Cell size is one of the critical parameters controlling the size of intracellular structures. A well-known example is the constant nuclear-to-cytoplasmic ratio (N/C ratio) [1-5]. The length of the metaphase spindle is proportional to cell size, but it has an upper limit during early embryogenesis [6]. During anaphase, the mitotic spindle elongates and delivers the centrosomes and sister chromatids near the centers of the nascent daughter cells. Here, we quantified the relationship between spindle elongation and cell size in the early embryo of Caenorhabditis elegans and propose possible models for cell-size-dependent spindle elongation. Quantitative measurements revealed that the extent and speed of spindle elongation are correlated with cell size throughout early embryogenesis. RNAi knockdown of Galpha proteins and their regulators revealed that the spindles failed to fully elongate and that the speed of spindle elongation was almost constant regardless of cell size. Our results suggest that spindle elongation is controlled by two qualitatively distinct mechanisms, i.e., Galpha-dependent and -independent modes of elongation. Simulation analyses revealed that the constant-pulling model and the force-generator-limited model reproduced the dynamics of the Galpha-independent and Galpha-dependent mechanisms, respectively. These models also explain how the set length of spindles is achieved.

Background. An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To determine a definite statistical relation, a histopathologic study was performed on tissues from in three races, because there is a racial and age‐related difference in the susceptibility to thyroiditis. Methods. The prevalence and severity of thyroiditis combined with adenomatous goiter, follicular adenoma, or papillary carcinoma was defined by examination of surgically resected materials from Japanese (626 patients), and white and African Americans (330 and 90 patients, respectively). Results. The prevalence of lymphocytic infiltrates, which are indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma than in patients with adenomatous goiter or follicular adenoma among Japanese females (63.0%) and males (50.0%), white females (76.0%), and African American females (46.2%). Lymphocyte infiltration into the follicular adenoma or papillary carcinoma correlated with the severity of combined thyroiditis. Conclusion. An association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed in the Japanese, and white and African American populations. The possibility of autoimmune thyroiditis as a predisposing factor for papillary thyroid carcinoma, is suggested. Cancer 1995; 76:2312–8.

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Nuclear size changes dynamically during development and has long been observed to correlate with the space surrounding the nucleus, as well as with the volume of the cell. Here we combine an in vitro cell-free system of Xenopus laevis egg extract with microfluidic devices to systematically analyze the effect of spatial constraints. The speed of nuclear expansion depended on the available space surrounding the nucleus up to a threshold volume in the nanoliter range, herein referred to as the nuclear domain. Under spatial constraints smaller than this nuclear domain, the size of microtubule-occupied space surrounding the nucleus turned out to be limiting for the accumulation of membranes around the nucleus via the motor protein dynein, therefore determining the speed of nuclear expansion. This mechanism explains how spatial information surrounding the nucleus, such as the positioning of the nucleus inside the cell, can control nuclear expansion.

Following fertilization, a number of molecular events are triggered in the mammalian zygote. As biochemical studies using mammalian gametes and zygotes have inherent difficulties, the molecular nature of these processes is currently unclear. We have developed a method to visualize these events. In vitro transcribed mRNAs encoding for proteins fused with green fluorescent protein were microinjected into oocytes or embryos and fluorescence signals were observed. Using this technique we succeeded in obtaining images of the DNA methylation status in living mouse and rabbit embryos. Moreover, time-lapse images were acquired of spindle and nuclear formation during second meiosis and first mitosis. Importantly, the microinjected embryos developed to the normal offspring even after observation, suggesting that the technique is relatively noninvasive. Thus, our method may help elucidate the molecular aspects of fertilization and preimplantation development and, based on the real-time genetic and epigenetic status, could become a tool to select "good quality" embryos before implantation.

An equation is presented that accounts for the quantitative relationship between mitotic spindle width, spindle length, and ploidy in Caenorhabditis elegans embryos. It shows a subproportional relationship among the three parameters that is known as allometric, providing a new quantitative basis for understanding spindle morphogenesis.

Quantification of mitotic chromosomes in Caenorhabditis elegans embryos and a Xenopus laevis egg extract system indicates that the chromosome amount per nuclear space, or “intranuclear DNA density,” regulates chromosome condensation. This suggests an adaptive mode of chromosome condensation regulation in metazoans.

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.