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Biomedical subjects

J Urban

Publications and source records attributed to J Urban.

At least 73 records · Page 4Linked to original sources

Oligomerization supports transport of a mutant secretory protein out of the endoplasmic reticulum.

To examine the transport of the single subunits of the glycoprotein complex gp80 (clusterin, apolipoprotein J), a marker protein for apical exocytosis and main secretory product of Madin-Darby canine kidney (MDCK) cells, several mutant cDNAs were constructed and expressed in the fibroblastic baby hamster kidney (BHK-21) cell line. In the absence of the second subunit the mutant proteins formed disulfide-linked homodimeric complexes. In the homodimeric form lys-gp45, a lysozyme-tagged mutant representing the C-terminal subunit, acquired competence for transport to the cell surface. Biogenesis and transport of this hybrid protein were also examined in stably transfected MDCK cells. In these cells which express both the endogenous gene and the mutant cDNA lys-gp45 was linked via disulfide bonds to the gp80 complex. These heterooligomeric complexes were secreted predominantly at the apical cell surface. Thus, oligomerization regardless of whether it resulted in homodimeric or heterooligomeric complexes conveyed transport competence to the mutant protein.

Animals↗

Incontinentia pigmenti (Bloch-Sulzberger syndrome): multisystem disease observed in two generations.

Incontinentia pigmenti is a rare genodermatosis that most commonly involves the skin, eyes, teeth, and central nervous system. We describe it in two generations. Two twin girls were observed at birth with a characteristic whorling pattern of erythema, patch, and plaques, and were later found to have dental anomalies and eye findings consisting of black pigment granules around the macula and optic nerve head. One child also had strabismus, the most common eye change, and an atrial septal defect. A scarring scalp alopecia was evident in both twins and their mother, who also had typical dental findings.

Adult↗

[Carpal bone protuberance].

The term "carpe bossu" has been coined to bony eminence at the base of II or III metatcarpal, sometimes expanding to the trapezoid and capitate dorsally. The condition is usually symptom free. Pain is spontaneous or elicited by overuse and aggravated by palmar flexion of the wrist. The subluxation of extensors tendons overlying the boss may occur in more cases. Bony eminence, regular in shape is evident on lateral radiographs. Conservative treatment usually renders remission of symptoms but if it fails surgery is indicated.

Adult↗

[Texture of cruciate ligaments as a modifying factors of grafts].

In the last ten years hundreds of alloplastic prostheses of cruciate ligaments of knee (ACL) have been implanted. The remote results after surgeries of this kind were univocally bad. All the known synthetic fibres undergo the process of aging and of constant decrease of their mechanical properties. Research of graft fulfilling the conditions of resistance ACL and investigations over the ways of delaying its degradation are continued. The author investigated 5 kinds of polyester prostheses ACL made of homogeneous polyester fibres with the same mechanical properties only with different texture. To estimate biocompatibility he implanted them to piglets weighing 20-30 kg and to rabbits into dorsum muscles in the place of the cut out ACL. After 3 and 6 months a section of the piglets was made estimating the macroscopic, histological and radiological picture. For the rabbits a section was made after 14 days and 3 months. The investigations confirmed a high biocompatibility of the grafts. Large differences in hypertrophy of particular grafts with fibrous tissue were noticed.

Animals↗

Targeted ablation of glia disrupts axon tract formation in the Drosophila CNS.

Glial cells are thought to play a role in growth cone guidance, both in insects and in vertebrates. In the developing central nervous system of the Drosophila embryo, the interface glia form a scaffold prior to the extension of the first pioneer growth cones. Growing axons appear to contact the glial scaffold as the axon tracts are established. We have used a novel technique for targeted cell ablation to kill the interface glia and thus to test their role in establishment of the embryonic axon tracts. We show that ablation of the interface glia early in development leads to a complete loss of the longitudinal axon tracts. Ablation of the glia later in embryonic development results in defects comprising weakening and loss of axon fascicles within the connectives. We conclude that the interface glia are required first for growth cone guidance in the formation of the longitudinal axon tracts in the Drosophila embryo and then either to direct the follower growth cones, or to maintain the longitudinal axon tracts.

Animals↗

The homeobox gene repo is required for the differentiation and maintenance of glia function in the embryonic nervous system of Drosophila melanogaster.

We describe the cloning, expression and phenotypic characterisation of repo, a gene from Drosophila melanogaster that is essential for the differentiation and maintenance of glia function. It is not, however, required for the initial determination of glial cells. In the embryo, the gene, which encodes a homeodomain protein, is expressed exclusively in all developing glia and closely related cells in both the central and peripheral nervous systems. The only observed exceptions in the CNS are the midline glia derived from the mesectoderm and two of three segmental nerve root glial cells. Using a polyclonal antibody we traced the spatial and temporal pattern of the protein expression in detail. Embryos homozygous for null alleles of the protein exhibit late developmental defects in the nervous system, including a reduction in the number of glial cells, disrupted fasciculation of axons, and the inhibition of ventral nerve cord condensation. The expression of an early glial-specific marker is unaffected in such homozygotes. By contrast, the expression of late glial-specific markers is either substantially reduced or absent. The specificity of expression is also observed in the locust Schistocerca gregaria and is thus evolutionarily conserved.

Animals↗

[The effect of polyene phosphatidylcholine (Essentiale forte) in the treatment of liver steatosis and ultrasound findings--preliminary study].

BACKGROUND: Steatosis of the liver is the most frequent diffuse liver disease and its detection increased markedly due to ultrasonography. The presence of lipid particles in hepatocytes alters the ultrastructure of cellular membranes. The damaged cell is unable to meet adequately the energy requirements of phospholipid synthesis, the latter being the basic component of cellular and subcellular membranes. Substitution of "essential" phospholipids plays an important role in their regeneration. OBJECTIVE: The objective of the open trial without controls was to obtain preliminary information on the effectiveness of Essentiale forte cps. in the treatment of steatosis of the liver of varying etiology in a group of 30 women, focused on changes in the ultrasonic pictures and a parallel follow-up of laboratory findings and subjective feelings, to be followed subsequently by a placebo controlled double blind trial. METHODS AND RESULTS: Ultrasonic examinations were made using a Hewlett-Packard apparatus (77065AR). The sonographic criterium of steatosis was the finding of a diffusely enhanced echogenicity of the liver parenchyma associated as a rule with varying degrees of hepatomegaly with a smooth rounded margin and readily apparent hepatic veins with a normal lumen. The preparation Essentiale forte, cps. Rhône-Poulenc Rorer Co., contains natural "essential" phospholipids, diglyceride esters of cholinephosphoric acid (enriched with unsaturated fatty acids (linolic, linoleic, oleic) 300 mg, vitamin B1 6 mg, vitamin B2 6 mg, vitamin B6 6 mg, vitamin B12 6 micrograms, nicotinamide 30 mg, vitamin E 6 mg. Six tablets per day (2 x 3 tablets) were administered for six months. The clinical, ultrasonic and laboratory examination were made at the onset of the trial and then after the second and sixth month. From the total number of 28 women who completed treatment in 29 % (8 woman) were free from sonographic signs of steatosis and only in 25 % (7 women) the finding remained unaltered. In the remainder the ultrasonic picture improved only partly, in 10 of 11 women (91 %) the non-homogeneity of the parenchyma disappeared, in 3 of 12 women (25 %) the conduction of acoustic signals improved. The authors recorded also regression of hepatomegaly from 12.9 +/- 1.5 cm to 11.4 +/- 1.0 cm (p < 0.0001). There was also a significant decline of laboratory values: ALT from 1.650 +/- 1.612 mu kat/l to 0.812 +/- 0.392 mu kat/l (p < 0.0014), AST from 1.308 +/- 1.341 mu kat/l to 0.613 +/- 0.206 mu kat/l (p < 0.0038), GMT from 2.525 +/- 3.374 mu kat/l to 0.976 +/- 0.727 mu kat/l (p < 0.0078). A statistically significant decline was also found in mean values of total bilirubin (p < 0.0316), cholesterol (p < 0.0129) and triglycerides (p < 0.001). In all patients subjective sensations improved (p < 0.05). CONCLUSIONS: The authors provided evidence than in 53.6 % of patients the effect of six-month treatment with Essentiale forte was very good (improvement of all investigated parameters), partial in 42.9 % (improvement of laboratory findings and subjective complaints) ad not quite satisfactory in 3.6 % (only improvement of subjective feelings).

Adolescent↗

Antigen-specific activation, tolerization, and reactivation of the interleukin 4 pathway in vivo.

The outcome of immune responses critically depends on the pattern of lymphokines secreted by CD4+ T cells. CD4+ T cells may differentiate into interleukin 2 (IL-2) and interferon gamma secreting T helper 1 (Th1)-like cells or IL-4/IL-5/IL-10 secreting Th2-like cells. However, the mechanisms that regulate production of IL-4 or other T cell lymphokines in vivo remain unknown. We use the superantigen, Staphylococcus enterotoxin A (SEA), as a model antigen to characterize the signals that regulate the production of IL-4 in vivo. Induction of IL-4 in normal CD4+ T cells required stimulation with both antigen and IL-4. SEA-specific CD4+ T cells produced large amounts of IL-4 when restimulated within 10 d after in vivo priming. Repetitive application of both signals was required to prevent downregulation of IL-4 production. Although controversy exists regarding the susceptibility of Th2-like cells to tolerogenic signals, high doses of superantigen readily abolished the capacity to produce IL-4 in both naive T cells and in T cells already primed for IL-4 production. Infection with the nematode, Nippostrongylus brasiliensis, reversed the established T cell tolerance, whereas the signals which induced IL-4 production in normal T cells, antigen and IL-4, were not capable of reversing superantigen-specific tolerance in vivo. The major parameter that correlated with the capacity of parasitic infection to break tolerance was magnitude of the lymphoproliferation seen during the course of the infection. The capacity to activate or tolerize the IL-4 pathway in an antigen-specific fashion should prove useful in the design of antigen-specific therapies for autoimmune and allergic diseases.

Animals↗

In vitro studies on the DNA impairments induced by Cr(III) complexes with cellular reductants.

The influence of Cr(III) complexes with ascorbic acid, cysteine and glutathione on DNA has been studied spectrophotometrically and chromatographically. The toxic and genotoxic activities of these complexes were also investigated. It was found that these complexes bind to DNA weaker than hexaaqua Cr(III) complexes. It could be explained through the greater strength of the bi- and tridentate ligands coordinated to chromium in comparison to water molecules. The formation of DNA-DNA intermolecular bonds and DNA interstrand cross-linking has been also observed. These complexes were found to be non-toxic and non-genotoxic in the bacterial test.

Ascorbic Acid↗

Todralazine influence upon the mutagenicity of some direct- and indirect-acting mutagens.

Todralazine decreased the mutagenic activity of tested direct- and indirect-acting mutagens. Despite the marked differences between efficient todralazine doses (ED50) it was observed that, in the case of tested indirect mutagens as well as in some of the direct mutagens, the decrease of mutagenicity by todralazine was very strong, exceeding 80% in some cases.

4-Nitroquinoline-1-oxide↗

Hierarchical structure of mitochondrial DNA gene flow among humpback whales Megaptera novaeangliae, world-wide.

The genetic structure of humpback whale populations and subpopulation divisions is described by restriction fragment length analysis of the mitochondrial (mt) DNA from samples of 230 whales collected by biopsy darting in 11 seasonal habitats representing six subpopulations, or 'stocks', world-wide. The hierarchical structure of mtDNA haplotype diversity among population subdivisions is described using the analysis of molecular variance (AMOVA) procedure, the analysis of gene identity, and the genealogical relationship of haplotypes as constructed by parsimony analysis and distance clustering. These analyses revealed: (i) significant partitioning of world-wide genetic variation among oceanic populations, among subpopulations or 'stocks' within oceanic populations and among seasonal habitats within stocks; (ii) fixed categorical segregation of haplotypes on the south-eastern Alaska and central California feeding grounds of the North Pacific; (iii) support for the division of the North Pacific population into a central stock which feeds in Alaska and winters in Hawaii, and an eastern or 'American' stock which feeds along the coast of California and winters near Mexico; (iv) evidence of genetic heterogeneity within the Gulf of Maine feeding grounds and among the sampled feeding and breeding grounds of the western North Atlantic; and (v) support for the historical division between the Group IV (Western Australia) and Group V (eastern Australia, New Zealand and Tonga) stocks in the Southern Oceans. Overall, our results demonstrate a striking degree of genetic structure both within and between oceanic populations of humpback whales, despite the nearly unlimited migratory potential of this species. We suggest that the humpback whale is a suitable demographic and genetic model for the management of less tractable species of baleen whales and for the general study of gene flow among long-lived, mobile vertebrates in the marine ecosystem.

Animals↗

Study of the mechanism of todralazine antimutagenic activity: the effect upon mutagenicity of daunorubicine.

Todralazine markedly reduced the mutagenic activity of the standard direct-acting mutagen--daunorobicine (DRC)--in the Ames test. Spectrophotometric measurements proved that todralazine did not interact with DRC in water solution. Todralazine neither interacted with calf thymus DNS in vitro, nor changed the interaction of DRC with DNA. Therefore we concluded that the decrease of DRC mutagenicity observed in the Ames test should be explained rather in terms of a bioantimutagenic than a desmutagenic activity of todralazine.

Animals↗

Laparoscopic vasectomy.

A case is presented in which a laparoscopic vasectomy was performed concomitantly with laparoscopic hernia repair. A laparoscopic vasectomy should not replace an office procedure done under local anesthesia and minimal complications. Reanastomosis after laparoscopic vasectomy is a more complicated procedure. The additional benefit of laparoscopic surgery to those men who desire infertility while having elective pelvic laparoscopic procedures is presented.

Adult↗

[MR angiography of the heart and thoracic blood vessels. Use of rapid ECG-triggered techniques with multiplanar reconstruction capability].

Segmented 2D times-of-flight (TOF) magnetic resonance angiography (MRA) with ECG gating is a suitable adjunct to conventional magnetic resonance tomography. Based on our experience with 106 patients, cardiovascular MRA primarily aids in the diagnosis of congenital heart disease, but is of minor importance for the evaluation of acquired cardiovascular disease, such as aortic aneurysms. Changes in flow dynamics as a result of spin dephasing may render partial signal loss. Due to flow turbulence and resulting signal loss distal to stenoses, difficulties may arise in correctly determining the degree of stenosis and differentiating between partial thrombosis and slowly flowing blood. The most promising approach for optimizing 2D TOF MRA is enhancement of the intravascular signal and suppression of background signal. For the equipment we use with a 0.5 Tesla scanner, the most powerful combination to enhance intravascular signal and suppress back-ground noise was applying a flip angle of 65 degrees and a short inversion prepulse. The influence of the flip angle and prepulse on the intravascular signal varies, dependent on the flow velocities and heart rates. Secondary reconstructions, such as the MIP technique, contribute to better spatial orientation by using rotating projection views. To avoid overprojection artifacts and loss of diagnostic information, 2D single slices should be the primary source of image analysis.

Aortic Diseases↗

[Antibiotic activity of cortalcerone and its 7-diphenylhydrazone derivative].

The present paper investigates the antibiotic properties of the novel antifungal antibiotic agent cortalceron and its semisynthetic derivative cortalceron 7-diphenylhydrazone. The MIC values were assayed by the agar diffusion method. Cortalceron was found to weakly inhibit the growth of E. coli and B. subtilis. The growth of yeast was not influenced. On i.v. administration to mice [correction of rats], the agent produced breathing disorders and convulsions which later disappeared. The diphenylhydrazine derivative of cortalceron inhibited the growth of most yeasts tested as well.

Animals↗

Specificity mapping of HIV-1 protease by reduced bond inhibitors.

A series of 47 N-truncated reduced bond inhibitors, systematically modified at individual positions (P1, P'1, P'2, P'3, and P'4), were synthesized and used to map the subsite preferences of HIV-1 protease. The tight binding inhibitor of HIV-1 protease t-butoxycarbonyl-Phe-[CH2NH]Phe-Glu-Phe-NH2 (Ki = 0.2 nM) was chosen as the parent structure for further modifications. The P'2 glutamic acid was found to fit well into the S'2 subsite of the protease. The conformational restriction of any phenylalanine residue or saturation of more than one phenylalanine side chain in P'1 or P'3 lead is to a large Ki increase. Introduction of tyrosine in the P1 position improves the binding by an order of magnitude. The S'4 subsite of the protease was shown to accommodate large structural changes in the inhibitor at this position. Therefore P'4 may serve as an ideal region for further modification in order to improve bioavailability of this type of compound. An improved method of direct comparison of tight binding inhibitors with subnanomolar Ki values has been described.

Binding Sites↗