Search PubMed⌕ Search

Biomedical subjects

S Bianchi

Publications and source records attributed to S Bianchi.

At least 163 records · Page 9Linked to original sources
PubMed1996

Loss of p53 gene mutation after irradiation is associated with increased aggressiveness in recurring head and neck cancer.

The p53 gene plays a pivotal role in the control of a checkpoint during G1 and in the apoptotic program. It has been postulated that alterations of p53 may influence radio-sensitivity and prognosis in several malignancies. We studied the p53 gene status of 35 consecutive head and neck cancer patients who failed primary radiotherapy (RT) in preirradiated and postirradiated tumor samples using DNA single-strand conformational polymorphism analysis. Sixteen of 35 (46%) preirradiated samples presented with band shifts suggestive of point mutations in one or two exons. Eleven of these tumors (69%) showed the same shift even in the postirradiated samples. Exons 5 and 8 were prevalently affected in this group. Five tumors (31%) lost the mutation following RT. The missed mutations clustered in exon 7. All mutations were confirmed by sequencing. Actuarial analysis demonstrated increased survival in patients with tumors bearing a p53 gene mutation in both preirradiated and postirradiated samples (P = 0.05 and P = 0.01, respectively). We also found that loss of p53 gene mutation in postirradiated cancers is associated with a significantly shorter disease-free interval (P < 0.02) and a worse prognosis (P < 0.05). A possible explanation in such cases is clonal selection by RT of more aggressive and radioresistant cell subpopulations, which are wild-type for the p53 gene. Taken together, our data suggest that not only p53 gene status but also the pattern of mutations could modulate the response of tumor cell to RT in vivo.

DNA Mutational Analysis↗
PubMed1995

p53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome.

BACKGROUND: Recent studies of the molecular biology of cancer have demonstrated that p53 tumor suppressor gene aberration is associated with the development and progression of several different cancer types. METHODS: To analyze the expression of the p53 oncoprotein in parotid gland neoplasms, 72 parotid gland tumors (including 46 malignant and 26 benign cases) were studied immunocytochemically using the murine monoclonal DO-7 anti-p53 antibody. In parotid gland cancers, no and low expression (-/+) or moderate and high expression (++/+++) of the p53 oncoprotein were examined for correlation with patient survival and other clinicopathologic features, including clinical stage, tumor size, regional lymph node status, facial nerve paralysis, local infiltration, and distant failures. RESULTS: Positive staining was observed focally in 3 of 26 (11%) benign tumors and in 31 (67%) of 46 malignant tumors. Cancers showing moderate and high expression of p53 tended to be more advanced and larger than those with no expression or low expression, and presented at diagnosis more frequently, with signs of local aggressiveness. Tumors with moderate and high expression of p53 were associated more frequently with regional and distant metastases (P = 0.07 and P = 0.004, respectively). Multiple logistic regression analysis showed that regional and distant metastases were associated independently with p53 expression (P = 0.068 and P = 0.047, respectively). Moreover, patients whose cancers had moderate or high p53 expression had lower disease free and overall actuarial survival rates than those with no or low p53 expression (P = 0.021 and P = 0.033, respectively). Univariate and multivariate analysis confirmed the independent predictive prognostic value of p53 expression in patients with parotid gland cancer (P = 0.044 and P = 0.039, respectively). Furthermore, p53 expression did not correlate positively with patients' smoking habits in this series. CONCLUSION: The p53 tumor suppressor gene may be involved in salivary gland carcinogenesis, and its oncoprotein expression is an independent indicator of clinical aggressiveness in patients with carcinoma of the parotid gland.

Gene Expression↗
PubMed1995

Bidirectional regulation of osteoclast function by nitric oxide synthase isoforms.

Nitric oxide (NO) produces rapid osteoclast detachment and contraction in vitro, and this effect is accompanied by a profound inhibition of bone resorption. Work by others has confirmed these findings in vivo: inhibition of NO synthase [NOS; L-arginine, NADPH: oxygen oxidoreductase (NO-forming), EC 1.14.13.39] in normal rats is followed by increased bone resorption reflected by a marked loss in bone mineral density. In our present study, immunocytochemistry and Northern blotting show the presence of the constitutive calcium-sensitive NOS isoform (cNOS) in normal rat osteoclasts and in the human preosteoclast cell line (FLG 29.1). The inducible NOS isoform (iNOS) was also clearly demonstrable in the rat cells especially after treatment with gamma interferon (IFN-gamma) and bacterial wall products [lipopolysaccharide (LPS)], while a basal level of transcript was detected in the untreated human preosteoclast line. However NADPH-diaphorase activity was intense only in neonatal rat osteoclasts attached to bone, perhaps reflecting either enhancement of cNOS activity by calcium or increased amounts of the inducible isoform in activated osteoclasts in situ compared with isolated neonatal rat osteoclasts. These actively resorb devitalized bone but the untreated cells contain relatively low levels of NOS; they are extremely sensitive to inhibition by NO. The iNOS inhibitor aminoguanidine markedly enhances in vitro resorption by activated NOS-rich chick osteoclasts and by normal rat osteoclasts treated with LPS or IFN-gamma. In contrast, the nonselective NOS inhibitor NG-monomethyl-L-arginine inhibits resorption by untreated neonatal rat osteoclasts. Thus, osteoclast function may require intermittent calcium-stimulated increases in NO production by cNOS against a basal inhibitory background activity of the iNOS isoform. However, bone resorption depends on precursor replication and on the activity of the mature cells, and we found that the NO donor 3-morpholinosydnonimine (SIN-1) (50 microM) profoundly depressed replication in the human preosteoclast line. Taken together, these results strongly suggest that NO maintains a central control of bone resorption in both avian and mammalian species by exerting a powerful tonic restraint of osteoclast numbers and activity. The presence of NOS in human cells implies a similar function in man and that conventional views of calcium homoeostasis and skeletal metabolism will need substantial revision. Since NO also influences behavior of the osteoblast, the bone-forming cell, in vitro, a similar effect in vivo might imply a general influence on bone remodeling.

Adult↗
PubMed1995

Intramuscular ganglia arising from the superior tibiofibular joint: CT and MR evaluation.

OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and computed tomography (CT) in the diagnosis of intramuscular ganglia (IMG) that arise from the superior tibiofibular joint (STFJ). MATERIAL AND METHODS: Our series consisted of three men and three women. Four patients were studied by MRI, one by CT only, and two by both modalities. Contrast was used in one of the two patients studied by CT. MRI was obtained in at least two orthogonal planes to demonstrate the relation of the ganglia to STFJ. RESULTS: The MR and CT appearance of these ganglia was basically that of a well-defined soft tissue mass with low attenuation on CT images consistent with the presence of fluid. On MR studies, they had an isointense signal on T1-weighted images and a homogenous high-intensity signal on T2-weighted images. MRI demonstrated the attachment of these ganglia to the STFJ. CONCLUSION: CT and MRI were effective, noninvasive modalities in the evaluation of IMG. The imaging features on both modalities were consistent with the presence of fluid- containing lesions that had close proximity and were attached to the STFJ. The combination of location and the fluid consistency of these lesions facilitated the diagnosis.

Adult↗
PubMed1995

P-glycoprotein is expressed in parathyroid epithelium and is regulated by calcium.

P-glycoprotein (Pgp), the multidrug resistance (mdr) gene product, has been described in normal tissues with diverse physiologic functions. A broad role as a transporter protein for toxins, hormones, and physiologic metabolites has been provisionally deduced, based on structural analysis and immunoanatomic localization. Recently, significant levels of Pgp have been demonstrated in endocrine and hormonally responsive tissues and tumors. We examined calcium-regulated, clonal parathyroid epithelial (PT-r) and endothelial cells (BPE-1) and frozen parathyroid tissue from normal human parathyroid, parathyroid hyperplasia, parathyroid adenoma, and parathyroid carcinoma for expression of the multidrug resistance gene (Mdr1) and Pgp utilizing Northern and Western analysis and immunohistochemistry. We also investigated the effect of extracellular calcium (eCa) on Pgp expression in PT-r cells at the molecular/cellular level. Immunohistochemistry, utilizing three murine monoclonal antibodies (MAbs)--C494, JSB-1, and C219--which recognize spatially distinct cytoplasmic epitopes of Pgp, revealed strong immunoreactivity in PT-r cells, normal parathyroid, and parathyroid hyperplasia, and weak immunostaining in parathyroid adenomas. BPE-1 cells, endothelial cells, and parathyroid carcinoma were negative. PT-r cells showed a single 130 kDa band (120 KDa after glycosidase treatment) on Western blot and a 4.6 kb transcript on Northern analysis, consistent with Pgp. Western and Northern blot analysis of PTr cells cultured in different eCa concentrations showed that eCa up-regulated Pgp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Effects on bone mineral density of 12-month goserelin treatment in over 40-year-old women with uterine myomas.

We evaluated the effects on bone mineral density (BMD) of a 12-month treatment with goserelin depot, a gonadotropin-releasing hormone agonist, in a group of women with symptomatic uterine myomas requiring hysterectomy. Sixteen women, mean age 45.6 +/- 5.0, reporting menorrhagia associated with uterine myomas, candidates for hysterectomy, were scheduled to be treated with goserelin depot for 12 months. BMD was measured at the vertebral (L2-L4) and proximal femur level (femoral neck and trochanter) at the start of therapy and 6, 12, and 18 months later using dual energy X-ray absorptiometry (Hologic QDR 1000/W). The patients were followed for a minimum of 6 months after the end of treatment. Thirteen of the 16 women enrolled completed the treatment and three suspended it after 5, 6, and 7 months, respectively, because of side effects (hot flashes, insomnia, depression). Of the 13 women who completed the treatment, three underwent hysterectomy because of myoma regrowth and the recurrence of symptoms 3-18 months later; four reached the menopause 5-16 months later, and six were all menstruating normally with a follow-up varying from 6 to 18 months. After 12 months of therapy we observed a bone loss at vertebral, femoral neck, and trochanter of 4.4% (P < 0.05 versus baseline; P = not significant versus 6 months), 7.5% (P < 0.01 versus baseline, P < 0.01 versus 6 months), and 7.6% (P < 0.001 versus baseline, P < 0.05 versus 6 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evaluation of rubella virus E2 and C proteins in protection against rubella virus in a mouse model.

An animal model is described that can provide further information for evaluating novel vaccines against rubella virus (RV). A group of mice was immunized with the lysate of insect cells infected by a recombinant baculovirus expressing E2 and C proteins of RV. Another group of mice was immunized with the RA27/3 rubella vaccine. After 2 weeks, both groups of mice were challenged intramuscularly with live RV and the blood was drawn after 8, 24, 48 and 72 h. The presence of rubella challenge virus in an unnatural host, such as the mouse, was monitored by RT-PCR. The mice immunized with the RA27/3 rubella vaccine were the only ones able to inhibit the challenge virus replication, E2 and C proteins, which alone are not sufficient to protect animals against RV, served as a negative control for a protective vaccine against RV that expresses E1 protein of RV.

Animals↗
PubMed1995

p53 expression: a potential biomarker for risk of multiple primary malignancies in the upper aerodigestive tract.

The concept of field cancerisation assumes that in head and neck cancer patients (HNCP) with multiple malignancies the second primary cancers may arise independently from the entire upper aerodigestive tract as a consequence of massive exposure to common carcinogens. Since mutations and/or overexpression of the p53 tumour suppressor gene represent a genetic alteration frequently occurring in HNCP, we analysed immunocytochemically p53 oncoprotein expression in first primary, second primary cancers and in macroscopically uninvolved normal epithelium from different sites of the upper aerodigestive tract from 12 HNCP with multiple malignancies, in comparison with p53 expression in biopsy specimens of the upper aerodigestive tract from 5 non-neoplastic heavy smokers, as controls. In patients with multiple malignancies 6 cases (50%) showed positive staining of both first and second primaries, whereas 3 (25%) had positive labelling of first primary cancer but not of the subsequent second primary, 2 (17%) patients showed p53 expression only in the second primary cancer, and finally only 1 patient (8%) showed no p53 immunoreactivity in both first and second primary tumours. Moreover, 10 out of 12 (83%) HNCP with multiple cancers showed p53-positive staining in the normal epithelium from different sites of the upper aerodigestive tract, also at a significant distance from the site of first and second primary malignancies. contrast, sporadic p53 immunostaining was observed only in three out of 35 (8.5%) specimens from non-neoplastic controls. In addition, in 4 HNCP with multiple tumours the histological examination of apparently normal epithelium from the upper aerodigestive tract revealed signs of moderate or severe dysplasia, and in 1 case an in situ carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Sonographic evaluation of intramuscular ganglia.

The study presents the ultrasound appearance of the intramuscular ganglia arising from the superior tibio-fibular joint. An oval, anechoic septated mass with distal sound enhancement in the antero-lateral aspect of the leg was seen in five examined patients. In all the cases, ultrasound-guided needle aspiration was performed and viscous fluid characteristic of ganglia was obtained. All the patients were treated by surgical excision of mass. Local recurrence, which occurred in three cases, was confirmed by ultrasound. The study indicates that ultrasound is useful in diagnosing intramuscular ganglia, in planning the treatment, and in the follow-up examination. Ultrasound-guided needle aspiration is a helpful technique in confirming the diagnosis.

Adult↗
PubMed1995

p53 oncoprotein overexpression correlates with mutagen-induced chromosome fragility in head and neck cancer patients with multiple malignancies.

In this study, we analysed immunocytochemically p53 expression in first primary and second primary cancers from 25 head and neck cancer patients (HNCPs) with multiple malignancies in comparison with oncoprotein expression in tumour tissues from 25 historical HNCP controls with single cancer in a match-paired analysis. Moreover, we investigated bleomycin-induced chromosome fragility in both groups of HNCPs and in 21 additional healthy controls. Thirty-nine out of 75 tumour specimens analysed (52%) showed positive p53 immunostaining. Eleven out of 25 (44%) from single cancer patients and 28 out of 50 (56%) tumours from HNCPs with multiple malignancies were p53 positive. In the group of multiple primary cancers, nine patients (36%) showed positive staining of both first and second primaries, whereas six (24%) had positive labelling of first primary cancer but not of the subsequent second primary, four (16%) patient showed p53 expression only in the second primary cancer and six (24%) patients showed no p53 immunoreactivity in both tumours. Chromosomal analysis demonstrated a higher sensitivity to clastogens of HNCPs with multiple tumours than of HNCPs with a single cancer (P < 0.01), and a significant correlation between chromosome fragility and p53 overexpression (P < 0.01) only in HNCPs with multiple malignancies more than in those with single head and neck cancer (P = 0.11). Moreover, we found that patients with p53-positive staining of both first and second primaries showed a statistically significant higher mutagen sensitivity than those with a single p53 immunoreactive tumour or those in whom both cancers were p53 negative (P < 0.01). Our data suggest that subjects with increased susceptibility to carcingogens after exposure to tobacco or alcohol are at higher risk for multiple cancers in which one of the most common genetic events is aberrant p53 expression.

Aged↗
PubMed1995

Accuracy and reliability of frozen section diagnosis in a series of 672 nonpalpable breast lesions.

Frozen section (FS) diagnosis was routinely performed in a large series of nonpalpable breast lesions from 1977 through 1991. The original FS diagnoses of 672 patients were classified in four categories (1 = benign lesion, 2 = in situ carcinoma, 3 = invasive carcinoma, 4 = deferred diagnosis) and compared with the diagnoses obtained at review of the permanent paraffin sections to estimate the accuracy of FS. A review of the mammographic pattern of the lesion was also performed. Frozen section diagnostic conclusion was deferred to permanent paraffin sections in only 22 cases (3.3%). Benign or malignant (grouping in situ and invasive carcinomas) FS diagnoses were accurate in 623 of 650 cases (95.8%). Overall, the prevalence of malignant lesions was 44.8% with a benign/malignant ratio of 1.2. The diagnosis was modified on the basis of permanent sections in 27 cases (4.2%) with three false positives and 24 false negatives. Sensitivity and specificity of FS diagnoses were 91.7 and 99.2%, respectively. When the comparison between FS and histologic diagnoses was analyzed according to the mammographic pattern, sensitivity among patients with microcalcifications as the only alteration was lower (88.8%) than among patients with opacities (94.9%). On the basis of these results, FS is to be considered a feasible and reliable diagnostic procedure in nonpalpable breast lesions, particularly in cases excised because of a mammographic opacity that is identifiable on gross examination of the surgical specimen.

Breast Neoplasms↗
PubMed1995

Histological impact of medical therapy--clinical implications.

The medium- and long-term effects of gestrinone and danazol on the endometrium were examined in 36 patients with endometriosis. Endometrial biopsies were taken from each patient before treatment and after 3 and 6 months of treatment with 600 mg danazol daily (n = 17) or with 2.5 mg gestrinone twice weekly (n = 19). Endometrial samples were analysed by light, scanning and transmission electron microscopy. At 3 months' treatment the endometria of patients treated with danazol appeared more atrophic than those of the women treated with gestrinone; some cell organelle involution was evident in all patients. After 6 months of treatment a marked atrophy was observed in patients of both treatment groups. A complete involution of cytoplasmic organelles with cytoplasmic collapse and a shift of nucleoplasmic ratio in favour of the nucleus occurred in patients treated with danazol; the cytoplasmic organelle involution was less marked in patients treated with gestrinone. Compared with gestrinone, danazol induces more rapid endometrial atrophy, with greater impairment of the cytoplasm and cell secretory activity.

Adult↗
PubMed1995

Stimulation of cholinergic receptors in the medial preoptic area affects sleep and cortical temperature.

The medial preoptic area (MPA), a cholinoceptive brain area devoid of cholinergic cells, plays an important role in the regulation of different physiological functions, particularly sleep control and thermoregulation. To investigate the effects of the stimulation of cholinergic receptors in this area on sleep and cortical temperature (Tcort), carbachol (a mixed cholinergic agonist) was directly microinjected into the MPA of freely moving rats. Carbachol (0.25 and 0.5 microgram, corresponding to 1.37 and 2.74 nmol) microinjection induced an increase in wakefulness and an inhibition of both slow wave and desynchronized sleep phases. The temperature of the cerebral cortex was reduced in comparison with control conditions (saline microinjection). Sterile needle insertion and saline microinjections induced a significant increase in Tcort, but no changes in the sleep-wake cycle compared with the handling of the animal. The results suggest that 1) carbachol microinjection into the MPA can activate an arousal-generating system and affect thermoregulatory mechanisms, and 2) sleep and temperature responses may be dissociated.

Animals↗
PubMed1995

Insulin resistance in microalbuminuric hypertension. Sites and mechanisms.

Microalbuminuria in patients with essential hypertension is a marker of incipient glomerular dysfunction and clusters with lipid and hemodynamic abnormalities. Recent evidence has shown that hypertensive patients with microalbuminuria have a hyperinsulinemic response to oral glucose, suggesting the presence of insulin resistance. To directly test this possibility we studied insulin action in two accurately matched groups (n = 10 each) of hypertensive patients with or without microalbuminuria (14 +/- 2 versus 52 +/- 7 mg/24 h-1, mean of three 24-hour collections). In response to glucose ingestion microalbuminuric patients showed slight hyperglycemia (area under the curve, 928 +/- 43 versus 784 +/-19 nmol/L-1/2h-1, P < .02) and a marked hyperinsulinemia (26.8 +/- 3.3 versus 49.8 +/- 3.7 nmol/L-1/2h-1, P < 0.01). Basal arterial blood pressure, heart rate, and forearm blood flow were similar in the two groups and did not change significantly during a 2-hour euglycemic insulin clamp. Insulin-stimulated wholebody glucose uptake was 25% lower in microalbuminuric patients (33.5 +/- 2.5 versus 25.2 +/- 2.1 mumol/min-1/kg-1, P < .02). This difference was entirely due to a 40% reduction in glycogen synthesis (12.9 +/- 1.8 versus 21.3 +/- 3.2 mumol/min-1/kg-1, P < .05) as glucose oxidation was similarly stimulated in the two groups. In contrast there was no difference in the ability of insulin to suppress hepatic glucose production (by approximately 100% at the end of the clamp), to decrease fractional sodium and potassium excretions (by 35%), to lower circulating free fatty acids (by 80%), and to reduce plasma potassium concentrations (by 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗