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Biomedical subjects

P G Grigolato

Publications and source records attributed to P G Grigolato.

At least 19 recordsLinked to original sources
PubMed2006

Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner.

The soy isoflavone genistein targets adipose tissue and elicits physiological effects that may vary based on dietary intake. We hypothesized that the adipose effects of genistein are dose and gender dependent. Four-week-old C57BL/6 male and female mice received daily oral doses of genistein (50-200,000 microg/kg.d) or 17beta-estradiol (E2) (5 microg/kg.d) for 15 d or a diet containing 800 ppm genistein. Genistein increased epididymal and renal fat pad and adipocyte size at doses up to 50,000 microg/kg.d or at 800 ppm in the diet in males but not in females. The alteration in adipocity correlated with changes in peripheral insulin resistance. These treatments increased genistein serum concentrations from 35+/-6 to 103+/-26 nM 12 h after treatment and lowered plasma triglycerides and cholesterol levels. The 200,000 microg/kg.d genistein dose decreased adipose tissue weight similarly to E2. This genistein dose down-regulated estrogen receptor (beta more than alpha) and progesterone receptor expression and induced estrogen-dependent adipose differentiation factors; it did not change expression of the minimal consensus estrogen-responsive element in ERE-tK-LUC mice, which was positively modulated in other tissues (e.g. the lung). E2 down-regulated almost all examined adipogenic factors. Gene microarray analysis identified factors in fat metabolism and obesity-related phenotypes differentially regulated by low and high doses of genistein, uncovering its adipogenic and antiadipogenic actions. The lower dose induced the phospholipase A2 group 7 and the phospholipid transfer protein genes; the 200,000 microg/kg.d dose inhibited them. The antiadipogenic action of genistein and down-regulation of adipogenic genes required the expression of ERbeta. In conclusion, nutritional doses of genistein are adipogenic in a gender-specific manner, whereas pharmacological doses inhibited adipose deposition.

Adipocytes↗
PubMed2003

The collecting duct carcinoma of the kidney: a cytogenetical study.

OBJECTIVES: The Heidelberg classification of renal tumours identifies five histotypes of renal cancer, underlining for two of them (conventional and papillary renal cancers) a strict relation between the morphological aspect and the complement of alterations evidenced by the cytogenetic analysis of the neoplastic karyotype. Due to its low incidence, the collecting duct carcinoma (CDC) has not yet been characterized from a cytogenetic point of view. This study analyses the clinical, morphologic and cytogenetic features of the CDC observed and treated in our department. METHODS: From January 1995 to December 2002, among the 591 patients who underwent surgery for renal cancer, we observed 11 cases of CDC (prevalence 1.9%) treated either by radical (9 cases) or partial nephrectomy (2 cases). During radical nephrectomy a loco-regional lymphadenectomy was always performed. In the 9 cases observed after 1997, a complete cytogenetic analysis of the neoplastic karyotype was carried out. RESULTS: At pathological examination the disease was found to be confined to the renal capsule (TNM 1997 stage 1) in only 3 patients; venous neoplastic trombosis and nodal metastasis were present in 3 and 6 cases respectively; 2 patients showed distant metastases (lung, bone). Two of the patients affected with stage 1 tumours are still alive with no evidence of the disease at 48 and 88 months after surgery, while the third died following the systemic progression of a concomitant bladder carcinoma. One patient with stage 4 tumour (no. 11) is alive, but the follow up time is still limited (2 months). All the other 7 patients are dead after a mean survival time of 16.3 months (range 0-45). As for cytogenetic analysis, 2 CDCs didn't grow in culture and in one case no karyotype alterations were reported. In the remaining 6 cases hypodiploid stemlines and a homogeneous chromosome alteration pattern were observed, with multiple numerical and structural aberrations (mean 11.1, range 7-15) and the continuous involvement of chromosomes 1 and X or Y, both as traslocation and deletion/monosomy. Additional abnormalities of chromosomes 22 and 13 were found to be common but less frequent. CONCLUSIONS: The clinical behaviour of the CDC is aggressive and its prognosis is surely poor; surgical treatment seems to be curative only for organ-confined cancer, accounting for the minority of cases. This neoplasm is cytogenetically characterized by hypodiploid stemlines with common involvement of chromosome 1 and the autosomes.

Aged↗
PubMed2001

Dilated intercellular spaces as markers of reflux disease: histology, semiquantitative score and morphometry upon light microscopy.

BACKGROUND AND AIMS: A recent electron microscopy study suggested that dilated intercellular spaces (DIS) are specific for acid reflux-damaged esophageal epithelium. Electron microscopy is, however, expensive and difficult to apply to routine biopsies. The aims of this study are to establish a method for assessing DIS on light microscopy of esophageal biopsies and to estimate its association with current clinicopathological parameters of esophagitis. MATERIALS AND METHODS: 21 patients with reflux symptoms were investigated. Light microscopy biopsies were assessed for DIS size by a semiquantitative method and computer-assisted, static morphometry. A DIS score accounting for DIS size and distribution was assigned to each patient and its association with 30 clinicopathological variables investigated by univariate and multivariate logistic regression. RESULTS: Both the semiquantitative method and static morphometry identified 4 different classes of DIS size. The DIS score was significantly and independently associated with the esophageal symptoms score, the histological score of esophagitis and the relevant morphometry data. CONCLUSIONS: DIS may be efficiently assessed during light microscopy of routine esophageal biopsies. Since correlation with both the histology and the symptoms of esophagitis, the DIS score may be considered a novel parameter of esophagitis and is suggested for the routine evaluation of esophageal biopsies in patients with reflux disease.

Adult↗
PubMed1999

Serum from patients with severe heart failure downregulates eNOS and is proapoptotic: role of tumor necrosis factor-alpha.

BACKGROUND: Cytokine activation and endothelial dysfunction are typical phenomena of congestive heart failure (CHF). We tested the hypothesis that incubating human umbilical vein endothelial cells with serum from patients with CHF will downregulate endothelial constitutive nitric oxide synthase (eNOS) and induce apoptosis. METHODS AND RESULTS: We studied 21 patients with severe CHF. Levels of tumor necrosis factor-alpha (TNF-alpha) and several neuroendocrine parameters were assessed. eNOS was measured by Western Blot analysis and apoptosis by optical microscopy and flow cytometry. We observed (1) eNOS downregulation (difference versus healthy subjects at 24 hours [P<0.05] and 48 hours [P<0.001]), (2) nuclear morphological changes typical of apoptosis; and (3) a high apoptotic rate with propidium iodide (increasing from 2.1+/-0.4% to 11.3+/-1.2% at 48 hours; P<0.001 versus healthy subjects) and annexin V. An anti-human TNF-alpha antibody did not completely counteract these effects. A strong correlation existed between eNOS downregulation and apoptosis (r = -0.89; P<0.001). CONCLUSIONS: Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-alpha likely play a role, but they cannot be the only factor responsible.

Aged↗
PubMed1998

[Flow cytometry sutdy of DNA and cell kinetics in the adenoma- carcinoma sequence in the large intestine].

UNLABELLED: The quantitation of DNA and growth fraction in the different step from dysplastic to neoplastic process in large bowel is the aim of this study. 70 colonic polyps were studied. The fresh specimens were processed and DNA analysis was carried out using a Partec CA II flow cytometer and the growth fraction was tested with KI-67 monoclonal antibody. The percentage of S-phase cells has been calculated with the Multicycle program. Our results demonstrated that 7 adenomas were tubulo-villous with mild dysplasia, 39 with mild-moderate dysplasia, 1 with severe dysplasia, 5 were polypoid carcinomas, 2 juvenile polyps, 1 polypoid leiomyoma, 1 inflammatory fibroid polyps. DNA analysis showed a diploid DNA content in non adenomatous polyps, in all adenomas with mild dysplasia, in 37 with mild-moderate dysplasia, in 8 cases with moderate-severe dysplasia and 1 cancer. Aneuploidy was discovered in 2 cases with mild-moderate dysplasia, in 6 cases with moderate-severe dysplasia, in the case of severe dysplasia and in 4 cases of carcinomas. Best indexes of linear correlation (Pearson's r) has been found between S-phase and DNA index (r = .75) and between S-phase and KI-67 (r = .82). IN CONCLUSION: 1) No relationship was found between DNA content and age, sex, size and location of polyps. 2) Aneuploidy is strictly related to moderate-severe grade of dysplasia therefore it is an important element in the development of adenomacarcinoma sequence. 3) DNA-index, S-phase and KI-67 are strictly related.

Adenocarcinoma↗
PubMed1997

[DNA flow cytometry. Comparison of the methods for nuclear extraction from frozen and paraffin-embedded sections].

Cellular DNA content of solid tumors can be determined either from fresh, frozen, or formalin fixed, paraffin-embedded tissues. However, discordant results have been obtained using the paraffin-embedded technique, and lack of abnormal DNA stemlines in the paraffin-embedded as compared to either fresh or frozen tissues has been reported. In this study we evaluated the validity of nuclear extraction method from paraffin-embedded tissues, using 75 breast carcinomas whose DNA content was previously analyzed from frozen tissue and resulted either normal (12 cases) or abnormal (63 cases). From representative paraffin blocks, nuclei were extracted following Hedley's technique. The results revealed excellent cell counting and good histogram resolution from all paraffin samples; the loss of G2M abnormal peak in eight histograms with abnormal stemline did not compromise the correct interpretation of DNA content. In addition, the comparison between DNA indices obtained from corresponding paraffin and frozen samples showed a good correlation in 69 cases (r = 94); discordance in six cases was demonstrated to be related to tumor heterogeneity. In conclusion the paraffin extraction method is a sensible, and reliable technique, which can be applied for DNA flow cytometric studies on archival cases, as well as whenever fresh sample from the tumor is not obtainable.

Aneuploidy↗
PubMed1995

Different neurotransmitter systems are involved in the development of esophageal achalasia.

Clinical and pharmacological evidence suggests that several neurotransmitters are involved in the control of the esophageal motility; in fact, besides the well known cholinergic and sympathetic innervation, Vasoactive Intestinal Polypeptide (VIP)-containing fibers as well as dopamine (DA)-containing nerve endings have been identified within the esophageal wall. Lower Esophageal Sphincter (LES) achalasia is a neuromuscular disorder characterized by the absence of peristalsis in the body of the esophagus and by the failure of the LES to relax in response to swallowing. Stimulation of both VIP receptors and D-2 DA receptors induce a decrease in LES pressure, while D-1 receptors mediates LES contractions. In the present study we show that both VIP and DA system is disregulated in LES achalasia. In particular, this disease is associated not only with the lack of VIP nerves in the LES, but also with a failure in the responsiveness of postsynaptic receptors to VIP stimulation. Furthermore, we demonstrate a selective functional loss of the D-2 DA receptor component, without changes in the D-1 DA receptor mediated responses.

Adenylyl Cyclases↗
PubMed1995

Usefulness of the scraping method for DNA flow cytometry in breast tumors.

Flow cytometric DNA analysis is an important prognostic tool in breast cancer. We evaluated the possibility of performing DNA analysis on cell suspensions obtained by scraping the cut surface of breast tumors; 31 breast tumor nodules, including six benign and 25 malignant lesions, were studied. From each case, cell suspensions acquired by mechanical mincing of a fresh frozen tissue fragment and by two different scrapings (central and peripheral) from the cut surface of the tumor were analyzed via flow cytometry. In all cases, comparison of the DNA histograms for three samples showed no significant differences in the appearance of debris or in the value of coefficient of variation of the G0-G1 peak. All benign nodules showed a normal DNA stemline in all specimens. In 23 of 25 cases of breast carcinoma, the ploidy of the three preparations was similar, with a concordance in 12/14 (85, 71%) cases in DNA nondiploid tumors. Linear regression analysis showed a good correlation in DNA index between either scraping sample and the tissue fragment (r = .955 and r = .905). The results indicate that the scraping technique provides excellent cell suspensions and DNA histograms comparable to those obtained from mechanical mincing of tissue fragments. The technique minimizes preparation time and avoids consuming much tissue and, thus, is the method of choice when very small cancers have to be analyzed.

Biopsy↗
PubMed1995

DNA index, cellular proliferative activity and nucleolar organizer regions in cancers of the larynx.

The DNA index, expression of cell-cycle-related proteins--proliferating cell nuclear antigen (PCNA, cyclin) and Ki-67--and the content of silver-binding nucleolar organizer regions (AgNORs) were evaluated in 30 unselected consecutive primary squamous cell carcinomas of the larynx. Results were compared and subsequently related to histological grading, lymph node status, pT category, and pathological stage. DNA content was non-diploid in 9 cases (30%). Mean AgNOR counts per tumor ranged from 2.52 to 8.76. PCNA and Ki-67 expressions were similar in 10 cases (33%). In the remaining cases, PCNA-positive cells usually outnumbered Ki-67-positive cells. No significant correlation was found among DNA index, PCNA and Ki-67 expressions, and AgNOR counts. Although there was a positive trend when Ki-67 was compared with histological grading, findings were not statistically significant. In contrast, a significant correlation was found between DNA index and lymph node status (P = 0.035), with a higher incidence of neck node metastases in non-diploid tumors. These data suggest that tumor ploidy can be correlated with lymph node spread in laryngeal squamous cell carcinoma and might be used as an additional prognostic factor when planning treatment.

Biomarkers, Tumor↗
PubMed1991

KP1 (CD 68) staining of malignant melanomas.

The monoclonal antibody KP1, which recognizes the CD 68 antigen on macrophages and myeloid precursors, was tested on 28 malignant (primary and metastatic) melanomas, 28 naevi, and 17 skin biopsies showing either normal (10) or hyperplastic melanocytes (7). Sixteen of 20 primary melanomas and six of eight metastatic melanomas showed variable numbers of KP1 positive tumour cells. All but five benign melanocytic proliferations (two Spitz naevi and three intradermal naevi), as well as normal and hyperplastic melanocytes were negative. These results indicate that difficulties may occur with the use of KP1 in the differential diagnosis between melanomas and neoplasms derived from histiocytes-macrophages, and that the expression of CD 68 antigen might be related to tumour progression in melanocytic cells.

Antibodies, Monoclonal↗
PubMed1991

Basement membrane components in normal, dysplastic, neoplastic laryngeal tissue and metastatic lymph nodes.

The immunohistochemical localization of the basement membrane (BM) components laminin, type IV collagen and fibronectin was analyzed in normal, dysplastic and neoplastic laryngeal specimens. The distribution of these macromolecules was also investigated in metastatic lymph nodes. A regular and continuous staining for laminin and type IV collagen was present in normal and mild dysplastic epithelium (LIN I); interruptions and reduplications were more evident in severe dysplasia (LIN III), together with an increased positivity for fibronectin in the subepithelial connective tissue. In squamous cell carcinomas the distribution of BM components was related to the degree of cellular differentiation, with a decreased immunostaining being evident in moderately and poorly differentiated carcinomas. Furthermore, the positivity for laminin and type IV collagen was influenced by the pattern of neoplastic growth, being continuous around the "pushing" border and discontinuous where the neoplastic front had an "invading" appearance. Similar changes were present in cervical metastatic lymph nodes. These observations tend to support the theory that the neoplastic growth is a cyclic process, with BM component synthesis and reabsorbtion related to the shifts of cellular metabolism.

Antibodies, Monoclonal↗
PubMed1990

[Eosinophilic gastritis. Clinico-pathologic considerations on a case and review of the literature].

The clinical, radiographic and histological features of a case of eosinophilic gastritis in a 26 year old-man without personal or familial signs of allergy are reported. The Authors pointed out the importance of radiographic and histological aspects of the case studied. Therefore they represent essential methods for a correct diagnosis and an appropriate management that in this case is only pharmacological. The diagnosis of eosinophilic gastritis is, however, important for the recognition of specific allergens.

Adult↗
PubMed1990

A case of gastric carcinoma with massive eosinophilia and squamous differentiation. Histochemical, immunohistochemical and ultrastructural aspects.

We report the histological, histochemical, immunohistochemical, and ultrastructural features in a case of gastric carcinoma with squamous differentiation and massive eosinophil infiltration, with peripheral blood eosinophilia, without evidence of allergic or parasitic disease. The unfavourable prognostic significance of squamous differentiation and eosinophilia is pointed out. The hypothesis of more aggressive cellular clones, within the neoplasia, capable of expressing morphological changes and/or different functional activities is considered.

Aged↗