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Biomedical subjects

G Mameli

Publications and source records attributed to G Mameli.

At least 19 recordsLinked to original sources

Multiple sclerosis-associated retrovirus and optic neuritis.

One prognostic factor for early multiple sclerosis (MS) patients to develop a definite MS may be the presence of the MS-associated retrovirus (MSRV) in the cerebrospinal fluid (CSF). We designed a specific study on a cohort of optic neuritis (ON) patients to evaluate the MSRV-dependent conversion to MS relative to the prediction conferred by magnetic resonance imaging (MRI) and CSF abnormalities. At follow-up, 33.3% MSRV+ and 0% MSRV- ON patients developed MS (P = 0.03). The prediction value is lower than that given by CSF and MRI abnormalities (42.3%). This intriguing finding is discussed in the light of the abundant discrepancies observed in the MSRV literature. Multiple Sclerosis 2006; 12: 357-359. www.multiplesclerosisjournal.com

Adolescent↗

p73 modulates HIV-1 Tat transcriptional and apoptotic activities in human astrocytes.

HIV-1 Tat is a potent transcriptional activator of the viral promoter with the ability to modulate a number of cellular regulatory circuits including apoptosis. Tat exerts its effects through interaction with viral as well as cellular proteins. Here, we studied the influence of p73, a protein that is implicated in apoptosis and cell cycle control, on Tat apoptotic function in the central nervous system. We recently demonstrated the ability of Tat to associate with p73, and that this association modulates Tat transcriptional activity (Amini et al., Mol Cell Biol 2005; 18: 8126-8138). We demonstrated that p73 interferes with Tat-mediated apoptosis by preventing the up-regulation of Bax and down-regulation of Bcl-2 proteins in astrocytes. Thus, the interplay between Tat and p73 may affect Tat contribution to apoptotic events in the brain, limiting its involvement in the neuropathology often observed in the brains of HIV-1 patients.

Apoptosis↗

Multiple sclerosis-associated retrovirus and MS prognosis: an observational study.

MS-associated retrovirus (MSRV) in the CSF may have gliotoxic properties and could be associated with a more disabling MS. The authors tested this hypothesis in 15 untreated patients with MS: 6 MSRV- and 9 MSRV+ at the time of CSF withdrawal. After a 3-year mean follow-up, MSRV- patients showed a stable MS course, whereas MSRV+ patients had a progressive course (p = 0.01).

Adolescent↗

Multiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients.

Blood and CSF of Sardinian patients with MS and neurologic control subjects were tested for MS-associated retrovirus (MSRV). CSF detection in MS was 50% at clinical onset, increasing with temporal disease progression, and 40% in control subjects. In blood, MSRV was detected in all MS patients, in most patients with inflammatory neurologic diseases, and rarely in healthy blood donors. MSRV may represent a marker of neurologic diseases of inflammatory origin.

Adult↗

Apathetic Graves' disease and acquired hemophilia due to factor VIIIc antibody.

Acquired hemophilia due to autoantibody to Factor VIII coagulant (Factor VIIIc) is a rare event which may be observed in patients with different autoimmune diseases. To our knowledge, this association has been reported only once in patients with autoimmune thyroid disease. Here we describe a patient presenting with a severe hemorrhagic disorder due to Factor VIIIc antibody in whom biochemical screening for thyroid diseases led to a diagnosis of hyperthyroid Graves' disease not associated to overt clinical features. This case underlines the importance of carrying out a complete screening for autoimmunity, including thyroid autoimmune disease, in all patients with apparently isolated serum Factor VIIIc inhibitors.

Antithyroid Agents↗

Multiple sclerosis and multiple sclerosis-associated retrovirus in Sardinia.

The island of Sardinia has a high and increasing incidence of multiple sclerosis (MS). In a search for environmental factors that may account for this anomalously high incidence, we looked for evidence of multiple sclerosis-associated retrovirus (MSRV) that has previously been found in the plasma and cerebrospinal fluid of MS patients. We studied 25 MS patients and 25 matched healthy controls of ascertained Sardinian lineage. Blood samples were processed for extracellular RNA extraction. RNAs underwent reverse transcription/nested polymerase chain reaction (RT-PCR) with primers specific for MRSV-pol gene. We found a striking correlation between MSRV positivity and MS disease, but the virus was found also only in controls (100% and 12% respectively; Fisher's exact test, p<0.00001). It is unclear whether MSRV exerts any pathogenic role in MS. It is possible that this is simply an epiphenomenon, but even then, it may constitute a diagnostic marker.

Female↗

Are prothrombin fragment 1 + 2 and thrombin-antithrombin complexes useful in the management of oral anticoagulant therapy?

We investigated the behavior of prothrombin fragment F1 + 2 and thrombin-antithrombin complexes in 70 patients treated with chronic anticoagulant therapy. Moreover, in a longitudinal study 37 patients were evaluated twice and 16 patients three times. Twenty-eight age- and sex-matched healthy subjects were also studied as a control group. Prothrombin fragment F1 + 2 or thrombin-antithrombin values among patients with different International Normalized Ratios, nor in the same patients studied two or three times. Our results confirm that oral anticoagulant treatment can effectively reduce thrombin activity. However, strong anticoagulation does not induce a further significant decrease in fragment F1 + 2 values. Therefore, we feel measurement of fragment F1 + 2 might be less useful than thought in optimizing oral anticoagulant therapy.

Administration, Oral↗

Is there a hypercoagulable state in military fighter pilots?

BACKGROUND: A hypercoagulable state is associated with an increased incidence of cardiovascular disease, the most important cause of permanent grounding of flying personnel. HYPOTHESIS: The aim of our study was to investigate whether a hypercoagulable state is present in jet pilots, and whether it can be due to flight activity. METHOD: To this purpose we studied Fibrinopeptide A (FPA), Thrombin-Antithrombin complexes (TAT) and D-Dimer (DD), sensitive biochemical markers of blood coagulation and fibrinolysis activation, in 10 jet pilots after a standardized training flight mission, and in a control group. Also evaluated before flight were 6 jet pilots. RESULTS: We were able to show increased thrombin and plasmin activity both in jet pilots compared to the control group, and after flight in the 6 pilots who were evaluated twice. CONCLUSION: We conclude that a hypercoagulable state due to flight activity is present in jet pilots after flight. Possible mechanisms involve an effect of psycho-physical stress mediated by a neuroendocrine response to flight activity, or an effect of chronic +Gz exposure on cardiovascular structure and function.

Adult↗

Activation of blood coagulation and fibrinolysis in Graves' disease.

We studied blood coagulation and fibrinolysis activities in hyperthyroidism before and after methimazole or 131I. Fibrinopeptide A and B beta 15-42, in vivo indicators of thrombin and plasmin activity, were measured by RIA, while fibrinogen by the Clauss method. We studied 50 patients, affected by toxic diffuse goiter. We evaluated 21 of them before and after treatment. Fibrinogen, fibrinopeptide A, and B beta 15-42 were higher in patients than in controls (p less than 0.0001). There was no difference in fibrinopeptide A nor in B beta 15-42 before or after treatment. In euthyroidism fibrinogen returned to normal values. Inflammation of the thyroid gland secondary to autoimmunity may activate blood coagulation by release of tissue factor. High fibrinogen before treatment may be explained as an aspecific response. Since it persists in euthyroidism, autoimmunity could account for high fibrinopeptide A and B beta 15-42 aftertreatment.

Adolescent↗

Bleeding time is prolonged during oral anticoagulant therapy.

We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular "bleeding factor".

Administration, Oral↗