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C A Beltrami

Publications and source records attributed to C A Beltrami.

At least 37 records · Page 2Linked to original sources
PubMed1999

Myocyte death in the failing human heart is gender dependent.

Cardiovascular disease is delayed and less common in women than in men. Myocyte death occurs in heart failure, but only apoptosis has been documented; the role of myocyte necrosis is unknown. Therefore, we tested whether necrosis is as important as apoptosis and whether myocyte death is lower in women than in men with heart failure. Molecular probes were used to measure the magnitude of myocyte necrosis and apoptosis in 7 women and 12 men undergoing transplantation for cardiac failure. Myocyte necrosis was evaluated by detection of DNA damage with blunt end fragments, whereas apoptosis was assessed by the identification of double-strand DNA cleavage with single base or longer 3' overhangs. An identical analysis of these forms of cell death was performed in control myocardium. Heart failure showed levels of myocyte necrosis 7-fold greater than apoptosis in patients of both sexes. However, cell death was 2-fold higher in men than in women. Heart failure resulted in a 13-fold and 27-fold increase in necrosis in women and men, respectively. Apoptosis increased 35-fold in women and 85-fold in men. The differences in cell death between women and men were confirmed by the electrophoretic pattern of DNA diffusion and laddering of isolated myocytes. The lower degree of cell death in women was associated with a longer duration of the myopathy, a later onset of cardiac decompensation, and a longer interval between heart failure and transplantation. In conclusion, myocyte necrosis and apoptosis affect the decompensated human heart; each contributes to the evolution of cardiac failure. However, the female heart is protected, at least in part, from necrotic and apoptotic death signals.

Apoptosis↗
PubMed1999

Combined yolk sac tumor and adenocarcinoma in a gastric stump: molecular evidence of clonality.

BACKGROUND: Extragonadal yolk sac tumors of the gastrointestinal tract are extremely rare neoplasms. Their greater rarity compared with other extragonadal yolk sac tumors suggests that different pathogenetic mechanisms could be involved according to the site of origin. This report describes a case of a combined yolk sac tumor and adenocarcinoma that arose in a gastric stump in a man age 61 years 43 years after he underwent distal gastric resection and gastrojejunostomy (Billroth II operation) for a benign duodenal ulcer. The coexistence of an adenocarcinomatous component with the yolk sac component suggests that the two histologic patterns may represent distinct phenotypes arising from a common mucosal epithelial cell. METHODS: Immunohistochemical and molecular techniques were used to define the mutation pattern of p53 in both components of the tumor. RESULTS: Single-strand conformation polymorphism and sequencing analyses demonstrated the same pattern of p53 mutation in the adenocarcinomatous and yolk sac tumor components. CONCLUSIONS: This finding suggests that the two tumors could have been derived from the same cellular clone and supports the hypothesis that the two components represented a heterogeneous differentiation of the same tumor.

Adenocarcinoma↗
PubMed1999

Image sampling in static telepathology for frozen section diagnosis.

BACKGROUND: A frozen section diagnostic service is often not directly available in small rural or mountain hospitals. In these cases, it could be possible to provide frozen section diagnosis through telepathology systems. Telepathology is based on two main methods: static and dynamic. The former is less expensive, but involves the crucial problem of image sampling. AIMS: To characterise the differences in image sampling for static telepathology when undertaken by pathologists with different experience. METHODS: As a test field, a previously studied telepathology method based on multimedia email was adopted. Using this method, three pathologists with different levels of experience sampled images from 155 routine frozen sections and sent them to a distant pathology institute, where diagnoses were made on digital images. After the telepathology diagnoses, the glass slides of both the frozen sections and the definitive sections were sent to the remote pathologists for review. RESULTS: Four of 155 transmissions were considered inadequate by the remote pathologist. In the remaining 151 cases, the telepathology diagnosis agreed with the gold standard in 146 (96.7%). There was no significant divergence between the three pathologists in their sampling of the images. Each case comprised five images on average, acquired in four minutes. The overall time for transmission was about 19 minutes. CONCLUSIONS: The results suggest that in routine frozen section diagnosis an inexperienced pathologist can sample images sufficiently well to permit remote diagnosis. However, as expected, the internet is too unreliable for such a time dependent task. An improvement in the system would involve integrated real time features, so that there could be interaction between the two pathologists.

Frozen Sections↗
PubMed1999

Dynamic robotic telepathology: a preliminary evaluation on frozen sections, histology and cytology.

We evaluated the diagnostic efficacy of a dynamic robotic telepathology system for the delivery of pathology services to distant hospitals. The system provided static/dynamic features and the remote control of a robotic microscope using four ISDN lines. For evaluation purposes, 184 consecutive cases were diagnosed at distance using the system. The cases were 60 frozen sections, 64 cases of gastrointestinal pathology and 60 cases of urinary cytology. The telemedicine diagnoses obtained in this way were compared with traditional microscopic diagnosis. Diagnostic agreement ranged from 90% in urinary cytology to 100% in frozen sections. The results suggest that a dynamic robotic telepathology system can be a useful tool for supporting the pathology practice of isolated hospitals.

Evaluation Studies as Topic↗
PubMed1999

Human mammary gland and breast carcinoma contain immunoreactive inhibin/activin subunits: evidence for a secretion into cystic fluid.

OBJECTIVE: Inhibins and activins are members of the transforming growth factor beta superfamily and are known to modulate the growth and differentiation of several cell types. The present study investigated the localization of inhibin and activin subunits in human normal and pathological breast tissues. DESIGN: A cross-sectional study comparing the expression of inhibin/activin subunits alpha, betaA and betaB in surgical specimens from women undergoing reductive mammoplasty (classified, according to the phase of the menstrual cycle, as follicular, luteal, or postmenopausal), and patients submitted to lumpectomy for fibrocystic disease, benign (intraductal papilloma, adenomyoepithelioma, and hamartoma) or malignant breast neoplams (intraductal, intralobular, and invasive carcinoma). METHODS: Immunohistochemistry was used to localize inhibin alpha and activin betaA and betaB subunits in the cytoplasm of epithelial cells of mammary glands. Dimeric activin A, inhibin A and inhibin B were measured by specific two-site enzyme immunoassay in the cystic fluid collected from patients with fibrocystic disease. RESULTS: An intense staining for the alpha inhibin subunit and a mild staining for betaA and betaB subunits were present in samples obtained from normal breast tissue regardless of menstrual cycle phase, and in fibrocystic disease and benign neoplasms. Carcinoma cells stained weakly to moderately for alpha subunit and were negative for betaA and betaB subunits. Fibrocystic disease was associated with absence of betaA subunit expression in normal epithelial cells and intense staining for all subunits in the apocrine cells. Immunoreactive inhibin A, inhibin B, and activin A were also present in cystic fluid, suggesting a local secretion of these proteins. CONCLUSION: These data suggest a local expression and secretion of inhibin and activin in human normal, fibrocystic disease and neoplastic breast tissues. The low expression of these proteins may facilitate abnormal cell proliferation in breast carcinoma.

Activins↗
PubMed1999

Prognostic value of thyroid transcription factor-1 in primary, resected, non-small cell lung carcinoma.

Thyroid transcription factor-1 (TTF-1) is a 38-kDa nuclear protein expressed in thyroid follicular cells, in human fetal lung, and, after birth, in Type II epithelial cells of alveoli and in a subset of bronchial cells. Expression of TTF-1 was documented in neoplasms arising from cells that normally produce this transcription factor. In the present study, a series of surgically resected non-small cell lung carcinomas (NSCLCs) was evaluated for the expression of TTF-1 protein, and the correlation between TTF-1 expression and patient survival was retrospectively tested. Ninety-six patients with primary NSCLC underwent surgical resection between 1987 and 1992. All of the tissue specimens from these patients were examined for TTF-1 protein expression by immunohistochemical analysis. Tumor immunoreactivity for TTF-1 was categorized into three groups (-, +, and ++), according to the percentage of reactive cells. The relationship between TTF-1 expression and postsurgical survival was analyzed for 88 patients [60 squamous cell carcinomas (SCCs) and 28 adenocarcinomas (ACs)]. TTF-1 stain was always limited to nuclei. Of the 96 specimens of NSCLC, 59 (61%) were scored as -, 20 (21%) as +, and 17 (18%) as ++. TTF-1 expression was significantly higher in ACs than in SCCs (P < .0001). Survival curves among the -, +, and ++ groups were significantly different (log rank test, P = .04). Multivariate analysis showed that NSCLCs in the ++ group were associated with a poor prognosis (P = .009), independent of node (P = .01) or stage status (P = .0006). When subsets of patients with SCC and with AC were separately analyzed, TTF-1 was found to have an independent prognostic value only in patients with SCC (P = .04). The results of this study suggest that immunoreactivity for TTF-1 in NSCLC closely relates to clinical outcome, especially in patients with SCC.

Adenocarcinoma↗
PubMed1999

Analysis of cystic intracranial lesions performed with fluid-attenuated inversion recovery MR imaging.

BACKGROUND AND PURPOSE: T1-, T2-, and proton density (PD)-weighted sequences are used to characterize the content of cystic intracranial lesions. Fluid-attenuated inversion recovery (FLAIR) MR sequences produce T2-weighted images with water signal saturation. Therefore, we attempted to verify whether FLAIR, as compared with conventional techniques, improves the distinction between intracranial cysts with a free water-like content versus those filled with a non-free water-like substance and, consequently, aids in the identification of these lesions as either neoplastic/inflammatory or maldevelopmental/porencephalic. METHODS: Forty-five cystic intracranial lesions were studied using T1-weighted, T2-weighted, FLAIR, and PD-weighted sequences. By means of clustering analysis of the ratio in signal intensity between the cystic intracranial lesions and CSF, the intracranial lesions were classified as filled with a free water-like content or with a non-free water-like substance. The results were compared with their true content as evaluated either histologically or on the basis of clinical, neuroradiologic, and follow-up features (necrotic material, 13 cases; accumulation of intercellular proteinaceous/myxoid material, eight cases; keratin, five cases; CSF, 19 cases). Cystic intracranial lesions were divided into two clinical groups, neoplastic/inflammatory and maldevelopmental/porencephalic, to evaluate the level of accuracy of each MR technique. The difference in absolute value signal intensity between CSF and cystic intracranial lesion content was calculated on FLAIR and PD-weighted images. RESULTS: PD-weighted and FLAIR sequences, unlike T1- and T2-weighted sequences, accurately depicted all cystic intracranial lesions containing necrotic or myxoid/proteinaceous intercellular material (non-free water-like) and most CSF-containing cystic intracranial lesions (free water-like). All imaging techniques inaccurately showed some of the keratin-containing cystic intracranial lesions and pineal cysts. The overall error rate was 22% for T1-weighted, 27% for T2-weighted, 9% for FLAIR, and 13% for PD-weighted sequences. The signal intensity difference between CSF and cystic intracranial lesion content was higher with FLAIR imaging. CONCLUSIONS: FLAIR imaging depicts far more accurately the content of cystic intracranial lesions and better reveals the distinction between maldevelopmental/porencephalic and neoplastic/inflammatory lesions than do conventional sequences. FLAIR has the added advantage of a higher signal intensity difference between cystic intracranial lesions and CSF.

Adult↗
PubMed1999

Nuclear size of myocardial cells in end-stage cardiomyopathies.

OBJECTIVE: To determine the alteration of nuclear size in myocardial cells and the relationship between nuclear size and DNA ploidy classes in normal and cardiomyopathic human hearts. STUDY DESIGN: The study group consisted of 46 hearts obtained at biopsy. These patients had undergone cardiac transplantation for intractable congestive heart failure (18 cases with ischemic cardiomyopathy and 28 cases with idiopathic dilated cardiomyopathy). Another 10 hearts were collected at autopsy and used as control hearts according to preautopsy, autopsy and histology criteria. One hundred fibroblasts and 200 myocytes were evaluated in each ventricle. The nuclear area and DNA content were estimated using image cytometry. RESULTS: End-stage ischemic and dilated cardiomyopathies were characterized by an increase in nuclear size of both the myocyte and nonmyocyte population. The nuclear area of interstitial cells increased about 30% in cardiomyopathic hearts. Augmentation of average nuclear area of myocytes was 1.2-fold in the ischemic group and about 1.5-fold in the dilated group as compared with the control group. Also, a tendency was found for the coefficient of variation of average nuclear area to decrease in the interstitial cell population and increased in the myocyte population in cardiomyopathic situations. Furthermore, the nuclear area of myocytes enlarged as augmentation of nuclear DNA content. The relative nuclear areas of myocytes can be presented as: 2c:4c:8c:16c :32c:64c = 1:1.65:2.75:4.60:7.25:9.18. CONCLUSION: The increase in nuclear size follows either one of two different processes: the first does not involve an increase in DNA content, whereas the second is concomitant with an incremental increase in DNA content. In the first instance, the enlargement of nuclear size is limited. In the second, augmentation of nuclear size can become very impressive. In end-stage ischemic and dilated cardiomyopathies, the nuclear growth of myocytes and interstitial cells may be due to different mechanisms. Enlargement of the nuclear area of myocytes represents a complex process, including simple nuclear hypertrophy, polyploidization and multinucleation. The main pattern of nuclear growth of interstitial cells is nuclear hypertrophy without an increase in DNA content.

Adult↗
PubMed1998

Image-guided core breast biopsy: a suitable method for preoperative biological characterization of small (pT1) breast carcinomas.

Multiple prognostic indicators, namely histological grade and immunostaining for estrogen (ER) and progesterone receptors (PgR), MIB 1, bc1-2, and p53, were retrospectively determined on preoperative core biopsies from 75 patients with pT 1 breast carcinoma. The association of the preoperatively evaluated factors with those on the corresponding resected tumors (i.e. nodal status, histological grade, presence or absence of vascular invasion and necrosis) was assessed. In univariate analysis, histological grade on resected tumors was significantly associated with histological grade on core biopsy, p53 expression, MIB1 immunostaining. An inverse association was found between postoperative histologic grade and ER, PgR, and bc1-2. Necrosis was significantly associated with grade, p53, MIB1, and inversely with ER, PgR, and bc1-2. Nodal involvement and vascular invasion were significantly associated with MIB1. In multivariate analysis, histological grade and ER were the only independent core biopsy variables associated with postoperative histological grade and necrosis, respectively. This study showed that image-guided core biopsy is a suitable method that can be used to reveal some characteristics of the tumor biology in a preoperative stage.

Aged↗
PubMed1998

Myocyte proliferation in end-stage cardiac failure in humans.

Introduced several decades ago, the dogma persists that cardiac myocytes are terminally differentiated cells and that division of muscle cells is impossible in the adult heart. More recently, nuclear mitotic divisions in myocytes occasionally were seen, but those observations were challenged on the assumption that the rate of cell proliferation was inconsequential for actual tissue regeneration. Moreover, mitoses were never detected in normal myocardium. However, the analysis of routine histologic preparations constituted the basis for the belief that myocytes were unable to reenter the cell cycle and divide, ignoring the limitations of these techniques. We report here by confocal microscopy that 14 myocytes per million were in mitosis in control human hearts. A nearly 10-fold increase in this parameter was measured in end-stage ischemic heart disease (152 myocytes per million) and in idiopathic dilated cardiomyopathy (131 myocytes per million). Because the left ventricle contains 5.8 x 10(9) myocytes, these mitotic indices imply that 81.2 x 10(3), 882 x 10(3), and 760 x 10(3) myocytes were in mitosis in the entire ventricular myocardium of control hearts and hearts affected by ischemic and idiopathic dilated cardiomyopathy, respectively. Additionally, mitosis lasts less than 1 hr, suggesting that large numbers of myocytes can be formed in the nonpathologic and pathologic heart with time. Evidence of cytokinesis in myocytes was obtained, providing unequivocal proof of myocyte proliferation.

Adult↗
PubMed1998

TTF-1 protein expression in pleural malignant mesotheliomas and adenocarcinomas of the lung.

TTF-1 is a tissue-specific transcription factor expressed in the epithelial cells of thyroid and lung. This study investigates the immunohistochemical expression of TTF-1 in pleural malignant mesotheliomas (MM) and adenocarcinomas (AC) of the lung, respectively. For this purpose, 33 biopsy specimens of pulmonary AC and 24 specimens of MM were studied. TTF-1 immunoreactivity was identified in 19 of 33 cases of AC (57.5%) and in none of the 24 cases of MM. Positivity for TTF-1 was 100% specific and 57.5% sensitive for lung AC. Alternatively, negativity for TTF-1 was 57.5% specific and 100% sensitive for MM. These results suggest that TTF-1 can be favourably added to the immunohistochemical diagnostic panel for distinction between AC of the lung involving the pleura and pleural MM.

Adenocarcinoma↗
PubMed1998

Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study.

The purpose of this work was to investigate the prevalence, associated features and effect on survival of portal vein thrombosis (PVT) complicating hepatocellular carcinoma (HCC). The autopsy data of a series of 72 consecutive patients (57 male, 15 female) with HCC were reviewed. PVT was found in 32/72 patients (44%), and tended to be more common in female patients (10/15 versus 22/57, P = 0.052). Stratifying the data according to gender, it appeared that the mean age of patients with PVT compared to those without was greater in woman (71.9 +/- 5.9 versus 63.2 +/- 6.9 years, P = 0.024) and younger in men (58.8 +/- 8.9 versus 66.0 +/- 9.9 years, P = 0.007). When PVT was present, it was more likely that a definite diagnosis of HCC had been obtained before autopsy (P = 0.0001) and that death had been caused by bleeding complications (P = 0.007). Median survival times were similar, irrespective of the presence of PVT. During the natural history of HCC, PVT occurs in a substantial proportion of patients. Hormonal factors may have a permissive role in thrombus formation or neoplastic vascular invasion. Although in the presence of PVT a diagnosis of HCC is rarely missed and bleeding complications are likely to occur, patient survival does not seem to be significantly affected.

Age Factors↗
PubMed1998

DNA index shift with disease progression in colorectal adenocarcinoma: a morphological and flow cytometric study.

DNA index (DI) values seen in 86 sporadic colorectal adenocarcinomas were related to clinical, morphological, and disease progression features. DI, whose overall distribution was bimodal with peaks in the diploid and from hypotriploid to tetraploid ranges, was related to pathological lymph node staging (pN), staging, lymphoid reaction, and tubular configuration. With increasing severity in pathological features, an irregular shift in DI class prevalence was seen, with no steady increase from diploidy to higher degrees of aneuploidy. All UICC stage I tumors (13% of total) were aneuploid, 50% being hypertriploid; diploidy (35%) and hypertriploidy (22%) prevailed in stage II carcinomas (41% of total), diploidy (35%) and hypotriploidy (30%) in stage III (30% of total), and triploidy (33%) in stage IV (15% of total). Amongst features related to stage (lymphoid reaction, depth of neoplastic embolization, grading, tubular configuration, and polymorphism), few were associated with DI, and none influenced DI shift and class prevalence through the stages. The biological capabilities of colorectal adenocarcinoma in relation to stage are expressed by certain aneuploid DI classes (hypertriploidy: absence of extracolonic spread; hypotriploidy: lymph node metastases; triploidy: distant metastases). Diploidy is unrelated to criteria defining stage above I and predicts 50% of cases with development of metachronous metastases. Irregular DI class shift through the stages may be attributable to different pathways of cancerogenesis and disease progression in diploid versus aneuploid carcinomas. Alternatively, assuming that the diploid fraction in aneuploid tumors contains neoplastic cells, pure diploid carcinomas represent the selection of a vital clone that may give rise to a further mixed population whose aneuploid DI is different and best fitted to express the biological capabilities of that given stage.

Adenocarcinoma↗
PubMed1998

Image selection in static telepathology through the Internet.

A telepathology study was carried out to examine the differences occurring when the images were selected by an experienced pathologist, a junior pathologist and a first-year resident. One hundred and fifty-five consecutive frozen-section pathology cases were collected and sent for consultation to a remote experienced pathologist using multimedia email. Local diagnoses (as reported in the files of the Institute, not from the image selector) and remote diagnoses (based on the images) were compared with those performed on paraffin-embedded sections. Acquisition time and number of selected images were recorded for each case and used to compare the different behaviour of the three local pathologists. Of the 155 cases sent by telepathology, four were considered insufficient for a diagnosis by the remote pathologist and thus the diagnosis was postponed. In the remaining 151 cases, the overall diagnostic agreement between remote and definitive diagnosis was 96.7%. The results indicate that in the routine diagnostic work of a frozen-section service, an inexperienced pathologist can select images which are sufficiently informative for a remote diagnosis, in a sufficiently short time.

Clinical Competence↗
PubMed1998

BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine.

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.

2-Chloroadenosine↗
PubMed1997

Apoptosis in the failing human heart.

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.

Apoptosis↗