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Biomedical subjects

G Bussolati

Publications and source records attributed to G Bussolati.

At least 91 records · Page 5Linked to original sources

Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial.

OBJECTIVE: To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS. METHODS AND PATIENTS: Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required. RESULTS: Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls. CONCLUSION: Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies.

Analysis of Variance↗

Oxytocin and oxytocin-analogue F314 inhibit cell proliferation and tumor growth of rat and mouse mammary carcinomas.

The effects of oxytocin (OT) and the OT-analogue F314 were investigated an xenografts of mouse mammary and colon carcinomas (TS/A and C26 tumors) and of rat mammary carcinoma (D-R3230AC). In all cases, proliferation was previously assessed by cell counting in cultured cell lines, whereas tumor growth was checked by serial measures of tumor volume and by evaluation of tumor weight at the end of the experiment. Both cell proliferation and tumor growth were inhibited by OT and F314. These data support previous observations on the inhibitory effect of OT and F314 on the growth of MCF7, T47D and MDA-MB231 human breast cancer cell lines and open new prospects for testing the effect of this hypothalamic hormone and its analogues on the control of breast carcinoma growth.

Animals↗

Pleural epidermoid carcinoma from displaced skin following extrapleural pneumothorax in a patient exposed to asbestos.

This report illustrates a rare case of primary epidermoid carcinoma of the pleura in a patient previously treated by artificial extrapleural pneumothorax for active tuberculosis. The patient had also been occupationally exposed to asbestos. Light microscopic examination showed two different lesions: laminar pleural fragments were covered by normal squamous epithelium that was similar in all respects to epidermis, whereas nodular fragments were composed of well-differentiated infiltrating carcinoma. These findings support the hypothesis that the carcinoma arose from normal epidermis seeded in the pleural cavity during multiple air refills to maintain the pneumothorax. A possible interaction between asbestos fibres and chronic inflammation might have potentiated tumour development.

Aged↗

Reproducibility of histological diagnosis of breast lesions: results of a panel in Italy.

Sixteen pathologists independently examined and classified a series of 81 breast lesions selected from the files of several Italian Pathology Departments in the context of a national task force on breast cancer (FONCAM). A four category classification system was used for analysis; according to the majority diagnosis (MD), simply defined as the most frequently reported in the panel, the series included 37 benign lesions without atypia (45.7%), nine atypical hyperplasias (11.1%), 18 in situ (22.2%) and 17 invasive carcinomas (21.0%). Concordance, estimated for all possible pair-wise comparisons between pathologists, was good (mean kappa value: 0.59). A comparison between the diagnoses of each pathologist and the panel majority diagnosis was also made. Overall, a global kappa value of 0.72 was found (range 0.57-0.85), with category-specific values being excellent for invasive carcinoma (0.89) and benign lesions without atypia (0.77), relatively good for in situ carcinoma (0.69) but poor for atypical hyperplasia (0.38). These results confirm that quality assurance procedures are particularly indicated for large screening programmes for breast cancer, and suggest that for atypical lesions strict diagnostic criteria should be adopted.

Breast Neoplasms↗

Poorly differentiated oxyphilic (Hurthle cell) carcinomas of the thyroid.

A series of 60 cases of oxyphilic (Hurthle cell) carcinomas (HCC) of the thyroid were reviewed to determine whether it is possible to correlate morphologic and clinical features as a means of assessing prognosis. Twenty cases showing predominant solid or trabecular patterns (as described in poorly differentiated carcinomas with a follicular pattern) were selected and the clinicopathological features were investigated. Based on cell size, two groups of solid or trabecular HCCs were identified: The first group (17 cases) was made up of typical large granular oxyphilic cells, and the second (three cases) had small oxyphilic cells. All tumors were reactive for thyroglobulin and for a mitochondrial antigen, selectively marking oxyphilic, mitochondrial-rich cells. Nuclear pleomorphism in individual cells was a common feature, but foci of anaplastic carcinoma were never found. Four cases overexpressed p53 protein and 10 expressed bcl-2 gene product. At follow-up, among the high-stage (pT3-pT4) tumors, seven patients had recurrences or metastases, six of whom were alive with disease or died of disease. In the control group of HCC with predominant follicular patterns, only one of 40 cases had a fatal outcome. The difference was statistically significant. Small-cell patterns and a p53 protein-positive/bcl-2 gene product negative phenotype were features of clinically aggressive HCC cases. We suggest that within the spectrum of oxyphilic (Hurthle cell) tumors, poorly differentiated HCC showing solid or trabecular patterns are a distinct group, based on both morphological and clinical features.

Adenocarcinoma↗

In situ hybridization study of messenger RNA for estrogen receptor and immunohistochemical detection of estrogen and progesterone receptors in the human ovary.

The expression of estrogen and progesterone receptors (ER and PR), as well as the presence of messenger RNA for estrogen receptor (ER-mRNA), were analyzed by immunohistochemistry and in situ hybridization, respectively, in the ovary of 25 healthy eumenorrheic women. Ovarian biopsies were taken in different phases of the menstrual cycle during laparotomy or operative laparoscopy performed for extraovarian benign diseases. A total of 126 follicles (105 primordial, 13 preantral and eight antral) and 50 corpora lutea (eight active and 42 atretic) was analyzed. Granulosa cells stained positively for ER, PR and ER-mRNA in 13.3, 9.5 and 17.1% of primordial follicles, respectively. The proportions of preantral and antral follicles with ER-positive granulosa cells were 23.1 and 37.5%, respectively; these follicles were positive for PR in 23.1 and 37.5% of cases, and for ER-mRNA in 30.7 and 37.5% of cases, respectively. For thecal cells, 38.5% of preantral and 37.5% of antral follicles were PR-positive, but no more than 25% stained positive for ER and ER-mRNA. Active corpora lutea stained positive for ER, PR and ER-mRNA in 50, 62.5 and 50% of cases, respectively. Corpora albicantes always stained negative. In all subjects the stroma surrounding both follicles and corpora lutea contained several fibroblast-like cells which stained positive for ER, PR and ER-mRNA. Oocytes and blood vessels stained negative in all cases. This study supports the hypothesis that estrogens and progesterone play a role in the intraovarian regulation of follicle growth from the first steps of follicle development, and participate in the regulation of corpus luteum.

Adult↗

Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast.

Recent evidence indicates that oxytocin (OT), in addition to the induction of myometrial and myoepithelial cell contraction, can influence proliferation and differentiation in developing mammary glands and in breast cancer cells, hence the interest in detecting and locating OT receptors (OTRs). We produced rabbit antisera and a monoclonal antibody against a synthetic peptide corresponding to the carboxy terminus of the predicted OTR sequence. We tested their specificity in immunoblasts and immunocytochemical tests. All of the antibodies specifically stained myometrium (at term of pregnancy). In the human breast, OTRs were detected in myoepithelial cells along ducts of normal lobules and in sclerosing adenosis. Intraductal cells in benign hyperplastic lesions were also positive. OTRs were demonstrated in cases of primary and metastatic carcinomas of the breast. In the same tissues, OTR gene expression was shown by reverse transcriptase polymerase chain reaction procedures detecting the specific mRNA. These results suggest that the interaction between OT and its receptors might play a role in the origin and evolution of non-neoplastic lesions and carcinomas of the breast.

Amino Acid Sequence↗

Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction.

We previously reported the presence of somatostatin (SS-14)-binding sites in a wide panel of human neuroblastoma (NB) tumor cell lines. Given that the adrenal gland and its relative embryonal and adult tumors express an abundance of mRNA for somatostatin receptor type 2 (sst2) mRNA, we studied the quantitative expression of sst2 in 6 NB cell lines and 15 primary tumors using competitive reverse transcription (RT)-PCR. This method uses an insertion mutant of the target gene as a competitor for the RT-PCR reaction, thus allowing exact quantitation of sst2 mRNA abundance. We found expression of specific transcripts for sst2 in all of the NB cell lines and tumors investigated (range, 9 x 10(5)-4 x 10(9) molecules/microg RNA). In NB cells, the expression of sst2 was highly correlated with SS-14-binding sites (R = 0.93). In primary tumors, sst2 was positively related to the expression of the neuroendocrine marker secretogranin II (P < 0.05) and negatively related to N-myc amplification (a poor prognostic factor, P < 0.005) and metastatic dissemination (P < 0.05). In addition, Kaplan-Meier curves indicate that sst2 expression is positively related to survival (P = 0.01). In a patient with stage IVs disease (a spontaneously regressing form), we found the highest sst2 expression (4 x 10(9) molecules/microgram RNA), a value relatively similar to that of normal adrenal. In conclusion, these data indicate that quantitation of sst2, as assessed with competitive RT-PCR, could represent a new prognostic tool in the neuroendocrine tumor NB. Since sst2 recognizes octreotide with high affinity, these findings could also have both diagnostic and therapeutic value.

Adult↗

Neural and mesenchymal differentiations in Ewing's sarcoma cell lines. Morphological, immunophenotypic, molecular biological and cytogenetic evidence.

Three established Ewing's sarcoma (ES) cell lines (TC106, 6647, A4573), grown both in vitro and as xenograft tumors, were analyzed. In all 3 lines and tumors, the ES characteristic reciprocal translocation (11;22), as well as the presence of the ES-associated p30/32MIC2 antigen, were documented. However, these cell lines showed discrepancies in their neural and mesenchymal differentiation. The TC106 line was characterized by expression of the neuroendocrine marker secretogranin II (SgII) which was detectable by Northern blot and by radioimmunological detection (RIA) in the culture medium of secretoneurin, a proteolytic product of SgII. In contrast, TC106 cells were immunohistochemically and radioimmunologically secretoneurin-negative. Rapid cellular secretion of the peptide is probably the explanation of such a discrepancy. The 6647 and A4573 cell lines were SgII/secretoneurin-negative and the former presented morphological and immunocytochemical evidence of mesenchymal differentiation. In fact, the 6647 xenograft tumor showed osteosarcomatous-type morphological features and the neoplastic cells were immunocytochemically positive for osteonectin and osteocalcin antigens. Expression of the CgA gene, which is typical of neuroblastomas, was absent in the Ewing's sarcoma cell lines investigated. Our findings provide experimental evidence that Ewing's sarcoma is a heterogeneous tumor which may show either neuroectodermal or mesenchymal differentiation. SgII/secretoneurin analysis by hybridization and RIA procedures is a reliable approach to the identification of ES with neuroendocrine differentiation.

Animals↗

Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast-cancer cell lines and on immortal mammary cells.

The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast-cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15 observed in this study in both "normal" and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP-15 in breast-cancer progression should be considered.

Apolipoproteins↗

Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining.

Clear morphological criteria for differentiating benign from malignant parathyroid tumors are not yet available and unfavorable prognosis cannot be predicted by histopathological parameters alone. A retrospective study of a series of parathyroid lesions was designed to evaluate the diagnostic role of the cell cycle-associated Ki-67 antigen detected by MIB-1 monoclonal immunocytochemistry. The mean tumor proliferative fraction (TPF), expressed as the number of Ki-67-positive nuclei per 1,000 cells, was 0.8 in normal parathyroid glands (nine specimens), 26.0 in hyperplasias (11 specimens), 32.8 in adenomas (11 specimens), and 60.5 in a group of tumors with histological features consistent with carcinoma (12 specimens). The difference between the latter two values was statistically significant (P < .05). When the five most clinically aggressive tumors were considered, the difference was even more remarkable (TPF, 78.6; P < .001). Oncocytic and pleomorphic cell components were found to proliferate with a labeling pattern similar to that of the chief cells. We conclude that proliferative activity is an additional useful parameter for evaluating parathyroid tumors diagnostically. Aggressive behavior may be expected in those tumors with a TPF greater than 6%.

Adenoma↗

Diagnostic problems in medullary carcinoma of the thyroid.

Medullary carcinoma of the thyroid (MCT), the tumor entity related to parafollicular C cells of the thyroid gland, is characterized by peculiar morphological, functional and behavioral features. Apart from the constant finding of calcitonin production by MCT, heterogeneous patterns of growth as well as different associations with other lesions in the setting of MEN II syndrome have been observed. This review addresses these points, as were discussed at the 1992 European School of Pathology courses. Heterogeneity of histological patterns of MCT suggests caution in the interpretation of any thyroid tumor. Immunohistochemical demonstration of calcitonin is apparently the only valid criterion for a differential diagnosis. A correct identification of MCT is important for the individual patient (to plan proper therapy) but also for patient's relatives to screen other familiar cases in the setting of MEN II syndromes.

Carcinoma, Medullary↗