Intracytoplasmic crystals in endothelial cells.
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Biomedical subjects
Publications and source records attributed to P Luzi.
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Desmosomes exhibit quantitative alterations in neoplastic diseases. We used direct and stereological measurements to quantify these structures in basal cell carcinomas and in seborrheic keratoses, in comparison with the basal stratum of normal epidermis. Tissue fragments were processed for electron microscopy. Random sampling procedure was used to obtain micrographs of cells from each of the three groups. The following parameters were calculated: volume of the 'average' cell (Vcell), relative surface area of plasma membrane occupied by desmosomes (Ss), mean desmosome diameter (delta) and mean desmosome surface area (s), number of desmosomes per unit surface area (Ns), mean surface area of plasma membrane (Spm), total surface area (Sdes) and number of desmosomes on the 'average' cell (Ndes). Cell volume to surface ratio (V/S) and volume density of intercellular space (Vvint) were also determined. The parameters Ns, Sdes, and Ndes decreased both in basal cell carcinomas and in seborrheic keratoses. The lowest values were obtained in basal cell carcinomas. Instead, the parameters delta, Ss and Vvint increased in both lesions.
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.
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Although 60% of Stage I renal carcinoma patients die from tumor within 5 years postoperatively, a considerable percentage survive that period. Nuclear grading can help to predict the outcome, but many of the patients are Grade 2, and the prognosis of this subclass is uncertain. Therefore, nuclear morphometry was carried out in 41 patients with Stage I renal cell carcinoma. Of these, 24 died within 5 years and 17 have survived that period. Using a mean nuclear area of 32 micron 2 as the decision threshold, none of the 24 short-term survivors are below that threshold and three of the long-term survivors exceed that value (18% false-positives) (99% confidence limit). Separate analysis with sets for learning and testing and Grade 2 patients gave similar results. The results show the essential prognostic value of morphometry in this set of patients with Stage I renal cell carcinoma.
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.
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)
Wistar rats were injected intratracheally with pyrite particles and after 6 and 12 mo, lungs were evaluated for histological changes. Results were compared with rats that were given particles of galena, lead silicate, travertine, and quartz. Under the light microscope no significant changes were observed in the lungs from animals treated with galena, lead silicate, and travertine. In the lungs from animals that received quartz, a typical nodular fibrosis was observed. Moreover, both pyrite-treated rats and quartz-treated rats developed pulmonary alveolar lipoproteinosis; the lesions were much less prominent and severe in animals injected with pyrite than with quartz. These results indicate that pyrite, like only a few other types of dust that are different from quartz, can evoke the development of pulmonary alveolar lipoproteinosis in rats.
A case of chronic hepatitis with ultrastructural changes resembling alterations usually occurring in Wilson's disease is presented in an elderly man. At the time of the diagnosis, the patient did not show clinical and laboratory data consistent with the diagnosis of Wilson's disease. Subsequently, the patient developed neurologic symptoms similar to that resulting from hepatolenticular degeneration. The possibility that such lesions are caused by an abnormal copper metabolism in consequence of acquired liver disease is considered.
The authors present a case of benign oncocytoma (oxyphil cell adenoma) of the nasal cavity in a young woman. This is the fifth case reported in that region. Immunohistochemical stains revealed positivity only for cytokeratin.
A combination of quantitatively evaluated morphological parameters and of conventional prognostic indicators has been used to study 19 cases of invasive ductal breast carcinoma from patients treated only by surgery, later developing recurrences or metastases. This set of patients not treated with adjuvant therapy (radiotherapy, cytostatic or hormonal therapy), was selected from 350 consecutive breast cancers which had been treated with surgical therapy. The aim was to investigate whether the morphometrical features are correlated with disease-free survival. Of the single features, the mitotic activity index (MAI) is most strongly correlated with prognosis. Ten of the 19 patients had an MAI value above 9, and all of them recurred within 18 months. In contrast, of the 9 other patients with low mitotic rate (MAI below or equal to 9), none recurred within 24 months. Further, a correlation exists between disease-free survival, mean and standard deviation of nuclear and nucleolar area, and tubular component of the tumors. There is no correlation between nuclear form factors and recurrence. The multivariate prognostic score is also significantly correlated with recurrence, but not as strongly as in other publications. This is obviously due to the blurring influence of the lymph node status, which was not significantly correlated with the prognosis. Thus, in this small set of patients not treated with any adjuvant therapy, the results of morphometric analysis are in agreement with earlier data and emphasize the prognostic significance of quantitative microscopical analysis in breast cancer.
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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).
Using an experimental model of pancreatitis in the rat, the role of trypsin and elastase in mediating lung vascular injury in this condition was examined. The induction of pancreatitis by injection of sodium cholate in the pancreas resulted in a significant decrease in serum trypsin inhibitory capacity, and in a complete saturation of serum elastase inhibitory capacity matched by the appearance of endothelial injury of pulmonary capillaries and edema formation. The complete lack of serum elastase inhibitory capacity was associated with the presence of elastase activity in serum and bronchoalveolar lavage (BAL) fluids. The pretreatment of animals with N-furoyl saccharin (a potent inhibitor of many serine proteinases) prevented lung capillary injury and the imbalance of serum proteinase-anti-proteinase activities as well as the appearance of any elastolytic activity in serum and BAL fluids. These findings which clearly demonstrate the protease dependence of the pulmonary vascular injury in our experimental model, strongly suggested a major role for elastase(s). The suppression, in the experimental model, of the serum elastase inhibitory capacity by using chloramine-T resulted in an earlier onset of lung vascular damage, a marked worsening of pulmonary lesions, and an increase of elastolytic levels in serum and BAL fluids. Furthermore the physical properties of the protein molecule with enzyme activity detected in BAL fluids were consistent with those of rat pancreatic elastase. The reported data strongly support the hypothesis that pancreatic elastase plays a major role in the development of pulmonary vascular injury after acute pancreatitis.
Morphometrical measurements of nuclear area and form factors are carried out by means of a semiautomated image analyzer on 90 cases of ductal breast cancers and on lymph node tumor deposits. The value of the mean nuclear area in lymph node metastases is significantly higher than in primary tumors regardless of the size of the tumor. Since the value of mean nuclear area is also significantly higher in primary tumors with lymph node involvement than in those without lymph node involvement it is possible to assume that primary tumors with large-nucleus areas are more liable to invade lymph nodes. No significant differences are noted as far as the form factors are concerned.
Differentiation between diffuse lung tumours and interstitial pulmonary diseases often requires open lung biopsy. We report two cases of bronchiolo-alveolar carcinoma presenting as diffuse pulmonary disease, in which the diagnosis was made by cytological examination of bronchoalveolar lavage. Bronchoalveolar lavage can, thus, differentiate between diffuse lung tumours and interstitial pulmonary diseases.
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