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Biomedical subjects

G Galli

Publications and source records attributed to G Galli.

At least 181 records · Page 10Linked to original sources
PubMed1988

Poly(A) site choice rather than splice site choice governs the regulated production of IgM heavy-chain RNAs.

Alternative processing of the immunoglobulin mu primary transcript results in regulated production of mRNAs encoding the secreted (microseconds) and membrane-bound (micro m) form of IgM heavy chain during B-cell development. To elucidate the basis for this control, we analyzed the expression of altered forms of the mu transcription unit. Deletion of intron sequence between the microseconds and micro m exons, which reduces the distance between the two poly(A) sites as well as the distance between micro m splice sites, enhances production of micro m RNA. Correct expression is restored by insertion of heterologous sequences, demonstrating that spacing is indeed the critical aspect. The altered spacing appears to affect poly(A) site usage rather than splice site usage, since it was the distance between the poly(A) sites rather than the distance between splice sites that was found to be decisive. Finally, removal of either the C mu 4 splice donor or the m1 splice acceptor, thus eliminating normal micro m splicing, does not increase usage of the microseconds poly(A) site. We therefore conclude that the major factor in determining the ratio of microseconds to micro m is a poly(A) site choice rather than a splicing choice.

Gene Expression Regulation↗
PubMed1988

Nonsteroidal antiinflammatory drugs aggravate acute myocardial ischemia in the perfused rabbit heart: a role for prostacyclin.

Myocardial ischemia was induced in perfused paced isovolumic left heart preparation of the rabbit by reducing, for a period of 40 min, the flow rate from 20 ml/min to 0.2 ml/min (severe model) and to 1 ml/min (moderate model). The relationship between prostaglandin biosynthesis and cardiac ischemic damage was evaluated in the two experimental models. The results obtained indicate that the total amount of 6-keto-PGF1 alpha generated increases with the severity of the ischemia, particularly during the 20 min of reperfusion (moderate model 81.8 +/- 13.7 ng: severe model 375 +/- 102 ng). The inhibition of the prostaglandin synthesis, prostaglandin-E2, and 6-keto-prostaglandin-F1 alpha (PGE2 and 6-keto-PGF1 alpha levels below the detection limits) by Aspirin (20 micrograms/ml) and Indomethacin (1 microgram/ml) in moderate myocardial ischemia was correlated with greater increments in resting diastolic tension (nearly 100% and 40%, respectively). This phenomenon was also associated to a further decrease on cardiac contractility and increase on coronary perfusion pressure upon reperfusion. On the contrary drugs which stimulated prostaglandin generation in myocardial tissue, such as Defibrotide (400 micrograms/ml), completely protected the organ from ischemia. U-60257 (3 micrograms/ml) and FPL-55712 (2 micrograms/ml), compounds, which respectively inhibits biosynthesis and the effects of leukotrienes, displayed a beneficial activity on this moderate model of ischemia. The present data suggests that the deleterious effect of nonsteroidal antiinflammatory drugs in low flow myocardial ischemia and reperfusion damage may be associated with removal of PGI2 and PGE2 from ischemic myocardium.

Animals↗
PubMed1988

Proinflammatory lipoxygenase products from peripheral mononuclear cells in patients with rheumatoid arthritis.

The formation of 5-lipoxygenase products (5-hydroxyeicosatetraenoic acid [5-HETE], leukotriene B4 [LTB4], and leukotriene C4 [LTC4]) by polymorphonuclear and mononuclear leukocytes isolated from peripheral blood of patients with rheumatoid arthritis was evaluated and compared with the data obtained from a group of control subjects. Although the levels of arachidonic acid metabolites via 5-lipoxygenase pathway by stimulated polymorphonuclear cells were comparable between patients and controls, mononuclear leukocytes from patients synthesized, when stimulated, significantly greater amounts of 5-HETE, LTB4, and LTC4 than did cells isolated from normal subjects. In addition, the release of superoxide anion, stimulated by either a particulate or a soluble stimulus, was increased in mononuclear cells from patients. The enhanced capacity of peripheral mononuclear leukocytes isolated from patients with rheumatoid arthritis to generate proinflammatory metabolites of arachidonic acid and oxygenated species with bactericidal and tissue-damaging properties may contribute to the pathogenesis of this complex disease.

Arthritis, Rheumatoid↗
PubMed1988

Leachability of a new plasticizer tri-(2-ethylhexyl)-trimellitate from haemodialysis tubing.

In two groups of patients on chronic haemodialysis treatment, the common PVC-DEHP blood tubing was replaced with tubing containing tri-(2-ethylhexyl)-trimellate (TOTM) as plasticizer. The aim of the present study was to measure the amount of TOTM and/or its metabolites (TAE s) in plasma, resulting from TOTM that might leach from the dialysis tubes. The arterial levels of TAE s at the start of the dialysis sessions were monitored by Selected Ion Monitoring (SIM) analysis once a week for a period of 42 days. A gradual decrease in TAE was observed during the first 21 days of the haemodialysis treatment with the PVC-TOTM tubes. After three weeks, the TAE levels remained constant until the end of the study. On day 120 of the haemodialysis treatment, the plasma TAE concentrations from the inflow and outflow tubes of the dialyzer were monitored during a single haemodialysis session at different times after starting dialysis. At the beginning of the dialysis session, the mean concentration of TAE was 55.81 +/- 14.98 ng/ml (mean +/- standard error), while at the end the levels were 73.34 +/- 17.05 ng/ml. There were no significant differences between venous and arterial sampling points in the trimellitic ester concentrations. Less TOTM is apparently leached from haemodialysis than DEHP. TOTM can be recommended as an alternative plasticizer to DEHP, but its possible toxicity in humans should be investigated before it can be used routinely.

Adult↗
PubMed1988

Prostaglandin synthetase inhibition and formation of lipoxygenase products in immunologically challenged normal human lung parenchyma.

Normal human lung parenchyma, passively sensitized with an hyperimmune serum, releases eicosanoids from the cyclo-oxygenase pathway and from different lipoxygenases (5-, 12-, 15-HETE) upon anti-IgE challenge. Prostaglandin D2 represents almost 50% of the total arachidonate metabolites whereas, among sulphidopeptide leukotrienes, LTE4 is the one present in larger amounts. Pretreatment of the passively sensitized tissue with indomethacin (1.5 X 10(-5) M) inhibits cyclo-oxygenase by more than 90% without a concomitant shift of arachidonate metabolism towards leukotriene formation.

Biological Assay↗
PubMed1988

The fate of leached di-(2-ethylhexyl)-phthalate (DEHP) in patients on chronic haemodialysis.

The fate of the plasticiser di-(2-ethylhexyl)-phthalate and/or its metabolites, phthalic acid esters (PAE), in 12 patients on chronic haemodialysis was studied. The total amount of PAE retained by the patients was estimated by monitoring the plasma concentrations from the inflow and outflow tubes of the dialyzer during 4-h dialysis sessions. There was an estimated uptake of 46 mg of PAE during a single dialysis session. The values for a volumetric factor (Vf) related to the increment in plasma PAE concentrations were found to increase during the first hour of treatment (72 litres at steady-state), and then to progressively decrease. The changes in the kinetic parameters during the dialysis session were grouped into three phases according to the fate of the plasticiser in the patient. We also monitored the plasma concentrations of PAE in the same patients for 40 days during dialysis with another kind of plasticised (tri-(2-ethylhexyl)-trimellitate [TOTM]) tubes. The PAE concentrations were similar to those found in healthy humans after about 5 weeks.

Adult↗
PubMed1988

Single dose pharmacokinetics of aminoglutethimide by a rapid SIM methodology.

The kinetics of unchanged aminoglutethimide and of its major metabolite N-acetylaminoglutethimide were investigated in healthy volunteers with a new multiple selected ion monitoring (SIM) technique. This method allows a rapid detection of both the unchanged drug and of its metabolite with a single injection and after minimal handling of the samples. This rapid method provided similar kinetic findings, compared to those described with the more time consuming high pressure liquid chromatographic (HPLC) procedure. Moreover, the SIM method allowed the detection of the N-acetylamino metabolite in plasma at longer time intervals vs. the HPLC method. Some typical features of the kinetic behavior (e.g., a discontinuity in the plasma die-away curve for both unchanged drug and metabolite), attributable to partial liver extraction, could also be more clearly observed with the new procedure. This new, rapid technique confirms that aminoglutethimide and N-acetylaminoglutethimide have very similar plasma die-away curves in subjects with a normal conjugating capacity, and that kinetic patterns or individual blood levels can be readily obtained by SIM with minimal acquisition of supplementary equipment.

Adult↗
PubMed1988

Lumbar disc herniation: diagnosis, surgical treatment, recurrence. A review of 872 operated cases.

This review is based on 972 cases treated surgically for lumbar disc herniation between 1974 and 1984. The authors discuss several problems related to this condition. The importance of the history and clinical assessment are emphasized, as well as the role of instrumental tests such as radiculography and CT scan. The authors report what they believe to be the treatment of choice to avoid recurrence, based on an analysis of two groups of patients. The first group consisted of patients in whom lumbar and radicular pain persisted after operation. The second group consisted of patients in whom these symptoms recurred after an interval of complete relief. This analysis leads to the following conclusions: 1) clinical examination is pre-eminent; CT scan and radiculography are complementary to an accurate neurological examination; 2) hemilaminectomy is the operation of choice because it is sufficient to ensure accurate exploration of both root and disc; 3) most recurrences are due to errors in diagnosis or surgical technique.

Adolescent↗
PubMed1987

Lipophilic beta-adrenoceptor antagonists stimulate cholesterol biosynthesis in human skin fibroblasts.

The effect of a series of beta-adrenoceptor antagonists on cholesterol biosynthesis was studied in vitro in normal human skin fibroblasts. Some, but not all, of the drugs studied stimulated the incorporation of [2-14C]-acetate into cell sterols in a dose-dependent manner. This effect was unrelated to beta-blocking potency, selectivity for beta 1 or beta 2 adrenoceptors and partial agonistic activity of the drugs, thus ruling out a beta-receptor mediated mechanism. A positive, statistically significant correlation was found, however, between the drug lipophilicity and the stimulation of sterol biosynthesis. Propranolol, the most effective agent in increasing [2-14C]-acetate incorporation into cellular sterols, also enhanced the conversion of 3-hydroxy-3-methylglutaryl CoA (HMGCoA) into mevalonic acid, suggesting an interference of lipophilic beta-adrenoceptor antagonists with HMHCoA-reductase, the feed-back regulated rate limiting step of cholesterol biosynthesis.

Adrenergic beta-Antagonists↗
PubMed1987

Relative position and strengths of poly(A) sites as well as transcription termination are critical to membrane versus secreted mu-chain expression during B-cell development.

During B-cell differentiation, there is a dramatic switch in the RNA products of the immunoglobulin mu heavy chain transcription unit. In the mature B cell there is roughly equal production of the microseconds and the micron RNA, whereas in the antibody-secreting plasma cell there is nearly exclusive production of the microseconds RNA. A plasmid containing the entire mu transcription unit was properly regulated when assayed by transient transfection in a B lymphoma and a plasmacytoma. In contrast, no such regulation was observed with separate plasmids that could produce only one or the other RNA. Instead, the micron poly(A) site was utilized more efficiently than the microseconds poly(A) site, irrespective of the cell type. We also found that transcription termination prior to the micron poly(A) site in plasmacytomas contributes to preferential production of microseconds RNA in these cells. Finally, reducing the distance between the two poly(A) sites improved the use of the micron site at the expense of the use of the microseconds in B lymphoma cells, suggesting a competition for a limiting factor. Such competition was not apparent in plasmacytomas. We conclude that relative poly(A) site strength and the position of the poly(A) sites within the transcription unit, coupled with a changing concentration of a limiting factor, as well as transcription termination prior to the micron poly(A) site, all play a role in determining the expression of the mu locus during B-cell development.

Animals↗
PubMed1987

Results of combined surgical and medical therapy in patients with prolactin-secreting pituitary macroadenomas.

To assess the long term effectiveness of combined sequential surgical and medical therapy in the management of prolactin-secreting pituitary macroadenomas, we followed 21 patients for 46 +/- 6 months (mean +/- SE) after diagnosis (range, 12 to 96 months). All patients underwent operation. Six were also treated with bromocriptine, 7.5 mg/day immediately after operation. A group of 15 patients with tumor sizes similar to those of the first group was followed without medical therapy until signs of regrowth of the neoplasia were evident. No patient of the combined therapy group experienced a recurrence of the disease. On the other hand, only 2 patients of the second group were recurrence-free at the end of follow-up. In the other 13 cases, adjunctive therapy had to be established for clinical and radiological evidence of tumor recurrence 26 +/- 7 months after operation. We conclude that combined sequential surgical and medical therapy may be useful in the management of macroprolactinomas. Our hypothesis must be confirmed by studies that compare patients treated with operation plus bromocriptine with patients treated with bromocriptine alone.

Adenoma↗