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PubMed1977

Applicability of some of the assumptions used to estimate the weight of the skeleton in the growing pig and beagle.

Assumptions used in indirectly estimating skeletal weight were tested on 55 pigs (ages day 0-week 12) and 42 beagles (ages day 0-1 year). One of the assumptions was that skeletal weight constitutes a constant proportion of lean body mass (fat-free wet weight). In the beagle the skeletal weight was not constant, but a decreasing proportion of LBM during growth. In the pig there were no significant changes comparable to those in the beagle, probably because only a small part of the growth period was studied. Also, the assumption that bone mineral was 65% of fat-free dry weight of the skeleton was not applicable to the beagle, where it increased from 55% (day 0-week 12) to 70% (mouth 4-1 year). In both species skeletal growth was a function of total fat-free dry weight (FFDWt), but in the beagle the ratio Kt/FFDWt increased from 130 (day 0-week) 12) to 160 (month 4-1 year) and reflected changes in the contribution of body cell mass and skeletal to FFDWt.

Animals↗
PubMed1998

Comparison of macroscopic cranial methods of age estimation applied to skeletons from the Terry Collection.

A total of 963 skeletons (408 Whites and 555 Blacks) from the Terry Collection were studied to examine macroscopic cranial methods of age estimation. The methods of Acsádi and Nemeskéri, Masset, Baker and Meindl and Lovejoy were applied to every skull. The results indicate that the most accurate techniques in this application were those that consider endocranial suture closure. The methods of Acsádi and Nemeskéri and Masset were the most accurate in all the subsamples (by population, sex, sex within population and in total), although the relative accuracy could vary in application to other populations.

Adolescent↗
PubMedDate not supplied

Reconstruction of the frontal sinus and frontofacial skeleton with hydroxyapatite cement.

OBJECTIVE: To evaluate the efficacy of a newly developed biomaterial, hydroxyapatite cement, for use in frontal sinus and anterior craniofacial skeletal reconstruction. DESIGN: A nonrandomized patient cohort that was compared with historical controls of standard treatment with methyl methacrylate implants. SETTING: Craniofacial reconstructive surgery services at 3 referral health care centers. Eligible patients had frontal-cranial defects limited to a maximum size of 25 cm2. Patients were randomly selected volunteers with preexistent, acute traumatic or acute surgically induced defects of the frontal sinus and anterior craniofacial skeleton. All patients provided informed consent, and the study was approved by the 3 institutional review boards. Forty patients underwent reconstruction of defects of the anterior craniofacial region, and 38 of these patients were evaluable at 24 months. MAIN OUTCOME MEASURES: Hydroxyapatite cement was used to reconstruct full-thickness anterior craniofacial skull defects. Standard surgical techniques were used to place all implants. The primary outcome measurement was maintenance of implant volume determined at 24 months by computed tomography and clinical examination. Secondary outcome measures included incidence of complications and infections necessitating implant removal. RESULTS: Of the 38 evaluable patients, 31 had successful reconstructions at the end of the study, for an overall success of 82% for frontal sinus and frontofacial region reconstruction. Seven patients underwent explantation, 5 for surgical access to the site. Two implants were removed because of infection in the wound, for an overall incidence of approximately 5%. Explant biopsy specimens confirmed implant osseointegration and vascularization. CONCLUSIONS: Hydroxyapatite cement successfully reconstructs full-thickness defects of the frontal sinus and frontofacial region at 24 months. Hydroxyapatite cement appears to be superior to acrylic implants for frontal-cranial reconstruction and by allowing implant osseointegration with improved biocompatibility.

Adult↗
PubMed1996

Pattern of malformations in the axial skeleton in human trisomy 18 fetuses.

We examined and described the development and abnormalities of the axial skeleton in 10 human trisomy 18 fetuses. Whole-body radiographs and radiographs of midsagittal tissue blocks of the cranial base and the spine were studied. In 3 fetuses no spinal radiographs were available. Seven osseous regions or fields along the body axis were analyzed, four in the spine, and three in the cranial base and nasal bones. Malformations occurred in the occipital field in all fetuses. This was a characteristic notching, either unilateral or bilateral, of the basilar part of the occipital bone. Nasal bones were abnormal in 8 cases, either absent or hypoplastic. Malformations were found in the thoracic and/or lumbosacral field in 7 fetuses. A single abnormality was found in the cervical spine in one fetus. The pattern of axial skeletal malformation in trisomy 18 fetuses recorded in the present study has not been described previously. Axial skeletal radiography should be included in autopsies of fetuses when chromosome disorders are present or suspected. The methods applied here are unaffected by autolysis.

Chromosomes, Human, Pair 18↗
PubMed1998

Cortical metastatic lesions of the appendicular skeleton from tumors of known primary origin.

BACKGROUND AND OBJECTIVES: Metastatic disease represents the most common neoplastic process involving bone. Recently, a small subset of cortical based metastatic lesions has been identified. We attempted to delineate the incidence, origin, location, and possible significance of these lesions within an orthopaedic patient population. METHODS: A chart and radiographic review of patients treated for metastatic disease to bone over a 17-year period was performed. Inclusion criteria for lesions were as follows: 1) an appendicular skeletal site, 2) histopathologic confirmation of origin, and 3) presence within a patient diagnosed with a single, known neoplastic process. The lesions were classified as either cortical or medullary based. RESULTS: Eighty-three lesions (70 patients) satisfied inclusion criteria. Most lesions were of pulmonary (26), breast (22), renal (16), or prostatic (8) tumor origin. Eighteen lesions (22%) from 15 patients were identified as cortical and represented initial presentation in 7 patients. These lesions were of pulmonary (11), renal (5), and breast (2) tumor origin. CONCLUSIONS: Cortical based metastases within the appendicular skeleton may occur more frequently than previously expected. While tumors of pulmonary and renal origin accounted for 42 of the 83 (51%) appendicular lesions, they were responsible for 16 of the 18 (89%) cortical metastases. This preponderance of pulmonary and renal metastases to the cortex is consistent with previously published reports. Our findings may be of value when diagnosing and treating patients whose initial presentation is a cortically based lesion.

Adenocarcinoma↗
PubMed1999

Expression of the paired-box genes Pax-1 and Pax-9 in limb skeleton development.

Vertebrate Pax genes encode a family of transcription factors that play important roles in embryonic patterning and morphogenesis. Two closely related Pax genes, Pax-1 and Pax-9, are associated with early axial and limb skeleton development. To investigate the role of these genes in cartilage formation we have examined the expression profiles of Pax-1 and Pax-9 in developing chick limb mesenchyme in vivo and in vitro. Both transcripts are detected by reverse transcription polymerase chain reaction and Northern blotting throughout chick limb development, from the early bud stages (Hamburger-Hamilton 20-23) to fully patterned appendages (stage 30). Whole-mount in situ hybridization reveals complex, nonoverlapping expression domains of these two genes. Pax-1 transcripts first appear at the anterior proximal margin of the limb buds, while Pax-9 is expressed more distally at what will be the junction of the autopod and the zeugopod. In situ hybridization to serial sections of the girdles reveals that in the pectoral region Pax-1 is expressed proximally in condensed mesenchyme surrounding the junction of the developing scapula, humerus, and coracoid. In the pelvis, Pax-1 is expressed between the femur and the developing acetabulum and along the ventral edge of the ischium; this transcript was also found in the distal hindlimb along the posterior edge of the fibula. Pax-9 transcripts were not detected in the pectoral girdle at any stage, and only weakly in the pelvis along the ventral ischial margin. In the distal parts of both wings and legs, however, Pax-9 is strongly expressed between the anterior embryonic cartilages (e.g., distal radius or tibia) and the anterior ectodermal ridge. The expression of both genes was strongest in undifferentiated cells of precartilage condensations or at the margins of differentiated cartilages, and was absent from cartilage itself. In micromass cultures of chondrifying limb bud mesenchyme expression of Pax-1 and Pax-9 is maintained for up to 3 days in vitro, most strongly at the end of the culture period during chondrogenic differentiation. As seen in vivo, transcripts are found in loose mesenchyme cells at the outer margins of developing cartilage nodules, and are absent from differentiated chondrocytes at the nodule center. Taken together, these investigations extend previous studies of Pax-1 and Pax-9 expression in embryonic limb development while validating limb bud mesenchyme culture as an accessible experimental system for the study of Pax gene function and regulation. Our in vivo and in vitro observations are discussed with reference to 1) the relationship between somitic and limb expression of these two Pax genes, 2) what regulates this expression in different regions of the embryo, and 3) the putative cellular functions of Pax-1 and Pax-9 in embryonic skeletogenesis.

Animals↗
PubMed1999

Molecular and cellular mechanisms of estrogen action on the skeleton.

The many recent and exciting advances that have taken place in the field of estrogen action on the skeleton are the subjects of this review. Leading these new developments is the discovery of alternative estrogen receptors that exhibit differential mechanisms of transcriptional control of estrogen-responsive promoters, thereby broadening both the ranges of possible target cells and their responses. More potentially important genes under estrogenic control have been identified in vitro, and the skeletal phenotypes caused by disruption of estrogen signaling due to mutations in humans and mice have been described. Lastly, clinical studies in humans have revealed a greater appreciation for the importance of estrogen in bone mass maintenance in both sexes. J. Cell. Biochem. Suppls. 32/33:123-132, 1999.

Animals↗
PubMed1996

Mutagenesis of ser41 to ala inhibits the association of GAP-43 with the membrane skeleton of GAP-43-deficient PC12B cells: effects on cell adhesion and the composition of neurite cytoskeleton and membrane.

To investigate the molecular basis for GAP-43 function in axon outgrowth, we produced a mutant, GAP-43 (Ala41), whose interaction with calmodulin in vitro was unaffected by increasing Ca2+ concentrations, and stably transfected it into GAP-43-deficient PC12B cells. Several lines that expressed wild-type or mutant protein at levels that resembled endogenous GAP-43 expression in PC12 controls were subcloned and characterized. GAP-43 (Ala41) was significantly more extractable with Nonidet P-40 and less tightly associated with the membrane skeleton than the wild-type protein. Furthermore, GAP-43 (Ala41) expression by PC12B cells profoundly affected their phenotype: First, observation of living cells using video-enhanced microscopy revealed irregular plasma membranes with numerous blebs and protrusions and neurites that appeared thin and varicose. Second, both the cells' ability to remain attached to laminin substrates and the amount of alpha 1 beta 1 integrin expressed on the cell surface was significantly decreased. Finally, peripherin transport, which is abnormal in PC12B cells, could be rescued by transfection of wild-type GAP-43 but not the GAP-43 (Ala41) mutant. The phenotypic abnormalities resemble other cell types in which membrane skeleton/plasma membrane interactions have been functionally decoupled, and our results are consistent with the notion that these interactions may be abnormal in GAP-43 (Ala41)-expressing PC12B cells, either as a direct consequence of the mutation or arising secondarily to the altered availability of calmodulin in the growing neurite.

Alanine↗
PubMed1998

Paradox segmentation along inter- and intrasomitic borderlines is followed by dysmorphology of the axial skeleton in the open brain (opb) mouse mutant.

In open brain (opb) mutant embryos, developmental defects of the trunk spinal cord were spatially correlated with severe defects of the epaxial somite derivatives including sclerotomes, whereas hypaxial somite derivatives are much less affected. Later in development, the neural arches (epaxial sclerotome derivatives) formed but were severely disorganized, and also the distal ribs (hypaxial sclerotome derivatives) were malformed. Adjacent neural arches and vertebral bodies were often fused where joints should have formed suggesting defects of the intrasomitic borderlines. Moreover, neural arches frequently and ribs sometimes were split into halves at distinct levels along the dorso-ventral body axis. This suggests that 'resegmentation' of sclerotomes across the somite borders did not completely occur. These prominent skeletal defects were preceded by reduced expression of Pax1 along the intrasomitic borderlines, and incomplete maintenance of somite borders between central sclerotome moieties. The defects of the axial skeleton were accompanied by segmentation defects of the myotomes which were split distally, and also partly fused from adjacent segments across somite borders. The segmentation defects observed suggest that in opb mutants both segmental borderlines, the somite borders and the intrasomitic borderlines (fissures), were affected and behaved paradoxically.

Animals↗
PubMed1999

Reaction of Hypercoordinate Dichlorosilanes Bearing 8-(Dimethylamino)-1-naphthyl Group(s) with Magnesium: Formation of the 1,2-Disilaacenaphthene Skeleton.

Migration of NMe(2) from C(naphthyl) to Si and Si-Si and Si-C bond formation to give a 1,2-disilaacenaphthene skeleton occurred in the reaction of hypercoordinate dichlorosilanes bearing the 8-(dimethylamino)-1-naphthyl group with two equivalents of magnesium [e.g., Eq. (a)]. The intermediate was isolated as the 1-isopropoxy derivative after quenching the reaction mixture with isopropyl alcohol.

Journal Article↗
PubMed1976

Late effects of therapeutic irradiation on the skeleton and bone marrow.

Sequelae in the skeleton and bone marrow can be important late consequences for survivors following radiation therapy of cancer. Skeletal sequelae of radiation therapy often are predictable, although they may not be avoidable. The growth suppressive effects of therapeutic irradiation may occur in any bone, but most often are noted in the spine after doses in excess of 2000 rads. Mature bone and cartilage may be devitalized by irradiation without clinical consequence until stressed. Although malignant tumors may arise in irradiated bone and cartilage, the risk is minimal and is readily accepted in modern-day radiation oncology. Radiation-induced suppression of bone marrow function usually is of immediate rather than late consequence; however, functional recovery after therapeutic irradiation, while prolonged, is more complete than formerly thought. Leukemia rarely develops secondary to therapeutic irradiation.

Age Factors↗
PubMed1979

Adjuvant immunotherapy of lung cancer with BCG cell wall skeleton (BCG-CWS).

Four hundred fifty-five patients with lung cancer were treated with oil-attached cell-wall skeleton of bacillus Calmette-Guérin (BCG-CWS) as adjuvant immunotherapy following initial conventional therapy. The overall survival period of the patients was prolonged significantly as compared with that of 380 patients in a historical control group receiving initial conventional therapy alone (p less than 0.0001). The prolongation of the survival period of the patients was also statistically significant when classified according to clinical stages and histological cell types. The therapeutic effect was remarkable in patients combined with malignant pleurisy. Intrapleural injection of BCG-CWS resulted in not only prevention of accumulation of pleural effusion and abrogation of tumor cells but also in prolongation of survival period (P = 0.016). No serious side effects due to BCG-CWS were experienced. From the previous experimental studies and clinical experiences with human tumors, it can be concluded that adjuvant immunotherapy with BCG-CWS is a useful therapeutic modality for lung cancer, especially in cases combined with malignant pleurisy.

Adenocarcinoma↗
PubMed1979

Intralesional immunotherapy of malignant melanoma with mycobacterium smegmatis cell wall skeleton combined with trehalose dimycolate (P3).

The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.

Cell Wall↗
PubMed1986

Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia rubra cell-wall skeleton and irradiated allogeneic AML cells.

The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5-year relapse-free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.

Adolescent↗
PubMed1982

The fine structure of the developing pelvic fin dermal skeleton in the trout Salmo gairdneri.

The morphogenetic and ultrastructural features of the dermal skeleton in the pelvic fin bud of a teleost, the rainbow trout Salmo gairdneri, have been examined by light and electron microscopy. The principal structural components observed are lepidotrichia and actinotrichia. Lepidotrichia consist of two parallel and symmetrical bony demirays that form jointed segments within the fin. The demirays calcify in a proximodistal direction within the extracellular collagen network of the basal lamella belonging to the epidermal-dermal interface of the fin. Needle- and plate-like particles of a solid mineral phase appear to be associated with the collagen fibrils and with a fine, granular, interfibrillar material central to the demirays. Cellular processes and membrane-bound vesicles are absent from the regions of calcification. During fin growth, the bony, acellular lepidotrichia are separated from the epidermal-dermal interface by infiltrating mesenchymal cells in proximal fin regions; in distal areas, the lepidotrichia remain within the basal lamella. The actinotrichia are extensive unmineralized rods of elastoidin that occupy the distal margin of the fin and precede the differentiation of lepidotrichia. Once the lepidotrichia form, actinotrichia lie preferentially between their demirays. In some instances, structural interactions are suggested between actinotrichia and lepidotrichia. Considerations of embryologic and structural features of fin components fail to support the hypothesis that individual segments of lepidotrichia are modified scales in all fish.

Animals↗
PubMed1986

Quantitative genetic variation in the skeleton of the mouse: II. Description of variation within and between inbred strains.

Variation in the skeletons of over 400 male and female mice from 12 genotypes was investigated by using multivariate statistical methods. A series of discriminant functions explains the differences in the shape of six bones: mandible, os coxae, femur, tibia-fibula, scapula, and humerus. The anatomical features of bone shape described by these functions are summarized together with illustrations of the typical shapes of each bone from the 12 genotypes. Variability within genotypes was investigated by using the Mahalanobis D2 distance--a measure of the difference between two points representing multivariate data--from the group mean. A series of variants were detected ranging from grossly abnormal bones to bones showing subtle differences localized to specific regions. Examples of the variants found are illustrated.

Animals↗
PubMed1991

Liver units in three dimensions: I. Organization of argyrophilic connective tissue skeleton in porcine liver with particular reference to the "compound hepatic lobule".

Liver units were investigated in pig livers by means of histologic serial tracing, physical model building, and computer-aided three-dimensional imaging. Observations of the argyrophilic connective tissue skeleton were based mainly on the celloidin-embedded serial sections treated with silver impregnation. The parenchymal mass that clothed the initial segments of hepatic venous radicles was demarcated by fibrous septa which formed isolable units with two basic patterns: the simple hepatic lobule (SHL) and the compound hepatic lobule (CHL). Both lobule types presented regular limiting structures circumscribing each unit. Three-dimensional studies revealed that 25% of the lobules in a section belonged to the SHL type and 75% to the CHL type, the latter being predominant among the surface lobules. When considered in only two dimensions, however, the SHL-like lobules constituted the majority. Polygonal analysis disclosed that the pentagonal lobule was the most typical, instead of the "hexagonal" or "classic" lobule. The CHLs represented a multiaxial unit containing a system of venous tributaries in accordance with intralobular septation, whereas the SHLs were found with one axial vessel having a dendritic tendency at the incipient end; some SHLs were drained eccentrically by separate vessels into a sublobular vein. It was observed that, in dividing CHLs, whereas particular sinosoids were transformed into portal twigs, other sinusoids were changed into central venous tributaries. Fibrous deposition occurred along the septal-line sinusoids, bringing into view the septum-initiating plane. Fibroconnective tissue was supplied from the portal area and central (sublobular) adventitia, where portal triad structures and adventitial arterioles, respectively, were included. The findings of the present study facilitate the understanding of several characters of the lobules that have been reported previously, or occasionally postulated, such as the portal-central bridging tendency, the intralobular arterioles or ductules, the translobular artery or portal vein, the "portal-portal" or "portal-central" anastomoses, and the apposition of pericentral zone close to periportal zone. Based on differences in argyrophilia of sinusoidal reticulum, in proportion of lobule types, and in vasculature, the anatomic heterogeneity of liver unit was demonstrable in zonality, regionality, and locality.

Animals↗
PubMed1989

Extracellular matrix, cell skeletons, and embryonic development.

During embryonic development, the extracellular matrix (ECM) promotes the production of differentiated products by epithelial cells and the migration of mesenchymal cells, and probably also plays a role in epithelial-mesenchymal transformation. Here we examine the role of the cell skeleton (actin, microtubules, intermediate filaments) in mediating matrix effects on mesenchymal cell morphology, migration, and formation. The interaction of both epithelial cells and mesenchymal cells with ECM seems to involve the actin cortex, which is best developed in the base of the epithelial cell, where it attaches to underlying matrix via membrane-intercalated receptors. To interact with the matrix, the fibroblast has appropriate ECM receptors and an actin cortex around the whole cell. The actin cortex is absolutely required for assumption of bipolar shape, elongation, and movement through the matrix. Since the cortex seems to be anchored to the matrix, it is unlikely that it moves during cell migration. A new hypothesis states that the microtubule- and intermediate filament-rich endoplasm, containing the nucleus, moves past the actin cortex-receptor-matrix complex into the newly synthesized front end of the mesenchymal cell to effect forward movement. When epithelial cells transform into mesenchyme in the embryo, or when they are induced to do this in vitro, they switch from the keratin intermediate filament profile to one rich in vimentin, and the effect of cell matrix interaction on cell shape is profoundly altered. Vimentin-actin interactions with ECM may be a major factor in the ability of a cell to become mesenchymal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗