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PubMed1966

The synthesis of DNA, RNA, and nuclear protein in normal and tumor strain cells. II. Fresh embryo mouse cells.

Interferometric and photometric measurements have been made on replicating embryo mouse cell cultures. From a study of the relations between successive physical measurements on individual cells, it was found that the net syntheses of DNA, nuclear RNA, nuclear protein, and cytoplasmic RNA are closely associated during interphase. In auxiliary experiments, an inhibition of the onset of DNA synthesis (produced by a dose of X-rays) was found to block the majority of the accumulation of nuclear protein and nuclear RNA. These results are consistent with others previously reported in dividing cell cultures freshly prepared from normal tissues.

Animals↗
PubMed1971

Formation and distribution of nuclear pore complexes in interphase.

The possibility of nuclear pore formation in the interphase nucleus was investigated in control and phytohemagglutinin (PHA) stimulated lymphocytes by the freeze-etching technique. 48 hr after the addition of PHA, the newly formed blasts which had not as yet divided had at least twice the number of pores per nucleus as controls. This clearly demonstrates that in lymphocytes nuclear pore formation can take place during interphase. It has generally been assumed that the distribution of nuclear pore complexes in somatic animal cells is random. However, we have utilized freeze etched rat kidney cells and a computer program to evaluate pore distribution. We find a minimum pore center-to-center spacing of approximately 1300 A and multiples thereof with high frequency. This is strong evidence for a nonrandom distribution of nuclear pores. The nonrandomness may be related to an underlying chromosomal organization in interphase. Using three criteria for identifying prospective pore sites (membrane specialization, nonrandomness, and alteration of heterochromatin distribution), we have found forming pores in sectioned material from cultured human melanoma cells. While nuclear pore formation may take place in conjunction with reformation of the nuclear membrane, a mechanism also exists for their formation during interphase.

Animals↗
PubMed1973

A morphometric study of the removal of phenobarbital-induced membranes from hepatocytes after cessation of threatment.

It is well known that phenobarbital (PB) treatment produces an increase in the amount of cytoplasmic membranes of hepatocytes, with a parallel enhancement in the activity of drug-metabolizing enzymes. However, little is known about how the induced membranes are removed after the drug treatment is stopped. To consider this problem, the recovery of rat hepatocytes from PB induction (five daily injections, 100 mg/kg) was followed morphometrically. Treatment with PB produced a cellular enlargement (26%) due to increases in the volume of the cytoplasmic matrix (20%) and the volume (100%) and surface area (90%) of the smooth-surfaced endoplasmic reticulum (SER). The volume of the nuclei and the surface area of the Golgi apparatus were also increased, but no changes were detected in the volumes of the mitochondria or peroxisomes. The SER membranes induced by the PB were removed within 5 days after the end of the treatment period. During this period of membrane removal, we observed an increase in the volume (800%) and number (96%) of autophagic vacuoles without a change in dense bodies. A morphometric analysis of the content of the autophagic vacuoles showed that the endoplasmic reticulum membranes were preferentially removed, and from this we conclude that the formation of autophagic vacuoles was not a random process. Our findings show that the removal of excess cytoplasmic membranes is associated with an increase in autophagic activity and thus demonstrates the presence of a specific cellular mechanism which may be responsible for the bulk removal of PB-induced membranes.

Animals↗
PubMed1984

Morphometry of bone cell nuclei and their location relative to bone surfaces.

The shapes and locations of lining cells, osteoblasts and osteoprogenitors in sections of rat bone have been quantified by means of a digitiser. The nuclei of all three types of cells can be characterised by oblate spheroids (ellipsoids of revolution). The axis dimensions, their relative variations and the correlation between these parameters have been determined by computer simulation. The nuclear volume of progenitors (288 microns) is more than twice the volume of osteblasts and lining cells (127 microns and 113 microns, respectively). The true mean perpendicular distances of nuclei are 3.1 microns, 5.7 microns and 7.7 microns for lining cells, osteoblasts and progenitors, respectively. The probability densities for true perpendicular distances have been calculated and analytical expressions are given that formally characterise these densities.

Animals↗
PubMed1989

Morphometric analysis of the homogeneity of lymphoid cell populations in fine-needle aspiration cytology smears.

Quantitative morphometry was used to evaluate the homogeneity of lymphoid cell populations in fine-needle aspiration cytology smears of lymph nodes from eight non-Hodgkin's lymphomas and four benign lymphoid proliferations. Using the standard deviation of log-transformed nuclear areas as the measure of lymphoid cell homogeneity, diffuse small cell lymphomas were found to be significantly more homogeneous than diffuse large cell lymphomas or benign lymphoid proliferations, but there was no significant difference in the homogeneity of the latter two groups. Two of four large cell lymphomas showed a bimodal distribution of nuclear areas. Methodologic issues--including the random selection of cells, the number of cells that should be counted in each case, the significance of microscopic field-to-field variation in this setting, and the significance of drift in observations during the examination of individual cases--are discussed.

Adult↗
PubMed1989

Computerized interactive morphometry. An expert system for the diagnosis of lymphoid-rich effusions.

The authors present experimental techniques for the diagnosis of malignant lymphoma and benign lymphocytosis in lymphoid-rich effusions with the use of an inexpensive microcomputer-based video system for computerized interactive morphometry (CIM). Lymphoid cells were randomly selected by a trained observer from real-time images of Papanicolaou-fixed and -stained cytospin smears prepared from pleural, peritoneal, or pericardial effusions. The lymphoid cells were classified by the instrument, based on the size and shape of their nuclear profiles. The morphometric data collected by the instrument were interpreted by a simple rule-based expert system that classified the smears as benign or malignant. One hundred four cases, including 28 malignant lymphomas, 63 benign lymphocytoses, 8 chronic lymphocytic leukemias, and 5 cases with incomplete immunopathologic data, were studied retrospectively. Sixty-three of these effusions had been stained to detect light chain monoclonality. Ninety-one effusions were correctly classified by the expert system. There were four potential false negative diagnoses and one potential false positive diagnosis by the CIM system. Eight effusions from patients with chronic lymphocytic leukemia (CLL) were consistently classified as benign. Although the author's series of patients with a history of CLL is small, their results suggest that CIM is unsuitable for the diagnosis of malignancy in these effusions. If only those effusions from patients with a history of CLL are excluded, the predictive value of a diagnosis of malignant lymphoma was 96.5%, whereas the predictive value of a diagnosis of benign lymphocytosis was 94.0%.

Algorithms↗
PubMed1987

Dermatofibroma with monster cells.

Nineteen cases of dermatofibroma associated with monster cells are reported. The term "monster" (an animal with a strange or terrifying shape, one unusually large for its kind) implies a strikingly atypical cell with an extremely large nucleus. Except for monster cells, these 19 lesions had all of the typical histopathological findings of dermatofibroma. The clinical diagnosis for 16 of these lesions was dermatofibroma (or histiocytoma). Three lesions were submitted without any clinical diagnosis. Eighteen of 19 lesions occurred on the extremities. One was on the back. Monster cells are seen in the early, histiocytic stage of dermatofibroma when lipophages and/or siderophages are usually present in large numbers. Only rarely were mitotic figures seen in dermatofibromas with monster cells, and they were neither numerous nor atypical. It is important for histopathologists to distinguish dermatofibroma with monster cells from cutaneous malignant fibrous histiocytoma and radiation sarcoma. The criteria for differentiation concern primarily the architectural pattern of the lesion rather than its cytological features.

Adult↗
PubMed1994

Estimates of nuclear volume in plaque and tumor-stage mycosis fungoides. A new prognostic indicator.

It is well documented that mycosis fungoides (MF), a cutaneous T-cell lymphoma, has a variable clinical course. Unbiased stereological estimates of three-dimensional volume-weighted mean nuclear size (nucl vV) of mycosis cells were obtained in a retrospective study of 18 patients with a total of 34 biopsies of cutaneous plaque and tumor-stage MF. The value of nucl vV in the first sampled biopsy, as well as the average and highest values, were determined in biopsies from each patient. The patients were divided into two groups, either above or below the group median. There was a strong positive correlation between shorter survival and an average value of nucl vV > 104 microns 3 or a highest value of nucl vV > 126 microns 3 (2p = 0.002 and 0.003, respectively). A nucl vV > 91.6 microns 3 in the first biopsy was also suggestive of a shorter survival (2p = 0.07). There was no clear pattern of nucl vV evolution in the patients with multiple biopsies, but the impact of various therapeutic regimens cannot be assessed. Certain estimates of nucl vV appear to be good prognostic indicators in plaque and tumor-stage MF, but further study of a larger series of patients is needed to corroborate these results and assess the impact of differing therapeutic regimes.

Adult↗
PubMed1994

Nuclear morphometry in xeroderma pigmentosum-associated malignant melanomas.

Previous clinical observations have indicated that the metastatic potential for thick malignant melanoma is lower for patients with xeroderma pigmentosum than for other patients. In a prospective study using computerized image analysis to measure the morphometric characteristics of nuclei in these neoplasms, we found that the nuclei of malignant melanoma cells were smaller and more ovoid in patients with xeroderma pigmentosum than in other patients. Objective evaluation and grading of these subtle histopathologic variables could provide a means of establishing prognostic factors unrelated to the thickness of the neoplasm.

Cell Nucleus↗
PubMed1998

Estimation of the volume-weighted mean nuclear volume discriminates keratoacanthoma from squamous cell carcinoma.

Keratoacanthoma (KA) is a fairly common neoplasm that in the past has been considered by many to be benign. Keratoacanthoma is usually differentiated from squamous cell carcinoma (SCC) by histopathologic criteria. However, the cytologic features of KA and SCC are often similar. Hence, KA may be confused with SCC at the histopathologic level. Volume-weighted mean nuclear volume (Vv) is determined by a technique that permits an unbiased and efficient estimation of nuclear volumes in tissues without any assumptions regarding nuclear shape. In this study, the volume-weighted mean nuclear volume was determined in 18 KAs and 19 SCCs to investigate whether this stereologic approach may be of use in the differentiation of these two tumors. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on Feulgen-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. The mean Vv of KA was 704.5 microm3 (SD +/-170.5), whereas SCC exhibited a significantly lower Vv of 533.9 microm3 (SD+/-164.9) (p = 0.006). The sensitivity and specificity of Vv for the discrimination between KA and SCC was 0.80 and 0.78, respectively. We found that KAs show a significantly larger Vv than SCCs and thus, the estimation of the volume-weighted mean nuclear volume may be regarded as a helpful tool for the differential diagnosis of KA and SCC.

Aged↗
PubMed1992

Well differentiated follicular neoplasms of the thyroid: reproducibility and validity of a 'decision tree' classification based on nucleolar and karyometric features.

This study was conducted on fine-needle aspirates of well differentiated follicular neoplasms of the thyroid. A 'decision tree' classification based on the percentage of nucleolated nuclei, percentage of nuclei with two or more nucleoli and mean major nuclear diameter was adopted. We observed that the reproducibility and the validity of the follicular adenoma vs follicular carcinoma discrimination are greater than in the subjective evaluation. Moreover, similar classification results were obtained when measurements were performed either with a fully automated image analysis system or with semiautomatic or manual instrumentation. As for reproducibility of the inter-instrument comparisons, the k statistic values ranged from 0.85 to 1.00 (mean value 0.90, that is, an 'almost perfect' degree of agreement); in the subjective evaluations, the inter-observer comparisons showed values ranging from 0.20 to 0.56 (mean value 0.37, that is, 'fair'). In the decision tree classification, feature value thresholds were selected in order to have specificity of 100% and the predictive value of a positive result (carcinoma) of 100%; accuracy was 87% (range 86-89%), sensitivity 74% (71-79%), the predictive value of a negative result (adenoma) 79% (78-82%). In the subjective evaluation the values were as follows: accuracy 67% (64-71%), sensitivity 57% (50-64%), specificity 77% (71-79%), predictive value of a negative result (adenoma) 64% (61-69%), predictive value of a positive result (carcinoma) 71% (67-75%). The conclusion is that, by using a routine microscope equipped with a micrometer, the preoperative diagnosis of follicular carcinoma from smears can be formulated with a high degree of certainty.

Adenocarcinoma↗
PubMed1987

Nuclear DNA in anaplastic thyroid carcinoma with a differentiated component.

Fifteen cases of anaplastic thyroid carcinoma, including eight cases with a differentiated component, were studied by DNA analysis. All areas of anaplastic carcinoma showed an aneuploid DNA content. The eight cases of anaplastic carcinoma with differentiated component (two follicular carcinomas, two papillary carcinomas, one Hürthle cell carcinoma and three poorly differentiated carcinomas) exhibited aneuploid DNA content in the differentiated area of the tumour. Karyometric parameters allowed a fairly clear separation between giant cell, spindle cell and differentiated components. The results support the hypothesis that patients with aneuploid differentiated carcinoma represent a higher risk group and are probably more prone to developing anaplastic carcinoma.

Carcinoma↗