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Biomedical subjects

G Graziani

Publications and source records attributed to G Graziani.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of pelvic osteosarcoma.

Pelvic osteosarcoma is a very rare disease, with poor prognosis affecting young people. Since June 1987 we have observed 26 patients, F/M: 12/14, median age 23 years (range 14-55), 7 with lung metastases at diagnosis. Four patients underwent surgery as first line treatment; 4 patients received intravenous (i.v.) chemotherapy; eighteen out of 26 received 1-3 cycles of neoadjuvant chemotherapy consisting of high dose i.v. methotrexate plus leucovorin rescue, intraarterial cisplatin and i.v. epidoxorubicin. We obtained 8 PR, 9 SD, 1 PD. Hemipelvectomy has been performed in 4 cases (0%, 0%, 50%, 70% necrosis). The other 14 patients, judged not operable, received radiotherapy plus daily low doses of cisplatin. All patients have been treated with i.v. epidoxorubicin, ifosfamide, high dose methotrexate, cisplatin and etoposide. Two out of four patients who underwent surgery died at 17 and 18 months, 2 are alive and free of disease at 28+ and 17+ months from surgery. Among the 14 patients treated with radiotherapy, 9 died with a median survival of 18 months (5-22); 5 are alive with a median survival of 20 months (14-31). Although pelvic osteosarcoma has a limited cure rate at present, results could be improved in the future by means of earlier diagnosis and better combined treatment.

Adolescent↗
PubMed1992

Prevalence of hepatitis C virus antibodies in hemodialysis patients in the area of Milan.

We studied the seroprevalence of antibodies to hepatitis C virus (HCV Ab) in a cohort of 229 chronic hemodialysis patients followed by 6 Dialysis Units in the Milan area. HCV Ab was present in 51 (22.3%) of 229 examined patients. Previous blood transfusions and surgery did not clearly influence HCV seroconversion, whereas duration of dialysis treatment seems to be strictly related to HCV Ab positivity.

Adult↗
PubMed1992

Induction of Xenopus oocyte meiotic maturation by the dbl oncogene product.

The dbl oncogene was originally identified by transfection of NIH3T3 cells with DNA from a human diffuse B-cell lymphoma. The dbl oncogene product is a cytoplasmic phosphoprotein distributed between the cytosolic and cytoskeletal matrix-associated membrane fractions. Nucleotide sequence analysis has indicated that the predicted dbl product is very hydrophilic with no detectable similarity to known oncogene products. We have more recently discovered that a region of dbl essential for its transforming activity shows significant sequence similarity to a yeast cell cycle gene, CDC24, which is involved in cell polarity and bud formation in the division cycle of Saccharomyces cerevisiae. This sequence similarity suggests a possible role for dbl in cell division. We report here that the dbl oncogene product is able to induce maturation of Xenopus oocytes. Germinal vesicle breakdown (GVBD) was observed when oocytes were microinjected with the soluble fraction of SF9 insect cells infected with a dbl recombinant baculovirus as well as with the in vitro-transcribed dbl mRNA. Moreover, extracts of oocytes microinjected with dbl mRNA showed activation of H1 histone kinase activity. These findings define a new biologic activity of the dbl product and provide the opportunity to analyse dbl interactions with other components of signaling pathways involved in oocyte maturation.

Animals↗
PubMed1992

Factors affecting chronic renal failure progression: results from a multicentre trial. The Northern Italian Cooperative Study Group.

In order to evaluate the prognostic factors concerning the rate of progressive deterioration of renal function, we made an inductive analysis of the behaviour of 456 patients in a multicentre, formal prospective trial aimed at clarifying the possible role of protein restriction in retarding the progression of chronic renal insufficiency (CRI). The main clinical and laboratory findings in patients whose plasma creatinine (PCr) levels doubled in comparison with baseline randomization values or who needed dialysis within 24 months after onset of the study were compared with those of the other patients. In addition, independently of the assigned diet, we tested the main variables that might affect CRI progression (sex, systolic and diastolic blood pressure, change in body weight, hematocrit, calcium-phosphate product, proteinuria, protein catabolic rate, total cholesterol and triglycerides). We used multiple regression analyses and also plotted the mean values of these parameters in each patient against an estimate of the deterioration of chronic renal failure based on the difference between the final and the initial reciprocal of the PCr and the creatinine clearance (CCr) levels. A descriptive analysis of the behaviour of PCr in the three CRI groups and in the four underlying diseases groups was made. PCr levels at entry, underlying disease and proteinuria were prognostic factors for CRI progression. The increase in PCr was 0.0102 mg/dl/month in patients with nephrosclerosis, 0.0203 mg/dl/month in interstitial nephropathy, 0.0360 mg/dl/month in glomerulonephritis and 0.0704 mg/dl/month in polycystic kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency. Northern Italian Cooperative Study Group.

A multicentre, prospective trial was organised to clarify the role of protein restriction in the progression of chronic renal insufficiency (CRI). 456 adult patients were assigned either a low-protein diet (0.6 g/kg body weight daily; n = 226) or a "normal" controlled-protein diet (1.0 g/kg daily; n = 230) and were stratified into three groups (A-C) with increasing baseline plasma creatinine concentrations. Each patient was followed up for 2 years or until an endpoint (a doubling of the baseline plasma creatinine or a need for dialysis) was reached. The difference between the diet groups in cumulative renal survival defined by these endpoints (27 low-protein, 42 controlled-protein) was of borderline significance (p less than 0.06). The difference in renal survival between the low-protein and controlled-protein diet groups was of borderline significance in group A (0 vs 4 endpoints), significant in group B (10 vs 21 endpoints; p less than 0.025), and not significant in group C. There were no differences among the diet groups or subgroups in mean plasma creatinine concentrations, creatinine clearance, the slope of the plasma creatinine reciprocal, or mean blood pressures. Compliance was good in the controlled-protein group but poor for the low-protein diet: the difference in protein intake between the groups was substantially less than that required by the protocol. However, there was no correlation between the progression of renal failure and protein catabolic rate. These findings offer little, if any, support to the hypothesis that protein restriction retards CRI progression: careful medical care and a "normal" controlled protein intake also allow very slow progression of CRI.

Actuarial Analysis↗
PubMed1991

Requirement of phospholipase C-catalyzed hydrolysis of phosphatidylcholine for maturation of Xenopus laevis oocytes in response to insulin and ras p21.

Recent studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine both by growth factors and by the product of ras oncogene, ras p21. Also, evidence has been presented indicating that the stimulation of this phospholipid-degradative pathway is sufficient to activate mitogenesis in fibroblasts. In Xenopus laevis oocytes, microinjection of transforming ras p21 is a potent inducer of maturation, whereas microinjection of a neutralizing anti-ras p21 antibody specifically inhibits maturation induced by insulin but not by progesterone. The results presented here demonstrated that microinjection of phosphatidylcholine-hydrolyzing phospholipase C is sufficient to induce maturation of Xenopus laevis oocytes. Furthermore, microinjection of a neutralizing anti-phosphatidylcholine-hydrolyzing phospholipase C specifically blocks the maturation program induced by ras p21/insulin but not by progesterone.

Animals↗
PubMed1991

Role of GTPase activating protein in mitogenic signalling through phosphatidylcholine-hydrolysing phospholipase C.

Recent evidence has accumulated showing that activation of PLC-catalysed hydrolysis of phosphatidylcholine (PC-PLC) is a critical step in mitogenic signal transduction both in fibroblasts and in oocytes from Xenopus laevis. The products of ras genes activate PC-PLC, bind guanine nucleotides, have intrinsic GTPase activity, and are regulated by a GTPase-activating protein (GAP). It has been suggested that, in addition to its regulatory properties, GAP may also be necessary for ras function as a downstream effector molecule. In this study, evidence is presented that strongly suggests that the functional interaction between ras p21 and GAP is sufficient and necessary for activation of maturation promoting factor (MPF) H1-kinase activity in oocytes, and that PC hydrolysis is critically involved in this mechanism. Therefore, we identify GAP as a further step required for signalling through PC-PLC, and necessary for the control of oocyte maturation in response to ras p21/insulin but not to progesterone.

Animals↗
PubMed1991

Multi-fractal nature of radioactivity deposition on soil after the Chernobyl accident.

Fractal analysis is introduced in the field of environmental health physics. In particular, it is applied to the complex and inhomogeneous deposition pattern of radioactivity after the Chernobyl accident. The patchiness of 137Cs hot spots is quantified by a fractal dimension as low as 1. The problem of finding hot spots that might be of health concern is discussed.

Accidents↗
PubMed1991

Alternative splicing generates at least five different isoforms of the human basic-FGF receptor.

Fibroblast growth factors (FGFs) are polypeptide mitogens that induce the proliferation of a wide variety of cell types. Of the seven family members, the best characterized are basic and acidic FGF. In addition to their mitogenic effects, they participate in angiogenesis, differentiation and maintenance of survival of neurons, cell migration and embryonal development. Of all family members, keratinocyte growth factor (KGF) is unique in that it is a specific mitogen for epithelial cells and does not interact with the FGF receptor of fibroblasts. To study the interactions between KGF and its receptor, we isolated KGF and FGF receptors from keratinocytes and fibroblasts, respectively. In the course of this study, we isolated five different variants of the FGF receptor from human fibroblasts and showed that all were derived from a single genetic locus. Four of these variants encode transmembrane receptors and can be divided into two subgroups that differ from one another with respect to the number (two or three) of immunoglobulin (Ig)-like domains. Within each subgroup, one receptor differed from the other by the presence of a two-codon insertion. Thus, all the variations among the four isoforms are localized to their ligand binding domains. The fifth isoform encodes a molecule truncated just 3' to the first Ig-like domain and thus could be secreted from the cell. The transcripts encoding the long and short isoforms were found to be expressed in many cell types, but their relative levels of expression varied greatly depending on the cell type. These findings indicate that alternative splicing generates diverse FGF receptor isoforms in human cells.

Amino Acid Sequence↗
PubMed1991

Expression of the human dbl-oncogene and proto-oncogene products in insect cells using a baculovirus vector.

Among the expression vectors, the baculovirus system has been successfully developed and it has been shown to be suitable as a helper-independent viral expression vector for high level of production of recombinant proteins in cultured insect cells. The high efficiency of this system derives from the viral strong promoter of the polyhedrin gene. Recombinant viruses containing foreign DNA inserted into the polyhedrin gene, will no longer produce polyhedrin and will form plaques morphologically different from the plaques produced by the wild type virus. We have expressed, at high level, the dbl and proto-dbl proteins using the baculovirus system. dbl and proto-dbl gene products produced in insect cells resulted to have the same post-translational modifications and subcellular localization observed in dbl and proto-dbl transfectants.

3T3 Cells↗
PubMed1991

Dominant dysplasia of the lens in transgenic mice expressing the dbl oncogene.

To study the transforming activity of the dbl oncogene and its effect on normal development in vivo, we linked dbl cDNA to promoters with different cell type specificities and used the constructs to generate transgenic mice. The promoters included the mouse alpha A-crystallin promoter, the rat insulin II promoter, and a mouse metallothionein promoter. We also generated transgenic mice carrying a recombinant cosmid clone that contains the entire dbl gene. Mice with the crystallin promoter construct developed cataracts and expressed the dbl protein in their lenses. The architecture of the lenses suggested a block to the normal pattern of differentiation and elongation of the secondary fiber cells. Mice with the insulin II promoter expressed dbl protein in the pancreas but showed no evidence of diabetes and no apparent pancreatic beta-cell defects. Similarly, mice with the metallothionein promoter expressed dbl protein in heart and testes, but showed no pathologic abnormalities in these tissues even after treatment with heavy metals. However, one family of mice carrying the metallothionein promoter construct showed cataracts and a dramatic fibroblastic dysplasia of the lens. One family with the cosmid-dbl gene showed a nearly identical lenticular dysplasia, but with a slower developmental time course. Thus, although the dbl oncogene did not induce neoplasia in any of the mice studied, it is apparently capable of interfering with the ability of the lens epithelial cells to differentiate into lens fiber cells, and of inducing metaplasia of the epithelial cells into fibroblastic cells.

Animals↗
PubMed1991

A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr.

Proto-dbl is a human proto-oncogene, whose oncogenic activation was initially detected by DNA transfection. We report significant sequence similarity between the predicted proto-dbl product and the products of CDC24, a Saccharomyces cerevisiae cell division cycle gene required for correct budding and establishment of cell polarity, and bcr, a gene implicated in the pathogenesis of chronic myelogenous leukemia (CML). Of 925 residues of the predicted proto-dbl protein, a stretch of 238 residues showed 29% and 22% identity over a region of similar length of the CDC24 and bcr proteins, respectively. When evolutionarily conservative substitutions were taken into account, the similarities were 68.8% and 71.6% for proto-dbl/CDC24 and proto-dbl/bcr gene products, respectively. Moreover, all three sequences were predicted to be markedly hydrophilic over this region. Very small deletions within the conserved region completely abolished transforming activity of dbl, while extensive deletion outside of this region had no effect. Even substitutions over a small stretch of close similarity with the other proteins substantially impaired transforming activity. Cells transformed by the dbl oncogene, like cdc24 mutants arrested at the nonpermissive temperature, form multinucleate cells. Thus, our findings indicate that the conserved region is an essential domain that may reflect important functional similarities among these otherwise highly divergent molecules.

Amino Acid Sequence↗
PubMed1990

Response of renal transplanted patients to oral calcium load.

In a previous study we demonstrated that cyclosporin-treated renal transplanted patients have a reduced 1,25(OH)2D3 synthesis in comparison with azathioprine-treated transplanted patients. To assess the impact of this defect on intestinal calcium transport we compared the plasma calcium variation and the urinary calcium excretion in 14 cyclosporin-treated and in 12 azathioprine-treated patients, in fasting conditions and 4 hours after an oral calcium load (1 g). In ten cyclosporin patients we also correlated cyclosporin plasma values with plasma 1,25(OH)2D3 values before and after a 25(OH)D3 oral load. After the oral calcium load, plasma and urinary calcium increased significantly in the azathioprine group, while remaining unchanged in the cyclosporin group. A negative correlation between plasma concentrations of cyclosporin and the increment in 1,25(OH)2D3 after 25(OH)D3 oral load was also observed. Thus, our data suggest that cyclosporin impairs 1-alpha hydroxylase activity and alters the response to an oral calcium load.

Adult↗
PubMed1990

Renal and humoral effects of ibopamine, a dopamine agonist, in patients with liver cirrhosis.

We investigated the renal and humoral effects of short-term administration of ibopamine, an orally active dopamine agonist, in patients with liver cirrhosis. The patients were divided into two groups on the basis of sodium excretion with a constant sodium intake of 40 mEq/d. We also compared the effects of ibopamine with those induced by intravenous infusion of dopamine hydrochloride (3 micrograms/kg per minute) in similar patients. Ibopamine caused significant increases in urine output, glomerular filtration rate, and sodium excretion throughout the 4 hours of the trial in patients with basal sodium excretion rate greater than 20 mmol/d. These renal effects were associated with a significant reduction in plasma aldosterone concentration. In contrast, only a transient increase in glomerular filtration rate and a diminution in plasma aldosterone concentration were observed after ibopamine in the patients with a basal sodium excretion rate less than 20 mmol/d. The infusion of dopamine had renal effects similar to those of ibopamine in both groups of patients. These results indicate that in cirrhotic patients with normal sodium excretion, ibopamine exerts a diuretic and natriuretic effect similar to that of dopamine infusion. However, these properties of dopaminergic agents are apparently lost in patients with avid sodium retention.

Adult↗
PubMed1990

[Intra-arterial neoadjuvant chemotherapy of sarcoma of the extremities].

Since 1987 we have treated 17 patients with bone sarcomas of the extremities (14 osteosarcomas, 3 malignant fibrous histiocytomas), with 2 cycles of neoadjuvant chemotherapy, consisting in iv high dose Methotrexate, Cis-Platin in 3 days in continuous infusion, and iv Adriamycin every 29th day. We obtained "good necrosis" (greater than 90%) in 13 patients (76.5%). We briefly report the possible correlations between angiographic findings after the first cycle and response to chemotherapy. All patients but one (94%), underwent conservative surgery. To date no patients have had local recurrence; 12 patients (70.5%) are disease free at a median follow up of 21.5 months; in 5 patients lung metastases appeared. To define overall survival and disease-free survival a longer follow up is required.

Adolescent↗
PubMed1989

Haemodialysis efficiency after long-term treatment with recombinant human erythropoietin.

In 11 chronic haemodialysis patients we investigated whether the increase in haematocrit during recombinant human erythropoietin (rHuEPO) treatment might alter the long-term efficiency of haemodialysis. After correction of anaemia with rHuEPO (mean Ht 35 +/- 2% vs 19 +/- 2% at baseline) (p 0.001), mean predialysis creatinine and urea did not change, while predialysis phosphate (1.77 +/- 0.38 vs 1.51 +/- 0.29 mmol/l) were significantly increased (p 0.01). In six of the 11 rHuEPO treated patients a post- versus pre-dialysis haemoconcentration (haematocrit 44% vs 35%) not attributable to different ultrafiltration regimes, was observed. In these 6 patients mean predialysis phosphate, creatinine and urea tended to be higher, but not significantly, in comparison to he remaining 5 patients who did not haemoconcentrate. Dialyser clearances and total extractions for urea, creatinine, phosphate and inulin were compared to those of 11 matched haemodialysis patients with anaemia. No differences were observed either for small and middle molecule clearances or their extractions between rHuEPO and anaemic patients. In conclusion, dialysis efficiency is not affected if haematocrit values are kept about 35%.

Adult↗