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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 253 records · Page 14Linked to original sources
PubMed2000

Blood chemistry, nutrient metabolism, and organ weights in fetal and newborn calves derived from in vitro-produced bovine embryos.

Calves born after in vitro production (IVP) of embryos often show reduced perinatal viability. The present experiment investigated a series of physiological variables in the immediate prenatal and postnatal period of IVP dairy calves. Fetal IVP and control calves (each n = 7) were prepared with vascular catheters at 248+/-1 day gestation (term = 280 days), and blood samples were taken for five days before premature delivery by cesarean section. IVP fetuses compared with controls had significantly elevated arterial hemoglobin and oxygen content (8.41 vs. 7.52% and 5.75 vs. 3.79%, respectively) whereas lactate level was lowered (1.89 vs. 2.26 mM). The umbilical venous-arterial concentration differences in oxygen, lactate, and glucose indicated that IVP fetuses relied more on lactate and less on glucose as oxidative substrates. The fetal glucose tolerance, and the basal and adrenocorticotropin-stimulated cortisol levels were similar between the groups. In the immediate postnatal period, IVP calves showed elevated venous blood pH (7.294 vs. 7.270), hemoglobin (9.06 vs. 8.25%), oxygen contents (6.33 vs. 4. 64%), K(+) levels (4.89 vs. 4.56 mM), and rectal temperature (38.9 vs. 37.4 degrees C), and lowered blood Na(+) (139.9 vs. 141.0 mM), Cl(-) (100.2 vs. 103.1 mM) and glucose levels (2.86 vs. 3.11 mM). There were no differences in body dimensions and organ weights, except that the fore legs and hind legs were slightly longer in the IVP group (76.1 vs. 72.4 cm and 93.4 vs. 88.8 cm, respectively). Although prenatal and neonatal IVP calves differed from control calves in a number of variables, the effects were relatively minor and provide no direct evidence for the hypothesis that IVP calves have an impaired capacity to adapt to life ex utero. In fact, several parameters indicated enhanced rather than retarded maturation of IVP calves when data from premature calves were compared with data from a group of control calves delivered at term.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Coordinating the care of the chronically ill in a world of managed care.

The systems required to provide coordinated health care to the chronically ill within a managed care contract are complex. As an integrated health care delivery system assuming shared financial risk of enrollees in a Medicare + Choice contract, many care processes need to be created to meet the needs of the clients and administrators. Nursing case management and physician partnering are integral to the creation of the care model. The fiscal data demonstrated, for clients in this model, that there was an overall decrease in the inpatient length of stay, hospital days per thousand, and 30-day readmission rates.

Case Management↗
PubMed2000

Follow-up of differentiated thyroid cancer: comparison of multiple diagnostic tests.

The radioablation of thyroid remnants improves the prognosis of differentiated thyroid cancer. In our prospective study an activity of 3.7 GBq 131I failed to completely ablate the remnants in 46 out of 101 patients, but a 3-year follow-up period was uneventful. One other patient had a recurrence early after thyroidectomy. In view of possible stunning effects of 131I it might be advantageous to visualize such remnants by imaging modalities which do not emit beta-particles. Our data have revealed that neither magnetic resonance imaging (MRI), nor ultrasonography (US), nor 99Tcm-sestamibi scintigraphy, nor positron emission tomography could detect or reliably exclude minimal remnants. Such remnants did not produce thyroglobulin (Tg). A 123I and 131I uptake of> 10% after thyroidectomy was associated with about a 90% probability of persistent remnants. On the other hand, MRI was helpful in the patient group (n = 32) with Tg>4ng x ml(-1) at the second whole-body scintigraphy (TSH>30 mU x l(-1)) for planning the management of lymph node metastases (n = 15 patients): 12 patients had subsequent surgery and three patients radioiodine therapy. We recommend that MRI be used early in follow-up care when Tg is elevated. The decision of whether or not to treat persistent thyroid remnants should not be made on the basis of MRI, US or nonspecific scintigraphic methods. Complete ablation did not appear to have any clinical benefit in our study group.

Adolescent↗
PubMed2000

Colloidal particles in emulsions

We propose a statistical mechanical model for colloidal particles suspended in an emulsion of liquid droplets. The particles are modeled as hard spheres. The interaction between droplets is also hard, but the particles are able to penetrate the droplets. A swelling of droplets is taken into account to ensure material conservation of the droplet liquid. Hence the presence of the colloids generates droplet polydispersity. Using computer simulation and liquid state theory, we find that the relative polydispersity exhibits nonmonotonic behavior as a function of the particle packing fraction and can be traced back to hard sphere bulk density fluctuations.

Journal Article↗
PubMed2000

Density functional for additive mixtures

We present a density functional theory for mixtures of particles interacting with a radially symmetric pair potential. The approach is suitable for systems with soft or hard interactions between like species. The cross interactions between unlike species are restricted to obey an additivity constraint. The functional is a generalization of the soft fundamental measure theory (SFMT) for one-component systems and reduces to Rosenfeld's functional in the case of hard sphere mixtures. It respects both, the zero-dimensional limit and the virial expansion. The structure of the homogeneous fluid phase is an output. As an application, we calculate the pair distributions of colloidal hard spheres mixed with star polymers and find good agreement with computer simulation results.

Journal Article↗
PubMed2000

Fluid structure from density-functional theory

We treat various common fluid models, like the inverse-power, Asakura-Oosawa, and Lennard-Jones potentials, within the soft fundamental measure theory (SFMT). We show that this recently proposed density-functional approach is able to predict the pair correlations in the fluid phase reliably compared to computer simulations. Explicit expressions for certain quantities of SFMT are given, namely, for the weight functions and the fundamental measures. These technical tools permit practical calculations for a large class of inhomogeneous systems.

Journal Article↗
PubMed2000

Fluid of penetrable spheres: testing the universality of the bridge functional

Penetrable spheres have been the object of recent extensive investigations as a prototype for intermicellar interactions in a solvent, and as representing a class of bounded potentials allowing complete interpenetrability of the particles. Here we compare density-functional and simulation results for the pair-correlation functions in a bulk fluid of penetrable spheres, as a stringent test for the approximation of "universality" of the bridge functional. Considering either a fundamental-measure functional for penetrable spheres or a perturbative treatment using a fundamental-measure hard-sphere functional, we conclude that hard-sphere-type bridge functionals are applicable also for bounded potentials with high penetrability.

Journal Article↗
PubMed2000

Topological defects in nematic droplets of hard spherocylinders

Using computer simulations we investigate the microscopic structure of the singular director field within a nematic droplet. As a theoretical model for nematic liquid crystals we take hard spherocylinders. To induce an overall topological charge, the particles are either confined to a two-dimensional circular cavity with homeotropic boundary or to the surface of a three-dimensional sphere. Both systems exhibit half-integer topological point defects. The isotropic defect core has a radius of the order of one particle length and is surrounded by free-standing density oscillations. The effective interaction between two defects is investigated. All results should be experimentally observable in thin sheets of colloidal liquid crystals.

Journal Article↗
PubMed2000

Adeno-associated virus type 2 Rep78 induces apoptosis through caspase activation independently of p53.

Adeno-associated virus (AAV) type 2 Rep78 is a multifunctional protein required for AAV DNA replication, integration, and gene regulation. The biochemical activities of Rep78 have been described, but the effects of Rep proteins on the cell have not been characterized. We have analyzed Rep-mediated cytotoxicity. We demonstrated that Rep78 expression is sufficient to induce cell death and disruption of the cell cycle. Cell death was found to be mediated by apoptosis. Rep78 expression resulted in the activation of caspase-3, a terminal caspase directly involved in the execution of cell death. A peptidic inhibitor of caspase-3, Z-Asp-Glu-Val-Asp-fluoromethylketone (Z-DEVD-FMK), abrogated Rep78-induced apoptosis, indicating that Rep78-mediated apoptosis is caspase-3 dependent. Rep78 induced apoptosis in wild-type p53-containing human embryonal carcinoma NT-2 cells and in p53-null promyelocytic human HL-60 cells, indicating that at least one pathway of Rep78-induced apoptosis is p53 independent. Apoptosis was shown to occur during the G(1) and early S phases of the cell cycle. By analyzing the effects of Rep78 mutations on cell viability, the cause of cell death was attributed in part to two biochemical activities of Rep78, DNA binding and ATPase/helicase activity. The endonuclease activity of Rep78 did not contribute to apoptosis induction.

Adenosine Triphosphatases↗
PubMed2000

Regulation of the resident chromosomal copy of c-myc by c-Myb is involved in myeloid leukemogenesis.

c-myb is a frequent target of retroviral insertional mutagenesis in murine leukemia virus-induced myeloid leukemia. Induction of the leukemogenic phenotype is generally associated with inappropriate expression of this transcriptional regulator. Despite intensive investigations, the target genes of c-myb that are specifically involved in development of these myeloid lineage neoplasms are still unknown. In vitro assays have indicated that c-myc may be a target gene of c-Myb; however, regulation of the resident chromosomal gene has not yet been demonstrated. To address this question further, we analyzed the expression of c-myc in a myeloblastic cell line, M1, expressing a conditionally active c-Myb-estrogen receptor fusion protein (MybER). Activation of MybER both prevented the growth arrest induced by interleukin-6 (IL-6) and rapidly restored c-myc expression in nearly terminal differentiated cells that had been exposed to IL-6 for 3 days. Restoration occurred in the presence of a protein synthesis inhibitor but not after a transcriptional block, indicating that c-myc is a direct, transcriptionally regulated target of c-Myb. c-myc is a major target that transduces Myb's proliferative signal, as shown by the ability of a c-Myc-estrogen receptor fusion protein alone to also reverse growth arrest in this system. To investigate the possibility that this regulatory connection contributes to Myb's oncogenicity, we expressed a dominant negative Myb in the myeloid leukemic cell line RI-4-11. In this cell line, c-myb is activated by insertional mutagenesis and cannot be effectively down regulated by cytokine. Myb's ability to regulate c-myc's expression was also demonstrated in these cells, showing a mechanism through which the proto-oncogene c-myb can exert its oncogenic potential in myeloid lineage hematopoietic cells.

Animals↗
PubMed2000

Ligating clips for three-dimensional MR angiography at 1.5 T: in vitro evaluation.

Artifact size on three-dimensional (3D) magnetic resonance (MR) angiograms and safety of various vascular clips (15 titanium and three absorbable polydioxanone clips) were assessed. All evaluated clips were completely safe. Biodegradable clips rendered no artifacts; titanium clips were associated with susceptibility effects. Artifact size was dependent on clip size, clip orientation, echo time, and degree of k-space coverage. In the presence of titanium vascular clips, fast 3D MR angiography should be performed with the shortest echo time and full k-space coverage.

Artifacts↗
PubMed2000

GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis.

We wished to determine whether exogenous glucagon-like peptide (GLP)-2 infusion stimulates intestinal growth in parenterally fed immature pigs. Piglets (106-108 days gestation) were given parenteral nutrient infusion (TPN), TPN + human GLP-2 (25 nmol. kg(-1). day(-1)), or sow's milk enterally (ENT) for 6 days. Intestinal protein synthesis was then measured in vivo after a bolus dose of [1-(13)C]phenylalanine, and degradation was calculated from the difference between protein accretion and synthesis. Crypt cell proliferation and apoptosis were measured in situ by 5-bromodeoxyuridine (BrdU) and terminal dUTP nick-end labeling (TUNEL), respectively. Intestinal protein and DNA accretion rates and villus heights were similar in GLP-2 and ENT pigs, and both were higher (P < 0.05) than in TPN pigs. GLP-2 decreased fractional protein degradation rate, whereas ENT increased fractional protein synthesis rate compared with TPN pigs. Percentage of TUNEL-positive cells in GLP-2 and ENT groups was 48 and 64% lower, respectively, than in TPN group (P < 0.05). However, ENT, but not GLP-2, increased percentage of BrdU-positive crypt cells above that in TPN piglets. We conclude that GLP-2 increases intestinal growth in premature, TPN-fed pigs by decreasing proteolysis and apoptosis, whereas enteral nutrition acts via increased protein synthesis and cell proliferation and decreased apoptosis.

Animals↗
PubMed2000

Cloning and characterization of the breakpoint regions of a chromosome 11;18 translocation in a patient with hamartoma of the retinal pigment epithelium.

Mutations of various tumor suppressor genes, e.g., PTEN, TSC1, and TSC2, are known to be responsible for different inherited diseases presenting with multiple hamartomas, a benign tumor resembling neoplasia that results from faulty organ development. Combined hamartoma of the retinal pigment epithelium (RPE) and retina is a rare, congenital, focal malformation of the fundus. So far, no disease gene has been associated with this disorder. By molecular analysis of an apparently balanced and reciprocal translocation between the short arms of chromosomes 11 and 18, t(11;18)(p13;p11.31), in a patient with hamartoma of the RPE and retina, we selected PAC clones crossing the breakpoints on both derivative chromosomes 11 and 18. For the overlapping chromosome 11 clone, two EST clusters were identified, suggesting the existence of at least two genes in the breakpoint region. We constructed a PAC contig and showed that at least three exons of a novel gene map to the breakpoint region on chromosome 18. Based on the results of FISH analysis with the PAC clones of this contig, we suggest the occurrence of a complex rearrangement.

Adult↗
PubMed2000

Xenon anaesthesia.

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Anesthetics, Inhalation↗
PubMed2000

Expression of (beta)-catenin in the developing chick myotome is regulated by myogenic signals.

The developmental signals that govern cell specification and differentiation in vertebrate somites are well understood. However, little is known about the downstream signalling pathways involved. We have shown previously that a combination of Shh protein and Wnt1 or Wnt3a-expressing fibroblasts is sufficient to activate skeletal muscle-specific gene expression in somite explants. Here, we have examined the molecular mechanisms by which the Wnt-mediated signal acts on myogenic precursor cells. We show that chick frizzled 1 (Fz1), beta-catenin and Lef1 are expressed during somitogenesis. Lef1 and beta-catenin transcripts become restricted to the developing myotome. Furthermore, beta-catenin is expressed prior to the time at which MyoD transcripts can be detected. Expression of beta-catenin mRNA is regulated by positive and negative signals derived from neural tube, notochord and lateral plate mesoderm. These signals include Bmp4, Shh and Wnt1/Wnt3a itself. In somite explants, Fz1, beta-catenin and Lef1 are expressed prior to activation of myogenesis in response to Shh and Wnt signals. Thus, our data show that a combination of Shh and Wnt1 upregulates expression of Wnt pathway components in developing somites prior to myogenesis. Thus, Wnt1 could act through beta-catenin on cells in the myotome.

Animals↗
PubMed2000

Adrenocortical function in patients with macrometastases of the adrenal gland.

OBJECTIVE: Metastases of the adrenal gland are a frequent finding in patients with malignant tumors like bronchogenic carcinoma or breast cancer. Only limited and conflicting data on adrenocortical function in these patients are available. DESIGN: Cross-sectional study. METHODS: We investigated the impact of adrenal macrometastases on adrenocortical function in a series of 28 tumor patients using the ACTH(1-24) stimulation test and dexamethasone suppression test. Seven normal controls (Con), eleven patients without adrenal metastases (No Met), eight patients with unilateral (Uni Met) and nine patients with bilateral adrenal metastases (Bil Met) were investigated. RESULTS: The prevalence of adrenal insufficiency was low in our study population, with only two of nine patients with bilateral metastases having subclinical adrenocortical insufficiency. In the remaining patients with uni- or bilateral metastases, baseline and stimulated cortisol concentrations were higher than in controls and cancer patients without metastases (baseline cortisol (in nmol/l): Con: 307+/-33.2 vs Uni Met: 440+/-53.5, and Bil Met: 637.6+/-92.1, P=0.04 by ANOVA; cortisol 60 min after ACTH(1-24): Con: 794.6+/-41.2 vs Uni Met: 990.8+/-92.9, and Bil Met: 1151.4+/-155.5, P=0.03 by ANOVA). Simultaneously, baseline and stimulated serum aldosterone concentrations were significantly blunted in the tumor groups. CONCLUSIONS: Adrenal insufficiency is infrequent and develops only in patients with bilateral metastases. However, the majority of patients have activation of the hypothalamic-pituitary-adrenal axis despite adrenal metastases with strongly elevated cortisol concentrations.

Adrenal Cortex↗
PubMed2000

Conversion of dehydroepiandrosterone to downstream steroid hormones in macrophages.

Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with immunomodulatory effects such as inhibition of the production of monokines. Whether DHEA itself or the downstream steroids are the immunomodulatory effector hormones in target cells is not known. In this study, we investigated the conversion of DHEA to downstream steroid hormones in target macrophages. Within 1 day of culture with radiolabeled DHEA, monocyte-derived macrophages converted DHEA to significant amounts of Delta5-derivatives such as 16OH-DHEA, 3beta, 17beta-androstenediol (A'diol), and 3beta,16alpha, 17beta-androstenetriol (A'triol). However, the production of Delta4-steroids (androstenedione (A'dione), testosterone (T), and 16OH-T) and estrogens (estrone, estradiol, and estriol) was relatively low. Further cultivation of macrophages for 5 days with radiolabeled DHEA resulted in a significant (P<0.05) increase of the molar amounts of A'triol (P=0.012), 16OH-T (P=0.008), and estriol (P=0.003). In contrast to monocyte-derived macrophages, monocytes did not express aromatase mRNA, which was demonstrated by RT-PCR (P<0.01). Furthermore, DHEA in macrophages significantly inhibited one of the downstream converting enzymes, the aromatase, which was not demonstrated in the presence of the typical macrophage activator, lipopolysaccharide (LPS) (P<0.01). In conclusion, conversion of DHEA to physiologically relevant amounts of Delta5- and Delta4-steroids and estrogens was demonstrated in monocyte-derived macrophages. The conversion depends on maturation of monocytes and local factors such as the presence of LPS. The conversion of DHEA leads to an increase of downstream effector hormones in target macrophages which may be an important factor for local immunomodulation.

Aromatase↗