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C D Bell

Publications and source records attributed to C D Bell.

At least 19 recordsLinked to original sources

Is mitotic chromatid segregation random?

The question of whether mitotic segregation of chromatids is random or programmed assumes great significance for cellular differentiation if one recognizes that sister chromatids may have epigenetic differences and carry them from one generation into the next. The literature was examined for evidence of non-random chromosomal and chromatid segregation. Many organisms were described as undergoing non-random homologue segregation in meiosis I. The explanations for these phenomena were attributed in some instances, to peculiarities of the meiotic spindle, though in some convincing experiments, the epigenetic heterochromatin of the kinetochores was implicated. The few existing descriptions of non-random mitotic segregation were also described. Existing literature on ultrastructural, immunohistochemical, and physiological features of the chromatid kinetochores during the mitotic process was searched for evidence of asymmetry or structural differences between sister chromatids, which is presented. Also reported are descriptions of how epigenetic changes and cell differentiation can influence centromeric function and ultimately, kinetochore function. Fundamental to the hypothesis of gene regulation presented here, is the assumption that genetic foci on different chromosomes interact, and must be proximate to each other and stereologically compatible for interactions to occur. Also described are spatial changes in chromosomal territories associated with function and differentiation. These territories can be in varying nuclear locations depending on gene function, and may show asymmetry between daughter cells. Despite evidence presented for the possibility of non-random chromatid segregation at mitosis, this question will remain unanswered until the matter is specifically addressed by experiment.

Animals↗

Symmetry applied to nuclear microanatomy: a review of gene function and cell differentiation.

The purpose of this paper is to review current knowledge and understandings of gene control and cell differentiation, based upon an appreciation of a possible role that nuclear microanatomy and considerations of steric symmetry might play. Metaphase sister chromatids have identical base codes but show a mirror image symmetry of higher order coiling. Chromosomes in the interphase nucleus have spatially well defined domains and are anatomically distinct and ordered. Chromosomes are known to have interactions i.e. sex chromosome inactivation, PEV, etc. An hypothesis of gene activation is made based on steric interactions among chromosomes and between chromosomes and activating and repressor proteins. These interactions may be influenced by the handedness of higher order chromatid coiling, since homologues show mirror-image symmetrical coiling in metaphase, which might be retained to a certain degree in interphase. This may result in a binary switching of genes. All possible combinations of chromatids in the interphase nucleus, would be enabled by a differential segregation of homologous chromatids at mitosis. To conserve patterns of interchromatid interactions, there must be a programmed segregation of chromatids towards one of the two spindle pole attachments. This orientation might be effected by preferential attachment of microtubules to kinetochore attachment sites, by steric hindrance of the kinetochore by condensed chromatin which initially allows only unidirectional tubule attachment, or possibly by a tethering of interacting chromatids which would migrate en masse. An attempt to apply this hypothesis to some illustrative pathological conditions is made.

Animals↗

The 'dark nucleus' and disruptions of follicular architecture: possible new histological aids for the diagnosis of the follicular variant of papillary carcinoma of the thyroid.

AIMS: In order to facilitate the diagnosis of malignancy in solitary thyroid nodules which are non-invasive low-grade tumours, i.e. follicular variant of papillary carcinoma (FVPC) for which few histological discriminators exist, a search was made for additional diagnostically useful histological features. METHODS AND RESULTS: Haematoxylin and eosin (H & E)-stained sections of 70 resection specimens of solitary thyroid nodules were re-evaluated by a panel of three pathologists, and their consensus and original diagnoses compared. In addition, H & E- and periodic acid-Schiff-stained sections were evaluated for various histological features and sections were stained by various immunohistochemical markers to evaluate their discriminative powers. The above features were also assessed in a group of 24 papillary carcinomas of the thyroid (PTCs) associated with regional metastases. The finding of 'Orphan Annie eye' nuclei was the best indicator of malignancy, and was closely related to the presence of nuclear grooves and cells with dense, dark nuclei. In addition, distorted follicular architectural features, i.e. 'interconnecting cell masses' and 'fenestration', were also significant indicators of malignancy. Tumours diagnosed as FVPCs had a significantly lower incidence of associated lymph node metastases than the classical PTCs. CONCLUSIONS: The use of optically clear nuclei as a diagnostic criterion when found only focally may not be sufficiently stringent in distinguishing FVPCs from follicular adenomas. When classical histological indicators of malignancy are equivocal, the diagnosis of FVPC may be facilitated by the above-mentioned features.

Adenoma↗

Histologic, immunohistochemical, and ultrastructural findings in a case of minocycline-associated "black thyroid".

We report on a 37-yr-old woman with known antemortem ingestion of minocyclin who died suddenly from a ruptured cerebral aneurysm. At autopsy, her thyroid gland, although not enlarged, was diffusely black, caused by the deposition of a melanin-like pigment that stained positive with Schmorl's reagent. The pigment could be bleached with permanganate, and on examination by electron microscopy, it appeared to be deposited within the thyrocyte lysosomes. Additional immunostaining with many antibodies revealed an increase in vimentin staining in the follicular epithelium compared with normal control thyroid glands. Staining for cytoplasmic thyroglobulin was markedly reduced, despite normal thyroid indices performed on stored antemortem blood. Stainable ubiquitin in the follicular epithelium appeared reduced compared with control thyroid tissues. These immunohistochemical findings may reflect disruptions of lysosomal transport and function associated with the abnormal accumulation of pigment. This appears to be the only case of minocyclin-associated "black thyroid" in which extensive immunohistochemical investigations have been performed.

Adult↗

Papillary carcinoma of thyroid metastatic to the pituitary gland.

We describe a 35-year-old woman who presented with diabetes insipidus caused by metastatic papillary carcinoma of the thyroid involving the pituitary gland, 25 years after treatment for a papillary carcinoma of thyroid and 17 years after treatment for multiple pulmonary metastases. The literature contains 10 previously described cases of metastatic thyroid carcinoma involving the sella, but only 2 of these cases had unequivocal metastases to the pituitary gland, making the present case, to our knowledge, the third reported case of unequivocal hematogenous metastasis of thyroid carcinoma to the pituitary gland. The pituitary tumor was removed by transsphenoidal surgery, and the tissue was examined by conventional histology, extensive immunohistochemistry, and electron microscopy. The findings confirmed the tumor to be papillary thyroid carcinoma. To our knowledge, this is the first report citing use of thyroid transcription factor-1 to establish a thyroid source of a pituitary metastasis.

Adult↗

Molecular phylogeny and biogeography of Linanthus (Polemoniaceae).

To better understand the evolutionary history of Linanthus (Polemoniaceae) and its relatives, molecular phylogenies based on DNA sequence data from the internal transcribed spacer (ITS) region of nrDNA and the chloroplast gene matK were estimated using several methods. Our data suggest two separate and well-supported lineages of Linanthus in close association with two other genera-Leptodactylon and Phlox. These results agree with previous molecular systematic work on the Polemoniaceae, but do not support the traditional classification of the genus as a natural group, nor do they support the sectional classification within the genus. With a distribution centered primarily in western North America and a high degree of endemism in the California Floristic Province, it has been suggested by Raven and Axelrod that the origin and diversification of Linanthus and its relatives were tied to the development of a summer-dry climate in western North America, which began around 13-15 million years ago (mya). Increased drying during the Pliocene (1.2-5 mya) has also been hypothesized by Axelrod to have led to an increase in plant speciation in California and adjacent areas. Divergence times within the Linanthus lineages were estimated from the ITS and matK gene trees. A log-likelihood ratio test could not reject clock-like evolution for the matK data; however, the clock was strongly rejected for the ITS data set. Although ITS molecular evolution was not clock-like, the estimated times of divergence were similar to those of the matK data set. Within both lineages of Linanthus there seems to have been considerable diversification that has occurred since the Pliocene.

Journal Article↗

The relationship of cytoplasmic intermediate filaments and membrane antigens with hormone receptors, nuclear staining density, and mode of stromal invasion in human breast cancer.

Serial sections on biopsies of 26 women with invasive breast carcinoma were stained for low molecular weight keratins (LKER), high molecular weight keratins (HKER), epithelial membrane antigen (EMA), vimentin (VIM), carcinoembryonic antigen (mCEA and pCEA), and nuclear estrogen (mER) and progesterone receptors (mPGR), using monoclonal and polyclonal sera. Specified areas were identified on serially sectioned slides and staining reactions were compared among areas as well as among patients. The study concludes: (1) LKER staining was positively related to (a) the percentage of tumor cells with densely stained nuclei, (b) a trabecular mode of stromal invasion, and (c) HKER and EMA staining, and inversely related to (d) VIM staining and gross tumor size. (2) HKER was also inversely related to gross tumor size. (3) VIM staining was positively related to pCEA staining. (4) VIM staining was inversely related to staining ER and PGR. (5) LKER, HKER, and EMA staining was stronger in areas of trabecular rather than confluent areas of stromal invasion within the same biopsy. (6) Staining for ER and PGR was not related to mode of stromal invasion, but showed a strong inverse relationship with mitotic index. Positive staining for LKER may be an indicator of better differentiation together with densely staining nuclei and trabecular mode of stromal invasion, whilst VIM and pCEA appear to be related to features indicative of lack of differentiation. Hormone receptor positivity seems to be strongly related to mitotic activity rather than differentiation.

Adult↗

The 'vapour-phase' migration of styrene from general purpose polystyrene and high impact polystyrene into cooking oil.

General purpose and high impact polystyrene (GPPS and HIPS, respectively) are used in many food packaging applications. In some packaging configurations, where there is no direct contact of a liquid surface with the polymer, 'vapour-phase' migration of styrene monomer from the polymer with subsequent absorption into food is thought to be a significant mode of transfer. Correlation of residual styrene concentrations in polystyrene with vapour-phase styrene migration is of interest in order to predict potential consumer exposure to styrene from food-packaging applications of this configuration. Studies of the migration of styrene from GPPS and HIPS into air with subsequent absorption of the monomer into cooking oil, 'vapour-phase' migration, was determined in a sealed system. The results showed that for both polymers the amount of styrene migrating from the polystyrene and being absorbed by the oil was proportional to the square root of the time of exposure. The diffusion coefficients calculated for the vapour-phase migration of styrene from both polymers were found to be in good agreement with the diffusion coefficients previously determined for the 'liquid-phase' migration of styrene from similar polymers where the polymers were completely submerged in the cooking oil. These results indicate that the styrene concentrations measured in both experiments were attributable to the intrinsic diffusion of styrene from polystyrene, and that contact with cooking oil did not accelerate migration in previous experiments.

Diffusion↗

The relationship of nuclear staining density and mode of stromal invasion with axillary metastases and hormone receptor status in human breast cancer.

Biopsies from 52 cases of infiltrating duct carcinoma of breast were assessed for proportions of tumor infiltrating stroma as "thin" strands and as confluent cell sheets. The proportions of cell nuclei arbitrarily designated "dark" were determined for each whole tumor and for their above-mentioned invasive compartments and were compared with the tumor's nuclear grade, mitotic index, gross size, axillary metastatic status, and hormone receptivity. Well-differentiated tumors tended to have more cells with "dark" nuclei and more of the tumor mass invading the stroma as "thin" strands than poorly differentiated ones. Tumors that had axillary metastases also tended to have high mitotic indices, low proportions of cells with "dark" nuclei (and conversely high proportions of cells with vesicular nuclei) in confluent sheets. Tumors that had positive results for one or both hormone receptors had a greater component of trabecular stromal invasion than tumors with negative results for both hormone receptors that grew as confluent cell sheets. It is suggested that tumor cell nuclear staining "density" might be a clinically useful prognostic index despite the finding that semiquantitative assessments of nuclear density can be modified by the mode of stromal invasion.

Adult↗

Hidden loop jejunostomy--an experimental model.

A hidden loop jejunostomy, the placement of a proximal small bowel loop under the skin of dogs, is described. A feeding tube was inserted in the loop at a later date, which enabled feeding for at least 6 weeks. This procedure was well tolerated by the 10 dogs involved in this experimental model. It should be considered as a possible surgical procedure at initial explorative laparotomy in patients with advanced cancer originating at the gastric cardia or esophagogastric junction.

Animals↗

Relationship of nuclear appearance to stromal invasion in human breast cancer.

Two biopsies of intraductal and invasive lobular carcinoma of the breast and 11 biopsies of intraductal and invasive carcinoma of the breast were examined by automated micromensurative techniques for mean nuclear area of carcinoma cells in intraductal and in invasive compartments. The nuclei of invasive carcinoma cells tended to be smaller when they invaded stroma as single cells or as "thin strands" than when they invaded as part of large sheets of cells. Cells in direct apposition with the stroma usually had smaller nuclei than cells which were found centrally in large confluent sheets of cells. Intraduct carcinoma cells approached, in size, invasive cells which formed confluent sheets, rather than cancer cells which invaded as single cells. The nuclei of cells which invaded in small groups were usually darker than those of cells in confluent sheets, which were usually more vesicular.

Adult↗

The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens.

The clinical and pathological characteristics of endometrial hyperplasia simulating or coexisting with secretory endometrium were studied in 35 cases of women with at least one biopsy diagnosed as secretory endometrium and another biopsy diagnosed as endometrial hyperplasia or neoplasia. The biopsy samples were examined histologically by semiquantitative methods to detect features that could aid in distinguishing secretory endometrium from hyperplastic endometrium existing focally in secretory endometrium or simulating secretory endometrium. Important histologic features were focal architectural abnormalities, epithelial pseudopalisading, a vesicular nuclear appearance, nuclear atypia, mitoses, the presence of metaplastic ciliated and "clear" cells, and a sharp luminal margin indicating absence of cytoplasmic secretion. The distribution of patients' ages fell between that of perimenopausal women with only secretory features on biopsy (curettage) and that of women with hyperplastic endometrium on biopsy. Twenty-nine per cent of the women in the study group had diabetes or hypertension, and 29 per cent had leiomyomata or adenomyosis at eventual hysterectomy. Patients followed up showed persistence of hyperplasia and progression to a more severe degree of cytologic atypia on later biopsy samples. Recommendations are made for improved detection of these hyperplastic changes and for careful follow-up of patients.

Adult↗

Tumor differentiation and histological type in human breast cancer.

Biopsies from 61 women with breast cancer were assessed for various histological features. These results were statistically analyzed for associations of gross tumor size, patient age, stage of disease, tumor hormone receptor status, with accepted systems of nuclear and histological grading for differentiation. Tumors with highly differentiated grading had smaller cell nuclei, stromal elastasis, intraduct carcinoma and tubular formations. Poorly differentiated tumors had large vesicular cell nuclei and increased mitotic indices. Gross tumor size was also linked with stromal elastosis, intraduct carcinoma, a specific pattern of stromal infiltration, and mitotic index. No relationship could be found between any of the above features and the patients clinical statuses or their tumors' hormone receptivities. The existence of two distinct histological patterns of breast carcinoma is proposed; the patterns may either represent stages in the development of the tumor or different biological types.

Breast Neoplasms↗

Variability of cell size in primary and metastatic human breast carcinoma.

Macroscopic measurements and histometrical estimates of cell cytoplasmic (Cx) and nuclear areas (Nx) were made on 24 primary and 37 metastatic tumors from patients with human breast carcinoma. Within the small metastases, the cancer cells were smaller and showed greater variation in size (CVC, CVN) than those in their respective primary tumors. In the larger metastases, the cells were larger and more uniform in size. Studies of primary tumors showed that both Cx and Nx of tumor cells bore a direct relationship to the gross size of the primary tumor. Comparisons of measurements from the 14 primary tumors with metastases and the 10 primary tumors with no metastases revealed no significant differences between the groups. In all tumors, Cx bore a predictable and direct relationship to Nx.

Adult↗

Invasive multiple supraglottic squamous cell papillary carcinoma in an adult. Report of a case.

Invasive papillary squamous cell carcinoma of the supraglottic larynx is described in an adult male. The clinicopathological appearance was that of a multiple growth which displayed various gradients of neoplastic changes: in situ, microinvasion, frank invasion of cartilage and cervical node metastases. No previous history of radiotherapy was elicited. The growth was excised by supraglottic laryngectomy and neck dissection. Typical metastatic papillary formations were observed in lymph nodes.

Carcinoma, Papillary↗