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Biomedical subjects

A Conti

Publications and source records attributed to A Conti.

At least 163 records · Page 9Linked to original sources
PubMed1993

Neuroimmunotherapy of advanced solid neoplasms with single evening subcutaneous injection of low-dose interleukin-2 and melatonin: preliminary results.

On the basis of the demonstrated existence of immunoneuroendocrine interactions and on the previously observed synergistic action between the pineal hormone melatonin (MLT) and interleukin-2 (IL-2), we have designed a neuroimmunotherapeutic combination consisting of low-dose IL-2 and MLT in the treatment of advanced solid neoplasms. The study included 24 patients with advanced solid tumours (non-small cell lung cancer 9; colorectal cancer 7; gastric cancer 3; breast cancer 2; cancer of pancreas 1; hepatocarcinoma 1; unknown primary tumour 1), 21 of whom showed distant organ metastases. Not all patients responded to previous chemotherapies, or had tumours for which no standard therapy was available. Moreover, not all patients were able to tolerate IL-2 immunotherapy at the conventional doses. IL-2 was given subcutaneously at a dose of 3 x 10(6) U/day at 8:00 p.m. for 6 days/week for 4 weeks. MLT was given orally at a dose of 50 mg at 8:00 p.m. every day, starting 7 days before IL-2 injection. In non-progressed patients, a second cycle was given after a 21-day rest period. A partial response was seen in 3/24 patients (lung 2; stomach 1; duration: 11, 4, 4 months, respectively). Moreover, a minimal response (duration: 8+ months) was seen in 1 lung cancer patient. Stable disease was obtained in 14/24 patients (median duration: 6+ months), while the remaining 6 patients progressed. An improvement in performance status was seen in 7/24 patients. No important toxicity was observed. Mean eosinophil and lymphocyte levels significantly increased during the immunotherapy, and their rise was significantly higher in patients with response or stable disease than in those with progressive disease. These preliminary results show that neuroimmunotherapy with low-dose IL-2 and the pineal hormone MLT is a biologically active and well tolerated strategy, capable of determining an apparent control of tumour growth in patients with advanced solid neoplasms, for whom no standard effective therapy is available.

Adult↗
PubMed1993

Plasma levels of brain natriuretic peptide in healthy subjects and patients with essential hypertension: response to posture.

1. To examine whether posture-induced changes in central volume affect brain natriuretic peptide secretion, plasma levels of human brain natriuretic peptide-32-like immunoreactivity (hBNP-32-li) were measured by radioimmunoassay in 11 healthy subjects and 20 patients with essential hypertension after 15 min supine, 15 min sitting and 15 min with the legs raised at 60 degrees, together with plasma atrial natriuretic peptide concentration, plasma renin activity and plasma aldosterone concentration. 2. In the supine position, the plasma hBNP-32-li level was 1.57 +/- 0.10 fmol/ml in healthy subjects and significantly higher in hypertensive patients (2.39 +/- 0.13 fmol/ml, P < 0.001). In both groups, plasma hBNP-32-li level significantly (P < 0.001) decreased when sitting (normotensive, 1.22 +/- 0.08 fmol/ml; hypertensive, 1.85 +/- 0.15 fmol/ml, P < 0.001 versus normotensive) and increased again after leg raising (normotensive, 2.13 +/- 0.12 fmol/ml; P < 0.002 versus resting; hypertensive, 2.84 +/- 0.16 fmol/min, P < 0.001 versus resting, P < 0.025 versus normotensive). 3. The plasma atrial natriuretic peptide concentration showed similar behaviour to the plasma hBNP-32-li, whereas plasma renin activity and plasma aldosterone concentration increased during sitting and decreased during leg raising in both healthy subjects and hypertensive patients, who had significantly higher plasma aldosterone levels when supine and sitting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone.

OBJECTIVE: There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release. DESIGN: The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 micrograms i.v. bolus). Study 2: GHRH (100 micrograms i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100 micrograms i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 micrograms i.v. bolus) of GHRH. SUBJECTS: Four groups of eight normal male subjects, ages 22-35 years, were randomly assigned to each protocol. MEASUREMENTS: Growth hormone was measured by RIA at 15-minute intervals. RESULTS: Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100 micrograms) or submaximal (3 micrograms) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH. CONCLUSIONS: Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established.

Administration, Oral↗
PubMed1993

New markers of bone and collagen turnover in children and adults with growth hormone deficiency.

Serum bone Gla protein (BGP), a marker of osteoblastic function, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a marker of bone resorption, and serum aminoterminal propeptide of type III procollagen (PIIINP) levels, an index of collagen synthesis, were determined in seven children and eight adults with congenital growth hormone deficiency (GHD). In children with GHD, serum BGP (mean +/- s.e.: 12.9 +/- 0.7 ng/ml), ICTP (8.3 +/- 1.3 ng/ml) and PIINP (3.5 +/- 0.5 ng/ml) levels were significantly lower (P < 0.001) than those recorded in normal children (BGP 18.9 +/- 0.8 ng/ml, ICTP 14.4 +/- 0.5 ng/ml and PIIINP 6.7 +/- 0.7 ng/ml). Total alkaline phosphatase (184.7 +/- 13.4 IU/l) and bone alkaline phosphatase (77.8 +/- 4.1 IU/l) levels were also significantly lower (P < 0.0001) than in controls (338.1 +/- 14.9 IU/l and 181.0 +/- 7.8 IU/l, respectively). Serum BGP, ICTP and PIIINP levels were not significantly correlated with height velocity values. In adults with GHD, mean BGP levels (3.8 +/- 0.3 ng/ml) were significantly lower (P < 0.0001) than those recorded in normals (5.4 +/- 0.1 ng/ml). On the contrary, serum ICTP levels were similar to those found in controls (patients: 4.7 +/- 0.8 ng/ml vs normals: 4.1 +/- 0.3 ng/ml), suggesting the presence of a normal resorption activity associated with a reduced osteoblastic function. This finding was also confirmed by the presence of reduced bone alkaline phosphatase levels (GHD: 44.9 +/- 6.9 IU/I vs controls: 58.3 +/- 2.0 IU/I; P<0.02), while the less specific total alkaline phosphatase levels (119.5 +/- 14.8 IU/I) were similar to those recorded in normal subjects (122.3 +/- 4.0 IU/I). Serum PIIINP levels (3.7 +/- 0.6 ng/ml) were similar to those recorded in normals (3.2 +/- 0.2 ng/ml), suggesting that in adulthood the collagen turnover is not negatively influenced by the chronic GHD. No significant correlations were found between BGP/ICTP/PIIINP and IGF-I levels. In conclusion, our data show that in children with GHD the lack of GH insulin-like growth factor-I (IGF-I) effects on bone and collagen turnover is associated with a significant reduction of bone turnover (low bone formation plus low bone resoRption) and collagen synthesis. On the contrary, adult GHD seems to exert less relevant effects on bone and collagen turnover, probably due to the fact that in adult life further hormones or local factors might partially counteract the negative consequences of chronic GH-IGF-I deficiency.

Adult↗
PubMed1993

Extinction of insulin-like growth factor II gene expression in intratypic hybrids of rat liver cells.

The expression of the developmentally regulated insulin-like growth factor II (IGF-II) gene has been studied in somatic cell hybrids derived from rat liver cells. BRL3A cells, dedifferentiated variants of rat hepatocytes, producing high levels of IGF-II, were fused to BRL30E or FAO cells of the same embryonic lineage but not expressing detectable levels of IGF-II mRNA. We report here that the IGF-II gene is subject to extinction, since its specific RNA levels are decreased both in heterokaryons and stable cell hybrids. Transcriptional analysis in isolated nuclei from parental and hybrid cells showed that the IGF-II gene is transcribed at a similar rate in all cell types. Likewise, the stability of IGF-II cytoplasmic mRNA was equivalent in the high-expressing parental cells and in the hybrids. In contrast, the distribution of IGF-II mRNA between the nuclear and the cytoplasmic compartments differed markedly in parental and hybrid cell lines. The data presented show that the expression of the IGF-II gene is subject to a dominant negative control and suggest that the phenomenon involves mechanisms that operate at the posttranscriptional level.

Animals↗
PubMed1992

Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.

On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.

Adult↗
PubMed1992

Costimulation of T cell receptor/CD3-mediated activation of resting human CD4+ T cells by leukocyte function-associated antigen-1 ligand intercellular cell adhesion molecule-1 involves prolonged inositol phospholipid hydrolysis and sustained increase of intracellular Ca2+ levels.

Activation of resting human CD4+ T cells mediated by mAb ligation of the TCR/CD3 complex requires costimulatory signals to result in proliferation; these can be provided by intercellular cell adhesion molecule-1 (ICAM-1, CD54) a natural ligand of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18). We analyzed early signaling events involved in T cell activation to determine the contribution by the LFA-1/ICAM-1 interaction. We studied in detail the hydrolysis of phosphatidylinositol(4,5)bisphosphate and intracellular levels of free Ca2+ during stimulation with beads coated with the CD3 mAb OKT3 alone or in combination with purified ICAM-1 protein. Our investigations show no response to LFA-1/ICAM-1 alone, but that costimulation by LFA-1/CAM-1 interaction induces prolonged inositol phospholipid hydrolysis (up to 4 h), resulting in generation of both inositol(1,4,5)phosphate3 and inositol(1,3,4,5)phosphate4 and their derivatives. Based on studies with cycloheximide, this costimulatory effect of prolonged inositol phospholipid hydrolysis appears dependent in part on de novo protein synthesis. A sustained increase in intracellular levels of free Ca2+ level is also observed after LFA-1/ICAM-1 costimulation, which is at least partly dependent on extracellular sources of Ca2+. Kinetic studies indicate that costimulation requires a minimal period of 4 h of LFA-1/ICAM-1 interaction to provide maximal costimulation for OKT3-mediated T cell proliferation. Thus, the necessary costimulation required for OKT3-mediated proliferation in this model system may be provided by an extended LFA-1/ICAM-1 interaction that in combination with OKT3 mAb leads to signal-transducing events, resulting in prolonged phospholipase C activation and phosphatidylinositol(4,5)bisphosphate hydrolysis, and a sustained increase in intracellular levels of free Ca2+.

CD4-Positive T-Lymphocytes↗
PubMed1992

Microfilament assembly modulates phospholipase C-mediated signal transduction by the TCR/CD3 in murine T helper lymphocytes.

Cytoskeletal involvement in the response to TCR/CD3 ligation and in signal transduction was investigated in a murine Th cell type 2 clone. Cells coated with the hamster anti-CD3 mAb, 145-2C11 (2C11 mAb), and exposed to goat anti-hamster demonstrated an increase in polymerized actin as well as an increase in inositol phospholipid hydrolysis mediated by activation of phospholipase C. Pretreatment with cytochalasins (Cyt) (D or B), drugs that interact with cellular actin, prevented actin polymerization, and augmented the initial rate and total amount of inositol phosphates produced. Drugs modifying microtubule function were ineffective. The intracellular Ca2+ rise attributed to InsP3 and InsP4 generated in response to CD3 perturbation was augmented by CytD. CytD treatment did not affect inositol phosphate generation resulting from the stimulation of guanine nucleotide-binding proteins with aluminium tetrafluoride, indicating that the action of CytD was specific for receptor-mediated inositol phospholipids. CytD decreased the rate of anti-CD3-induced receptor internalization. These data suggest that the assembly of microfilaments plays a role in CD3 internalization and that a CytD-sensitive mechanism uncouples the TCR/CD3 complex from phospholipase C-mediated signaling.

Actin Cytoskeleton↗
PubMed1992

Effect of adrenergic agents on hematopoiesis after syngeneic bone marrow transplantation in mice.

We show that adrenergic agents modulate hematopoietic reconstitution after syngeneic bone marrow transplantation (BMT) in mice. Chemical sympathectomy by 6-hydroxydopamine (6-OHDA) significantly increased the number of peripheral blood leukocytes after syngeneic BMT. The alpha 1-adrenergic antagonist prazosin mimicked and extended the effect of 6-OHDA, with an additional rapid and significant increase of platelets, marrow granulocyte-macrophage colony-forming units, and nucleated spleen cells. Differential leukocyte counts and spleen histology from prazosin-treated mice confirmed that myelopoiesis was greatly enhanced and accelerated. In contrast, the beta-adrenergic blocker propranolol abolished the prazosin-induced increase of platelets. The detailed mechanisms by which prazosin exerts these interesting effects remain to be elucidated.

Animals↗
PubMed1992

Isolation of a new ligand-carrying casein fragment from bovine mammary gland microsomes.

Whilst looking for components involved in retinol metabolism in secreting mammary gland cells, a 12 kDa protein was isolated. This protein had bound a ligand with characteristics of retinol. N-Terminal sequencing and amino acid analysis showed that this protein is highly homologous with an alpha-s1-casein fragment. No ligand was found for beta-lactoglobulin, previously thought to be involved in retinol metabolism.

Amino Acid Sequence↗
PubMed1992

Increased intracellular cyclic AMP inhibits inositol phospholipid hydrolysis induced by perturbation of the T cell receptor/CD3 complex but not by G-protein stimulation. Association with protein kinase A-mediated phosphorylation of phospholipase C-gamma 1.

Modulation of inositol phospholipid (InsPL) hydrolysis in response to increasing intracellular concentrations of cyclic AMP (cAMP) was studied in a murine T helper type II (Th2) lymphocyte clone, 8-5-5. Intact 8-5-5 cells produced maximal amounts of cAMP in response to prostaglandin E2 (PGE2), cholera toxin (CTx) or 7 beta-deacetyl-7 beta-(gamma-N-methylpiperazino)butyryl forskolin (dmpb-forskolin). cAMP generation reached a plateau after 5 min of treatment with dmpb-forskolin (300 microM) or PGE2 (1 microM), but required 60 min of treatment with CTx (1 microgram/ml). Preincubation of 8-5-5 cells with 1 microM-PGE2 or 300 microM-dmpb-forskolin (10 min at 37 degrees C) or with 1 microgram of CTx/ml (60 min at 37 degrees C) completely inhibited InsPL hydrolysis induced by perturbation of the T cell receptor (TCR)/CD3 complex with the monoclonal antibody 145.2C11. Preincubation with the cAMP analogue 8-bromo-cyclic AMP (8-Br-cAMP) also inhibited InsPL hydrolysis. Tetanolysin-permeabilized 8-5-5 cells produced cAMP in response to PGE2, dmpb-forskolin and guanosine 5'-[gamma-thio]triphosphate (GTP[S]), a non-cell-permeating, non-hydrolysable analogue of GTP that directly activates G-proteins. No inhibition of TCR/CD3-induced InsPL hydrolysis was observed under these conditions. InsPL hydrolysis was also unaffected when permeabilized cells were incubated with up to 10 mM-8-Br-cAMP, suggesting that permeabilized cells lost (a) soluble effector molecule(s) involved in mediating the inhibitory effect observed in intact cells. Treatment of 8-5-5 cells with dmpb-forskolin or CTx prior to permeabilization resulted in inhibition of TCR/CD3-induced InsPL hydrolysis, but did not affect InsPL hydrolysis induced via G-protein stimulation with GTP[S]. Treatment of permeabilized 8-5-5 cells with purified cAMP-dependent protein kinase (PKA) resulted in inhibition of TCR/CD3- but not GTP[S]-induced InsPL hydrolysis. This effect was associated with phosphorylation of phospholipase (PLC)-gamma 1 in the absence of phosphorylation of components of the TCR/CD3 complex. These results suggest that PKA-mediated phosphorylation of PLC may regulate TCR/CD3-induced InsPL hydrolysis.

Animals↗
PubMed1992

Role of pineal melatonin and melatonin-induced-immuno-opioids in murine leukemogenesis.

The relationship between the pineal gland, melatonin and melatonin-induced-immuno-opioids with the response of C57Bl/6 mice to A-RadLV induced T cell lymphomas was investigated. Mice were injected at day 0 with A-RadLV and from day 10 they were treated chronically with melatonin 4 mg/kg body weight, naltrexone 1 mg/kg or phosphate buffered saline, throughout the experiment. In another protocol, groups of mice were a) surgical pinealectomized at day-14, b) functional pinealectomized (24:24 hours light) from day -20 and c) sham pinealectomized. At day 0 each group was inoculated intrathymically with A-RadLV. The results show that melatonin accelerated (p < 0.005) leukemogenesis whereas the surgical pinealectomy and the functional pinealectomy delayed it (p < 0.005 and p < 0.01). Moreover, the action of melatonin was blocked by naltrexone (p < 0.005), indicating the involvement of melatonin-induced-immuno-opioids in the development of the lymphomas.

Animals↗
PubMed1992

The amino-acid sequence of two isoforms of alpha-lactalbumin from donkey (Equus asinus) milk is identical.

The complete primary structure of donkey alpha-lactalbumin A and B has been determined by sequencing of the peptides obtained after tryptic, Glu-C proteinase or cyanogen bromide cleavage. Although preparative purification of alpha-lactalbumin by flat-bed isoelectric focusing gave two protein fractions A and B, their amino-acid sequence revealed no differences. Donkey alpha-lactalbumin shows two, four and five differences in comparison to the horse alpha-lactalbumin A, B and C. Thus donkey alpha-lactalbumin is homogeneous and belongs to the horse A-type variant.

Amino Acid Sequence↗
PubMed1992

[Radiodiagnosis of ureteral and bladder hernia. A further case contribution].

The radiologic features of ureteral and bladder hernias are poorly known. These hernias can be located in 5 compartments, being extremely rare in 2 of them--the chest and lumbar sectors, where only 2 cases are reported in literature. In the other 3 compartments--i.e., ischiatic, crural and inguinal sectors--bladder and ureteral hernias are less uncommon findings. Over a relatively short period of time, 5 bladder hernias were observed--3 ischiatic, 1 inguino-scrotal and 1 crural cases--and 1 double ureteral hernia, which was inguinal on the right-hand side and ischiatic on the left-hand side. Thus, we reviewed the main urographic and cystographic signs on the basis of a previous report by one of us. In discussing the new cases, we emphasize the importance of a few typical diagnostic signs, which follow: asymmetry and anomalous location of herniated organs, ureter protrusion beyond the pelvic bones outline, the presence of ureteral spiral ("curlicue sign"), and bladder walls indentation.

Female↗
PubMed1991

[Postoperative mortality and morbidity of patients in their late eighties].

During the 12 year period, 1978-1989, 555 operations were performed at the Department of Clinica Chirurgica III of the University of Bologna, on 530 patients greater than 80 years old at the time of surgery. These were the indications for surgical procedure in these patients: malignant neoplasm of digestive system (243), other diseases of the digestive system (111), abdominal wall hernia (74), biliary disease (77), miscellaneous (50). The purpose of this paper is to define the role of surgery in patients over 80 years old. An acute complication required an emergency operation in 295 cases (53%). In all the other cases (260, 47%) an elective operation was performed. There were 63 deaths with an operative mortality rate of 11%. Among the patients who underwent elective surgery there were 11 deaths (4%); in the emergency group there were 52 deaths (17.6%). These rates were found to be statistically significant. The overall morbidity rate was 37.6% in the elective group and 49% in the emergency group. Also these rates were found to have a statistic significance. Then we have compared morbidity and operative mortality of over-eighty years old patients with the ones of two younger groups of patients: I group (age greater than 80 years), II group (age 65-80 years), III group (age less than 65 years). Patients of the three groups had undergone identical surgical operations for the same pathology. The operative mortality was 11% in the I group, 5.2% in the II group and 1.4% in the III group. The morbidity was 46%, 30% and 17% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

DNA binding properties of a new class of linked anthramycin analogs.

We have investigated the DNA binding properties of the anthramycin analogues 4, 5, and 6 using fluorescence spectroscopy. A considerable fluorescence enhancement occurs when pyrrolo [1,4] benzodiazepines (P[1,4]Bs) are covalently attached to duplex DNA, which was used to show that neither the presence of RNA, single-stranded DNA, or protein had any effect on the degree of fluorescence enhancement resulting from the incubation of 5 and 6 with DNA. The enhancement was found to be dependent on the presence of the imine functionality in each of the compounds. A wavelength of 320 nm was used to excite the chromophore and its emission wavelength maximum was 420 nm. Additionally, we have discovered that the P[1,4]B ring system exhibits exceptionally favorable fluorescence polarization anisotropy (FPA) decay characteristics. For these more detailed fluorescence measurements, we used the structurally simpler analogue 4,. The time resolved maximum FPA for 4 in glycerol at 25 degrees C is 0.28. This result indicates that the P[1,4]B family of antibiotics could serve as sensitive probes of DNA dynamics in the 0.1 to 35 ns time scale.

Animals↗