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Biomedical subjects

A Giuliani

Publications and source records attributed to A Giuliani.

At least 109 records · Page 6Linked to original sources
PubMed1997

Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells transfected with mutated K-ras gene.

Strong immunogenicity is induced by antitumor triazene compounds in tumor cells through a mutagenic mechanism. A highly immunogenic < > clone, isolated from a dacarbazine-treated L5178Y leukemia of DBA/2 mice, was transfected with K-ras mutated at codon 12 (i.e. ras(m12)). This transfected clone presents at least 2 mutations, one concerning K-ras gene, and the other affecting an unrelated gene, responsible for the generation of a highly immunogenic, MHC class I restricted non-self peptide. The results indicate that cells of < > clone transfected with ras(m12) were less immunogenic than cells of the same origin transfected with the vector alone. Moreover, ras(m12)-transfected cells showed lower levels of H-2K(d) gene expression with respect to those detectable in control cells. In addition, in vivo and in vitro sensitization against < > clone carrying mutated ras did not result in a strong cytotoxic T lymphocyte response against ras(m12)-transfected non immunogenic L5178y target cells. These preliminary results suggest that K-ras mutation could down-regulate the level of tumor immunogenicity, possibly acquired through a mutagenic process affecting other unrelated genes.

Animals↗
PubMed1997

Carcinoma of the duodenum: management and survival in 14 cases.

AIMS: The aim of this study is to evaluate the role of surgery in the treatment of adenocarcinoma of the duodenum. METHODS: From 1955 to 1994, 14 patients with primary adenocarcinoma of the duodenum underwent surgical treatment in our department. Presenting signs and symptoms were mainly related to obstruction and bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were confirmed histologically. The tumors were staged pathologically according to the new TNM classification (UICC, 1992). Eight patients received palliative treatment or exploratory laparotomy. The remaining 6 patients were resectable for cure. RESULT: Operative mortality was 35.7%. The 5-year survival rate for patients who underwent curative resection was 33.3%. None of the patients who underwent palliative procedures or exploratory laparotomy survived for more than 11 months. CONCLUSIONS: In the management of resectable adenocarcinomas of the duodenum surgical radicality including lymphadenectomy should be pursued. Unresectable adenocarcinomas treated with palliative procedure had a very poor prognosis.

Adenocarcinoma↗
PubMed1997

Postoperative combined radiohyperthermia in Astler-Coller stages B2 and C distal rectal cancer.

Pelvic perineal recurrence rate is the major therapeutic problem after curative surgery of extraperithoneal rectal cancer, after lower anterior resection as well as abdomino-perineal resection: local failure rate is high, particularly for stages B2-C. Radiotherapy alone or in combination with chemotherapy proved to be an useful adjunct to surgery. Postoperative radiotherapy, with 40 to 50 Gy doses, has shown local improvement, but causing intestinal damaging. There is now evidence that hyperthermia enthances radiation effects, by killing radioresistant acid tumor cells. In order to give high postoperative radiation doses, without intestinal damage, and to kill acid tumor cells by hyperthermia, we developed a device, able both to displace intestinal loops and to produce combined hyperthermia. From 1993 to 1995, four patients with Astler-Coller stages B2 (2 patients), C1 (1 patient) and C2 (1 patient) distal cancer, were operated by Hartmann's procedure and treated with postoperative radio-hyperthermia with our device. Overall radiation dose delivered in the pelvic area was of 65 Gy, associated with three heating sessions at 43 degrees C for 30 minutes. Pelvic infection occurred in one patient; all pelvic byopsies were negative and no bowel damage was found. Three patients underwent recanalization, one had anasthomotic leackage. The C1 and C2 stage patients died from hepatic metastasis, 18 and 11 months after recanalization; one B2 stage patient is still under treatment and the other is alive and disease free 13 months after recanalization. Our technique allows to give high postoperative radiation doses, without small intestine damage, and to give a good hyperthermia for better control of local failure.

Adenocarcinoma↗
PubMed1997

Pregnancies in patients with premature ovarian failure.

We present 5 women with premature ovarian failure (POF) who were treated with different regimes and conceived. Three patients conceived spontaneously while on cyclic estrogen/progestagen replacement therapy. One patient conceived after high-dose gonadotrophin treatment. Embryo transfer with oocytes donated from a third party donor was performed in one patient abroad. Due to legal reasons the heterogeneous oocyte donation for patients with POF cannot be performed in some countries such as Austria. Therefore, many patients who desire pregnancy cannot receive optimal treatment for their condition.

Adult↗
PubMed1997

Rare manifestations of the ovarian hyperstimulation syndrome: a report of two cases.

The increasing practice of ovulation induction has made ovarian hyperstimulation syndrome (OHSS) a frequent clinical problem which can also become life-threatening. Two unusual cases of OHSS are described. The first patient presented with a unilateral pleural effusion. The second patient developed severe OHSS after a low-dose protocol with highly purified follicle stimulating hormone (FSH HP) and in the absence of risk factors.

Adult↗
PubMed1996

The metabolism of sphingo(glyco)lipids is correlated with the differentiation-dependent autophagic pathway in HT-29 cells.

Recently it was demonstrated that the metabolism of both glycoproteins and sphingo(glyco)lipids is dependent upon the state of enterocytic differentiation of HT-29 cells. Furthermore, it was shown that undifferentiated HT-29 cells display an important autophagic sequestration, controlled by a heterotrimeric Gi3 protein. In order to correlate the metabolism of sphingo(glyco)lipids with the extent of autophagic sequestration, we have incubated undifferentiated and differentiated HT-29 cells with tritium-labelled GM1 ganglioside and sphingosine in the absence and presence of pertussis toxin (an inhibitor of autophagic sequestration) or asparagine (an inhibitor of autophagic vacuole maturation). In addition, undifferentiated HT-29 cells transfected with a cDNA encoding the G alpha i3 protein (cells expressing an amplified autophagic pathway) were labelled with both GM1 and sphingosine. The results show that the catabolism of sphingo(glyco)lipids is dramatically enhanced in parallel with the increase of the autophagic pathway while at the same time their biosynthesis is reduced. The inhibition of autophagy in both undifferentiated cells and alpha i3-overexpressing cells restores sphingo(glyco)lipid metabolism, as normally expressed in differentiated cells, as well as in other mammalian cell types. We conclude that autophagy plays an important role in governing the metabolic fate of sphingo(glyco)lipids in HT-29 cells. Since autophagy regulates the N-linked glycoprotein metabolism in this cell line, our results corroborate the idea that glycolipid and glycoprotein metabolisms are controlled by similar mechanisms.

Asparagine↗
PubMed1996

Micro- and macrostructure of learning in active avoidance: a quantitative approach.

The dynamics of learning in the Active Avoidance test was analyzed at the trials level as well as at the level of daily sessions, each comprising numerous trials. The two scales (large scale for the sessions and small scale for the trials) were demonstrated to be mutually independent. The intermediate derived scales (blocks of trials) were found consistent among themselves and with small scale but independent of the large one. Moreover, the two extreme scales were kinetically discriminable. These results point to the existence of two independent mechanisms for large and small scale learning together with the need to postulate a consolidation process during the rest period.

Animals↗
PubMed1996

A Markovian formalization of heart rate dynamics evinces a quantum-like hypothesis.

Most investigations into heart rate dynamics have emphasized continuous functions, whereas the heart beat itself is a discrete event. We present experimental evidence that by considering this quality, the dynamics may be appreciated as a result of singular dynamics arising out of non-Lipschitz formalisms. Markov process analysis demonstrates that heart beats may then be considered in terms of quantum-like constraints.

Animals↗
PubMed1996

[Value of ultrasound in early detection of endometrial carcinoma].

OBJECTIVE: The purpose of our study was to examine the diagnostic value of the biometry of the endometrium for the early detection of endometrial carcinomas in postmenopausal women as well as to compare our results with those of other authors. METHODS: In 69 post menopausal women the endometrial thickness measured by vaginosonography before diagnostic curettage or hysterectomy was compared with the histological results. RESULTS: Using a cutoff value of 6 mm, a sensitivity of 96%, a specificity of 24%, a positive predictive value of 16%, and a negative predictive value of 97% were established. CONCLUSIONS: Endovaginal ultrasound evaluation of the endometrial thickness is not specific enough to be used screening method for the early detection of endometrial carcinoma.

Aged↗
PubMed1996

Drug-induced changes of carcinoembryonic antigen expression in human cancer cells: effect of 5-fluorouracil.

Previous studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivity of the human colon carcinoma cell line HT-29 with a monoclonal antibody (COL-1) directed against carcinoembryonic antigen (CEA). In the present study, we show that short-term exposure (i.e., 1 hr) of cancer cells to 5-FU mediates a marked increase of CEA expression, that is concentration-dependent and lasts up to day 5 after treatment. This phenomenon is the result of the drug-mediated enhancement of the CEA expression, but not of the selection of the CEA-positive cells operated by the antimetabolite. This is supported by the finding that the increase of the CEA expression detected by cytofluorimetric analysis is observed not only in the parental HT-29 line, but also in its C22.20 subclone, endowed with a low basal level of CEA and with chemosensitivity to 5-FU lower than that of the parental cell line. Moreover, increase of CEA expression occurs not only in the plasma membrane, but also in the cytosolic cellular compartment, as indicated by the results of Western blot analysis. Northern blot analysis of total RNA extracted from 5-FU-treated HT-29 or C22.20 cells shows an increase in the steady-state levels of CEA and CEA-related transcripts (e.g., biliary glycoprotein). Moreover 5-FU-mediated augmentation of the CEA transcript appears to be attributable mainly to enhanced transcription rather than to increased mRNA stability. It is concluded that induction of enhanced CEA protein expression in cancer cells treated with 5-FU could be of clinical interest for the development of immunochemotherapeutic protocols based on CEA protein as the target molecule.

Carcinoembryonic Antigen↗
PubMed1995

The different inhibiting effect of cholera toxin on two leukemia cell lines does not correlate with their toxin binding capacity.

The murine leukemia cell lines L1210 and WEHI-3B show a very different sensitivity to the cholera toxin (CT). The in vitro growth of L1210 is completely inhibited by 10(-8) M CT, while WEHI-3B growth shows the same inhibition at 10(-11) M. The analysis of membrane ganglioside pattern of the two cell lines shows that in L1210 cells the major component is the GM1a ganglioside while the monosialogangl oside fraction from WEHI-3B is entirely composed of gangliosides of the 'b' series among which GM1b is the more represented. The total cholera toxin binding capacity of the ganglioside extract from L1210 cells is more than hundred fold higher than that of WEHI-3B and this difference is also confirmed by the number of CT receptors/cell and by the binding of FITC-B subunit of CT on the cells. These surprising data are in conflict with the poor sensitivity to CT evidenced by L1210 compared to WEHI-3B cells. In order to clarify this discrepancy we investigated the cAMP accumulation, the cell viability and the clonogenicity of these two leukemia cell lines following the treatment with CT and forskolin (FRSK). The treatment of WEHI-3B cells with CT induces a dramatic increase of intracellular cAMP which highly correlates with cell death and the decrease of clonogenicity and this result is partially obtained by the treatment with FRSK. L1210 cells do not evidence significant cAMP accumulation neither with CT nor with FRSK treatment. These data suggest that the different inhibiting effect of CT on WEHI-3B and L1210 cells does not correlate with their different pattern of gangliosides and the related toxin binding capacity. Further they indicate that the growth inhibition of WEHI-3B cells is closely related with a cAMP-dependent cell killing mechanism, while the inhibition of L1210 growth (produced by high concentration of CT) is mediated by a cAMP independent mechanism.

Animals↗
PubMed1995

Relationships among in vitro mutagenicity assays: quantitative vs. qualitative test results.

In previous investigations, we studied the relationships between the profiles of the qualitative responses of in vitro short-term tests (mutation in Salmonella typhimurium, chromosomal aberrations in CHO cells, sister chromatid exchanges in CHO cells, and mutation in mouse lymphoma cells) and common sets of chemicals. In this paper, we address the study of the quantitative responses (potency). We show that two analyses point to similar patterns of relationships: the mutation in mouse lymphoma cells assay is most similar to the CHO sister chromatid exchange assay, and the Salmonella assay is most similar to the CHO chromosomal aberrations assay.

Analysis of Variance↗
PubMed1995

In vitro infection of leukemic bone marrow with HTLV-I generates immortalized cell lines expressing T or myeloid cell phenotype.

Leukemic bone marrow cells ( > 90% blasts) of a patient with acute myeloblastic leukemia (AML), non-treated or pretreated in vitro with a mutagenic triazene compound, were infected with HTLV-I by coculture with irradiated virus-donor cells. Immortalized, HTLV-I+, double-positive CD4/CD8 euploid T cell lines, expressing HLA class I/II monomorphic determinants, and inappropriate myeloid and progenitor cell markers (ie CD13, CD14, CD15 and CD33 antigens) were obtained. In one out of 10 triazene-pretreated samples, HTLV-I infection resulted in the appearance of a rapidly growing triploid cell line (ie MTLC1 line) showing: (1) myeloid but not lymphoid phenotype; (2) beta and delta T cell receptor in germline configuration; (3) integrated, complete and incomplete HTLV-I provirus genome (also detected in a number of MTLC1 clones); (4) a high percentage of cells positive for non-specific cross-reacting antigen (a CEA-related molecule present in myeloid cells) under the influence of gamma-interferon; (5) absence of HLA class I/II antigen expression; (6) absence of tax gene transcription. Blast cell proliferation was marginal or absent when leukemic marrow was not subjected to retroviral infection. These results show that exposure of leukemic bone marrow to HTLV-I can be followed by immortalization of T and myeloid cells. Although no data are available to establish whether tax expression played a role in the early phase of the immortalization process of MTLC1 line, tax gene product was not required for maintaining long-term growth of MTLC1 cells.

Antigens, CD↗
PubMed1994

Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy.

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.

Acetylcarnitine↗