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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 361 records · Page 20Linked to original sources

Expression of insulin-like growth factor 1 (IGF-1) in the bovine oviduct during the oestrous cycle.

Growth factors are known to take part in the regulation of reproduction. Here we present evidence for the expression of insulin-like growth factor 1 (IGF-1) in the bovine oviduct. Two IGF-1 specific mRNA-transcripts of 1.5 and 4.4 kb were detected during the whole oestrous cycle, and showed increased expression after ovulation. Complete homology to the known IGF-1 sequence was achieved by specific RT-PCR (reverse transcription-polymerase chain reaction) amplification followed by dideoxysequencing of this 210 bp fragment. IGF-1 protein was localized in the secretory cells of the oviduct epithelium using immunohistochemical techniques. We suggest possible effects of IGF-1 during ovulation either on the oviductal cells or on the early embryo.

Animals↗

[The illness concept of children--review of the literature].

In this literature review a group of studies concerning illness concepts of children are discussed. Most of these studies are based on one of the three theory models of cognitive development as the main factor of development of illness concepts, the attributional theory (health locus of control) or the health belief model based on health seeking behaviour. The results yielded by these theories are comparable to a limited extent only. The development of children's illness concepts seems to be mainly influenced by age, developmental stage, self-consciousness and family ties.

Adaptation, Psychological↗

[Prognostic significance of extra-capsular invasion in cervical lymph node metastases of squamous epithelial carcinoma].

In a retrospective study we evaluated the clinical and histological datas of patients with squamous cell carcinomas of the head and neck to determine the influence of extranodal spread in metastases for the prognosis. Lymph nodes were dissected from the neck dissection specimens and investigated histologically with special regard to extranodal spread. 304 patients (58%) showed positive lymph nodes and 212 of this patients had additionally extranodal spread (70%). Hence, the rate of extranodal spread in the whole investigated group (522 patients) was 40%. For the patients with carcinomas of the hypopharynx the rate of extranodal spread was especially high (70%). Most extranodal spread could be found at levels 2, 3 and 4. We found a correlation between the appearance of extranodal spread and increasing T-stage. 5-year survival rates were greatly different for patients with no metastases (77%) and patients with extranodal spread (28%). We discuss the use of the criteria extranodal spread for the planning of adjuvant chemotherapy.

Carcinoma, Squamous Cell↗

Electromanometrical investigations in patients with isolated neuronal intestinal dysplasia (NID).

In a retrospective study the manometrical findings of 27 patients with histochemically confirmed isolated NID were compared with the findings of 14 patients with habitual constipation. In a second group NID or other neuronal disorders of the distal colon were excluded by histology/histochemistry. Significant differences were found only for the amplitude and frequency of anorectal fluctuations and for presence or absence of rectoanal inhibitory reflexes (RAIR). All other investigated parameters were not significant. In conclusion a reliable diagnosis of isolated NID is only possibly by combined use of anorectal manometry and histochemistry. Nevertheless anorectal manometry remains an important tool for screening in constipative disorders and should be performed prior to other investigations i.e. radiology or biopsy.

Anal Canal↗

The small GTP-binding protein rab6 functions in intra-Golgi transport.

Rab6 is a ubiquitous ras-like GTP-binding protein associated with the membranes of the Golgi complex (Goud, B., A. Zahraoui, A. Tavitian, and J. Saraste. 1990. Nature (Lond.). 345:553-556; Antony, C., C. Cibert, G. Géraud, A. Santa Maria, B. Maro, V. Mayau, and B. Goud. 1992. J. Cell Sci. 103: 785-796). We have transiently overexpressed in mouse L cells and human HeLa cells wild-type rab6, GTP (rab6 Q72L), and GDP (rab6 T27N) -bound mutants of rab6 and analyzed the intracellular transport of a soluble secreted form of alkaline phosphatase (SEAP) and of a plasma membrane protein, the hemagglutinin protein (HA) of influenza virus. Over-expression of wild-type rab6 and rab6 Q72L greatly reduced transport of both markers between cis/medial (alpha-mannosidase II positive) and late (sialyl-transferase positive) Golgi compartments, without affecting transport from the endoplasmic reticulum (ER) to cis/medial-Golgi or from the trans-Golgi network (TGN) to the plasma membrane. Whereas overexpression of rab6 T27N did not affect the individual steps of transport between ER and the plasma membrane, it caused an apparent delay in secretion, most likely due to the accumulation of the transport markers in late Golgi compartments. Overexpression of both rab6 Q72L and rab6 T27N altered the morphology of the Golgi apparatus as well as that of the TGN, as assessed at the immunofluorescence level with several markers. We interpret these results as indicating that rab6 controls intra-Golgi transport, either acting as an inhibitor in anterograde transport or as a positive regulator of retrograde transport.

Alkaline Phosphatase↗

Analysis of the mouse tyrosinase promoter in vitro and in vivo.

The restricted expression of the tyrosinase gene in cells producing pigment suggests the presence of cis-regulatory elements and trans-acting tissue-specific factors. Since 270 bp upstream of the transcriptional start site contain sufficient information for tissue-specific and developmentally regulated expression, we confined our analyses to this region. In this article, we discuss the recent results we have obtained on the regulation of the mouse tyrosinase gene expression demonstrating the existence of one negative and two positive-acting elements in vitro. We have evidence that the positive elements do not determine pigment production in vivo but rather modulate transcription of the mouse tyrosinase gene.

3T3 Cells↗

Two FK506 resistance-conferring genes in Saccharomyces cerevisiae, TAT1 and TAT2, encode amino acid permeases mediating tyrosine and tryptophan uptake.

The macrocyclic lactone FK506 exerts immunosuppressive effects on T lymphocytes by interfering with signal transduction leading to T-cell activation and also inhibits the growth of eukaryotic microorganisms, including Saccharomyces cerevisiae. We reported previously that an FK506-sensitive target in S. cerevisiae is required for amino acid import and that overexpression of two new genes, TAT1 and TAT2 (formerly called TAP1 and TAP2), confers resistance to the drug. Here we report that TAT1 and TAT2 encode novel members of the yeast amino acid permease family composed of integral membrane proteins that share 30 to 40% identity. TAT1 is the tyrosine high-affinity transporter, which also mediates low-affinity or low-capacity uptake of tryptophan. TAT2 is the tryptophan high-affinity transporter. FK506 does not reduce the levels of TAT1 and TAT2 transcripts, indicating that the inhibition of amino acid transport by the drug is posttranscriptional.

ATP-Binding Cassette Transporters↗

[Sudeck's disease in osteoblastoma of the right talus and depression in a 12-year-old boy. Case report].

This is a case report of a 12-year-old boy with reflex sympathetic dystrophy who had surgery for two benign tumors of the right talus. The reflex sympathetic dystrophy began before the first tumor was diagnosed and at a time when the boy was under emotional stress because of conflicts relating to his parents' divorce. The case is typical of reflex sympathetic dystrophy in children, which is only rarely reported. Associated with the syndrome are anxiety, depressive symptoms, emotional instability and acute stressful life events, which makes an interdisciplinary approach imperative.

Bone Neoplasms↗

Desmosomes--dual junctional principles of intra- and supracellular order in epithelial differentiation and tissue formation.

The cells of most normal and malignantly growing tissues are connected by "adhering junctions", i.e. distinct sites of "homotypic" contact between the plasma membranes of two cells of the same or a similar kind, associated on the cytoplasmic side by a dense plaque at which often bundles of cytoskeletal filaments anchor. Of the various types of adhering junctions desmosomes are characteristic of epithelia and carcinomas but also occur in some other cell types. Their molecular components have recently been identified and characterized by cDNA-cloning and sequencing. Unexpectedly, the molecular complement of desmosomes has been found to show certain differences in different epithelia, with particularly complex patterns in stratified squamous epithelia as well as in tumors and cultured cell lines derived therefrom. In addition, molecular principles important in the assembly of desmosomes and in the specific anchorage of intermediate-sized filaments (IFs) at desmosomal plaques have been elucidated. The possible value of cell type-specific isoforms of desmosomal components as markers for the subtyping of carcinomas and the role of desmosomal cadherins during invasion and metastasis of carcinomas are discussed.

Cell Adhesion Molecules↗

Desmosomes and cytoskeletal architecture in epithelial differentiation: cell type-specific plaque components and intermediate filament anchorage.

Among the diverse kinds of intercellular, plaque-bearing, cadherin-containing junctions, desmosomes (maculae adhaerentes) represent a major type characterized by the presence of specific transmembrane glycoproteins, i.e. desmosomal cadherins of the desmoglein and desmocollin categories, and the cytoplasmic plaque proteins, desmoplakin I and plakoglobin. Recent studies, however, have shown that the composition of desmosomes is not identical in the various normal and tumorous desmosome-forming tissues and cell cultures, including diverse forms of epithelia and carcinomas, meningothelia and meningiomas, myocardium and the lymph node follicle reticulum. Desmosomes can differ in their specific complement of desmogleins, Dsg1-3, and desmocollins, Dsc1a-3b, as well as in the additional presence and in their relative amounts of certain accessory plaque proteins such as desmoplakin II and plakophilin 1, a basic member of the larger plakoglobin family of proteins ("band 6 protein"). Assembly and function of desmosomes are effected by the interaction of the specific complement of desmosomal cadherins with certain cytoplasmic proteins. In particular, the cytoplasmic portions ("tails") of the desmosomal cadherins contain certain domains and amino acid sequence motifs, identified by mutagenesis and transfection assays, that are essential elements in desmosome formation, notably the assembly of plaque proteins, and in the site-specific anchorage of intermediate-sized filaments (IFs) of the cytoskeleton, thereby contributing to the specific intracellular as well as supracellular, i.e. tissue, architecture.

Amino Acid Sequence↗

Characterization of transcripts from the Dictyostelium discoideum retrotransposable genetic element DRE.

All of the approximately 150 copies of the Dictyostelium discoideum retrotransposable element DRE are integrated 50 +/- 4 nucleotides upstream from different transfer RNA genes. These genomic regions are generally devoid of informative DNA why integration of the retrotransposon at these position never causes phenotypic mutations. This property makes DRE attractive as a tool in gene therapy where vectors with predictable integration specificities are still not available. Due to the nature as retrotransposon transcription is a prerequisite for the element to integrate at a new genomic position. Here we describe some transcription properties of DRE based on Northern blot analyses and on the characterization of in vitro synthesized cDNAs.

Animals↗

Analysis of molecular functions of the tumor metastasis promoting surface molecule CD44v4-v7 using transgenic mice.

In certain circumstances, metastatic tumor cells may mimic the molecular properties and behaviour of lymphocytes. Support for this hypothesis has come from the observation that activated lymphocytes and some tumor cells need a CD44 variant isoform (CD44v) to survive and/or expand in the lymphatic system. CD44 variant (CD44v) isoforms are created by differential splicing from a pool of at least ten variant exons (v1-v10), the encoded sequences of which are absent in the CD44 standard isoform (CD44s). To dissect the molecular interactions of CD44v, transgenic animals have been generated that constitutively express a variant of CD44 containing sequences encoded by exons v4 to v7 on the surface of T cells. Lymphocytes derived from these transgenic animals show accelerated entry into S phase upon antigenic stimulation, and a subpopulation of the cells constitutively express early lymphocyte activation markers. Our data support the hypothesis that the presence of CD44v4-v7 on the surface of T cells mediates intercellular or intracellular processes which result in the promotion of T cells towards a preactivated state.

Animals↗

Quantification of mitral regurgitation by colour flow Doppler imaging--value of the 'proximal isovelocity surface area' method.

In this study 97 patients with mitral regurgitation (age 62 +/- 11 years, 55 men, 42 women) quantified by angiography were studied using colour flow Doppler imaging of isovelocity surface areas in the flow convergence region proximal to the regurgitant orifice. The radii of the proximal isovelocity surface areas for the flow velocities of 28 and 41 cm/s were measured. A flow convergence region was imaged in 100% (96%) of the patients with Grade I/II or more and in 92% (64%) of the patients with Grade I mitral regurgitation for a flow velocity of 28 (41) cm/s. The radii of the proximal isovelocity surface areas correlated significantly with the angiographic grade in patients with sinus rhythm as well as atrial fibrillation. A correct differentiation of Grade I to II from Grade III to IV mitral regurgitation was provided in more than 90% of all patients for both flow velocities investigated. Assuming hemispheric proximal isovelocity surface areas, in 11 patients the regurgitant volumes from echocardiography (range: 2.6-241 (0.9-198) ml for a flow velocity = 28 (41) cm/s) correlated with, but considerably overestimated the values from cardiac catheterization (range: 1.4-72.5 ml) with r = 0.79 (0.82) (P < 0.01) and SEE = 57.9 (42.4) ml for a flow velocity of 28 (41) cm/s. It was concluded that colour flow Doppler imaging of the flow convergence region enables the diagnosis of mitral regurgitation and the differentiation between Grade I to II and Grade III to IV mitral regurgitation, but may be of little value in estimating the regurgitant volume, assuming a hemispheric symmetry of the proximal flow convergence region.

Coronary Angiography↗

Binding of AP-1 Golgi adaptors to membranes requires phosphorylated cytoplasmic domains of the mannose 6-phosphate/insulin-like growth factor II receptor.

In mammalian cells, clathrin-coated vesicles mediate transport of the lysosomal enzyme receptors from the trans-Golgi network to the endocytic pathway. A critical step of this process is the recruitment of Golgi-specific adaptors onto Golgi membranes for efficient clathrin polymerization. An in vitro assay was used here to quantitate this event in streptolysin-O-permeabilized NRK cells. At 37 degrees C, these interactions are cytosol- and energy-dependent, sensitive to GTP gamma S (guanosine 5'-O-(thiotriphosphate)) and brefeldin A. We report that Golgi-specific adaptor binding is enhanced in mannose 6-phosphate/insulin-like growth factor II (IGF II) receptor-overexpressing cells and reduced in mannose 6-phosphate receptor-deficient cells. Furthermore, adaptor binding is partially inhibited after addition of soluble cytoplasmic domains of the mannose 6-phosphate/IGF II receptor. Almost complete inhibition is only observed when this domain is phosphorylated on serines 2421 and 2492, a major modification acquired during exit of the receptor from the Golgi. These results show that the mannose 6-phosphate/IGF II receptor is part of the components that recruit the Golgi-specific adaptors and that its phosphorylation is an important feature for high affinity interactions with sorting components.

Animals↗

Coregulation of the APO-1 antigen with intercellular adhesion molecule-1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas.

APO-1 is a 48-Kd transmembrane glycoprotein identical to the Fas antigen and belongs to the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor family of surface molecules. Cross-linking of APO-1 induces apoptotic cell death in sensitive cells. We show here that APO-1 is an activation molecule on B cells. It was induced/enhanced on dense and buoyant tonsillar B cells, respectively, through surface Ig cross-linking in combination with interleukin-2 or by interferon-gamma together with tumor necrosis factor-alpha. These conditions also increased the amount of intercellular adhesion molecule-1 (CD54) on these cells. Epstein-Barr virus transformants of peripheral B cells coexpressed APO-1 and CD54 at very high levels. Immunohistologically, Apo-1 was detectable at low levels in a subpopulation of follicle center B blasts and, at higher levels, in sinusoidal B cells. APO-1 was undetectable in follicular mantle B cells and plasma cells. In isolated tonsillar B cells, APO-1 was expressed in CD10+ follicle center cells. In acute B lymphoblastic leukemia, chronic B lymphocytic leukemia, and Burkitt's lymphomas, APO-1 and CD54 molecules were immunohistochemically undetectable. Coordinate expression of these antigens was found in mediastinal B-cell lymphomas. The mode of APO-1 and CD54 expression was correlated in follicle center cell lymphomas (P < .0019), but less stringently in hairy cell leukemia. No association was found in plasmacytomas. This was in line with the differential expression of these molecules found in reactive plasma cells. Expression of APO-1 in B cells of different stages of differentiation and, correspondingly, in certain B-cell neoplasias might suggest a role of this molecule in the induction of B-cell apoptosis. This function might be influenced by CD54 and CD54-mediated signals.

Antigens, Surface↗

Color Doppler echocardiographic determination of mitral regurgitant flow from the proximal velocity profile of the flow convergence region.

Flow rate across an orifice can be determined from color Doppler echocardiographic maps of the flow convergence region proximal to the orifice. Different methods have been developed in vitro. The proximal velocity profile method was prospectively evaluated in patients with mitral regurgitation. Color Doppler echocardiography was performed in 74 patients before cardiac catheterization. The increasing velocities within the flow convergence region were determined in an apical plane on the straight line from the transducer to the leak; thus the proximal velocity profile was established and plotted on a nomogram. Instantaneous regurgitant flow rate was derived from the position of the resulting curve in relation to the nomogram's reference curves, which were derived from in vitro measurements. Regurgitant stroke volume was calculated as regurgitant flow rate.regurgitant velocity-time integral/regurgitant peak velocity, using additional continuous-wave Doppler. The 55 patients with angiographic regurgitation had a close association between regurgitant flow rate (0 to 600 ml/s) and angiographic grade (Spearman's rank correlation coefficient = 0.91; p < 0.0001). Regurgitant flow rate did not overlap between grades < or = 2+, 3+ and 4+. In 16 patients, regurgitant stroke volume by echocardiography correlated well with that by the angiography/Fick method (r = 0.88; SEE = 17.1 ml), with a regression line close to identity (y = 0.89x + 12.7 ml). The proximal velocity profile method enables determination of mitral regurgitant flow and estimation of regurgitant volume.

Blood Flow Velocity↗