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Biomedical subjects

M Cintorino

Publications and source records attributed to M Cintorino.

At least 73 records · Page 4Linked to original sources
PubMed1988

Expression of cytokeratin polypeptides in human papillomavirus (HPV) lesions of the uterine cervix: 1. Relationship to grade of CIN and HPV type.

A series of 74 punch biopsies, derived from 513 women prospectively followed for cervical human papillomavirus (HPV) infections (including HPV-NCIN, HPV-CIN I, HPV-CIN II, and HPV-CIN III lesions), and 43 control cases (consisting of normal epithelia, nonspecific cervicitis, and classical CIN lesions) were analysed for expression of cytokeratin polypeptides using the ABC technique and monoclonal antibodies SK 56-23 (wide-spectrum antibody), SK 60-61 (specific for keratins 8 and 18), and SK 2-27 (detecting keratins 14, 16, and 17). HPV typing was carried out using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18, and 31. All layers of the exocervical epithelium were regularly stained with the antibody SK 56-23, and the staining pattern remained unaltered in all cervical lesions studied. In contrast to the normal exocervical epithelium, which remained negative with SK 60-61, positive staining was observed in 3 of 15 cervicitis cases and 6 of 23 classical CIN lesions. Interestingly, the majority (69 of 74, 93.2%) of both HPV-NCIN and HPV-CIN lesions showed positive staining with this antibody either in all layers or in suprabasal cells. Antibody SK 2-27 stained the basal cells of the normal exocervical epithelium with remarkable specificity. In 18 of 19 HPV-NCIN lesions, basal cells could not be stained by SK 2-27 monoclonal, but the suprabasal cells were stained instead. In HPV-CIN, but not in classical CIN, this antibody demonstrated the presence of the epitope typical of the cytokeratins 14, 16, and 17 in all layers of the epithelium, the highest frequency (9 of 12, 75%) being found in HPV 16-induced lesions. These disturbances of cytokeratin patterns in cervical epithelium could be associated with cell transformation by HPV, leading to development of HPV-CIN, and could be specific for this virus. The present data are of interest in assessing the stage of maturation of the squamous cells in progressing cervical HPV infections.

Antibodies, Monoclonal↗
PubMed1988

Comparative morphometric analysis of nuclear area and shape in peripheral T-zone lymphomas and in paracortical areas of normal and reactive lymph nodes.

The areas and shapes of cell nuclei were morphometrically analyzed in peripheral T-zone lymphomas, which have a characteristic nuclear pleomorphism, as well as in paracortical areas of normal and reactive lymph nodes; the aim of the study was to compare the neoplastic and nonneoplastic lymphoid cell populations. Although the means and standard deviations (SDs) of nuclear area and shape features differed significantly between the T-zone lymphomas, reactive nodes and normal nodes, there was considerable overlap between the lymphomas and the reactive lymph nodes in all of the features investigated. Therefore, the composition of populations of nuclei was studied. In lymphomas, the frequencies of regular and irregular nuclei were about the same in all nuclear area classes, whereas increasingly larger nuclei had an increasingly regular shape in reactive lymph nodes. An attempt to classify the cells, divided into those with small nuclei (less than 25 sq microns) and those with large nuclei (greater than 25 sq microns), on the basis of their morphometric shape features showed the usefulness of form factors in the class of nuclei with a large area. The results show that, while means and SDs of nuclear area and shape are not very accurate descriptors of the differences between the T-zone lymphomas and nonneoplastic lymph nodes, analysis of the percentage of regularly shaped nuclei in a certain nuclear area class can describe the differences much more accurately. The compositional differences in nuclear shape are in agreement with subjective impressions and can objectively support the pathologist's qualitative impression of pleomorphism in malignant T-zone lymphomas.

Adult↗
PubMed1988

Site-specific monoclonal antibodies against peanut agglutinin (PNA) from Arachis hypogaea. Immunohistochemical study of tissue-cultured cells and of 27 cases of Hodgkin's disease.

The purpose of this study was to increase the sensitivity of the staining reaction for the T antigen on the surface of neoplastic cells grown in vitro with the use of site-specific monoclonal antibodies (MAbs). The authors describe anti-peanut agglutinin (PNA) MAbs selected by screening the hybridomas with PNA and PNA bound to bovine serum albumin conjugated with the T antigen. The selected hybridomas (F2C8, F3D12, F3A5) were then grown in pristane-sensitized mice or in the Amicon Hollow Fiber System (F2C8). The affinity constant values for PNA were measured, and all the purified MAbs were tested on both native and denatured PNA, wheat germ agglutinin, concanavalin A, and ricin by using the immunoassay dot test and immunoblotting methods. Eleven different cell lines were stained with the three MAbs; similar results were obtained with F2C8 and F3D12. In each case the fluorescence, if present, was associated with the cell membrane, and the intensity of the staining was always stronger when the cells were incubated with the MAbs than when stained with fluorescein-labeled PNA. On the other hand, F3A5 failed to stain unfixed cells preincubated with PNA but stained the same cells after fixation, independently of the presence of PNA. One of the antibodies, F2C8, was used to stain histologic preparations from 27 cases of Hodgkin's disease and was compared with the anti-granulocyte antibody, Leu-M1, which has been used by numerous authors to identify the characteristic Reed-Sternberg cells. The results obtained were qualitatively similar; ie, F2C8 was at least as efficient as anti-Leu-M1 in its ability to stain the typical diagnostic cells in Hodgkin's disease.

Animals↗
PubMed1988

Correlation between differentiation and lung colonization by retinoic acid-treated F9 cells as revealed by the expression pattern of extracellular matrix and cell surface antigens.

For study of the correlation between differentiation and organ colonization properties of tumor cells, F9 embryonal carcinoma (EC) cells were treated with retinoic acid, an inducer of differentiation; and their organ colonization pattern was assessed by the experimental metastasis assay. Untreated cells were found to colonize the liver, whereas treated cells colonized the lungs. This pattern held true when metastases were scored after spontaneous death or after a careful microscopic search for micrometastases. Histologic examination revealed that both the tumor nodules produced by the untreated and the treated cells had the characteristics of EC devoid of any evidence of differentiation. The immunohistochemical study of the expression of markers typical of embryonal carcinoma cells or of the extracellular matrix components laminin and collagen type IV, typical of differentiated cells, confirmed these results. However, the lack of expression of stage-specific embryonal antigen 1 (SSEA-1), a marker generally associated with the undifferentiated state, observed only in the tumors obtained after injection of treated cells, indicates that the lung nodules probably derive from cells that have responded to the induction in vitro but have dedifferentiated in vivo.

Animals↗
PubMed1987

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes.

To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.

Animals↗
PubMed1987

Mycosis fungoides. Detection of OKT6+ cells by cytofluorographic analysis in one case.

An 86-year-old woman had a subjective history of pruritus and intermittent fever. The clinical diagnosis of mycosis fungoides was confirmed by cutaneous and lymph node biopsies. Immunohistochemical, cytofluorographic, and ultrastructural analysis was performed. According to immunohistochemical findings the lymphoid cells infiltrating the skin and lymph nodes were phenotypically T-helper cells. Cytofluorographic and ultrastructural analysis of the peripheral blood detected a small number of cerebriform lymphoid cells. By immunohistochemistry, these cells showed the same phenotype that was found in the skin and lymph nodes. OKT6+ cells, which are not usually present, were also found in the peripheral blood. These findings may suggest a functional relationship between the skin and the lymphoid system.

Aged↗
PubMed1986

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. I. Morphometric assessment of lymph node immunoreactivity and analysis of circulating antibodies.

To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the lymph nodes with the functional assays measuring cytotoxic and tumor cell membrane-bound antibodies in mouse sera. Regional and non-regional (RLN, NRLN) lymph nodes, were subjected to stereological analysis to determine the volume fractions (Vv) of the cortex (C), the paracortex (PCA), the germinal centers (GC), and the medulla (M), using a computerized analysis system (IBAS I, Kontron). In both RLN:s and NRLN:s, lymphocyte subsets were identified and their ratios determined using the ABC (avidin-biotin peroxidase complex) technique and following monoclonal antibodies; Anti-Thy 1.2, Anti-Lyt 1, Anti-Lyt 2, and Anti-I-Ad. The 51Cr release assay was used to test the mouse sera for cytotoxic antibodies, and an indirect immunofluorescence (IF) technique to assess the sera for tumor cell membrane-bound antibodies. There was a marked enlargement of the RLN:s reaching the peak on day 12, due to increase of the Vv of the B-zone as well as of the T-zone. Evidence of distinct B-cell stimulation by the growing of P815X2 was provided by an early decrease of Thy1.2+/I-Ad+ cell ratio both in the RLN:s and in NRLN:s. This activation of B-cells seems to be parallel to the elevation of Lyt1+/Lyt2+ ratio in T-cell region on day 6. The IF-tests for or the presence of tumor cell membrane-bound antibodies were almost invariably negative. With exception of two sera, the 51Cr-release assay for cytotoxic antibodies against P815X2 targets was negative. The present study confirms the previous observations on failure to find circulating cytotoxic or cell membrane-bound antibodies in DBA/2 mice bearing P815X2 mastocytoma, despite the morphologically well definable activation in RLN:s and in NRLN:s of the B-cell areas. This is in alignment with the findings in the majority of human tumors, where B-cell predominance in RLN:s does not represent a favourable prognostic sign.

Animals↗
PubMed1986

Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. II. Morphometric assessment of immunoreactivity in the thymus and spleen related to lymphocyte subsets in peripheral blood.

To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the thymus and spleen with the functional assays measuring cytotoxic (51Cr-release assay) and tumor cell membrane-bound antibodies (IF test) as well as phenotyping (with monoclonal antibodies Anti-Thy1.2, Anti-Lyt1, Anti-Lyt2, and Anti-I-Ad) the lymphocyte subsets in peripheral blood. The volume fractions (Vv) of the cortex (C), and medulla (M) of the thymus, as well as central (C-PALS) and peripheral periarteriolar lymphoid sheath (P-PALS) in the spleen were determined morphometrically. There was a steady increase of the C/M ratio from the control levels until day 8, not accompanied by any major fluctuations in the percentages of Thy1.2+ or I-Ad+ cells in C and M. In M, two significant peaks were found in Lyt1+/Lyt2+ cell ratio. In the spleen P-PALS, Thy1.2+/I-Ad+ cell ratio was subject to major early elevation, followed by a rapid and permanent decline to levels below the controls. Two high peaks of Lyt1+/Lyt2+ ratio were found in P-PALS, on day 10 and 16. In the C-PALS, a marked decline in Thy1.2+/I-Ad+ ratio was observed throughout the experiment. As determined by Vv, there was a marked early enlargement of P-PALS reaching the peak on day 4, and followed by a steady reduction reaching the control values on day 10. In peripheral blood, there was an initial increase of T-cells, leading to elevated Thy1.2+/I-Ad+ ratio and a subsequent elevation of Lyt1+/Lyt2+ ratio on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Morphometric distinction of granulomas in tuberculosis and sarcoidosis. Difference in nuclear profiles.

Morphometric measurements were carried out on epithelioid-cell nuclei of noncaseating granulomas in paraffin-embedded sections of lymph node biopsy specimens originating from 15 patients with sarcoidosis and from 18 patients with tuberculosis. The results, which were obtained with the help of a computer-assisted tracing device, established highly significant differences in shape and size of epithelioid-cell nuclear profiles in these two diseases. Direct measurements and computations on these results showed that epithelioid-cell nuclear profiles in sarcoidosis have a smaller mean and median perimeter (boundary length), area and long diameter (maximum length of the nuclear profile) and exhibit a more plump, elliptical-like shape than do those in tuberculous granulomas. Epithelioid-cell nuclear profiles of the latter, as a whole, show more irregular contours, resembling those, e.g., of the sole of a shoe or other elongated patterns. Differences in shape of nuclear profiles were best demonstrated by a size-independent form factor (4 pi *area/perimeter2).

Adolescent↗
PubMed1983

A morphometric semiautomated method for analyzing cell nuclei in lymph node sections from non-Hodgkin's lymphomas. Significance of data.

A semiautomated electronic system has been employed for sizing nuclear area and for evaluating nuclear form factors in non-Hodgkin's lymphomas with the purpose to correlate these parameters with survival and histotype. By mathematical models for best fits correlating the dependent variables with the survival has been demonstrated that an inverse correlation corresponding to a negative exponential function exists between mean nuclear area and survival. It has also been shown that the nuclear form is less irregular (i.e. more similar to an ellipse) when the mean nuclear area ranges from 12.5 to 20 mu2 and from 30 to 37.5 mu2 than when it ranges from 20 to 30 mu2. Lymphomas of low-grade malignancy are characterized by a mean nuclear area which is significantly lower than that of lymphomas of high-grade malignancy. The authors believe that morphometrical analysis of the nuclear area and of the form factors may eliminate subjectivity and give reproducible data to be used in both classification and prognosis of lymphomas.

Autoanalysis↗
PubMed1982

Involution patterns of the human thymus. I Size of the cortical area as a function of age.

Thymic tissue obtained at autopsy from 123 victims of sudden death, ranging from neonates to individuals older than 80 years and predominantly male, was studied with histometric techniques, i.e. a combination of test point analysis and planimetry on unit optical fields. The pattern of 'natural' age-dependent involution of the thymic cortex was examined using computerized mathematical models. The range of variations of results was greatest in children and young adults, followed by the very old, then the middle age group. In a first approximation, regression for thymic cortical volume in individuals older than 15 years corresponded better to a negative exponential than to a negative linear function of age. Best fits for the data suggest at least a two-component negative exponential function of age, with a steeper slope of the regression for individuals beyond the age of 30 years. Extrapolation on a log-normal plot of regression lines for thymic cortical involution points to near-zero values at an age range below the estimated maximum human life span, corresponding to the steepest slope of survival curves in Western Europe.

Adolescent↗