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PubMed2004

Absolute and relative growth of the rat craniofacial skeleton.

UNLABELLED: Growth of the craniofacial region involves a mosaic of intramembranous and endochondral growth sites that grow at varying rates and mature at different times. OBJECTIVE: The goal of this study was to compare absolute and relative growth of the craniofacial skeleton in wild-type Lewis rats to measures of somatic growth. DESIGN: Lateral and dorsoventral X-rays of the head as well as the hindlimb were obtained weekly from 4 to 9 weeks of age. The X-rays were scanned, digitized, and selected linear distances were measured between points. Multilevel statistical models were used to generate absolute growth curves. RESULTS: Although most growth curves were linear, several were quadratic (exhibiting a deceleration with age), and one displayed a third-order curve. Considerable variation in relative maturity was evident at the first time interval, ranging from 42% of mature (9 week) size (weight) to 97% of mature size (cranial width). Tibial length and body weight were less mature than most, but not all, craniofacial measures. With one exception (bizygomatic width), width measures were relatively more mature than vertical or depth measures. Vertical measures tended to be among the least mature of the craniofacial dimensions. Among the depth (length) measurements, there was a trend of higher maturity for cranial vault/cranial base measures and lower maturity for facial measures. CONCLUSIONS: The wide spectrum of relative and absolute growth potentials demonstrated in this study indicate that the rodent craniofacial complex is amenable to testing the hypothesis that a component's response potential is related to its growth potential.

Animals↗

PubMed2004

Expression, purification, crystallization and preliminary X-ray analysis of strictosidine glucosidase, an enzyme initiating biosynthetic pathways to a unique diversity of indole alkaloid skeletons.

Strictosidine beta-D-glucosidase, a plant enzyme initiating biosynthetic pathways to about 2000 monoterpenoid indole alkaloids with an extremely large number of various carbon skeletons, has been functionally expressed in Escherichia coli and purified to homogeneity in mg scale. Crystals suitable for X-ray analysis were found by robot-mediated screening. Using the hanging-drop technique, optimum conditions were 0.3 M ammonium sulfate, 0.1 M sodium acetate, pH 4.6 and PEG 4000 (10%) as precipitant buffer. The crystals of strictosidine glucosidase belong to the space group P42(1)2 with unit cell dimensions of a=157.63, c=103.59 A and diffract X-rays to 2.48-A resolution.

Catharanthus↗

PubMedDate not supplied

Antibodies to betaISigma2 spectrin identify in-homogeneities in the erythrocyte membrane skeleton.

The cortical cytoskeleton of the mammalian red cell, composed of spectrin, actin, protein 4.1, adducin, and protein 4.9, is generally regarded as a homogeneous structure that maintains the integrity of the membrane and the lateral disposition of integral membrane proteins. The major component of this structure is a hetero-oligomer of alphaI and betaISigma1 spectrin. In other tissues, most notably muscle and brain, a transcript of the betaI spectrin gene is generated by alternative exon utilization, yielding a protein that has the COOH-terminal 19 residues of betaISigma1 spectrin replaced by 210 novel residues to generate betaISigma2 spectrin. This new transcript contains a pleckstrin homology (PH) domain and may even exist under some conditions in a homopolymeric form. Using antibodies specific for the COOH-terminal domains of either betaISigma1 or betaISigma2 spectrin, we find that contrary to previous understandings, mature human erythrocytes contain a subpopulation of spectrin that is immunoreactive with antibodies to the betaISigma2 isoform, and that this spectrin is distributed into distinct plasma membrane patches. These results suggest that the native mammalian erythrocyte membrane skeleton, rather than being homogeneous, contains discrete submicron-scale microdomains that differ in both their composition and dispersion across the cell surface. The precise nature and role of these putative microdomains is under active investigation.

Antibodies, Monoclonal↗

PubMed2006

Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors: Dual activities and metabolic activation.

Ligands possessing dual vitamin D(3) (VD(3))-agonistic and androgen-antagonistic activities with various activity spectra were prepared based on a substituted 3,3-diphenylpentane (DPP) skeleton. Among the compounds, (R,S)-DPP-1023 [(R,S)-7b] and (S,S)-DPP-0123 [(S,S)-7c] showed the most potent vitamin D(3)-agonistic activity [with potency comparable to that of 1alpha,25-dihydroxyvitamin D(3) (1,25-VD(3))] and nuclear androgen receptor (AR)-binding activity (with higher affinity than that of hydroxyflutamide), respectively. Metabolic activation (reduction of the carbonyl group) of pivaloyl analogs [DPP-1113 (3a), DPP-1013 (3b), DPP-0113 (3c), and DPP-0013 (3d)] in HL-60 cells was found to be necessary for binding to nuclear vitamin D(3) receptor (VDR).

Androgen Receptor Antagonists↗

PubMed2005

A new class of androgen receptor antagonists bearing carborane in place of a steroidal skeleton.

A new class of androgen receptor antagonists containing dicarba-closo-dodecaborane (carborane) as a hydrophobic skeletal structure is described. The designed molecules bear the characteristic polar components of endogenous agonists, but have a hydrophobic carborane cage instead of the steroidal skeleton. These compounds bind to androgen receptor and show anti-androgenic activity towards androgen-dependent SC-3 cells with almost the same potency as the known anti-androgen hydroxyflutamide.

Androgen Antagonists↗

PubMed2006

Novel skeleton terpenes from Celastrus hypoleucus with anti-tumor activities.

Celahypodiol 1, an unusual 17-membered carbon diterpenoid with a novel skeleton, and a new triterpenoid 12-oleanene-3beta,6alpha-diol 2, together with four known compounds furreginol 3, suigol 4, 20(30)-lupene-3beta, 29-diol 5, and 20(29)-lupene-1beta,3beta-diol 6, were isolated from the stalks of Celastrus hypoleucus (Oliv.) Warb. Their structures were established by means of spectroscopic analysis, including 2D NMR. The new compounds exhibited anti-tumor activities against a panel of human tumor cell lines.

Antineoplastic Agents↗

PubMed2003

Enabling bone formation in the aged skeleton via rest-inserted mechanical loading.

The mild and moderate physical activity most successfully implemented in the elderly has proven ineffective in augmenting bone mass. We have recently reported that inserting 10 s of unloaded rest between load cycles transformed low-magnitude loading into a potent osteogenic regimen for both adolescent and adult animals. Here, we extended our observations and hypothesized that inserting rest between load cycles will initiate and enhance bone formation in the aged skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week mechanical loading protocols utilizing the noninvasive murine tibia loading device. We tested our hypothesis by examining whether (a) inserting 10 s of rest between low-magnitude load cycles can initiate bone formation in aged mice and (b) whether bone formation response in aged animals can be further enhanced by doubling strain magnitudes, inserting rest between these load cycles, and increasing the number of high-magnitude rest-inserted load cycles. We found that 50 cycles/day of low-magnitude cyclic loading (1200 microepsilon peak strain) did not influence bone formation rates in aged animals. In contrast, inserting 10 s of rest between each of these low-magnitude load cycles was sufficient to initiate and significantly increase periosteal bone formation (fivefold versus intact controls and twofold versus low-magnitude loading). However, otherwise potent strategies of doubling induced strain magnitude (to 2400 microepsilon) and inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high-magnitude rest-inserted load cycles (2400 microepsilon, 250 cycles/day) were not effective in enhancing bone formation beyond that initiated via low-magnitude rest-inserted loading. We conclude that while rest-inserted loading was significantly more osteogenic in aged animals than the corresponding low-magnitude cyclic loading regimen, age-related osteoblastic deficits most likely diminished the ability to optimize this stimulus.

Age Factors↗

PubMed2004

Severe hypophosphatemic osteomalacia in hormone-refractory prostate cancer metastatic to the skeleton: natural history and pitfalls in management.

We report the case of a severe symptomatic hypophosphatemic osteomalacia in a 66-year-old patient with hormone-refractory prostate cancer metastatic to the skeleton. A follow-up of 2 years from diagnosis to development of hormone refractoriness and death allowed us to study the natural history of this uncommon disturbance of mineral homeostasis in this common malignancy. Relevant to the difficult management of the late stages of prostate cancer is the failure of hypophosphatemia to respond to conventional therapeutic approaches and the favorable outcome of antitumor therapy suggesting that this group of patients, although having a poor prognosis, could still benefit from aggressive second line therapy. In this malignancy in which metastases have a predilection for bone, failure to recognize osteomalacia can only result in significantly increasing the burden of skeletal complications.

Bone Neoplasms↗

PubMed2005

GPI-specific phospholipase D (GPI-PLD) is expressed during mouse development and is localized to the extracellular matrix of the developing mouse skeleton.

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is abundant in serum and has a well-characterized biochemistry; however, its physiological role is completely unknown. Previous investigations into GPI-PLD have focused on the adult animal or on in vitro systems and a putative role in development has been neither proposed nor investigated. We describe the first evidence of GPI-PLD expression during mouse embryonic ossification. GPI-PLD expression was detected predominantly at sites of skeletal development, increasing during the course of gestation. GPI-PLD was observed during both intramembraneous and endochondral ossification and localized predominantly to the extracellular matrix of chondrocytes and to primary trabeculae of the skeleton. In addition, the mouse chondrocyte cell line ATDC5 expressed GPI-PLD after experimental induction of differentiation. These results implicate GPI-PLD in the process of bone formation during mouse embryogenesis.

Animals↗

PubMed2005

3-D quantification and visualization of vascular structures from confocal microscopic images using skeletonization and voxel-coding.

This paper presents an image processing approach for information extraction from three-dimensional (3-D) images of vasculature. It extracts quantitative information such as skeleton, length, diameter, and vessel-to-tissue ratio for different vessels as well as their branches. Furthermore, it generates 3-D visualization of vessels based on desired anatomical characteristics such as vessel diameter or 3-D connectivity. Steps of the proposed approach are: (1) pre-processing, (2) distance mappings, (3) branch labeling, (4) quantification, and (5) visualization. We have tested and evaluated the proposed algorithms using simulated images of multi-branch vessels and real confocal microscopic images of the vessels in rat brains. Experimental results illustrate performance of the methods and usefulness of the results for medical image analysis applications.

Animals↗

PubMed2004

MRI of the marrow in the paediatric skeleton.

Magnetic resonance imaging (MRI) has greatly advanced evaluation of marrow diseases of the paediatric skeleton. As with many other aspects of paediatric radiology it is important to recognize the normal variations in the appearance of the marrow that occur in the growing child. These normal variations need to be differentiated from diseases and conditions that affect the marrow. This review describes the normal changes that occur in children with age, and the appearances of the pathological changes seen in infection, infiltration, haematological disorders, transplantation and radiation therapy.

Bone Marrow Diseases↗

PubMed2005

Traumatic luxations of the appendicular skeleton.

Traumatic luxation of joints of the appendicular skeleton is common.Timely and accurate identification of the luxation is essential to restoring normal function. Physical examination and radiographic assessment are commonly utilized for accurate identification and categorization. Conservative and surgical techniques are employed for treatment of luxations solely and in combination. Selection of appropriate reparative techniques is dependent on the joint injured as well as on other joint- and injury-specific factors.

Animals↗

PubMed2005

Skeletonized bilateral internal mammary arteries for non-elective surgical revascularization in unstable angina.

OBJECTIVE: The aim of this study was to evaluate the feasibility, safety and outcome of skeletonized bilateral internal mammary arteries (BIMA) in patients with unstable angina (UA) undergoing non-elective myocardial revascularization. METHODS: Between January 1997 and December 2003, 758 patients, mean age 62+/-12 years, underwent non-elective coronary artery bypass grafting (CABG) for unstable angina. Two hundred and five (27%) were operated emergently and 503 (73%) urgently. BIMA were employed in 320 (42%) patients (Group B) and isolated left IMA and/or saphenous vein grafts in the remaining 438 (58%) patients (Group M). RESULTS: In-hospital mortality (B = 5.9% and M = 5.3%), and perioperative myocardial infarction (B = 2.2%; M = 1.96%) were similar between the two groups (P = ns). Actuarial survival at 1, 3 and 7 years was 98.7, 97.5 and 96.2% in B and 99, 94.3 and 88.4% in M (P < 0.05 at 7 years follow-up). At 7 years follow-up, the event-free cardiac survival (92 vs. 87%, P = 0.021), angina-free survival (98.6 vs. 94%, P = 0.039), reoperation-free cardiac survival (98 vs. 95%, P = 0.04) and infarct-free cardiac survival (98.7 vs. 96%, P = 0.05) were better in Group B. Multivariate analysis identified age > 65 years (P = 0.02), LVEF < 35% (P = 0.01), > 1 ischemic irreversible area (P = 0.03) as independent predictors for late deaths, while the use of the LIMA (P=0.006) and both mammary arteries (P=0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in non-elective CABG for UA is safe and effective. Mid-term outcome, however, are superior with improved freedom from cardiac death, from coronary reintervention and from myocardial infarction.

Aged↗

PubMed2006

Bone and aging: effects on the maxillofacial skeleton.

The originally balanced system of normal bone metabolism with an equilibrium of bone resorption and bone formation experiences involutionary changes along with increasing age. This article provides an overview on the effects of aging on bone, in particular on the bone of the maxillofacial skeleton. It explains differences between the postmenopausal type and the senile type of osteoporosis, deals with age-related morphologic changes of bone, mechanisms leading to age-related changes, depicts bones at high fracture risk in aging persons, analyses the reduced bone quantity and quality in cranial bone, and discusses the preservation of maxillofacial bone dimensions by implants. Therefore, research on wound healing, in particular bone healing, and on the regenerative potential of tissue of mesenchymal origin is of major interest and will eventually translate into improved care for patients during daily clinical routine.

Aging↗

PubMed2004

The erythrocyte skeletons of beta-adducin deficient mice have altered levels of tropomyosin, tropomodulin and EcapZ.

The erythrocyte membrane cytoskeleton is organized as a polygonal spectrin network linked to short actin filaments that are capped by adducin at the barbed ends. We have constructed a mouse strain deficient in beta-adducin having abnormal erythrocytes. We show here that the levels of several skeletal proteins from beta-adducin mutant erythrocytes are altered. In fact, CapZ, the main muscle actin-capping protein of the barbed ends that in the erythrocytes is cytoplasmic, is 9-fold upregulated in mutant skeletons of erythrocytes suggesting a compensatory mechanism. We also detected upregulation of tropomodulin and downregulation of alpha-tropomyosin and actin. In addition, purified adducin can be re-incorporated into adducin-deficient ghosts.

Actins↗

PubMed2006

Hand fractures and dislocations in the developing skeleton.

Management of children's fractures requires a thorough knowledge of the developing skeleton, with recognition of the injury present and its potential course based on mechanism and anatomy, a dedication to complete and repeated clinical and radiologic examinations, and a willingness to intercede if unacceptable angulation or any rotation occurs in the course of treatment. The ability to remodel follows a well-defined course and may be anticipated within certain margins, but expectations of this ability should not be overemphasized or even contemplated outside the direction of joint motion. Growth arrest following injury, although a real concern, remains rare. Persistent stiffness, particularly at the PIP joint, occurs much more frequently than is perceived, particularly for phalangeal shaft, condylar, and neck fractures.

Bone Remodeling↗

PubMed2026

Chronic disease in a 15th-century skeleton from the first European settlement of the Canary Islands: Early evidence in the colonial Atlantic expansion (San Marcial de Rubicón, Lanzarote).

OBJECTIVE: This study seeks to evaluate morphological changes in a skeleton recovered from San Marcial de Rubicón, the earliest permanent European settlement in the Canary Islands. MATERIALS: The individual derives from a primary inhumation dated to the early fifteenth century. METHODS: Macroscopic observation was combined with conventional radiography, computed tomography, and mitochondrial DNA analysis. A systematic differential diagnosis considered metabolic, infectious, inflammatory, neoplastic, and degenerative conditions. RESULTS: The individual under investigation is an adult male with evidence of diffuse cortical thickening, periosteal new bone formation, heterogeneous radiodensity, cranial diploic expansion, long-bone bowing, severe degenerative joint disease, sacroiliac ankylosis, and elongated thoracic vertebral defects. Mitochondrial DNA analysis identified haplogroup X2c1, consistent with European maternal ancestry. CONCLUSIONS: The overall pattern is most consistent with polyostotic Paget disease of bone, although coexisting axial ankylosis and vertebral defects complicate the interpretation. These additional lesions are insufficient to support an alternative primary diagnosis. SIGNIFICANCE: This case provides an early extra-European archaeological example of Paget disease in the context of Atlantic colonial expansion. Rather than simply extending the geographic record of the disease, it shows how chronic skeletal conditions with strong European clinical and archaeological associations may be identified in frontier populations formed through mobility, settlement and colonial interaction. LIMITATIONS: The diagnosis is based on a single individual, and nuclear DNA data were insufficient to assess genetic susceptibility. SUGGESTIONS FOR FURTHER RESEARCH: Further radiological, genomic, and isotopic analyses of early colonial skeletal assemblages are needed to evaluate chronic disease, mobility, and biological diversity in Atlantic frontier populations.

Male↗

PubMed2005

Pedal symphalangism in modern American and Japanese skeletons.

Pedal symphalangism is a surprisingly common heritable trait of the human foot. In individuals exhibiting the trait, the joint between the intermediate and distal phalanges of one or more lateral toes never develops, resulting in toes with two phalanges rather than three. This study was undertaken to explore variation in the frequency of pedal symphalangism among groups with widely different geographic ancestry, and to consider the applicability of this trait to skeletal biological distance studies. A total of 460 Euro-American, 191 African-American and 99 Japanese skeletons were examined for presence of pedal symphalangism. The American individuals date to the first half of the 20th c, while the Japanese individuals date to the late 19th and early 20th c. Although the country of ancestry is unknown for most of the American individuals, the Euro-Americans appear to be largely northern European, with roots in Germany, Ireland and Scandinavia, while the African-Americans are primarily descendants of slaves with roots in west African countries such as Nigeria, Benin, Togo, Ghana and Sierra Leone. Frequencies of fifth toe pedal symphalangism were calculated and compared among all three samples and found to be significantly higher in modern Japanese (83.7%) than in either Euro-Americans (46.4%) or African-Americans (44.0%). The Euro- and African-American frequencies were statistically indistinguishable for symphalangism of the fifth toe. In the fourth toe, however, the opposite result was found. The African-American frequency (7.9%) was significantly higher than the Euro-American frequency (2.6%), while no difference was found between the African-Americans and Japanese (11.7%). Since fourth toe pedal symphalangism has never been observed in the absence of fifth toe involvement, some of the same genes are clearly involved in producing the trait in both toes. However, differences in the pattern of fourth and fifth toe expression among the three groups identified in this study suggest that additional genetic or developmental factors may play a role in expression of pedal symphalangism in each of the toes.

Adult↗