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Carlo Alberto Beltrami

Publications and source records attributed to Carlo Alberto Beltrami.

15 recordsLinked to original sources
PubMed2006

Number of pericryptal fibroblasts correlates with density of distinct mast cell phenotypes in the crypt lamina propria of human duodenum: implications for the homeostasis of villous architecture.

Pericryptal fibroblasts (PFs), a class of myofibroblasts, have strongly been implicated in the regulation of villous structure because of their location close to crypts and their ability to secrete cytokines affecting intestinal epithelial cell proliferation and differentiation. Recently, mast cells (MCs) have also been involved in the homeostasis of villous architecture. As myofibroblasts arise in a wide variety of settings concurrently with a local increase in the number of tissue MCs, we calculated in this study the density of both PF and distinct pericryptal MC phenotypes in the mucosa of human duodenum showing normal, defective, or atrophic villous profiles. In addition, we evaluated the statistical association between PF-MC densities and each pattern of villous architecture. Finally, we correlated the density of PF with the density of pericryptal MC phenotypes. For this purpose, samples taken by endoscopy from 30 patients complaining of inflammatory bowel disorders were studied by immunohistochemistry. The densities of alpha-smooth muscle actin-positive PFs as well as tryptase-, chymase-, and c-kit-positive MCs were determined in the crypt lamina propria. Villous architecture was found to be significantly associated with the number of PFs and tryptase-, chymase-, c-kit-positive MCs in the lamina propria (ANOVA group effect P < 0.001). High density of both PFs and MCs was found in intestinal samples with normal villous morphology while lower densities were associated with defective or atrophic villous profiles (Tukey's test for multiple comparison P < 0.001). In addition, a significant correlation was found between PF density and the density of each pericryptal MC phenotype (vs. tryptase-positive MCs, r = 0.913; vs. chymase-positive MC, r = 0.905; vs. c-kit-positive MC, r = 0.927; P < 0.001 in all cases). This study provides morphological support for an important cooperation between PFs and MCs in maintaining normal villous architecture.

Actins↗
PubMed2006

Hepatocyte growth factor and transforming growth factor beta1 ratio at baseline can predict early response to cyclophosphamide in systemic lupus erythematosus nephritis.

OBJECTIVE: To determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor beta1 (TGFbeta1) in systemic lupus erythematosus (SLE) nephritis could be a prognostic factor for response to therapy with cyclophosphamide (CYC) and steroids at 6 months, and to examine whether the molecular ratio of HGF to TGFbeta1 correlates with the activity index (AI) and chronicity index (CI) and has predictive value for remission at the sixth month. METHODS: Thirty-six SLE patients with new-onset nephritis, 25 of whom were treated with CYC and steroids, entered into a prospective observational cohort trial at a tertiary university referral center. Renal biopsy findings and clinical parameters were recorded for all patients. Histopathologic, clinical, and immunohistochemical data at baseline served to define the predictive value for the outcome at 6 months. RESULTS: AI and CI at baseline did not distinguish patients who had achieved remission from those who had not achieved remission after receiving CYC plus steroids. HGF and TGFbeta1 were expressed in the tubuli, not in the glomeruli. The CI correlated directly with the TGFbeta1 extension score (TGFbeta1-ES) (r = 0.43, P = 0.008), but correlated indirectly with the HGF intensity score (HGF-IS) (r = -0.39, P = 0.02) and the HGF-ES (r = -0.45, P = 0.006). An HGF-ES:TGFbeta1-ES ratio of >or=1 at baseline distinguished patients who had achieved remission from those who had not achieved remission, with a predictive value of 94%. CONCLUSION: These findings indicate that baseline expression of renal HGF and TGFbeta1 predicts short-term renal outcome after therapy with CYC and steroids.

Adult↗
PubMed2006

User attitudes in analyzing digital slides in a quality control test bed: a preliminary study.

The pathologist examines suitably stained glass slides through a bright field microscope in order to render histopathological or cytological diagnosis by looking at tissues and cells. Glass slides serve as a permanent record of the patient disease. Over the course of a patient's treatment slides may need to be reviewed at other institutions before treatment can commence. Due to their fragile nature a transportable permanent digital facsimile of the glass slide would be ideal. A digital slide is a set of digital images representing the whole slide normally used by the pathologist, or a significant part of it; it is usually made by a large amount of images, up to thousands, which makes its management difficult. The present paper provides a description of the requirements needed to reproduce glass slides and of the available technological equipment, then the features of the two systems we implemented on different hardware are described, together with those of the digital slide viewer. The viewer was evaluated in two experimental test phases, during which user behaviour and diagnostic reports were measured. Digital slides used in the two experiments were acquired with either system. Possible applications of digital slides are then discussed, including undergraduate and professional education, quality control, and image analysis on full samples as well as on tissue microarrays.

Attitude↗
PubMed2006

PAX8 expression in human bladder cancer.

PAX8 is a transcription factor with a role in ontogenesis of the urinary tract. The aim of the present investigation was to investigate PAX8 expression in normal bladder and in non-invasive urothelial tumours. Nine cases of normal urothelial mucosa, 2 cases of papillary urothelial neoplasia of low malignant potential, 12 cases of low grade non-invasive papillary urothelial carcinoma and 16 cases of high grade non-invasive papillary urothelial carcinoma were investigated by immunohistochemistry. PAX8 mRNA expression was evaluated by RT-PCR in a different set of normal bladder mucosas and tumours. In addition, PAX8 expression was evaluated by RT-PCR in bladder from 2 human embryos and in several continuous cell lines derived from bladder tumours (5637, RT-112, TCC-SUP, HT 1376). In immunohistochemical studies, PAX8 was expressed in 28 out of 30 non-invasive urothelial tumours, but not in the normal adult bladders. In RT-PCR studies, PAX8 was expressed in 13 out of 13 bladder tumours but not in the 6 normal bladder mucosa. Contrary to that in adults, PAX8 was expressed in 2 cases of bladder mucosa from 16-week-old embryos. PAX8 was expressed in all the cell lines from bladder tumours. Both in the bladder tumours and cell lines PAX8 expression was highly heterogeneous in terms of the splicing isoforms. Treatment of cell lines with sodium butyrate (NaB) induced several changes of the splicing isoforms. Therefore, only subsets of molecular events that determine the PAX8 mRNA splicing heterogeneity in bladder tumours are sensitive to NaB treatment.

Alternative Splicing↗
PubMed2005

Selective effect of infliximab on the inflammatory component of a colonic stricture in Crohn's disease.

Although infliximab has been shown to improve the clinical course of Crohn's disease, its effect on intestinal strictures is controversial. We describe the case of a woman with steroid-resistant colonic Crohn's disease presenting with intermittent obstruction because of a tight stricture in the splenic flexure. Compared with uninvolved areas, biopsies showed intense edema and inflammatory cell infiltration and immunohistochemistry revealed an excess of TNF-alpha. Her symptoms responded promptly (CDAI went from 444 to 168) to an infliximab infusion (10 mg kg(-1) BW), which also had a dramatic effect on the stricture, now presenting radiologically as a moderate residual, apparently fibrotic, narrowing of the lumen. Endoscopy and histology confirmed the resolution of inflammation and TNF-alpha virtually disappeared. The patient refused additional infusions and after a few months the disease recurred with features identical to the pre-treatment phase. She then opted for surgery. Histology of the resected strictured colon revealed edema, inflammation, and fibrosis, with TNF-alpha back to pre-treatment levels. This case indicates that, in the colon, infliximab specifically relieves the TNF-alpha-mediated inflammatory component of the stricture while having no effect on fibrosis and suggests that the response to infliximab treatment may depend on the nature of the, stricture itself.

Adolescent↗
PubMed2005

Piecemeal degranulation in human tumour pheochromocytes.

Piecemeal degranulation (PMD) has been recognized in two cases of human pheochromocytoma from the adrenal medulla, which were studied by transmission electron microscopy. Tumour pheochromocytes presented a highly characteristic cytoplasmic admixture of normal resting granules, swollen granules with eroded matrices and enlarged empty containers. Chromaffin granules that appeared to be normal and altered granules maintained their individual structure, and did not fuse with each other or with the plasma membrane. In accordance with the currently accepted model for granule discharge during PMD, electron-dense or clear vesicles 30-150 nm in diameter were seen either attached to the surface of chromaffin granules and the plasma membrane or free in the cytosol. This is the first description of PMD in human adrenal chromaffin cells and, in addition, is the first report of PMD in tumour secretory cells. These findings add further to the concept that PMD may have a broader spectrum of expression than hitherto recognized.

Adrenal Gland Neoplasms↗
PubMed2005

Selective heparanase localization in malignant melanoma.

Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate proteoglycans (HSPG), and its expression has been associated with increased growth, metastasis, and angiogenesis of tumors. Since metastatic melanoma cells express high levels of HSPG and because melanoma tumors grow highly vascularized, we analyzed melanoma tissue specimens for HPSE-1 expression from experimental animals as well as from patients. Laser capture microdissection microscopy was used to extract melanoma cell populations and to isolate them from adjacent tissue. In experimental animals, a 29-fold upregulation of HPSE-1 expression was detected by real-time PCR in metastatic melanoma compared to normal lung tissue. Additionally, immunohistochemistry (IHC) revealed selective HPSE-1 staining in human metastatic melanoma when compared to primary melanoma tumors from the same patient. IHC also showed a marked staining for the enzyme around blood vessels and in vascularized regions. Our results provide evidence demonstrating that HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma. These results further emphasize the importance that therapies designed to block HPSE-1 activity may aid in controlling this type of cancer.

Animals↗
PubMed2004

Neuropathological and clinical phenotype of an Italian Alzheimer family with M239V mutation of presenilin 2 gene.

Presenilin 1 and 2 are 2 highly homologous genes involved in familial Alzheimer disease. While more than 100 mutations in presenilin 1 are known to segregate with the disease in familial Alzheimer disease, only 9 mutations of presenilin 2 have been identified to date. We report the clinical and neuropathological phenotype of FLO10, the large Italian Alzheimer kindred associated with methionine to valine substitution at residue 239 of presenilin 2. The patients showed a remarkable variability in age of onset of symptoms, disease duration, and clinical presentation. The neuropathological study of 2 patients revealed peculiar features in addition to neurofibrillary changes and A beta amyloid deposits in the neuropil and vessel wall. Ectopic neurons in the subcortical white matter, often containing neurofibrillary tangles, were found in both patients, one of whom presented with epilepsy. Furthermore, 1 patient showed an unusually high number of ghost tangles in the cerebral cortex. These observations indicate that the Alzheimer kindred FLO10 associated with M239V mutation of presenilin 2 is characterized by some peculiarities of the clinical and neuropathologic phenotype compared to sporadic Alzheimer disease.

Age of Onset↗
PubMed2003

Piecemeal degranulation as a general secretory mechanism?

In this article we review the ultrastructural findings, functional aspects, and biological significance of piecemeal degranulation (PMD), a unique secretory pathway that has been described in basophils, mast cells, and eosinophils. Recent ultrastructural data suggestive of PMD in enteroendocrine cells of the gastrointestinal tract and chromaffin cells of the adrenal medulla are also presented and discussed. Further research on PMD in secretory cells of the endocrine and exocrine glands, as well as in neurons, is recommended, since the current data indicate that PMD has a broader spectrum of expression than was hitherto reported. The identification of the PMD phenotype in different cell types (e.g., basophils, mast cells, eosinophils, enteroendocrine cells, and adrenal chromaffin cells) suggests that PMD is a unique degranulation model for paracrine and endocrine secretion. Further investigation will clarify whether PMD can be considered as a general mechanism for the slow release of bioactive stored materials by granulated secretory cells.

Animals↗
PubMed2002

Granule changes of human and murine endocrine cells in the gastrointestinal epithelia are characteristic of piecemeal degranulation.

Piecemeal degranulation is a unique pattern of cell secretion that consists of a slow release of granule contents from cytoplasmic secretory granules, which leaves empty chambers that do not fuse with each other or with the plasma membrane. To our knowledge, no cell types other than mast cells, basophils, and eosinophils have been reported in the literature to show morphological features of piecemeal degranulation. In the present study we provide evidence for ultrastructural morphologies characteristic of piecemeal degranulation in entero-endocrine cells of the human and murine gastrointestinal epithelia. Human biopsy samples were taken from the mucosa of the distal duodenum, proximal jejunum, and colon in 10 patients undergoing endoscopic examination for malabsorption, diarrhea, and/or abdominal pain. Murine gastrointestinal samples were obtained from 10 adult C57 mice. All specimens were prepared for transmission electron microscopy (TEM) according to standard protocols. Results showed that different types of gastrointestinal entero-endocrine cells, in both humans and mice, were recognizable with ultrastructural features diagnostic for piecemeal degranulation, including specific granule and cytoplasmic changes. In the granules, the content was found to be loosely packed or diminished. Notably, altered granules did not fuse with each other or with the plasma membrane, and were characteristically intermingled with normal, resting granules. At times, the release events transformed the granules into enlarged, empty containers. Numerous entero-endocrine cells presented a rich supply of membrane-bound vesicles (50-200 nm in diameter) that were free in the cytoplasm or attached to granules. This finding of piecemeal degranulation in gastrointestinal entero-endocrine cells suggests that such a secretory model might be a general degranulation pattern in cells involved in paracrine-endocrine secretion.

Adolescent↗
PubMed2002

Adrenal angiosarcoma: report of a case.

Adrenal epithelioid angiosarcoma is an extremely rare tumor. Even if such tumors are very aggressive, a long survival may occasionally be observed after an adrenal ectomy. A 70-year-old woman suffering from persistent right flank pain showed a 5-cm right adrenal mass plus a 2-cm liver mass at the radiologic workup, and both were suspected of being malignant. No adrenal hypersecretion was demonstrated. During an explorative median laparotomy the right adrenal gland with the whole periadrenal tissue and locoregional lymph nodes was removed. A histological examination revealed an adrenal angiosarcoma. The resection margin was tumor-free with no lymph node infiltration. The liver mass turned out to be a cistobiliary adenoma. Since no distant metastases were observed, no adjuvant chemotherapy was performed. After an 18-month follow-up the patient is still well with no sign of a relapse. When this rare adrenal tumor is encountered and curative treatment is attempted initially extensive surgical procedures are essential.

Adrenal Gland Neoplasms↗
PubMed2002

Balance between cell division and cell death as predictor of survival in patients with non-small-cell lung cancer.

OBJECTIVE: To evaluate the prognostic value of the balance between apoptosis and proliferation in non-small-cell lung cancer (NSCLC). METHODS: Paraffin-embedded sections from a consecutive series of radically resected NSCLCs were scored for apoptosis (in situ DNA nick end labeling assay) and proliferation (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case, to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators (pT, pN, pStage and histology) and p53 status were also evaluated. RESULTS: Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The significant prognostic value of the combination 'low AI/high MIB-1' was also confirmed in a multivariate analysis after adjustment for other covariates. CONCLUSION: These results underline the importance of considering apoptosis and proliferation together to identify a subgroup of NSCLC associated with poor survival.

Aged↗
PubMed2002

Digital storage of glass slides for quality assurance in histopathology and cytopathology.

Proficiency testing programmes for measuring screening skills in pathology are mainly conducted using conventional glass microscope slides. However, the availability of robotic microscopes allows an entire conventional slide to be digitized. Our experiments have shown that, using a widely available robotized microscope and a PC, the image of a single field may be acquired in 2 s on average, including stage movements, autofocus and storage. Digitizing an entire slide, a fully automated procedure, takes up to 8 h. If the image of each field is compressed at an appropriate quality level (a compression ratio of, say, 35:1) it requires about 40 kByte to be stored, resulting in a total storage requirement of about 600 MByte per slide. Thus one CD-ROM can be used to store one virtual slide, as well as a self-installing program to provide a microscope simulator facility. This allows pathologists to examine the virtual case from their computer in a similar manner to looking at a glass slide on a conventional microscope. This permits a new, computer-based approach to proficiency testing in histopathology and cytopathology. Use of virtual slides should encourage the diffusion of national quality assurance programmes, which at present suffer from certain organizational and logistical limitations.

Analog-Digital Conversion↗
PubMedDate not supplied

Prognostic role of Ape/Ref-1 subcellular expression in stage I-III breast carcinomas.

The purpose of the study was to evaluate the prognostic role of the DNA repair protein APE/Ref-1 in breast carcinomas. Immunohistochemical analysis for APE/Ref-1 was performed in a series of 133 consecutive stage I-III breast carcinomas. The relationship between APE/Ref-1 and other prognostic and predictive factors such as tumor size, nodal status, histologic grade, p53 expression, hormonal receptor status, vascular invasion and necrosis was investigated. The prognostic value of APE/Ref-1 was studied by univariate and multivariate analysis. The predominant pattern of APE/Ref-1 immunohistochemical expression was nuclear, although cytoplasmic and mixed nuclear/cytoplasmic localization was also observed. The percentage of cells with APE/Ref-1 cytoplasmic stain directly correlated with the percentage of p53 positive cases (rho=0.28, p=0.013). The small group of women whose tumors showed mixed nuclear/cytoplasmic APE/Ref-1 localization (n=5) experienced a significantly poorer survival (p=0.014) and Cox proportional hazard model analysis identified APE/Ref-1 as an independent prognostic factor. The results suggest that subcellular localisation of APE/Ref-1 may influence the aggressiveness of breast carcinomas.

Adenocarcinoma↗