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Biomedical subjects

R Schubert

Publications and source records attributed to R Schubert.

At least 55 records · Page 3Linked to original sources
PubMed2001

A realistic model of human structure from the visible human data.

The computer-based 3D models of the human body reported to date suffer from poor spatial resolution. The Visible Human project has delivered high resolution cross-sectional images that are suited for generation of high-quality models. Yet none of the 3D models described to date reflect the quality of the original images. We present a method of segmentation and visualization which provides a new quality of realism and detail. Using the example of a 3D model of the inner organs, we demonstrate that such models, especially when combined with a knowledge base, open new possibilities for scientific, educational, and clinical work.

Anatomy, Cross-Sectional↗
PubMed2000

Mechanisms of NO/cGMP-dependent vasorelaxation.

Both cGMP-dependent and -independent mechanisms have been implicated in the regulation of vascular tone by NO. We analyzed acetylcholine (ACh)- and NO-induced relaxation in pressurized small arteries and aortic rings from wild-type (wt) and cGMP kinase I-deficient (cGKI(-/-)) mice. Low concentrations of NO and ACh decreased the spontaneous myogenic tone in wt but not in cGKI(-/-) arteries. However, contractions of cGKI(-/-) arteries and aortic rings were reduced by high concentrations (10 micromol/L) of 2-(N:, N-diethylamino)-diazenolate-2-oxide (DEA-NO). Iberiotoxin, a specific blocker of Ca(2+)-activated K(+) (BK(Ca)) channels, only partially prevented the relaxation induced by DEA-NO or ACh in pressurized vessels and aortic rings. DEA-NO increased the activity of BK(Ca) channels only in vascular smooth muscle cells isolated from wt cGKI(+/+) mice. These results suggest that low physiological concentrations of NO decrease vascular tone through activation of cGKI, whereas high concentrations of DEA-NO relax vascular smooth muscle independent of cGKI and BK(Ca). NO-stimulated, cGKI-independent relaxation was antagonized by the inhibition of soluble guanylyl cyclase or cAMP kinase (cAK). DEA-NO increased cGMP to levels that are sufficient to activate cAK. cAMP-dependent relaxation was unperturbed in cGKI(-/-) vessels. In conclusion, low concentrations of NO relax vessels by activation of cGKI, whereas in the absence of cGKI, NO can relax small and large vessels by cGMP-dependent activation of cAK.

Acetylcholine↗
PubMed2000

Effect of nucleoside analogues and oligonucleotides on hydrolysis of liposomal phospholipids.

The hydrolysis of the bilayer forming phospholipids resulting first of all in lysophospholipids and fatty acids is one limiting factor determining the shelf-life of liposomes. In several studies the influence of pH, buffer, lipid composition and other parameters on the hydrolysis of phospholipids have been demonstrated, but the influence of drugs has not yet been investigated systematically. In this study the influence of nucleoside analogues, especially 2', 2'-difluoro 2'-deoxycytidine (gemcitabine, dFdC) on the degradation of phospholipids was elucidated in more detail. It could be demonstrated that the interaction of dFdC with phospholipid bilayers promotes the hydrolysis of phospholipids in a concentration-dependent manner. Obviously two parts of the molecule, the amino group bound to the pyrimidine moiety and the 2', 2'-difluoro-2'-deoxyribose, seem to be responsible for the forced phospholipid hydrolysis. The dFdC-induced hydrolysis of phospholipids was influenced by pH, buffer, lipid composition and different anions. Optimization of the above parameters resulted in prolonged shelf-life of dFdC liposome dispersions, which is an important prerequisite for clinical practice.

Anions↗
PubMed2000

Development of a method for sample preparation for subsequent identification and measurement of 1,2,3,4-tetrahydroisoquinolines and other potentially neurotoxic compounds by high-performance liquid chromatography with ultraviolet and fluorescence detection in blood plasma of Parkinson's disease patients.

We developed sample preparation methods for the detection of various biogenic phenylethylamine derivatives such as 3,4-dihydroxyphenylalanine, and their cyclisation products with aldehydes, i.e., 1,2,3,4-tetrahydroisoquinoline derivatives in blood samples. 1,2,3,4-Tetrahydroisoquinolines are considered to play an essential role as neurotoxic compounds in the pathomechanism of Parkinson's disease. We used reversed-phase high-performance liquid chromatography with ultraviolet and fluorescence detection for separation and identification. Ultrafiltration, protein precipitation and solid-phase extraction were investigated for purification of blood samples and enrichment of various compounds with a wide range of hydrophilicity and hydrophobicity. Protein precipitation by methanol and perchloric acid is a fast method to separate the analytes from the plasma matrix. A higher yield of the analytes is attained with prior addition of an alkylsulfonic acid giving a fine-grained precipitate. With the addition of ion pairing compounds into the sample it is possible to enrich not only lipophilic compounds such as norharman, tryptamine and melatonin, but also hydrophilic ones such as 3,4-dihydroxyphenylalanine by reversed-phase solid-phase extraction. Ultrafiltration is not useful as a screening method.

Blood Proteins↗
PubMed2000

Antioxidative capacity in patients with common variable immunodeficiency.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation, detoxifying scavenger enzymes, and molecules with antioxidant capacity could contribute to the increased susceptibility to cancer and infections in severe humoral immunodeficiency. We studied antioxidant status, i.e., plasma antioxidant capacity (TEAC), retinol, alpha-to-copherol, ubiquinol, and the number of activated T cells in 16 patients with common variable immunodeficiency (CVID) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated HLA-DR and CD45RO-expressing T cells. Plasma levels of the endogenous ROS scavenger ubiquinol (Q 10) were significantly lower in patients as compared to controls. However, patients showed only slightly reduced levels of TEAC as well as the exogenous antioxidants retinol and alpha-tocopherol. Although no correlation of the number of activated T cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process in patients with common variable immunodeficiency.

Adolescent↗
PubMed2000

4-aminopyridine affects rat arterial smooth muscle BK(Ca) currents by changing intracellular pH.

The hypothesis whether or not 4-AP can affect vascular smooth muscle BK(Ca) currents was tested using the patch-clamp technique, pH- and calcium-fluorimetry, and freshly isolated rat arterial smooth muscle cells. Application of 4-AP reversibly inhibited BK(Ca) currents at an intracellular calcium ([Ca](i)) of 250 nM with a half-block of 2. 5 mM at +50 mV. The presence of 2 microM thapsigargin, 10 microM heparin, and 10 microM ryanodine did not alter the effect of 4-AP on BK(Ca) currents at [Ca](i) 250 nM. At [Ca](i)<100 nM 4-AP did not inhibit BK(Ca) currents. Application of 4-AP to the intracellular or extracellular side of excised BK(Ca) channels did not alter channel activity or channel amplitude. Replacement of the pH-sensitive calcium buffer EGTA by the pH-insensitive calcium buffer BAPTA in the intracellular solution turned the 4-AP-induced inhibition of BK(Ca) currents into a stimulation at [Ca](i) 250 nM. Application of 4-AP to single cells increased intracellular pH, which was accompanied by a reduction of [Ca](i) in EGTA-loaded cells and a stable [Ca](i) in BAPTA-loaded cells. Thus, these results suggest that in isolated vascular smooth muscle cells at [Ca](i)>100 nM 4-AP affects BK(Ca) currents via an alteration of intracellular pH.

4-Aminopyridine↗
PubMed2000

Spontaneous and oxidative stress-induced programmed cell death in lymphocytes from patients with ataxia telangiectasia (AT).

T cell lymphopenia in the peripheral blood lymphocytes (PBL) of patients with AT is mainly caused by a decrease of naive CD45RA+/CD4+ cells followed by a predominance of memory CD45RO+ lymphocytes. To relate these findings to the regulation of programmed cell death, we investigated the activation state and apoptotic level of PBL in 12 patients and healthy controls by flow cytometry. In accordance with previous investigations, the number of naive CD4+/CD45RA+ cells was significantly decreased in patients compared with healthy controls. This disturbed balance of CD45RA and CD45RO was also reflected in higher amounts of activated HLA-DR and CD95 expressing cells, with a concomitant decrease of Bcl-2 protected lymphocytes in the T cell population. With regard to its role in preventing oxidative-induced cell death, we analysed Bcl-2 expression and apoptosis in the presence of oxidative stress. In culture, cells of patients are more susceptible to spontaneous programmed cell death. However, in our stress-inducing system (hypoxanthine/xanthine oxidase system) the number of cells undergoing apoptosis was lower in patients' cell populations compared with controls. In addition, preliminary results suggest that Bcl-2 expression and level of spontaneous apoptosis in patients can be modified by IL-2 and interferon-gamma.

Adolescent↗
PubMed2000

Preoperative simulation of partial nephrectomy with three-dimensional computed tomography.

OBJECTIVE: To evaluate prospectively the accuracy of computer-aided three-dimensional (3D) volume-rendered computed tomography (CT) in determining the appropriate anatomical limits (tumour size, tumour location, multifocality and vascular supply) and as a potential tool in the preoperative simulation of nephron-sparing surgery (NSS) in patients with small-volume renal cell carcinoma (RCC). PATIENTS AND METHODS: The study included 36 patients who underwent transperitoneal radical nephrectomy for RCC of < 4 cm diameter. Helical CT was undertaken before surgery and the extent of the tumour, the course of major renal arteries and veins, and the relationship of the tumour to the collecting system were shown by 3D volume-rendered CT. The CT findings were compared with the pathological results of all kidney specimens, obtained using 3-mm step-sections. RESULTS: Before nephrectomy, 39 renal tumours were identified in the 36 patients; three renal lesions of < 4 mm were not detected. All main venous branches and 42 of 43 arteries were identified by 3D volume-rendered CT. Knowing these features, a partial nephrectomy was simulated; a surgical lesion to the pelvicalyceal or vascular system which would have been produced by the simulated surgery was displayed in colour on the simulated surface of the section. CONCLUSION: Computer simulation provided an excellent 3D reconstruction of all kidneys, including the tumour, vasculature and renal hilum, allowing a significantly better preoperative evaluation of the renal mass. Visualizing possible resection margins and predicting the operative risks seem to be major advantages of this new method, especially when preparing for complex surgery. Reconstructed 3D CT appears to be a useful tool for defining the indications for and limitations of NSS.

Adult↗
PubMed2000

Combination of hypospadias and maldescended testis as cardinal symptoms in gonosomal chromosome aberrations.

Intersexual genitals or distinct hypospadias in combination with maldescended testis can be caused by endocrinological as well as chromosomal abnormalities. Even in early childhood such clinical findings require specific diagnostic procedures and subsequent treatment which is often invasive but has special importance as regards the early diagnosis of gonadal tumors. We present a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadias. Cytogenetic analyses revealed a mosaic karyotype 45, X/46, X, idic (Yp) with unequal distribution of the mosaic in different tissues. In consequence of this chromosomal aberration the patient had mixed gonadal dysgenesis which is associated with an increased risk of tumor development in the aberrant gonads. The principles of pediatric, urological, cytogenetic and endocrinological diagnostics and the mode of data collection in the presented case are described and discussed. Furthermore, a protocol for preventive screening is presented, which combines urological and endocrinological investigations in males with malformations of the genito-urinary tract to minimize the risk of tumor development in the aberrant gonads.

Child, Preschool↗
PubMed2000

Influence of tableting forces and lubricant concentration on the adhesion strength in complex layer tablets.

The strength of adhesion in complex two-layer tablets is assessed using statistical methods with respect to the applied tableting forces for the first layer and for applying the second layer on the first, as well as regarding the fraction of the lubricant. These results, obtained on a single-punch tablet press, are compared with the results for three-layer tablets produced on a rotary press at production scale. The strongest negative influence on adhesion strength was exerted by the amount of lubricant in the central layer. As expected, compression forces for central-layer tableting also had a negative effect, whereas the compression forces for complex layer tableting exerted a positive effect on layer adhesion. The validity of the derived model equation was proved by experiments: It was shown that the adhesion strength in complex layer tablets produced in production scale can be predicted from laboratory-scale experiments. This makes optimization of the formulation and parameter settings at an early stage of development possible.

Adhesiveness↗
PubMed2000

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

BACKGROUND: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was performed to asses the accuracy of pre- and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions. MATERIALS AND METHODS: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand. RESULTS: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard. CONCLUSIONS: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2000

The role of tiagabine in the treatment of intractable epilepsy of childhood with multifocal independent spikes: a case report.

Multifocal independent spike syndrome (MISS) is an identifiable electroclinical syndrome, which combines intractable motor seizures, mental retardation and multifocal independent spike discharges. Similarities to the Lennox Gastaut syndrome cause frequent misdiagnosis; however, MISS is a distinct electroclinical syndrome in children with a better prognosis and a different EEG pattern. We report an 8-year-old boy with MISS, whose intractable seizures were completely controlled for the first time with tiagabine as add-on therapy. Tiagabine should be studied further in the treatment of intractable multiple seizures of childhood.

Anticonvulsants↗
PubMed1999

Acute and long-term stability studies of deoxy hemoglobin and characterization of ascorbate-induced modifications.

The reaction of ascorbate with recombinant hemoglobin (rHb1.1) in the presence of differing partial pressures of oxygen was studied. In the presence of 15 000 ppm (1.5%) residual oxygen, ascorbate/oxygen-mediated reactions resulted in an increased rate of autoxidation, modification of the beta-globin, increased oxygen affinity and decreased maximum Hill coefficient. One of the observed modifications to the beta-globin was a 72 Da addition to its N-terminus. Detailed characterization indicates the modification was an imidazolidinone type structure. Thorough deoxygenation of the hemoglobin solution to <150 ppm of oxygen prior to addition of ascorbate was required to prevent these modifications. Addition of ascorbate to the deoxy hemoglobin (deoxyHb) at pH 8 induced aggregation, eventually leading to precipitation. No such precipitation was observed at pH 7. Long-term storage of the hemoglobin was carried out by addition of ascorbate to deoxyHb at pH 7. The level of methemoglobin remained at <2% for up to 1 year at 4 degreesC, with no detectable precipitation of the protein. Modifications similar to those observed by the acute studies were observed over the 1-year period and correlated with disappearance of the added ascorbate.

Ascorbic Acid↗
PubMed1999

Characterisation, phenotypic manifestations and X-inactivation pattern in 14 patients with X-autosome translocations.

Here we describe a group of 14 patients carrying different X-autosome translocations and exhibiting phenotypes that demonstrate the range of alterations induced by such aberrations. All male carriers of an X-autosome translocation in our investigation group were infertile, whereas fertility in the female carriers was dependent on the position of the break-point in the X chromosome. Fertile women with translocation break-points outside of the critical region (Xq13-q26) in some cases passed on the translocation to their offspring. In balanced female carriers in our group, the normal X chromosome was usually inactivated, allowing full expression of genes on the translocated segments. In one case, disruption of the dystrophine gene in Xp21 led to the manifestation of Duchenne muscular dystrophy in a female carrier. Inactivation of the derivative X (Xt) in a balanced female carrier led to a partial monosomy of the autosome/disomy of the X chromosome and resulted in an aberrant phenotype. In unbalanced carriers, Xt is generally late-replicating/inactive, although failed spreading of inactivation to the autosomal segment often results in a partial trisomy, as evidenced by the case of an unbalanced translocation carrier in our group.

Adolescent↗
PubMed1999

Anti-oxidative capacity in patients with ataxia telangiectasia.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation and detoxifying scavenger enzymes could contribute to the increased susceptibility to cancer and infections in ataxia telangiectasia. We studied oxidative status, i.e. plasma total antioxidant capacity (TEAC), retinol, alpha-tocopherol, ubiquinol, and the number of activated T cells in 10 patients with ataxia telangiectasia (AT) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated human leukocyte antigen-DR and CD45RO expressing T cells. TEAC levels as well as the exogenous antioxidants retinol and alpha-tocopherol were significantly reduced in patients. In addition, patients showed slightly reduced plasma levels of the endogenous ROS scavenger enzyme ubiquinol (Q10). Although no correlation between number of activated T-cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process of patients with AT.

Adolescent↗
PubMed1999

On the accuracy of a new displacement instrumentation for rotary tablet presses.

The Portable Press Analyzer (PPA; Puuman Oy, Finland), a commercially available instrumentation for rotary tablet presses, was tested for accuracy of determination of force and displacement. The calibration of the force transducers (strain gauges) was tested under a static condition. The calibration of the displacement transducers (plastic film potentiometer) was compared for static and dynamic recordings. Force measurement was found precise (deviation < 1.1%) after alterations in the calibration procedure. Displacement measurement was affected by punch tilting and the application of the transducers. If tilting of punches was not considered, the deviation of displacement measurement from the true value (using steel tablets as a reference) was found up to 110 microns. By modifying the original PPA system by supplementing additional displacement transducers in the adjacent turret positions of the punches and adding a custom electronic device (Tilting Compensation Device), the accuracy of distance measurement was improved to 18.1 microns (+/- 3.64). Furthermore, machine and tooling deformation were recorded and found different under static and dynamic conditions. Correction of punch displacement for elastic deformation therefore should preferably be made from dynamic recordings.

Calibration↗