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Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy.

Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.

Adjuvants, Immunologic↗

The context of Stw 573, an early hominid skull and skeleton from Sterkfontein Member 2: taphonomy and paleoenvironment.

The reconstructed taphonomic and paleoenvironmental contexts of a ca. 4 million-year-old partial hominid skeleton (Stw 573) from Sterkfontein Member 2 are described through presentation of the results of our analyses of the mammalian faunal assemblage associated stratigraphically with the hominid. The assemblage is dominated by cercopithecoids (Parapapio and Papio) and felids (Panthera pardus, P. leo, Felis caracal, and Felidae indet.), based on number of identified specimens, minimum number of elements and, minimum number of individuals. In addition, the assemblage is characterized by a number of partial skeletons and/or antimeric sets of bones across all taxonomic groups. There is scant indication of carnivore chewing in the assemblage. These observations, in addition to other taphonomic data, suggest that the remains of many animals recovered in Member 2 are from individuals that entered the cave on their own-whether accidentally by falling through avens connecting the cave to the ground surface above or by intentional entry-and were then unable to escape, rather than primarily through systematic collection by a biotic, bone-accumulating agent. The taphonomic conclusion that animals with climbing proclivities (i.e., primates and carnivores) are preferentially preserved over other taxa, ultimately because of those proclivities, urges caution in assessing the fidelity of the assemblage for reconstruction of the Member 2 paleoenvironment. With that caveat, we infer that the Member 2 paleoenvironment was typified by rolling, rock-littered and brush- and scrub-covered hills, indicated by the abundant F. caracal and cercopithecoid fossils recovered and the identified presence of the extinct Caprinae Makapania broomi. In addition, the valley bottom may have retained standing water year-round, perhaps supporting some tree cover--a setting suitable for the well-represented ambush predator P. pardus and suggested by the presence of Alcelaphini. Finally, the reconstructed taphonomic and paleoenvironmental settings of Sterkfontein Member 2 are compared to penecontemporaneous sites in South and East Africa.

Anatomy, Comparative↗

Whole-body phantoms with anthropomorphic-shaped skeletons for evaluation of dual-energy X-ray absorptiometry measurements.

We have developed a set of four whole-body phantoms with anthropometric-shaped skeletons constructed of CaHPO4-doped epoxy resin, to simulate average body sizes of children at ages 4, 10, 15, and 18. Each phantom was measured on a Hologic QDR-2000 instrument with and without a set of polyethylene overlays to simulate excess body fat, and with and without a 0.6% NaCl/water mixture to simulate differences in lean tissue composition. Precision of total body BMC, based on 4 scans over 2 wk, were 0.5%-1.8%, and were correlated (r2 = 0.999, p < 0.001) with the chemical Ca content of the simulated skeleton. The addition of overlays to the phantoms to simulate increased body size and/or body fat resulted in small but significant increases in the measured values for BMC and bone area, but not that of BMD.

Absorptiometry, Photon↗

The potential of biomimesis in bone tissue engineering: lessons from the design and synthesis of invertebrate skeletons.

Synthetic bone replacement materials are now widely used in orthopedics. However, to date, replication of trabecular bone structure and mechanical competence has proved elusive. Maximization of bone tissue attachment to replacement materials requires a highly organized porous structure for tissue integration and a template for assembly, combined with structural properties analogous to living bone. Natural structural biomaterials provide an abundant source of novel bone replacements. Animal skeletons have been designed through optimization by natural selection to physically support and physiologically maintain diverse tissue types encompassing a variety of functions. These skeletons possess structural properties that provide support for the complete reconstruction and regeneration of ectodermal, mesodermal, and bone tissues derived from animal and human and are thus suited to a diversity of tissue engineering applications. Increased understanding of biomineralization has initiated developments in biomimetic synthesis with the generation of synthetic biomimetic materials fabricated according to biological principles and processes of self-assembly and self-organization. The synthesis of complex inorganic forms, which mimic natural structures, offers exciting avenues for the chemical construction of macrostructures and a new generation of biologically and structurally related bone analogs for tissue engineering.

Animals↗

Accelerator mass spectrometry radiocarbon ages of amino acid extracts from Californian palaeoindian skeletons.

A decade ago, aspartic acid racemization ages were determined for some skeletal remains found in California, near La Jolla, Del Mar and Sunnyvale, suggesting that people were present in North America during the Upper Pleistocene. These ages were obtained from the aspartic acid racemization rate, which was calibrated using a radiocarbon date of 17,150 +/- 1,470 yr BP determined for a skeleton found in Laguna Beach, California. These studies generated an intense controversy not only about the antiquity of human beings in the New World but also about the validity of racemization-based ages, and prompted efforts to date the finds by other means. Here we have used accelerator mass spectrometry (AMS) to determine the radiocarbon ages of the amino acid extracts used in the original racemization studies. Our studies indicate that some of the controversial Californian skeletons, which had been assigned to the Upper Pleistocene, are in fact Holocene.

Amino Acids↗

Paired gill slits in a fossil with a calcite skeleton.

The chordates, hemichordates (such as acorn worms) and echinoderms (such as starfish) comprise the group Deuterostomia, well established as monophyletic. Among extant deuterostomes, a skeleton in which each plate has the crystallographic structure of a single crystal of calcite is characteristic of echinoderms and is always associated with radial symmetry and never with gill slits. Among fossils, however, such a skeleton sometimes occurs without radial symmetry. This is true of Jaekelocarpus oklahomensis, from the Upper Carboniferous of Oklahoma, USA, which, being externally almost bilaterally symmetrical, is traditionally placed in the group Mitrata (Ordovician to Carboniferous periods, 530-280 million years ago), by contrast with the bizarrely asymmetrical Cornuta (Cambrian to Ordovician periods, 540 to 440 million years ago). Using computer X-ray microtomography, we describe the anatomy of Jaekelocarpus in greater detail than formerly possible, reveal evidence of paired gill slits internally and interpret its functional anatomy. On this basis we suggest its phylogenetic position within the deuterostomes.

Animals↗

Functional morphological similarities in the locomotor skeleton of miocene catarrhines and platyrrhine monkeys.

Noncercopithecid Miocene catarrhines share numerous features of their postcranial skeleton with extant platyrrhines, particularly pitheciines, cebines, and atelines. For any given fossil taxon, these similarities do not extend throughout the skeleton. Also there may be similarities to more than one platyrrhine taxon, within different parts of the postcranium or even within a single bone. These similarities are of two types. Features that are most likely to be retentions from the primitive anthropoid condition are present in many Miocene taxa. They are part of functional complexes associated with the performance of quadrupedal and possibly orthograde climbing activities. Other features, especially present in nonhominoid primitive catarrhines, are related to the performance of suspensory behaviors, and reflect a partial convergence on the suspensory ateline condition.

Animals↗

The Royal Princess Anna Vasa. Historical note and radiological examination of her skeleton.

Radiological findings on the skeleton of the Royal Princess Anna Vasa are presented. Anna Vasa (1568-1625) was the sister of Sigismund Vasa, who reigned as Sigismund III, king of Sweden and Poland. She was born in Sweden but spent most of her life in Poland. Her skeleton was removed from the tomb in Toruń during restoration work at St. Mary's Church in April 1994. It was then subjected to anthropological and radiological examinations (conventional radiography and CT). The studies revealed a number of anatomical deviations and pathological abnormalities; e.g. basilar impression and congenital anomalies of the spine. These findings can explain many of the complaints troubling Anna Vasa during her lifetime. A fragmentary historical outline and biography of Anna Vasa and Sigismund III are also presented.

Abnormalities, Multiple↗

Comparison of radiological and gross examination for detection of cancer in de-fleshed skeletons.

The reliability of visual examination of de-fleshed bones was assessed for detection of postcranial metastatic disease in individuals known to have had cancer. This was compared with standard clinical radiological techniques. The skeletons of 128 diagnosed cancer patients from an early 20th century autopsied skeletal collection (Hamann-Todd Collection) were examined. Radiological examination detected evidence of metastatic disease in 33 individuals, compared to 11 by visual examination of the postcranial skeletons. Four of these cases were detected by both techniques. Blastic lesions were most commonly overlooked on visual examination, because they were localized to trabecular (internal bone) structures. The ilium was the most commonly affected bone, with lytic or blastic lesions detected in 30 out of 33 individuals. While the proximal femur was affected in only nine individuals, X-ray of the proximal femur and ilium detected all individuals with postcranial evidence of metastatic disease. Skeletal distribution of metastases provides no clue to the location of origin or histological subtype of the cancer. A survey of archeological human remains for metastatic cancer requires radiological examination. Such skeletal surveys should X-ray at least the ilia and femora.

Autopsy↗

The oldest complete skeleton of an Australopithecus in Africa (StW 573).

Although 78 years have elapsed since the discovery at Taung of the Australopithecus africanus, and despite intensive fieldwork in East Africa which resulted in 32 years of non-stop excavation at Sterkfontein, there has not been a discovery to date of a reasonably intact skull and associated skeleton of an ape-man. The following report is an account of an extraordinary series of events that led to the discovery of a complete skeleton on an Australopithecus, and a preliminary assessment of the significance of the fossil, which is still 5 years after its discovery largely embedded in the Member 2 breccia of the Sterkfontein Caves near Krugersdorp, South Africa.

Animals↗

[Results of osteologic studies of medieval pediatric skeletons with special reference to the population of Anatolia].

Causes and frequency of diseases during childhood in populations of the Middle Ages were studied. The infant skeletons of ten populations from Central Europe and Anatolia were examined by macroscopical, radiological, endoscopical, histological, and scanning-electron microscopical techniques. Because only little is known about Anatolian populations, more attention was paid to the Byzantine populations. The infant skeletons are very well preserved. Therefore, the morbidity and the mortality could be studied in detail. The following disorders were diagnosed: anemia, C-avitaminosis, D-avitaminosis, osteomyelitis, meningitis-meningoencephalitis, otitis media and mastoiditis, perisinusitis, inflammation of the cavum nasi, inflammation of the paranasal sinuses, stomatitis, periodontal diseases, caries, pleuritis, trauma, and malformations. The frequency of diseases and the mortality depended on the type and the intensity of particular external life conditions. These may have been quite different in several social groups of the same population. In summary, these studies provide new information on the etiology and the epidemiology of diseases during childhood in the Middle Ages.

Age Determination by Skeleton↗

Definition of reference frames on human skeleton.

In our modeling study of the human cardiovascular system, some forms of subject motion or posture, e.g., those experienced or assumed by a fighter pilot, can not be neglected in considering the overall system dynamics. This investigation aims at establishing a set of reference frames on the human skeleton which are based on the observations and measurements taken on four skeleton systems. These frames are coupled together at the articulation positions to form a base of operation of 3-D translation and rotation. The coupling at a specified reference position was verified against the proportional measurements taken from X-ray films, CAT scan films, atlases and two human cadavers. A program was written to perform the forementioned transformations on the frames coupled at the reference position such that any posture can be achieved as long as the necessary angular anthropometric measurements are provided. If a set of angular profiles at all involved joints are given, the human motion can be mathematically animated to a certain degree of accuracy appropriate for specified computer simulation studies. Under this definition, any major segment of our cardiovascular system model can be specified in terms of spatial position and orientation. [table: see text]

Anthropometry↗

Hydroxyapatite cement in craniofacial skeletal reconstruction and its effects on the developing craniofacial skeleton.

OBJECTIVE: To assess the effects of hydroxyapatite cement (HAC) on the developing feline craniofacial skeleton. DESIGN: Fronto-orbital craniotomies were performed on 14 kittens and reconstructed by autograft or HAC. By design, animals in which the craniofacial skeleton was reconstructed with HAC also underwent obliteration of the left frontal sinus. After achievement of skeletal maturity, animals were sacrificed and compared by 11 standardized cranial measurements obtained by sliding caliper. Additional analyses included histological studies, histomorphometry, and computed tomography. SUBJECTS: Twenty-one 12-week-old female cats were divided into 3 groups, composed of 7 specimens. INTERVENTION: The control animals underwent periosteal elevation alone (group 1). The remaining animals underwent unilateral fronto-orbital craniotomy and subsequent reconstruction with orthotopic bone flap replacement (group 2) or HAC (group 3). RESULTS: All animals survived the study with no evidence of wound infection or implant failure. Gross morphological studies demonstrated excellent contour reconstruction in both experimental groups. Craniometric analysis detected 1 intergroup difference that consisted of a wider skull in group 3 on the reconstructed side. An intragroup difference in orbital height was also seen in group 3. Computed tomography demonstrated a solid appearance of the implant with obliteration of the left frontal sinus in group 3. Histological studies showed that HAC was osseointegrated to native bone, with areas of new bone interspersed throughout the implants. No significant inflammatory response or fibrous encapsulation was noted. Histomorphometry demonstrated that implants were replaced by osseous tissue in 44% to 50% of the animals within 5 months. CONCLUSION: Hydroxyapatite cement is safe and effective for craniofacial reconstruction in the developing feline and may be appropriate for similar applications in humans.

Animals↗

Lag screw fixation in the upper craniomaxillofacial skeleton.

Rigid internal fixation of the craniomaxillofacial skeleton has become commonplace in osseous reconstructive procedures of the face. While miniplates are useful in many traumatic, reconstructive, and congenital anomaly cases, they are often unnecessary. Lag screw fixation is routinely used in the mandible and has the advantage of maximal stability when compared with other fixation techniques. These principles can similarly be applied in a variety of situations in the upper facial skeleton, including fracture and bone graft fixation, as well as in pediatric craniofacial surgery. We review the technique and appropriate indications and demonstrate via case examples this diversity of applicability for using lag screw techniques. Finally, results of 83 cases in which this technique has been used will be reviewed, including complications.

Bone Screws↗

Pattern of malformations in the axial skeleton in human triploid fetuses.

We examined the axial skeleton in 15 human triploid fetuses (10 with XXX and 5 with XXY sex chromosomes). All fetuses 14-29 weeks of gestational age (GA), underwent whole-body radiography, permitting analysis of the nasal bone and the spine. From 9 of these, detailed radiographs were taken of midsagittal blocks of the cranial base and the spine, permitting detailed analysis of the cranial base. NASAL BONE: Of 14 fetuses, where the nasal bone was seen on lateral projection, it appeared short in 10 cases. SPINE: The spine was normal in 7 of 15 fetuses; malformations occurred in 8. These were osseous fusions between 2 or more vertebral bodies, most frequently in the cervical and thoracic regions, and disproportions in the sizes of the cervical bodies. Fusions occurred in 5 cases alone, and in one case in combination with disproportions of vertebral size. Disproportions alone occurred in 2 cases. CRANIAL BASE: Malformation of the basilar part of the occipital bone was found in 5 of the 9 fetuses investigated. Of 9 fetuses, bilateral ossification centers of the postsphenoid bone occurred in 7, and shell-like ossification centers in 2. There was no difference in the type of malformations in the different axial fields related to genotype (XXX and XXY). CONCLUSION: The most remarkable findings in the axial skeleton of triploid fetuses are vertebral fusions in 6 of 15 cases; clefts of vertebral bodies, previously reported as common findings in trisomy fetuses, are not demonstrated.

Abnormalities, Multiple↗

Mandibular ramus flexure: a new morphologic indicator of sexual dimorphism in the human skeleton.

In the skeleton, male and female characteristics lie along a continuum of morphologic configurations and metric values. Size alone is not the best indicator of sex. In contrast, morphologic differences that arise from genetically sex-linked growth and development allow better separation of the sexes. This study presents a new morphologic indicator of sexual dimorphism in the human mandible. A sample of 300 mandibles from adults of known sex primarily from the Dart collection was analyzed. Of these, 100 were found to have obvious bony pathologies and/or excessive tooth loss ("pathologic" sample). Thus, the normative sample consisted of 200 individuals (116 males, 84 females). Examination of morphologic features led to the discovery of a distinct angulation of the posterior border of the mandibular ramus at the level of the occlusal surface of the molars in adult males. Flexure appears to be a male developmental trait because it is only manifest consistently after adolescence. In most females, the posterior border of the ramus retained the straight juvenile shape. If flexure was noted, it was found to occur either at a higher point near the neck of the condyle or lower in association with gonial prominence or eversion. In the normative sample, overall prediction accuracy from ramus shape was 99%. When the "pathologic" sample was analyzed separately, 91.0% were correctly diagnosed. Because the African samples were overwhelmingly black, this trait was also tested on American samples (N = 247) of whites (N = 85), Amerinds (N = 66), and blacks (N = 96) that included a mix of healthy individuals and those with extensive tooth loss and evidence of pathology. The results were nearly identical to those of the "pathologic" African sample, with accuracies ranging from about 91% in whites and blacks to over 92% in Amerinds. Total accuracy for all African and American samples combined (N = 547) is 94.2%. In conclusion, at 99%, sexing from the shape of the ramus of a healthy mandible is on a par with accuracy attainable from a complete pelvis. Moreover, there is no record that any other single morphologic or metric indicator of sex (that has been quantified from the adult skeleton) surpasses the overall accuracy attained from the more representative mixed sample produced by combining all groups assessed in this study. The usefulness of this trait is enhanced by the survivability of the mandible and the fact that preliminary investigations show that the trait is clearly evident in fossil hominids.

Animals↗

Congenital solitary fibromatosis of the skeleton: case report of a variant of congenital generalized fibromatosis.

A study of a 3-month-old boy with a solitary form of congenital generalized fibromatosis of the skeleton is presented. Radiographic examination revealed a shortening of the right ulna and an osteolytic lesion in the distal metaphysis extending to the epiphysis. The histological appearance seems to be consistent with previously described cases of generalized congenital fibromatosis of soft tissues and skeleton. Ultrastructurally, the tumor cells resembled primitive fibroblasts. The lesion was curetted 3 times and filled with bone transplants before it finally healed. At follow-up of the boy at age 13, there were no signs of the tumor.

Bone Neoplasms↗

"Solid" variant of aneurysmal bone cyst (extragnathic giant cell reparative granuloma) in the axial skeleton and long bones. A study of its morphologic spectrum and distinction from allied giant cell lesions.

BACKGROUND: Giant cell reparative granuloma is generally considered to be a benign tumor-like bone lesion. Its involvement of axial skeleton and long bones is rare. METHODS: Seven cases of extragnathic giant cell reparative granuloma (GCRG), which arose in the axial skeleton and long bones, were analyzed clinicopathologically and compared with allied lesions consisting of 31 cases of aneurysmal bone cyst (ABC) and 83 cases of giant cell tumor of bone (GCT). RESULTS: These occurred in patients ranging in age from 8-36 years; two were in the vertebrae; two, in the clavicles; one, in a rib; one, in the humerus; and one in the tibia. None of the patients with GCRG had a recurrence despite incomplete resection. Its skeletal distribution and average associated patient age were similar to those of ABC. Histologically, they were characterized by florid fibroblastic proliferation with osteoclast-like giant cell-rich areas, stromal hemorrhage, and newly formed bone or osteoid trabeculae. The histologic features could be found around either the characteristic aneurysmal cysts or sinuses, although they were lacking any large blood-filled spaces. CONCLUSIONS: The overlapping clinical and histologic features between GCRG and ABC and their similar biologic behavior represent related responses to an intraosseous hemorrhage. The authors prefer to use the term "solid variant of aneurysmal bone cyst" to describe this lesion.

Adolescent↗