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Biomedical subjects

W F Grigioni

Publications and source records attributed to W F Grigioni.

At least 73 records · Page 4Linked to original sources

Changes in the alveolar connective tissue of the ageing lung. An immunohistochemical study.

The modifications of the extracellular matrix (ExM) components in the alveolar parenchyma of elderly subjects were investigated using a panel of polyclonal antibodies. The elastic fibers showed a notable decrease along the alveolar walls while type III collagen increased when compared with that of non-elderly controls. No variations of these components were detectable in the alveolar ducts or in the respiratory bronchioli. An increase in the thickness of the alveolar basement membranes was detected in some of the subjects when antibodies against type IV collagen and laminin were used, while antibodies to fibronectin and type V collagen did not reveal any modifications compared with the controls. The modifications revealed in the lungs of the elderly can be related to the alterations of the elastic recoil and pulmonary compliance observed in these subjects.

Aged↗

Reliability of 24-hour home esophageal pH monitoring in diagnosis of gastroesophageal reflux.

Twenty-four-hour home esophageal pH monitoring is proposed in order to study gastroesophageal reflux (GER) so that prolonged use of costly hospital equipment and staff can be curtailed and the diagnostic accuracy of the examination improved. Eighty-six patients affected by GER symptoms and 20 healthy volunteers underwent 24-hr home esophageal pH monitoring, x-rays, and endoscopy of the upper gastrointestinal tract to investigate reliability of outpatient recording. Fifteen more patients consecutively underwent out- and inpatient recording to detect possible differences between these methods in the two daily periods. Outpatient monitoring was well tolerated in 94.7% of the patients; 14.3% of them markedly reduced their routine activities. The range of normality of outpatient recording does not differ from that of inpatients. In the 15 patients who consecutively underwent out- and inpatient monitoring, no significant differences were reported. The sensitivity of 24-hr home esophageal pH recording is 0.85, the specificity 1, the accuracy for negative prediction 0.68, and the accuracy for positive prediction 1. The reliability of 24-hr home esophageal pH monitoring is comparable to inpatient recording. It allows hospital cost reduction and is also better tolerated by patients but has not greatly improved the diagnostic accuracy of the gastroesophageal reflux pH monitoring.

Adult↗

Class I and class II HLA antigen expression by transitional cell carcinoma of the bladder: correlation with T-cell infiltration and BCG treatment.

HLA class I and II glycoproteins from transitional cell carcinoma (TCC) and from perineoplastic and healthy vesical mucosa were characterized together with infiltrating cells by means of immunochemistry using specific monoclonal antibodies on frozen sections obtained during resection or radical cystectomy. Specimens were taken from 11 patients with TCC and five with healthy bladder mucosa. Four patients with TCC and four with healthy mucosa had been previously treated with a course of intravesical bacillus Calmette-Guerin (BCG). Ten out of 11 TCC samples expressed class I glycoproteins with a membrane pattern (diffuse in seven, focal in three) as normal epithelial cells from either controls or perineoplastic bladder. Interestingly, eight out of 11 TCC samples expressed class II antigens on their membrane that were also present in six cases in the perineoplastic tissue while the epithelial cells from four out of five normal bladders were completely negative. The epithelial display of class II antigens in the non-neoplastic areas and in the normal bladder correlates (p less than 0.001) with the degree of cellular infiltrate while such a relationship was not found between the HLA II expression of neoplastic cells and the infiltrate. BCG treatment was associated with a higher amount of inflammatory cells, prevalently T "activated" cells (CD5+,DR+), with a CD4/CD8 ratio always greater than 1. In the light of the role played by HLA glycoproteins in immune mechanisms, these results could help explain the positive action of BCG and the relative immunosensitivity of TCC.

Aged↗

Small liver masses in cirrhotic patients. A pathological clue for the morphogenesis of human hepatocellular carcinoma.

Eleven small primary liver lesions detected in four cirrhotic patients are reported in detail. Some lesions showed the histopathological features of macroregenerative nodules (MRN) containing foci of cellular and structural atypia or of hepatocellular carcinoma (HCC). Other lesions showed the histological abnormalities of the early developmental stage of HCC without a background of MRN. Finally one lesion is described with an equivocal background between benign and malignant, containing a focus of carcinoma. All lesions presented suggest the presence of different pathways in the morphogenesis of human HCC.

Adult↗

Different metastatic aggressiveness by murine TS/A clones: ultrastructure, extracellular glycoproteins and type IV collagenolytic activity.

Cell ultrastructure, extracellular matrix glycoproteins, and type IV collagenolytic activity have been examined in four murine TS/A clones characterized by different metastatic aggressiveness. In vitro, highly metastatic clones (E) exhibited slightly less differentiated ultrastructure, and high type IV collagenolytic activity, while low metastatic clones (F) showed a more differentiated cytotype, with either high and low collagenolytic activity. Type IV collagen, laminin, and fibronectin were expressed without correlation with the metastatic efficiency; keratin was slightly more evident in E than in F cells. The morphological differences between E and F clones were less evident in the tumors produced by subcutaneous injection, and markedly reduced in the relative metastases composed only of the less differentiated cytotype; differences were also reduced in cells cultured on extracellular-matrix-coated flasks. The present study shows that no general correlation is observed between the studied parameters and metastatic aggressiveness.

Adenocarcinoma↗

Hepatocellular carcinoma: expression of basement membrane glycoproteins. An immunohistochemical approach.

The identification and characterization of collagenous and non-collagenous glycoproteins have made it possible to use specific antibodies as tools for the topographical localization of the various connective tissue components, and thus to follow the progression of parenchymal-stromal interactions. This investigation is an approach to the study of in vivo relationships between basement membrane components (type IV collagen, laminin) and neoplastic cells of hepatocellular carcinoma. Ten cases of hepatic carcinomas were analysed and paraffin-embedded sections were immunostained with anti-laminin and anti-type IV collagen antibodies. The avidin-biotin-peroxidase complex technique was used. In well differentiated neoplasms with hepatic tumour cells organized in a trabecular pattern lined by sinusoid structures, type IV collagen was always detected at the sinusoidal level. Laminin was evident only in two cases with a prominent intraparenchymal vascular bed. In less differentiated neoplasms, sinusoids were almost absent and only large tumour vessels were positive for both laminin and type IV collagen. At the interface between tumour tissue and the surrounding stroma, some carcinomatous elements were surrounded by laminin and type IV collagen. Our data further support the hypothesis that basement membrane phenotypic expression may be influenced both by the degree of tumour differentiation and by the characteristics of the micro-environment.

Basement Membrane↗

Early gastric cancer in Italy. Clinical and pathological observations on 80 cases.

Of 542 gastric cancer patients operated in the period between 1976 and 1982, we found early gastric cancer (EGC) in 80 cases (15.3%). Patients with EGC did not show specific symptoms if compared with patients affected by gastric or duodenal peptic ulcer, gallstones, functional disorders of the upper gastrointestinal tract, or advanced gastric cancer (AGC). Single-contrast radiology showed a low sensitivity, especially in the depressed lesions. In contrast, endoscopy alone diagnosed 64 EGCs (80.0%) as malignant lesions. The five-year overall survival rate of the EGC patients was 85.9% and that of AGC patients was 43.8%. From a pathological point of view, our results confirm the usefulness of the studies on EGC for the comprehension of gastric carcinogenesis. The clinical relevance of EGC is linked to the good prognosis; however, the absence of clear symptoms and lack of alternative diagnostic methods to the endoscopy cast some doubts on the feasibility of mass detection programs.

Adenoma↗

Primary liver cell carcinoma. New insight for a more correct approach to its classification.

Hepatocellular carcinomas, cholangiocellular carcinomas, and "indeterminate" forms have been studied by immunohistochemical detection of several antigens: alpha-fetoprotein and CEA, as well as type IV collagen, laminin, and keratin. While the first two antigens were variably detectable in different samples, in the poorly differentiated areas of hepatocellular carcinoma type IV collagen and laminin were both absent. These basement membrane glycoproteins constantly surrounded the cholangiocellular carcinoma tubular structures and were always present in those areas of the "indeterminate" group where the cells were organized as pseudoglandular or ductular aggregates. Keratin was absent in all cases of hepatocellular carcinoma, was variably detectable in the "indeterminate" neoplasms and was always present in cholangiocellular tumors. The neoplasias with mixed histopathological features usually showed morphological and biochemical biliary differentiation at the periphery, in contact with the collagenous stroma. We postulate that in some cases hepatocarcinoma cells undergo metaplastic transformation giving rise to cholangiocellular forms. Type IV collagen, laminin, and keratin seem to be accurate markers of phenotypical differentiation and show that a continuous phenotypical spectrum exists between hepatocellular and cholangiocellular entities.

Adenoma, Bile Duct↗

Monoclonal antibody to HSV2 protein as an immunodiagnostic marker in cervical cancer.

The present study was designed to evaluate the possible use of monoclonal antibodies (mAbs) as diagnostic adjuncts to exfoliative cytology and tissue sections in intraepithelial (CIN) and invasive cervical cancer. Specimens were collected from 42 patients with various degrees of CIN, 15 patients with invasive cancer and two patients with condylomatous changes only. mAb H17, that recognizes a herpes simplex virus protein (ICP) representing a component of the viral ribonucleotide reductase, stained atypical exfoliated cells from 55% of patients with mild dysplasia and 100% of those with more severe lesions. The mean percentage of positive atypical cells increased as a function of the grading of CIN (32.6 +/- 6.3%, 63.5 +/- 2.7%, 67.9 +/- 8.1%, 81.4 +/- 10.1%, and 85.6 +/- 2.0% for mild, moderate, and marked dysplasia, CIS, and invasive cancer, respectively). Only a very small proportion of atypical cells from only two patients stained with a mAb to another herpes simplex virus protein (gA/B). Normal squamous, metaplastic, inflammatory, or koilocytotic cells did not stain with the mAbs. Of the 15 cases examined by cryostatic fresh sections with immunohistochemical techniques, only one case of invasive cancer did not stain with mAb anti-ICP, and all controls were negative. The high specificity and sensitivity of MAbH17 suggests that it may be a useful diagnostic/prognostic marker in CIN.

Animals↗

Immunohistochemical study of basement membrane antigens in bronchioloalveolar carcinoma.

Bronchioloalveolar carcinoma (BAC), not yet completely defined as a biologic entity, has recently been classified into two different types. Immunohistochemical investigations, aimed at characterizing basement membrane (BM) behavior in the two types of BAC, revealed different distribution patterns. The first (Type I BAC) showed a linear staining for laminin and Type IV collagen similar to normal lung. Fibronectin was widely present in the septal interstitium and patchily distributed along the BM. The second (Type II BAC) showed a variable reaction for Type IV collagen and fibronectin, whereas laminin was absent or appeared as short, interrupted tracts around the epithelial neoplastic population, similar to conventional adenocarcinoma of the lung. These results suggest that only Type I BAC shows structural characteristics different from those of conventional adenocarcinoma of the lung.

Adenocarcinoma↗

Gastric carcinoid: a clinical and endoscopic assessment of four cases.

We have established a pre-operative diagnosis in four cases of non-secretory gastric carcinoid of the body and fundus presenting as multiple polyps in three patients, and a single polyp mass in the fourth patient. Clinical and endoscopic findings are not specific, and the pre-operative diagnosis was established by means of biopsy or polypectomy. We observed biochemical and histological differences between multiple and single carcinoids, which might indicate different mechanisms of carcinoid pathogenesis.

Adult↗

Behaviour of basement membrane antigens in gastric and colorectal cancer. Immunohistochemical study.

Eighty gastric and colorectal lesions including cases of dysplasia and carcinoma were studied by immunohistochemical techniques to investigate the behaviour of laminin, type IV collagen and fibronectin. Their distribution was examined on frozen and formalin-fixed, paraffin-embedded samples. In the same lesions, interruption, fragmentation and absence of basement membrane (BM) antigen-staining were observed. Carcinomas with well differentiated glandular structures were always surrounded by a well defined BM as in normal, non-pathological tissues. On the contrary, undifferentiated areas arranged in nests or sheets were usually negative for laminin and type IV collagen. Anomalous BM staining was strictly related to the degree of differentiation of tumor tissue, while no correlation existed between carcinoma staging and BM antigen presence, either in gastric or colorectal neoplasms. Immunostaining with antibody against type IV collagenase showed a massive positivity in the early gastric carcinomas examined, while in colorectal cancer only granulocytes showed it.

Antigens↗

Detection of extracellular matrix antigens (fibronectin, laminin, type IV in collagen) in paraffin embedded sections by avidin-biotin-peroxidase complex labelling.

An avidin-biotin-peroxidase labelling method was applied to frozen sections and to routine-fixed, paraffin-embedded sections, and compared with immunohistochemical results of stromal antigen detection (type IV collagen, laminin and fibronectin) obtained in parallel on different neoplasias. Lung, breast and gastrointestinal tract tumors were studied. Superimposable sections were obtained from cryostat and formalin-fixed, paraffin-embedded specimens (previously digested by pepsin). The data demonstrate the potential use of immunohistochemical investigation of paraffin-embedded tissues for histological analyses of tumors.

Avidin↗

Gastric carcinoids of ECL cells. Pathological and clinical analysis of eight cases.

Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non-antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) "simple hyperplasia", b) "nodular hyperplasia", and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non-antral portion of the stomach with possible therapeutical implications.

Achlorhydria↗

Early gastric cancer. Clinico-pathological analysis of 125 cases of early gastric cancer (EGC).

The frequency and the pathological findings of 125 early gastric cancers (ECGs), and particularly of small and minute lesions, were evaluated in a retrospective study of 839 surgical specimens of gastric carcinoma. Sixty two ECGs were believed to have risen from gastric epithelium, 27 from areas of intestinal metaplasia, and 3 from cardio-pyloric mucosa. The remaining lesions showed mixed histological patterns. The most frequent macroscopic type was IIc (24.8%) followed by IIb (16.8%), I (16.8%), and III (14.4%). In 63 cases (50.4%) the cancer was limited to the mucosa. In all specimens, and particularly in small and minute lesions, the surrounding mucosa was accurately analyzed to detect any lesions, from which the cancer could have developed. Intestinal ECGs, especially if protruded, seem to arise from areas of intestinal metaplasia or of chronic atrophic gastritis. Rarely ECGs seem to stem from polypoid lesions both hyperplastic and adenomatous. On the contrary, most important seems to be the role of ulcerative lesions, since in 14 cases of our series, carcinomatous foci were observed within the regenerative epithelium covering the crater. No correlation was found between histologic type, size, staging, and frequency of node metastasis; this suggests the existence of ECGs with different biologic behaviour.

Adult↗

Mucin secretion and morphological changes of the mucosa in non-neoplastic diseases of the colon.

Changes in mucin secretion and increase in height of the colonic mucosa adjacent to colorectal carcinoma (transitional mucosa) have been considered pre-malignant. In this study similar changes (both morphological and histochemical) have been found in some cases of ulcerative colitis and ischaemic colitis, as well as in juvenile, inflammatory and hyperplastic (metaplastic) polyps. 'Transitional' patterns of mucin secretion also occur in some other cases of ulcerative colitis, colostomies and Crohn's disease of the colon in which the mucosa has a normal height, suggesting the changes in mucin secretion are independent of mucosal morphology. In all these pathological conditions, hyperplastic (metaplastic) mucosa also coexisted. These findings seem to suggest that: (1) 'transitional' changes more likely represent a secondary regenerative phenomenon rather than a premalignant one; (2) the pattern of mucin secretion is not selective enough to serve as a premalignant marker; therefore is not a valid prognostic indicator in colonic biopsies; (3) hyperplastic (metaplastic) changes might derive from 'transitional' mucosa as a result of a more mature phase of this exaggerated regenerative phenomenon. However, in some patients longstanding 'transitional' mucosa may lead to dysplasia under the influence of environmental and genetic factors.

Biopsy↗