Biomedical subjects
Publications and source records attributed to G Milanesi.
Bacillus subtilis bacteriophage SPP-I has separable complementary DNA strands. Fragments of nascent DNA isolated a very short time after phage infection show that these short chains are complementary to both phage DNA strands, as observed by hybridization techniques.
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The envelope gene of hepatitis B virus (HBV) consists of a large open reading frame which codes 3 different polypeptides by the variable use of 3 contiguous regions: the pre-S1, pre-S2 and S regions. The protein coded by the entire sequence (L protein) is identified by its unique pre-S1 epitopes and has a role in virus assembly and secretion. Pre-S1 antigens are expressed preferentially on virions and are less abundant, but present, on subviral particles. The pre-S2 sequence contains a species-specific receptor for polyalbumin, which has been implicated in virus binding to hepatocytes. Methods have been recently developed to measure pre-S1 and pre-S2 levels in serum and available data indicate that these assays may be useful in prognostic assessment of acute hepatitis B and to measure virus replication in chronic infection, although further studies are certainly needed to define specificity and sensitivity compared to conventional HBV markers. Both pre-S1 and pre-S2 are highly immunogenic and elicit anti-pre-S antibodies. Methods for detection of anti-pre-S in human sera have proved difficult to be developed due to unspecific reaction of serum components with pre-S sequences and epitope variability of the immune response in humans. Anti-pre-S2 seems a marker of recovery from acute infection, while evidence of its involvement in liver damage is weak. Both anti-pre-S2 and anti-pre-S1, but we have limited information on the latter, may be involved in virus neutralization. These issues are particularly relevant for future HB vaccine development, as it is proposed that inclusion of strategic pre-S sequences could increase efficacy.
The aim of this phase IV study was to assess the tolerability and efficacy of acipimox, a lipid-lowering drug, in 3009 type II diabetic out-patients with types II and IV hyperlipoproteinaemia. The study was carried out by 150 Italian diabetes centres. Acipimox was given at the dosage of one capsule (250 mg), two or three times daily for at least 2 months. Acipimox produced a mean fall of 43% in serum triglycerides and of 18% in total serum cholesterol levels compared with baseline. The lipid-lowering effect was present throughout treatment, but was most pronounced at the end of treatment. An increase in the serum concentration of high density lipoprotein cholesterol (15%) was also observed at the end of the trial. Fasting blood glucose and glycosylated haemoglobin levels showed a slight reduction during the study. Adverse events were reported in 263 (8.8%) cases and 165 (5.4%) patients discontinued the treatment. The female trial population showed a nearly two-fold greater incidence of adverse events than the males. In the majority of cases the adverse events experienced by patients were transient episodes of flushing and mild gastro-intestinal disturbances (e.g. gastric pain and pyrexia).
Platelets are involved in the progression of coronary atherosclerosis as well as in the development of the acute precipitating event. Recently, it has been shown that normal subjects present increased platelet aggregation between 6.00 a.m. and 9.00 a.m.; epidemiological studies have shown a higher incidence of myocardial infarction between these times. This study evaluated, by an impedence method using whole blood, platelet aggregation induced by ADP (3 microM) and collagen (2 microM/ml). Measurements were made at 6.00 a.m., 9.00 a.m. and 12.00 noon, the day before and the day after evening administration of 200 mg indobufen, a platelet aggregation inhibitor, in 12 patients with ischaemic heart disease. Patients showed a significant increase of platelet aggregation between 6.00 a.m. and 9.00 a.m. which was inhibited by the prior evening administration of indobufen.
A randomized clinical trial was undertaken to assess the efficacy of indobufen in inhibiting platelet adhesiveness in carotid thromboendarterectomy. The patients were treated under double-blind conditions with indobufen and with placebo, and were then assessed by means of scintigraphy with labelled platelets, ultrasonic tomography and angiography for a minimum follow-up period of 6 months. Haematological and clinical assessments were also performed. The results of the study suggest that platelet accumulation in carotid endarterectomy may be an early sign of restenosis; anti-aggregant treatment with indobufen carried out at an early stage prior to surgery inhibited platelet accumulation. The final result showed that anti-aggregant treatment had a positive influence on the short- and medium-term outcome of carotid endarterectomy.
Vitamin D receptor (VDR) has important effects not only on physiological processes related to Ca2+ metabolism but also on cell growth and differentiation. VDR is a member of the Steroid-Thyroid Receptors Superfamily (STRS). Work in our and other laboratories has shown that several other members of the STRS (androgen, estrogen, glucocorticoid, and progesterone receptors) are present in astrocytomas and glioblastomas. We now report the finding of VDR-like mRNA in human anaplastic astrocytomas and glioblastomas. VDR mRNA levels, as determined by a method, developed in our laboratory, based on the polymerase chain reaction, are significantly higher in glioblastomas compared to both low and high grade astrocytomas. We discuss the biological and clinical implications of our results.
The present study was undertaken in patients subjected to endarterectomy for extracranial carotid stenosis in order to verify the efficacy and the safety of medical treatment with indobufen (2-[4-(1-oxo-2-isoindolinyl)-phenyl] butyric acid), a drug which has been successfully used in the long-term treatment of cardiovascular ischemic diseases, and which showed a significant antiplatelet effect. One hundred thirty-eight patients entered into the study with previous diagnosis of cerebrovascular ischemic event within 3 months before surgery. Patients were treated after surgery with indobufen 400 mg/die/orally in the first 2 months after discharge and than 200 mg/die/orally. The planned duration of medical treatment was 24 months. Any patient interrupting the medical treatment for a cumulative period greater than 30 days/year was excluded from the analysis; the end points of the study were considered death and the occurrence of disabling stroke. Eleven patients were considered as dropped out because of treatment interruption. The operative (at 1 month after surgery) mortality rate was 0.79%. The cumulative operative mortality and morbidity rate was estimated in 2.37%. The mean follow-up period was 6 months and the cumulative mortality rate at 36 months was estimated in 7.14%. The cumulative risk/year of TIA or ischemic stroke is higher than the risk for myocardial infarction, but the long-term mortality rate mainly depends on the latter complication which occurred later. Treatment with indobufen after carotid surgery seems to be effective as far it was restricted to an homogeneous group of patients presenting symptomatic extracranial carotid disease.
We studied the expression of ten genes (encoding the receptors for glucocorticoid, mineralocorticoid, progesterone, androgen, estrogen, thyroid, retinoid acid, vitamin D) belonging to the steroid-thyroid hormone receptor superfamily (STRS) in 12 neuroepithelial tumors, 12 meningiomas and 2 human glioblastoma cell lines. Our method, based on the polymerase chain reaction, allowed the simultaneous amplification of cDNAs of the STRS genes. On average, 7 STRS genes were simultaneously expressed in each sample. Our study indicates that many STRS gene are commonly co-expressed in human CNS tumors. The importance of our results for the ongoing and proposed hormonal treatment trials is discussed.