A controlled clinical trial of the effects of the Twin Block and Dynamax appliances on the hard and soft tissues.

The aim of this controlled trial was to identify and quantify skeletal, soft tissue and dental changes during treatment, and immediately post-treatment with Twin Block (TB) or Dynamax appliance using the techniques of three-dimensional (3D)optical surface laser scanning, cephalometric, and clinical measurements. Sixty-two Caucasian subjects, 36 males aged 11-14 years and 26 females aged 10-13 years were enrolled in the study. The patients were placed in two groups, matched for gender and age and subsequently allocated randomly for treatment with either a TB or Dynamax appliance. Active treatment lasted 9 months followed by 3 months' post-treatment observation. Laser scanning and clinical measurements were taken at 3-monthly intervals and final cephalometric records after 12 months. Statistical analysis was performed using Wilcoxon's matched-pairs signed-rank tests. The non-compliance rates were the same for both groups (9 per cent), but a greater incidence of breakages was found in the Dynamax group. The TB was found to produce slightly more antero-posterior skeletal change, median ANB reduction, TB=2 degrees, Dynamax 1.1 degree (P=0.006), and similar forward movements of the chin and was associated with larger increases in the vertical facial dimension, median total anterior face height increase; TB=3.2 mm, Dynamax = 2.8 mm (P=0.03). The soft tissue vertical cephalometric increases were 3.6 mm with the TB, 2.0 mm with the Dynamax (P=0.036), and with laser scanning 5.05 and 2.6 mm, respectively, a difference which is likely to be more clinically relevant. The median post-treatment changes in soft tissue pogonion were -0.65 mm in the TB and +0.22 mm in the Dynamax group. The optical surface scanning mark and measure system is a valid method for quantifying soft tissue changes.

Analysis of mitotic microtubule-associated proteins using mass spectrometry identifies astrin, a spindle-associated protein.

We purified microtubules from a mammalian mitotic extract and obtained an amino acid sequence from each microtubule-associated protein by using mass spectrometry. Most of these proteins are known spindle-associated components with essential functional roles in spindle organization. We generated antibodies against a protein identified in this collection and refer to it as astrin because of its association with astral microtubule arrays assembled in vitro. Astrin is approximately 134 kDa, and except for a large predicted coiled-coil domain in its C-terminal region it lacks any known functional motifs. Astrin associates with spindle microtubules as early as prophase where it concentrates at spindle poles. It localizes throughout the spindle in metaphase and anaphase and associates with midzone microtubules in anaphase and telophase. Astrin also localizes to kinetochores but only on those chromosomes that have congressed. Deletion analysis indicates that astrin's primary spindle-targeting domain is at the C terminus, although a secondary domain in the N terminus can target some of the protein to spindle poles. Thus, we have generated a comprehensive list of major mitotic microtubule-associated proteins, among which is astrin, a nonmotor spindle protein.

Integrating centrosome structure with protein composition and function in animal cells.

The centrosome found in animal cells is a complex and dynamic organelle that functions as the major microtubule organizing center. Structural studies over the past several decades have defined the primary structural features of the centrosome but recent studies are now beginning to reveal structural detail previously unknown. Concurrent with these studies has been an explosion in the identification of the proteins that reside within the centrosome. Our growing understanding of how protein composition integrates with centrosome structure and hence with function is the focus of this review.

FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).

The hallmark of the 8p12 stem cell myeloproliferative disorder (MPD) is the disruption of the FGFR1 gene, which encodes a tyrosine kinase receptor for members of the fibroblast growth factor family. FGFR1 can be fused to at least 3 partner genes at chromosomal regions 6q27, 9q33, or 13q12. We report here the cloning of the t(8;9)(p12;q33) and the detection of a novel fusion betweenFGFR1 and the CEP110 gene, which codes for a novel centrosome-associated protein with a unique cell-cycle distribution. CEP110 is widely expressed at various levels in different tissues and is predicted to encode a 994-amino acid coiled-coil protein with 4 consensus leucine zippers [L-X(6)-L-X(6)-L-X(6)-L]. Both reciprocal fusion transcripts are expressed in the patient's cells. The CEP110-FGFR1 fusion protein encodes an aberrant tyrosine kinase of circa 150-kd, which retains most of CEP110 with the leucine zipper motifs and the catalytic domain of FGFR1. Transient expression studies show that the CEP110-FGFR1 protein has a constitutive kinase activity and is located within the cell cytoplasm. (Blood. 2000;95:1788-1796)

Autoantibodies to components of the mitotic apparatus.

Autoantibodies directed to a variety of cellular antigens and organelles are a feature of autoimmune diseases. They have proven useful in a clinical setting to establish diagnosis, estimate prognosis, follow disease progression, alter therapy, and initiate new investigations. Cellular and molecular biologists have used autoantibodies as probes to identify molecules involved in key cellular processes. One of the most interesting sets of autoantibodies are those that target antigens within the mitotic apparatus (MA). The MA includes chromosomes, spindle microtubules and centrosomes. The identification, localization, function, and clinical relevance of MA autoantigens is the focus of this review.

Autoantibodies to a group of centrosomal proteins in human autoimmune sera reactive with the centrosome.

OBJECTIVE: Human autoantibodies reacting with protein components of the microtubule organizing center of the cell, the centrosome, are rare and have not been extensively studied. We therefore investigated the number, type, and frequency of autoantibodies reactive with centrosomal proteins in a cohort of human sera. METHODS: To establish the type of autoantibodies found in autoimmune sera reactive with the centrosome, we used a prototype human serum, which was chosen for its intense reactivity with the centrosome throughout the cell cycle, to screen a HeLa complementary DNA (cDNA) (expression) library. Positive cDNA clones were sequenced and classified as encoding either known centrosomal autoantigens, known centrosomal proteins but unknown as human autoantigens, or previously unknown centrosomal antigens. To investigate whether these centrosomal autoantibody classes were characteristic of centrosomal-reactive sera, sera from 21 subjects with centrosomal reactivity by indirect immunofluorescence were characterized by Western blotting for reactivity to recombinant protein from each of the classes of centrosomal antigens. Clinical features were studied by retrospective chart review. RESULTS: In each of the sera, autoantibodies that recognize a group of centrosomal proteins were identified. This group included known centrosomal autoantigens (pericentrin and pericentriolar material 1 [PCM-1]), the human homolog of a known mouse centrosomal protein, ninein, which was previously unknown as a human autoantigen, and a novel centrosomal protein (Cep250). Autoantibodies to PCM-1 were the least common (8 of 21 subjects; 38%) while those to ninein, Cep250, and pericentrin occurred at roughly equal frequencies (17 subjects [81%], 17 subjects [81%], and 19 subjects [90%], respectively). There was no apparent correlation between serum autoantibody reactivity and the clinical diagnosis. CONCLUSION: Each of the autoimmune sera contained autoantibodies that reacted with a group of centrosomal proteins. We found that the centrosomal component ninein, first identified in mice, has a human homolog that is an autoantigen. Also, anticentrosomal sera contained antibodies to previously undetected centrosomal components. One of these novel antigens was identified and was designated Cep250. Thus, a characteristic of sera reactive with the centrosome is that they contain antibodies to a group of centrosomal proteins.