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Biomedical subjects

C Giorgi

Publications and source records attributed to C Giorgi.

137 records · Page 8Linked to original sources

Inhibition of HIV-1 transcription by cyclopentenone prostaglandin A1 in Jurkat T lymphocytes.

Cyclopentenone prostaglandins inhibit virus replication in several DNA and RNA virus models. In this report we investigated the effect of prostaglandin A1 (PGA1) on HIV-1 transcription in human CD4+ Jurkat T lymphocyte cells. A dramatic reduction of HIV-1 RNA levels was detected up to seven days post infection in both unstimulated and phorbol 12-mystrate 13-acetate (PMA)-stimulated cells treated with PGA1- PGA1 treatment of cells was also effective in inhibiting the transcription of a chloramphenicol acetyltransferase (CAT) reporter gene, under the control of HIV-1 LTR, in Jurkat-Tat cells. We also show that PGA1 induced the synthesis of 70-kDa heat-shock protein (HSP70) in this cell system and the induction correlated with the drug-antiviral activity. PGA1 was also found to induce the loss of the tumor suppressor p53 protein, in the "proliferative" conformation, in a time correlation with the induction of the HSP70 As the "proliferative" p53 has been involved in the positive trans-activation of the HIV-1 LTR its depletion could contribute to the inhibitory mechanisms of PGA1 on virus transcription.

CD4-Positive T-Lymphocytes↗

Exploiting the plant secretory pathway to improve the anticancer activity of a plant-derived HPV16 E7 vaccine.

The human papillomavirus 16 (HPV16) E7 oncoprotein can be considered a "tumor-specific antigen", and therefore it represents a promising target for a therapeutic vaccine against HPV-associated tumors. Efficient production of E7 protein with a plant-based transient expression system has been already described and it was demonstrated that E7-containing crude plant extracts confer partial protection against tumor challenge in a mouse model system. Before adopting the plant-based system as a cost-effective method for the production of an E7-based anti-cancer vaccine, some aspects, such as the oncoprotein yield, need further investigation. In the present study, we report the transient expression, mediated by a potato virus X (PVX)-derived vector, of the E7 protein targeted to the secretory system of Nicotiana benthamiana plants by using a plant-derived signal sequence. Targeting the antigen to the secretory pathway enhanced the E7 protein expression levels about five-fold. Mice immunized by s.c. administration with crude foliar extracts containing E7 showed strong stimulation of cell-mediated immune response after five boosters, as detected by ELISPOT. After challenging with the E7-expressing C3 tumor cells, tumor growth was completely inhibited in 80% of the vaccinated animals and a drastic reduction of tumor burden was observed in the remaining tumor-affected mice. These data demonstrate that, by enhancing E7 yield, it is possible to improve the anti-cancer activity of the plant-based experimental vaccine and open the way for a large-scale production of the E7 protein which could be purified or used as in planta formulation, also suitable for oral therapeutic vaccination.

Animals↗

Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are prognostic factors in cervical cancer, related to invasive disease but not to high-risk human papillomavirus (HPV) or virus persistence after treatment of CIN.

OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are important regulators of cancer invasion and metastasis. Their associations to high-risk (HR) human papillomavirus (HPV) in cervical intra-epithelial neoplasia (CIN) and cervical cancer (CC) are unexplored and their prognostic significance in CC remains controversial. MATERIALS AND METHODS: As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for MMP-2 and TIMP-2 and tested for HPV using PCR with 3 primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all squamous cell carcinoma patients and 67 CIN lesions had been monitored with serial PCR for HPV after cone treatment. RESULTS: MMP-2 increased with the grade of CIN, with major up-regulation upon transition to invasive cancer (OR 20.78) (95%CI 7.16-60.23) (p=0.0001). TIMP-2 retained its normal expression until CIN3, with dramatic down-regulation in invasive disease (p=0.0001 for trend). Thus, the MMP2:TIMP-2 ratio increased with progressive CIN, exceeding the value 1.0 only in invasive disease. Both MMP-2 and TIMP-2 are highly specific (TIMP-2; 100%) discriminators of CIN with 100% positive predictive value (TIMP-2), but suffer from low sensitivity and negative predictive value. Neither MMP-2 nor TIMP-2 showed any significant association with HR HPV or virus persistence/clearance. TIMP-2 (but not MMP-2) was a significant predictor of survival in univariate (Kaplan-Meier) analysis (p=0.007), but lost its significance in multivariate (Cox) analysis. CONCLUSION: The activities of MMP-2 and TIMP-2 in cervical carcinogenesis seem to be unrelated to HR-HPV The inverse MMP-2:TIMP-2 ratio is a sign of poor prognosis. A combination of a TIMP-2 assay with another test showing high SE and high NPV (e.g., HCII for HPV) should provide a potential screening tool capable of accurate detection of CIN.

Adult↗

Propofol in the treatment of convulsive status epilepticus: a report of four cases.

Propofol is a new anaesthetic agent commonly used because of its rapid pharmacokinetic. Lately, anecdotal reports suggest its utility in the treatment of convulsive status epilepticus. We describe four cases of convulsive status due to severe encephalopathy of various etiology. They were resistant to diazepam and other drugs and remitted only after treatment with propofol. The infusion, even protracted to 8 days, did not cause any toxic or proconvulsive side-effects. The very short duration of its central depressant action permitted monitoring of the underlying neurological status whenever needed.

Adult↗

Predictive accuracy of cell kinetics data in glial tumors investigated by serial stereotactic biopsy.

The prognostic accuracy of cell kinetics investigations in patients affected from glial tumors, submitted to serial stereotactic biopsy is reported. The methodology is described and the results obtained in 103 patients are discussed with particular regard to mature and anaplastic astrocytoma series. In conclusion the value of the procedure has been clearly demonstrated in glial tumors different form glioblastoma.

Adolescent↗

Three-dimensional neuroanatomic images in CT-guided stereotaxic neurosurgery.

A technique is described for three-dimensional reconstruction of human diencephalic structures based on information contained in a widely used stereotaxic brain atlas. Various methods of graphically representing the obtained diencephalic volumes are discussed and examples are given. The anatomic information contained in the computerized atlas can be implemented with computed tomography performed under stereotaxic conditions. Volume data provided by the tomograms are used for three-dimensional "stretching" of the volumes presented in the atlas. Improved accuracy in identifying "invisible" diencephalic targets in functional stereotaxic neurosurgery is expected to result from this new technique.

Brain↗

The masseteric inhibitory reflex in the diagnosis of multiple sclerosis.

In order to evaluate the reliability of the masseteric inhibitory reflex (MIR) as a screening method in the diagnosis of multiple sclerosis (MS), a series of 41 consecutive patients affected by clinically defined, long-duration forms (mean duration 10.9 years) of the disease was examined. In all cases magnetic resonance imaging and CSF isoelectrofocusing confirmed the diagnosis. Sensitivity of MIR, Blink Reflex and BAEPs were compared. Statistical analysis of data suggested the following considerations: 1) a significant concordance was found between MIR and the other neurophysiological tests performed (MIR vs. BAEPs in 78.4% of cases, p < 0.001; MIR vs. blink reflex in 68.3%, p < 0.02). 2) The S1 early component of MIR is a more reliable indicator than S2 late component. 3) In detecting brainstem lesions the sensitivity of MIR equaled that of the other neurophysiological tests. 4) Poor localizing concordance between neurophysiological tests and neuroimaging was found in our series. A possible utilization of MIR, as a part of a multimodal neurophysiological approach, even in patients affected by possible or probable MS is suggested.

Adult↗