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The fibrous skeleton in the human heart: embryological and pathogenetic considerations.

The fibrous skeleton of the human heart is composed of several parts which are formed from different, mainly extracardiac sources. The atrioventricular valve rings are formed by invagination of sulcus tissue at the atrioventricular and bulboventricular transitions. The atrial part of the central fibrous body is formed from an ingrowth of tissue from the dorsal mesocardium, the ventricular part from ingrowth of sulcus tissue towards an endocardial structure, the left bulbar ridge. During valve development the atrioventricular endocardial cushions, initially situated between the developing atrial and ventricular parts of the central fibrous body, are almost completely removed downwards into the ventricular cavities. However, a small portion of these cushions remains on top of the ventricular septum, is "trapped" by the surrounding sulcus tissues and becomes incorporated in the central fibrous body. These embryological findings on this centrally located area of the heart have implications for certain types of cardiac abnormalities. In this respect the atrioventricular conduction system, cor triatriatum sinistrum and atrioventricular defect are discussed.

Endocardium↗

Local expression of cytokines in rat bladder carcinoma tissue after intravesical treatment with Nocardia rubra cell wall skeleton and bacille-Calmette-Guerin.

This study aimed to investigate local immunotherapy with Nocardia rubra cell wall skeleton (N-CWS) and bacille-Calmette-Guerin (BCG) in chemically induced rat bladder carcinoma. After being fed with 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine for 26 weeks, female Wistar rats were treated once a week by intravesical instillation of 100 microg N-CWS or 5 x 10(6) Colony-Forming Units (CFU) BCG. Tissue specimens were obtained 4 h after the ninth instillation and analyzed by reverse transcription polymerase chain reaction (RT-PCR) for mRNA expression of rat cytokines. The analysis showed high expression of interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha, IL-2, and interferon (IFN)-tau in BCG (7/7, 7/7, 7/7, 5/7) and N-CWS (9/9, 9/9, 8/9, 8/9) treated tumors in comparison to low expression in controls (3/9, 0/9, 3/9, 3/9). Interestingly, intravesical instillation of N-CWS tended to be less effective at preventing local invasion of the tumors. It is speculated that this difference may result from a more strongly induced expression of T-helper cell-derived lymphokines (IL-2, IFN-tau) by BCG.

Actins↗

Immunostimulation in the urinary bladder by local application of Nocardia rubra cell wall skeleton preparation (Rubratin) for superficial bladder cancer immunotherapy--a phase I/II study.

OBJECTIVES: Twelve patients with superficial papillary transitional cell carcinoma of the bladder (pTa, pT1) were treated with six consecutive weekly intravesical instillations of Rubratin (in a dose of 1.5, 3.0, or 4.5 mg), a cell wall skeleton preparation of Nocardia rubra (NCW). The main objective of this study was to look for local immunomodulating effects of NCW and in the first four patients the effect on a marker lesion was also investigated. METHODS: Local immunostimulation in all 12 patients was determined by (1) measurement of cytokine induction [interleukin 1 beta (IL1 beta), IL2, IL6, and tumor necrosis factor alpha (TNF alpha)], (2) leukocyte influx into the urine, and (3) phenotypic analysis of the lymphocyte fraction of these leukocytes. RESULTS: Significantly elevated levels of Rubratin-induced IL1 beta (P < 0.001), IL2 (P < 0.001), IL6 (P < 0.01), and TNF alpha (P < 0.001) were found compared to control pretherapy levels. Rubratin also induced leukocyte influx into the urine. Fluorescence-activated cell sorter (FACS) analysis of the urinary leukocytes indicated T-cell activation (IL2 receptor and HLA-DR expression), while in two out of five patients the CD4/CD8 ratios were increased. Urinary cytokine induction by Rubratin was comparable with cytokine induction observed in nonresponding bacillus Calmette-Guérin (BCG) patients (recurrent tumor within 6 months), but less compared with responding BCG patients (no recurrent tumor within 6 months). Clinical results showed no response on the marker lesion and in five out of eight patients early recurrence was found after complete transurethral resection (TUR) of the bladder tumors. This biological response modifier caused no local or systemic side effects at the doses used. CONCLUSION: Although local immunostimulation by intravesical Rubratin administration can be induced, the amount of immunocompetent cells attracted to the bladder is not as high as observed in BCG-responding patients, resulting in lower amounts of cytokines produced. This could also explain the lack of clinical efficacy.

BCG Vaccine↗

[Fascia skeleton of the abdominal cavity--hernia and anorectal incontinence].

The abdominal cavity is the most primitive body cavity. Its musculo-fascial skeleton encompasses the abdominal wall, the pelvic floor, and the diaphragm. Comparative anatomical studies have demonstrated remarkable homology in the muscular and fascial architecture of each of these structures. In addition, all muscular sheets lining the abdominal cavity display a characteristic resting tone enabling them to act as a single functional unit. During pregnancy and childbirth the abdominal wall and the pelvic floor are prone to impairment from overstretching. This damage may result in postpartum paralysis of the abdominal wall or anorectal incontinence. Insight in the special anatomic and physiologic features of the abdominal muscle sheets may lead to a better understanding of the pathogenesis of primary and secondary abdominal hernias as well as postpartum anorectal incontinence and may improve surgical treatment.

Abdominal Muscles↗

[Some structural and functional peculiaritis of the growing skeleton and their significance in fracture healing (author's transl)].

The following properties of the growing skeleton are discussed in relation to fracture healing: (1) The pronounced reaction of periosteum and endosteum and their part in the correction of deformities, and the vascular pattern of cortical bone; (2) the microscopical structure and the vascular supply of the growth plate, with reference to their significance in injuries; (3) the involvement of growth plate and growing articular cartilage in the modeling of the end of long bones and in the correction of angular deformitis.

Bone Development↗

A model-independent comparison of the rates of uptake and short term retention of 47Ca and 85Sr by the skeleton.

1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.

Bone and Bones↗

Gorham's disease involving the thoracic skeleton. Plain films and CT in two cases.

Two cases of Gorham's disease (massive osteolysis, idiopathic osteolysis, vanishing bone disease) involving the thoracic skeleton are reported. Both patients were adolescent females with involvement of multiple ribs. Involvement of the thoracic spine and pleural effusions--unusual manifestations carrying a poor prognosis--were also present. The radiographic and computed tomographic appearances are included with discussion and review of this disease entity.

Adolescent↗

Effects of dietary protein and calcium on the skeleton of undernourished young rats.

A study has been made of the effects of various levels of dietary protein and calcium on the skeleton of young undernourished rats. The data for the study were obtained from physical properties of bone, from microradiographs of various parts of femur and histological sections of the bone. There were significant associations between a low protein intake and low bone mass, irrespective of calcium intake, and between a high protein intake and a high bone density at a normal calcium content of the diet. The influence of dietary protein on the composition of the bone was dependent on the calcium intake. Reduction in the protein level was associated with less trabecular bone and reduction in the calcium reduced mainly the amount of cortical bone.

Animals↗

The Minotaur syndrome: plastic surgery of the facial skeleton.

This article remarks on the possibility of recontouring the face by working on the facial skeleton with the sole purpose of softening the facial appearance. The author describes a one-step surgical procedure performed on a 38-year-old man who had serious social problems because of his aggressive and threatening facial appearance that contrasted with his gentle personality. The author coins the term Minotaur Syndrome to describe the discrepancy between the patient's true personality versus his negative facial appearance.

Adult↗

Radiological abnormalities of the skeleton in patients with sickle-cell anemia. A study of 222 cases in Tunisia.

The way in which bones are affected in cases of sickle-cell anemia is well known. Nevertheless, advances in treatment and in methods of transfusion mean that we are increasingly seeing cases of older patients with this disease. A retrospective analysis of 222 cases of sickle-cell anemia demonstrates the radiological appearance of the skeleton in the disease and reveals the various bone segments which are particularly vulnerable at certain periods of life. Correlation of X-rays permits the discovery of lesions which are not clinically apparent. The frequency and characteristics of epiphyseal osteonecrosis and osteitis are studied. Aggravation of the bone lesions when corticoids are administered poses the problem of differential diagnosis of the disease, especially in comparison with rheumatic fever.

Adolescent↗

[Diagnostics and therapy of osseous elbow lesions in the growing skeleton].

Osseous elbow lesions in the growing skeleton often involve problems of diagnosis, indication and therapy which are essentially different from those occurring in adult persons. Beyond its task to prove or to exclude a fracture line, X-ray diagnosis also has to search systematically for discernible soft tissue modifications (adipoid signs) or for disturbed correlations of positions and axes. When adopting an indication for conservative or surgical treatment, it has to be considered that rotation faults are not compensated during the further growth of bones and that an insufficient reposition of an epiphysis fracture causes a tendency towards an increase of the joint deformity when the bone is growing. The treatment of a bone fracture aims not only at a good elbow joint function which can be achieved even by a conservative, insufficient reposition, but also at an exact reposition and a reliable fixation during the short healing time. In most cases, the latter is only possible by means of fine metal implants (drilling wires and screws for little fragments which, by way of exception, do not touch the epiphyseal cartilage). This is the only way to avoid joint deformations and defective positions in adolescents which can promote the formation of destructive arthroses in adults. As opposed to fractures in adult persons, the functional result is not deteriorated by an additional immobilization for a period of three to four weeks effected in order to guarantee the so-called "minimal osteosynthesis".

Adolescent↗

Whole-body vibration in the skeleton: development of a resonance-based testing device.

Whole-body vibration (WBV) has been demonstrated to have a strong influence on physiological systems, ranging from severely destructive to potentially beneficial. Unfortunately, the study of WBV in a controlled manner is commonly constrained by space and budgetary factors, particularly where vibration in the low frequency range is considered. In the work presented here, a small, low-cost device for performing WBV of the human skeleton is developed to assist in studies of vertical acceleration in a clinical setting. The device design consists of a spring-supported plate driven by an 18 N peak-force electromagnetic actuator, and the associated driving and monitoring electronics. Animal and human lumped-mass models have been coupled with a model of the loading device to seek a resonance response in the vicinity of 30 Hz. This approach minimizes the loading requirements of such a device, and thus a major component of the cost, yet can provide peak accelerations of 0.15 g at a frequency of 30 Hz in a small, lightweight package capable of use in a clinical or laboratory setting.

Acceleration↗

Detergent-resistant membranes in human erythrocytes and their connection to the membrane-skeleton.

In cell membranes, local inhomogeneity in the lateral distribution of lipids and proteins is thought to exist in vivo in the form of lipid 'rafts', microdomains enriched in cholesterol and sphingolipids, and in specific classes of proteins, that appear to play specialized roles for signal transduction, cell-cell recognition, parasite or virus infection, and vesicular trafficking. These structures are operationally defined as membranes resistant to solubilization by nonionic detergents at 4 degree C (detergent-resistant membranes, DRMs). This definition appears to be necessary and sufficient, although additional manoeuvres, not always described with sufficient detail, may be needed to ensure isolation of DRMs, like mechanical homogenization, and changes in the pH and/or ionic strength of the solubilization medium. We show here for the human erythrocyte that the different conditions adopted may lead to the isolation of qualitatively and quantitatively different DRM fractions, thus contributing to the complexity of the notion itself of lipid raft. A significant portion of erythrocyte DRMs enriched in reported lipid raft markers, such as flotillin-1, flotillin-2 and GM1, is anchored to the spectrin membrane-skeleton via electrostatic interactions that can be disrupted by the simultaneous increase in pH and ionic strength of the solubilization medium.

Detergents↗

Conformationally constrained analogues of diacylglycerol having a perhydrofuro[3,4-c]furan-1,4-dione bis-gamma-butyrolactone skeleton.

Bis-gamma-lactones (1, 2) having a perhydrofuro[3,4-c]furan-1,4-dione skeleton were designed as conformationally constrained diacylglycerol analogues. They were synthesized from D-apiose in 11 steps, and evaluated as PKC-alpha ligands by measuring their ability to displace bound [3H]-PDBU from the enzyme. The compounds showed moderate binding affinities with Ki values of 13.89 (+/- 5.67) microM and 11.47 (+/- 0.89) microM, respectively. Their similar binding affinities indicate that these two bicyclic compounds were not effectively discriminated by PKC-alpha in terms of the direction of the side chain as other ligands built on similar bis-gamma-lactones.

Enzyme Inhibitors↗

The skeleton structure--an improved compression algorithm with perfect reconstruction.

This article presents an improved morphological image representation that can be used for image compression, obtaining very high compression rates. The new image representation described in this work is called skeleton structure and is a natural extension of the morphologic structure. This article will present its theoretical background, introduce the new representation, and show some application examples.

Algorithms↗

Quantitative analysis using the star volume method applied to skeleton patterns extracted with a morphological filter.

In this study, a morphological filter was combined with star volume analysis and applied to digital images to determine its potential usefulness in assessing trabecular structure. Three digital "geometric" test patterns (square, rectangle, circle) were created on a CRT (cathode ray tube). Each shape was arranged into five groups by size to yield 15 final "skeletal" patterns that were subsequently assessed with star volume analysis. Also, three digital X-ray images (background, soft tissue, bone block) were processed with a morphological filter to create three sets of 11 skeletal patterns each. These patterns were also assessed with star volume analysis and the ratio of extracted skeletal elements (in pixel numbers) to total pixel numbers was expressed as the pixel percentage. Star volume analysis was then applied to these digital skeletal images to yield the volume of extracted "skeletal" trabecular elements (Vsk) and the volume of nonskeletal (marrow space) elements (Vsp). The Vsk and Vsp were compared for all the different skeletal patterns. The pixel percentages were then compared to the star volume results for the X-ray test patterns. The Vsk decreased and Vsp increased as the number of operations (n) increased for both digital X-ray images and the geometric test patterns when the X-ray images were depicted by pixel percentages. Also, all true bone test patterns were clearly different both visually and quantitatively when compared to the noise skeletons extracted from background and soft tissue. Therefore, as Vsk was increased, so was connectivity. It can be concluded that the application of morphological filters and star volume analysis may be a useful tool in quantitatively determining the characteristics and continuity of trabecular skeletal structures. Further studies involving a larger number of bone samples and using models to compare measurements of calculated versus actual volume should reveal the true potential of this method for evaluating bone structure and its relationship to bone strength and also increase the tools available for evaluating bone diseases such as osteoporosis.

Femur↗

Dynamics of skeleton formation in the Lake Baikal sponge Lubomirskia baicalensis. Part I. Biological and biochemical studies.

In ancient Lake Baikal (East Siberia), freshwater sponges have diversified to an extraordinary degree. The skeleton of Lubomirskia baicalensis, which attains a size of up to 1 m, is constructed from spicules, which are cemented into longitudinal bundles. Our X-ray analysis revealed that the architecture of the specimens follows a highly ordered radiate accretive growth pattern. The spicules have a central axial canal with an axial filament inside. This organic filament is composed of silicatein, the major enzyme involved in silica formation of the spicules. We found that the specific activity of silicatein in samples from the non-growing (basal) zone is much lower than in those from the growth zone (tips) and that even the composition of this molecule differs in these regions. The present study shows for the first time that the turnover of silicatein, the major element of the axial canal of sponge spicules, changes within a sponge specimen depending on the region in which it is found.

Animals↗

Dynamics of skeleton formation in the Lake Baikal sponge Lubomirskia baicalensis. Part II. Molecular biological studies.

In a preceding study it has been reported that the freshwater sponge Lubomirskia baicalensis, living in Lake Baikal (East Siberia), is composed of spicules forming a characteristic pattern which follows radiate accretive growth. Here we report that the spicules are synthesized by the enzyme silicatein, a protein which is related to cathepsin L. The cDNAs for silicatein and the related cathepsin L were isolated and used as probes to show that the mRNA levels of silicatein in the bases of the spicule skeleton of the animals are low, while the mRNA level of cathepsin L in this region exceeds that of the growing zone. This is the first comprehensive study on the importance of the axial filament/silicatein as an essential structural and functional component determining the growth and stability of demosponge spicules.

Amino Acid Sequence↗