To characterize the relative toxicity of different bile salts, isolated hepatocytes were incubated with different concentrations of one bile salt or with identical concentrations of different bile salts and their conjugates. Incubation lasted for 1 hr; samples were taken at intervals and studied for enzyme release, urea synthesis and stimulation by glucagon, and by electron microscopy. While the trihydroxylated bile salt, taurocholate, did not produce alterations at concentrations up to 1,500 microM, the dihydroxylated salts, chenodeoxy- and deoxycholate, caused enzyme release and membrane lysis, and inhibited urea synthesis at concentrations above 500 microM. In contrast, ursodeoxycholate was ineffective at concentrations up to 1,500 microM. Conjugation of these bile salts did not result in significant differences with the exception of deoxycholate conjugates which induced enzyme leakage more rapidly. Studies of lipid membrane vesicles revealed corresponding alterations. The monohydroxylated salt, taurolithocholate, caused cellular damage as indicated by enzyme loss and impairment of hormonal sensitivity of cells at low concentrations (30 to 100 microM). Dihydroxylated salts produced a different time course of membrane leakage, ultrastructural changes and release of volume marker and lipid in liposomes, suggesting a possible different mechanism of damage induced by this bile salt. Both systems can readily be used to study bile salt membrane interactions.

Animals↗

PubMedDate not supplied

A computerized three-dimensional atlas of the human skull and brain.

PURPOSE: To develop an anatomic atlas of the human head based on a volume model derived from MR and CT. METHODS: Every voxel of this model was labeled by a neuroanatomist concerning its membership to a structural and/or functional region. A computer program was written that, instead of displaying precomputed images, allows the user to choose and compose arbitrary views. RESULTS: The user can subtract parts and ask for annotations just by using the mouse. Conversely, one can compose images by choosing objects from the list of anatomical constituents which is displayed on the screen. A set of dissection tools allows a "look and feel" that comes near to a true dissection. Operations that are not possible in a real dissection, such as reassembly or filling cavities, can be performed. CONCLUSION: The authors have developed a computerized model that can be used for anatomy teaching and also as a reference for radiologists or surgeons. To replace classical atlases, the spatial resolution must be improved and speed must approach real time. Functional imaging data (position emission tomography and single photon emission CT) can be added to the system. The system is mobile and can be situated in classrooms, operating rooms, reading rooms, and libraries.

Brain↗

PubMedDate not supplied

A new method for representing the human anatomy.

In current practice, anatomical atlases are based on a collection of planar images presented in a book or, recently, stored on digital media. We present a new method for generating interactive true three-dimensional (3D) anatomical atlases based on a volume model derived from MRI and CT. The model has a two layer structure. The lower level is a volume model with a set of semantic attributes connected to each voxel. The semantic attributes are assigned by an anatomist using a volume editor. The upper level is a set of relations between these attributes. Interactive visualization tools such as multiple surface display, transparent rendering, and cutting are provided. It is shown that the combination of this data structure with advanced volume visualization tools provides the "look and feel" of real dissection. First tests show that the atlas system cannot only be used successfully for anatomy teaching, but also as a reference for radiologists or surgeons. As a replacement of classical atlases, however, the spatial resolution has still to be improved.

Anatomy↗

PubMedDate not supplied

Exploring the Visible Human using the VOXEL-MAN framework.

In principle the Visible Human data sets are an ideal basis for building electronic atlases. While it is easy to construct such atlases by just offering the possibility of browsing through the 2D slices, constructing realistic 3D models is a huge project. As one rather easy way to establish 3D use, we have registered the Visible Human data to the already existing 3D atlas VOXEL-MAN/brain. This procedure enables one to lookup anatomical detail in an atlas based on radiological images. Concerning the segmentation problem, which is the prerequisite for a real 3D atlas, we have developed an interactive classification method that delivers realistic perspective views of the Visible Human. As these volume based methods require high-end workstations, we finally have developed a multimedia program that runs on standard PCs and uses Quicktime VR movies.

Anatomy, Cross-Sectional↗

PubMedDate not supplied

[Undescended testis and hypospadia in sex chromosomal aberrations].

If hermaphrodite genitals are present in the patient or a higher degree of hypospadia is shown with maldescensus testis, a chromosomal disorder must be considered as one potential cause of the anomaly. The case report of a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadia is presented as an example. A mosaic karyotype 45, X/46, X, idic (Yp) was diagnosed in this patient after chromosomal analysis. The cell line with the isodicentric Y chromosome could be demonstrated in about 90% of the lymphocytes, but only in 7% of the fibroblasts of the preputium. A derivative Y could not be detected in interphase nuclei in the buccal mucosa, i.e. only the cell line with monosomy X was presented. There was thus chromosomal mosaicism with unequal tissue involvement and a high potential for malignant transformation. Guidelines of pediatric urological, cytogenetic and endocrinological investigations and the diagnostic procedures are described and discussed. A prevention protocol for patients with comparable gonosomal mosaicism is presented.

Child, Preschool↗

PubMedDate not supplied

Protons inhibit the BK(Ca) channel of rat small artery smooth muscle cells.

The regulation of the activity of calcium-activated potassium (BK(Ca)) channels by intracellular proton ions (pH(i)) was investigated using the patch-clamp technique in smooth muscle cells freshly isolated from rat tail small arteries. Single-channel conductance and voltage dependence of activation were not different at pH(i) 7.0, 7.4 and 7.8. However, the membrane potential at which channel open probability reached 0.5 was 74 +/- 5 mV (n = 6) (mean +/- SE) at pH(i) 7.4 and 54 +/- 2 mV (n = 4) at pH(i) 7.8 under conditions of pCa 5.9, and 30 +/- 5 mV (n = 5) at pH(i) 7.4 and 62 +/- 4 mV (n = 5) at pH(i) 7.0 under conditions of pCa 5.4. Furthermore, at a membrane potential of 0 mV, the pD(2) for intracellular calcium ions was 5.19 +/- 0.04 (n = 26) (mean +/- SD) at pH(i) 7.8, 5.02 +/- 0.05 (n = 28) at pH(i) 7.4, and 4.82 +/- 0.05 (n = 30) at pH(i) 7.0. In addition, an alteration of pH(i) resulted in a profound change in the amplitude of BK(Ca) currents in intact cells; it reversibly attenuated the current-voltage relationship decreasing the current by 55 +/- 3% (n = 7) (p < 0.001) at 70 mV after lowering the extracellular NH(4)Cl concentration to decrease the calculated pH(i) from 7.2 to 6.8. Thus, alterations of pH(i) in the range from 7.0 to 7.8 did not affect single-channel conductance and voltage dependence of activation but markedly altered single BK(Ca) channel activity as well as intact cell BK(Ca) current amplitude, where an increase of the intracellular proton concentration inhibited this channel.

Acetylcholine↗

PubMedDate not supplied

Multiple ligand-ion solutions: a guide for solution preparation and computer program understanding.

This paper first gives an overview of the multitude of chemical reactions taking place in aqueous solutions with multiple ligands and ions. Then, recommendations to avoid pitfalls in preparing such solutions in daily laboratory work are summarized. Thereafter, the theoretical aspects for calculating multiple ligand-ion solutions are described in detail. Information necessary to perform corrections of the absolute stability constants for the influences of pH, ionic strength, and temperature are given. The calculation of apparent reaction constants for ligand-ion interactions by using the corrected absolute stability constants and considering all possible reactions between a ligand and an ion in an aqueous solution will be introduced. Thereafter, by employing the apparent reaction constants and an iterative method, the determination of multiple ligand-ion equilibria to find the desired ligand or ion concentrations are presented. Thus, this paper can be used as a guide to the principles of programs calculating multiple ligand-ion solutions, to choosing the appropriate program for one's special requirements, and to preparing multiple ligand-ion solutions properly.

Chemical Phenomena↗

PubMedDate not supplied

[Urocortin decreases phosphorylation of MYPT1 and increases the myosin phosphatase activity via elevation of the intracellular level of cAMP].

Urocortin, a peptide hormone related to the corticotropin releasing factor, is suggested to be involved in blood pressure regulation by dilating the peripheral blood vessels. In rat tail arteries, urocortin-induced vasodilation is due to a decrease in myofilament Ca2+ sensitivity the mechanism of which is still unclear. In this study, the hypothesis was tested that the decrease in Ca2+ sensitivity in mouse tail arteries results from the activation of myosin light chain phosphatase. The relaxation of KCl-precontracted (42 mM) intact mouse tail arteries by urocortin (1 nM and 10 nM) was significantly inhibited by 1 microM antisauvagine30, a CRF-2 receptor antagonist (p < 0.05, n = 3). The addition of 1 microM KT 5720, an inhibitor of PKA, to intact rat tail arteries did not affect the KCl-induced force but significantly attenuated the urocortin-induced relaxation (n = 5). In alpha-toxin permeabilized mouse tail arteries, urocortin relaxed submaximally activated preparations at constant pCa 6.1 by 37.6 +/- 8.2% (n = 5) as compared to control vessels (n = 5, p < 0.001). The relaxation in permeabilized vessels was inhibited by pre-treatment with 30 microM Rp-8-CPT-cAMPS, an inactive analogue of cAMP. In permeabilized mouse tail arteries, treatment with 100 nM urocortin was associated with dephosphorylation of MLC20(Ser19) and MYPT1(Thr696/Thr850). The effect of urocortin on MYPTI dephosphorylation was completely abolished by 30 M Rp-8-CPT-cAMPS and mimicked by the cAMP analogue Sp-5,6-DCI-cBiMPS. Based on these findings, we propose that the urocortin-induced relaxation is due to a decrease in calcium sensitivity mediated by a cAMP-dependent increase in the activity of MLCP.

Animals↗

PubMedDate not supplied

[Denture stomatitis therapy with nystatin containing gelatin foil].

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Denture Rebasing↗