-induced suppression of PC12 cell growth. Both agents inhibited the melatonin response suggesting that melatonin may be acting through one of its Gi coupled cell surface receptors. This is confirmed by Western blots demonstrating the presence of MT1 receptors in PC12 cells. Coupling of the Gi protein to these receptors is demonstrated by failure of melatonin to suppress cell growth in PKA deficient A126-1B2-1 mutant PC12 cells. Similarly, melatonin failed to prevent cell proliferation when cells were incubated in the presence of the PKA inhibitor, Rp-cAMP. Retinoic acid and dexamethasone, agents known to effect PC12 cell growth and/or differentiation, displayed differential effects on the actions of melatonin. In the presence of melatonin and low concentrations of retinoic acid (100 nM), PC12 cell proliferation was stimulated compared to that seen with either agent alone, whereas no increase in cell proliferation was observed when higher concentrations of retinoic acid (100 microM) were used. The effects of dexamethasone on suppression of PC12 cell growth were additive with that of melatonin whereas, 1,25-dihydroxyvitamin D(3) (IC(50)=10 nM), which by itself had no effect on PC12 cell growth, was found to inhibit the melatonin response. This study demonstrates that inhibition of PC12 cell growth, at physiological concentrations of melatonin, is mediated by cAMP-dependent cell surface receptors and this response is altered by other growth factors known to effect PC12 cell proliferation and differentiation.
Calcineurin, a ubiquitous calcium-activated serine phosphatase, plays an important role in the signal transduction. We have previously reported that cyclosporin A (CsA) inhibits the growth and survival of the rat C6 glioma cells due to the inhibition of signaling pathway involving calcineurin and transcription factor nuclear factor of activated T cells (NFAT). In the present study, we show that CsA affects the survival of reactive astrocyte cultures derived from striatal trauma. Exposure of reactive astrocytes to doses of CsA >50 microg/ml for 24--72 h produces morphological changes, including cell body shrinkage and loss of extensions, followed by cell death. This death was accompanied by apoptotic changes in nuclear morphology and DNA fragmentation, as revealed by Hoechst 33258 and positive TUNEL staining. We demonstrated the presence of calcineurin A subunit in reactive astrocytes and corpus callosum (brain structure enriched in astrocytes) and an additional calcineurin-like protein occurring solely in reactive astrocytes. FK506, a calcineurin inhibitor unrelated to CsA, inhibits proliferation of astrocytes and induces death accompanied by apoptotic changes in nuclear morphology and DNA fragmentation. Since calcineurin is a major target for both CsA and FK506, the results suggest that this phosphatase is involved in the regulation of reactive astrocyte survival.
The purpose of this paper is to extend the research on the Duss Fairy Tales in an Italian sample. Attention has been paid, in particular, to the study of some variables identified in a newly devised schedule. The protocols were scored for four indexes: (1) the main hero of the stories, (2) number and types of characters, (3) number of emotions expressed, and (4) number of heroes' and characters' actions and behaviors. Subjects were 70 children aged 3.5 to 10.5 yr. enrolled in kindergartens and elementary schools in Italy. The relationships of scores with age and sex were also investigated. There was an increase across three age groups in the richness of stories in terms of emotions and characters' identification.
Recent studies have suggested that cell-mediated immune response play a critical role in the pathogenesis of alopecia areata (AA). Eighteen patients with AA were included in the study. Fifteen healthy subjects served as controls. Serum levels of sTNF alpha RI and sIL-2R were measured using enzyme-linked immunosorbent assay technique. The serum levels of sTNF alpha RI were significantly elevated in patients with AA in comparison with control group. The serum levels of sIL-2R were higher in AA patients than in healthy subjects but not significantly. These results indicate, that immune mechanisms in AA are characterized by activation of T cells and other cells, possibly keratinocytes.
It is hypothesized that abnormalities of cell-mediated immunity participate in the pathogenesis of systemic sclerosis (SSc). However, the role of many cellular markers of immune activation remain still not well known, particularly as comparable with clinical status. The aim of this study was to examine the levels of some cytokines: IL-2, IL-6, TNF-alpha and to evaluate their role as parameters of disease activity and severity in systemic sclerosis. Fourty-seven patients with SSc we included in the study. Concentrations of cytokines were determined by an-enzyme-linked immunosorbent assay--ELISA. Controls were healthy age-and-sex marched volunteers. Interleukin-2 was identified in 45% of sera from patients with SSc, predominantly among patients with the rapidly progressive disease and with the diffuse SSc. The presence of IL-2 in SSc sera may also be indicative of disease activity. The frequency of positivity for IL-6 in examined SSc sera was similarly and was 50%. The prominently frequent incidence of the IL-6 in early stage of disease and in patients with severe systemic involvement indicated a potential role of this cytokine as a parameter of disease activity. TNF-alpha was not detected in the examined sera.
This study extended the research of the psychometric characteristics of Koppitz's 1963/1975 Developmental Scoring System of the Bender-Gestalt test. Attention was paid to relations among the 7 deviations. The test was administered by licensed psychologists to 1,065 white children, aged from 3 yr., 6 mo. to 11 yr., 5 mo., enrolled in the regular education track of kindergarten and elementary school in Italy.
The Reflective Self-function Scale was originally devised by Fonagy and coworkers to assess parents' capacity to understand and reflect on the mental states of the self and others. The aim of this paper was to describe early normative data for rating the reflective self-function to the Clinical Interview for Parents During Pregnancy. The interview was administered to 112 middle-class couples living in northern Italy and expecting their first baby. Reflective self-function was rated in three areas of the interview: the expected child, the couple's relationship, and the relationship of parents-to-be with their own parents. The paper describes the rationale, rating process, and early normative data in our sample.
Parathyroid hormone-related peptide (PTHrP) is the cause of humoral hipercalcaemia of malignancy syndrome (HHM). It is known that the peptide as well as its receptors are widely distributed in many normal organs and tissues, where it influences an array of diverse functions which are realized through paracrine or autocrine pathway. PTHrP is present in large amounts in lactating mammary gland but its function is not fully elucidated. In this study, production of parathyroid hormone-related peptide (PTHrP) by the Hs578Bst cell line corresponding to mammary myoepithelial cells was examined by immunocytochemistry. Using RNA extracted from these cells we analyzed expression of mRNA for PTHrP and for the PTH/PTHrP receptor by RT-PCR. The obtained results demonstrated that Hs578Bst cells produced PTHrP and synthesized mRNA for PTHrP and PTH/PTHrP type I receptor. It provides evidence that myoepithelial cells are target cells for PTHrP. The data support that PTHrP may be an important autocrine/paracrine factor, involved in the regulation of myoepithelial cell function as well as in growth and differentiation of the mammary gland.
Manipulation of gene expression in developing or in mature central nervous systems (CNS) holds a promise for the resolution of many compelling neurobiological questions, including the feasibility of gene therapy to treat diseases of the brain. In this context, a number of viral vectors have been used in recent years to introduce and express genes into the CNS. This article discusses a gene transfer system based on the Herpes Simplex Virus-1 (HSV-1). We describe here the use of non-replicating, non-toxic HSV-1 vector, 8117/43, in a series of studies carried in our joint program. This vector proves further the utility of HSV-1 as a delivery vehicle to a number of distinct sites within the CNS.
The purpose of this paper was to extend research on Koppitz's Developmental Scoring System to Italian samples. Specific attention has been given to the study of errors for the single designs to assess the relationship of these errors with total errors and to assess the designs' varying difficulty. A second purpose was to study possible cultural influences between different Italian regions. According to Koppitz (1975) research findings support that the rate of development in visuomotor perception differs among children of various ethnic groups. Subjects were 538 boys and 527 girls enrolled in the regular kindergarten and elementary schools in Italy. Detailed analyses were carried out on total mean errors and mean errors for each design. Mean errors decrease across age groups; that is, perceptuomotor integration is improved for older children. No significant differences were found between Northern and Southern Italy.
OBJECT: The authors studied the effect of gender and hormonal status on survival in nude rats implanted with human glioblastoma multiforme (GBM) cell lines. METHODS: Nude rats received intracerebral implants of either wild-type U87MG cells or U87MG cells transfected with the gene for endothelin-1 (U87/ET-1). In the initial study, survival was compared in males and females for each of the two cell lines. The six second-phase study groups were composed of: 1) males; 2) females; 3) ovariectomized females; 4) sham ovariectomized females; 5) ovariectomized rats given 10 microg/day estradiol benzoate for 21 days; and 6) ovariectomized rats given 20 mg/kg/day progesterone for 21 days. All rats in the second phase were implanted with U87/ET-1 cells. Animals were killed when they exhibited initial signs of neurological deterioration. Female nude rats survived longer than male rats implanted with either U87 or U87/ET-1 cells. In the second phase, ovariectomized, male, and progesterone-treated rats died at approximately 19 days, whereas the female, sham-treated, and estrogen-treated animals died 23 to 25 days after tumor cell implantation. CONCLUSIONS: The authors demonstrate that female nude rats implanted with human GBM cells have a survival advantage over male rats and that estrogen provides the advantage.
Patients with atopy and especially these with atopic skin diseases, hand eczema and dishidrosis have been identified as a high-risk group developing irritant hand dermatitis. To improve prevention pre-occupational examinations (screening tests) in youth have been proposed. Dermatological examinations, questionnaires and some bioengineering techniques are usually suggested. The necessity of application of ASD score has been confirmed. Because of the high irritant hand eczema morbility and socio-economic consequences detection of high-risk group plays a special role. It is possible by means of: 1. Special questionnaires 2. Dermatological examinations, education, observation 3. Conception and realization of skin--safe working conditions.
Topotecan is a topoisomerase (topo) I inhibitor with promising activity in preclinical studies. We hypothesized that low-dose intratumoral delivery of topotecan would be highly effective for gliomas. Human glioma cell lines (U87, U138 and U373) displayed different sensitivities to topotecan (IC50 range: 0.037 microM to 0.280 microM) in cell culture. The most resistant of the glioma cell lines (U87) was implanted stereotactically into the brains of nude rats. Twelve days later, at which time tumor diameter measured 2 to 2.5 mm, animals were randomized to three groups: group I, intratumoral topotecan infused via osmotic pump (n = 12); group II, intratumoral saline infusion (n = 7); and group III, no treatment (n = 10). Animals were sacrificed when signs of deterioration developed, or at 60 days. Animals in group I had a mean survival time (MST) of > 55 days (range = 40-60); whereas, those in groups II and III had MST of 26.1 (range = 21-31) and 26.5 (range = 20-30) days, respectively. The differences in survival between group I and each of the other groups were statistically significant (p < 0.0001; Logrank Mantel-Cox). None of the animals that survived 60 days had histological evidence of residual tumor at sacrifice. Measurement of topotecan levels in normal brain revealed cytotoxic concentrations up to 4.5 mm from the site of infusion. This study demonstrates that intratumoral topotecan delivered via an osmotic pump prolongs survival in the U87 human glioma model.
The aim of this paper is to extend work by Fisher and Cleveland on Barrier and Penetration scores to Italian samples of 286 normal adults and adolescents. The scores were based on Zulliger test protocols administered according to Exner's instructions. Two versions of the scores of both 1958 and 1970 versions were compared. Discussion also concerned variables which might have influenced the scores.
In 114 patients with peripheral lung lesions transthoracic needle biopsy was performed under USG control. This method enabled to achieve positive results in more than 90% of cases. Transthoracic needle biopsy is a simple diagnostic method which allows without serious complications to establish histo-pathological diagnosis of thoracic peripheral tumors.
An experimental animal model of meningeal leukemia was developed in the nude rat, rnu/rnu, using the human-derived acute lymphoblastic leukemia cell line HPB-ALL. Anesthetized rats were placed in a modified stereotaxic frame and then injected intrathecally, at the level of the cisterna magna, with human leukemic cells. Cerebrospinal fluid and tissue samples from brain, spinal cord, heart, liver, kidney, spleen, bone marrow, and cervical lymph nodes were subjected to histopathologic examination and molecular genetic screening by clonotype primer-directed polymerase chain reaction (CPD-PCR). Ninety-three percent of animals (n = 14) developed signs of meningeal irritation leading to death 30 to 63 days postinjection (median, 36.0 days, mean, 38.7); death occurred between 30 and 39 days in 77% of all animals. Leukemic cells progressively infiltrated the pericerebellar and pericerebral subarachnoid space and infiltrated the Virchow-Robin (perivascular) space. The infiltrating meningeal leukemia closely resembled the pathologic presentation in the human condition. By CPD-PCR, leukemic cells were first detected in cerebrospinal fluid (CSF) on day 4 postinjection, were variably present over the ensuing 17 days, and were consistently detected after day 21. At terminal stages, CPD-PCR tissue surveys showed leukemic DNA in all brains and spinal cords and rarely in cervical lymph nodes, but leukemic DNA was not detected in any other tissue screened. Leukemic meningitis was reliably produced with a predictable survival time. Intrathecal administration of leukemic cells was an efficient means of transmitting leukemic meningitis and it compartmentalized the disease to the central nervous system (CNS), eliminating potential complications of systemic illness. The use of human-derived cell lines may render this model more relevant to the development of future therapeutic strategies to treat leukemia and lymphoma that invade the CNS.