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Biomedical subjects

A Barth

Publications and source records attributed to A Barth.

At least 109 records · Page 6Linked to original sources
PubMed1994

Digital image analysis of self-similar cell profiles.

Many biological objects appear to have self-similar structures which can be characterized by their fractal dimension D. However, applications of the concept of fractal geometry are rather scarce in cell and tissue biology. Here we adapt and analyse critically 3 methods of digital image analysis to measure D of cellular profiles. As prototype examples we investigate in detail 2 samples of cells: (i) human T-lymphocytes from normal donors, and (ii) hairy leukemic cells. It is shown that D correlates to the structural complexity of the individual cell contour. The calculated D values for cells out of the same cell line scatter around a mean value D = 1.15 for T-lymphocytes (S.D. = 0.03) and D = 1.34 for hairy leukemic cells (S.D. = 0.04). Consequently, we interprete D as a statistical measure for the sample's fractal dimension.

Flow Cytometry↗
PubMed1994

Growth of small saccular aneurysms to giant aneurysms: presentation of three cases.

We report on three patients with a documented small saccular aneurysm growing to a giant size over several years. In the first patient, a small dilation of the left carotid bifurcation grew to an asymptomatic giant aneurysm of 2 cm in diameter over 11 years. In the second patient, a ruptured aneurysm of the proximal middle cerebral artery (MCA) was erroneously treated by partial ligature of the MCA. Twenty-three years later, the aneurysm had grown to a giant polylobed calcified mass compressing the neighboring brain. In the third patient, a ruptured aneurysm of the dorsal part of the carotid syphon grew over 17 years to a giant calcified mass of 5 cm in diameter despite Hunterian ligation of the common carotid artery in the neck. The three reported cases illustrate the continuous growth and the long-term risks of not treating or of insufficiently treating aneurysms.

Adult↗
PubMed1994

Influence of the xanthine derivative denbufylline and the anti-inflammatory agent nabumetone on microsomal free radical production and lipid peroxidation in rat liver.

The influence of denbufylline, nabumetone and its main metabolite BRL 10,720 on iron stimulated lipid peroxidation (LPO), cytochrome P 450 dependent H2O2 and chemiluminescence (CL) production was investigated in rat liver microsomes in vitro (10(-5)-10(-3) M) and in vivo after treatment of rats (5-300 mg/kg b.m. orally on three consecutive days). In rat liver slices the release of thiobarbituric acid reactants (TBAR) was measured after 1 hour of incubation with the drugs. Denbufylline, nabumetone and BRL 10,720 exerted a significant inhibition of iron stimulated LPO in vitro. Nabumetone showed the strongest antioxidative activity, which was also seen in liver slices. These antioxidative effects were not found after in vivo treatment of rats. Denbufylline (10(-3) M) additionally inhibited H2O2 formation and the luminol and lucigenin amplified CL in vitro. Unexpectedly, nabumetone increased H2O2 formation both in vitro and in vivo, but in vitro only lucigenin amplified CL. BRL 10,720 increased microsomal H2O2 production in vivo. Moreover, BRL 10,720 enhanced CL in vitro and in vivo significantly, which is interpreted as an increase of the production of superoxide anion radicals and other reactive oxygen species such as H2O2, but lipid peroxidation in liver microsomes was not enhanced. These results suggest that denbufylline, nabumetone and BRL 10,720 in contrast to the in vitro effects did not exert antioxidative activities after treatment of rats. On the contrary, BRL 10,720 was found to support the formation of reactive oxygen species in liver microsomes.

Animals↗
PubMed1994

Peroxidative status and glutathione content of the brain in normal weight and intra-uterine growth-retarded newborn piglets.

The peroxidative and glutathione status as well as the production of reactive oxygen species were studied in the brain of normal weight (NW) and intra-uterine growth-retarded (IUGR) newborn piglets. In NW as well as IUGR newborn piglets reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxides, iron stimulated lipid peroxidation, H2O2 production and lucigenin and luminol amplified chemiluminescence are very similar in the different brain regions, with one exception. In the cerebellum, higher GSH concentration, higher superoxide anion generation, lower levels of lipid peroxides and a tendency toward a lower capacity of H2O2 production were seen. But the intra-uterine growth retardation to body weights of half the average body weights of the respective litter did not influence the peroxidative status and the GSH/GSSG equilibrium in the brain of newborn piglets.

Animals↗
PubMed1994

Replacement of the phospholipid-anchor in the contact site A glycoprotein of D. discoideum by a transmembrane region does not impede cell adhesion but reduces residence time on the cell surface.

The contact site A (csA) glycoprotein of Dictyostelium discoideum, a cell adhesion molecule expressed in aggregating cells, is inserted into the plasma membrane by a ceramide-based phospholipid (PL) anchor. A carboxyterminal sequence of 25 amino acids of the primary csA translation product proved to contain the signal required for PL modification. CsA is known to be responsible for rapid, EDTA-resistant cohesion of cells in agitated suspensions. To investigate the role of the PL modification of this protein, the anchor was replaced by the transmembrane region and short cytoplasmic tail of another plasma membrane protein of D. discoideum. In cells transformed with appropriate vectors, PL-anchored or transmembrane csA was expressed under the control of an actin promoter during growth and development. The transmembrane form enabled the cells to agglutinate in the presence of shear forces, similar to the PL-anchored wild-type form. However, the transmembrane form was much more rapidly internalized and degraded. In comparison to other cell-surface glycoproteins of D. discoideum the internalization rate of the PL-anchored csA was extremely slow, most likely because of its exclusion from the clathrin-mediated pathway of pinocytosis. Thus, our results indicate that the phospholipid modification is not essential for the csA-mediated fast type of cell adhesion but guarantees long persistence of the protein on the cell surface.

Amino Acid Sequence↗
PubMed1994

Infarcts in the territory of the lateral branch of the posterior inferior cerebellar artery.

The territory of the lateral branch of the posterior inferior cerebellar artery (1PICA) supplies the anterolateral region of the caudal part of the cerebellar hemisphere. Because infarcts in the territory of the 1PICA have rarely been studied specifically, 10 patients with this type of infarct are reported. An 1PICA infarct was isolated in only three patients, whereas it was associated with brainstem infarct in four, with occipital infarct in one, and with multiple infarcts in two patients. The most common symptom at onset was acute unsteadiness and gait ataxia without rotatory vertigo (six patients). Unilateral cerebellar dysfunction was found in all patients, with limb ataxia (nine patients), dysdiadochokinesia (five patients), and ipsilateral body sway (four patients), but dysarthria and primary position nystagmus were notably absent. In the patients with a coexisting infarct in the brainstem, cranial nerve and sensorimotor dysfunction was prominent and often masked the signs of cerebellar dysfunction. Unlike other infarcts in the PICA territory, 1PICA territory infarcts were mainly associated with vertebral artery atherosclerosis (six patients), whereas cardiac embolism was less common (three patients). Unilateral limb ataxia without dysarthria or vestibular signs suggests isolated 1PICA territory infarction and should allow its differentiation from other cerebellar infarcts.

Aged↗
PubMed1994

Interaction of liposomal incorporated vitamin D3-analogues and human keratinocytes.

The influence of different liposomal qualities, loaded with a variety of vitamin D3-analogues, on the proliferation and interleucine 1 alpha-release (IL-1 alpha) of human keratinocytes was examined by fluorimetric and colorimetric measurements to optimize their use for psoriasis treatment. In comparison, the effects of the free drugs, as 25-hydroxyvitamin D3, calcipotriol, and calcitriol, as well as of empty liposomes have been studied. At the interaction between empty liposomes (< 200 nm) and HaCaT-cells has been looked by electron microscopy. Empty liposomes, made of DMPC as well as of egg-PC, can be used as drug carrier without any inhibiting effect on the proliferation of human keratinocytes at lipid concentrations of < 10(-4) M. Under the influence of the free drugs investigated an inhibition of cell growth as well as of the IL 1 alpha-release was measured at drug concentrations of > or = 10(-8) M. In comparison the related liposomal drug formulations didn't show any diminishing in the proliferation effects caused by the free drugs. A significant improvement, however, was only found in the action of DMPC-incorporated 25-hydroxyvitamin D3 at drug concentration of 10(-7) M. These results suggest that there is no remarkable improvement in the action of liposomal incorporated vitamin D3-analogues neither related to their proliferation nor their IL1 alpha-releasing effects. The influence of liposomal incorporated vitamin D3-analogues in keeping small their negative side effects has to be investigated at a more relevant model.

Cell Division↗
PubMed1994

Classification of serine proteases derived from steric comparisons of their active sites, part II: "Ser, His, Asp arrangements in proteolytic and nonproteolytic proteins".

The assignment of serine proteases to the families of (chymo)trypsins and subtilisins, respectively, is extended by including additional data from the Brookhaven Protein Data Bank. To better understand basic properties connected with this type of assignment the steric situation in the vicinity of the tetrad aminoacyl residues and atomic distances within the tetrads are considered. A new catalytic mechanism is suggested based on differences between tonin and kallikrein with respect to structure and reactivity of the catalytic tetrad. All protein structures available from the Brookhaven Protein Data Bank are analyzed with regard to the occurrence of Asp....His....Ser triads.

Amino Acid Sequence↗
PubMed1993

[Stereotactically-guided microsurgery in cerebral processes].

Stereotaxy-guided microsurgery offers significant advantages in the treatment of deep-seated cerebral lesions, or in lesions that cannot reliably be localized because of their small size or lack of evident landmarks. We report our experience with 16 stereotaxy-guided microsurgical procedures performed with the Leksell or the Lerch stereotactic system. Small superficial lesions were operated on in 6 patients and deep-seated subcortical lesions in 10 patients. The lesion size ranged from 10 to 50 mm and the depth of the lesions varied between 5 and 65 mm. A trans-sulcus approach was chosen in patients with cavernomas and a transcortical or transtumoral one in patients presenting with cerebral tumors. In no patient was a new postoperative neurologic deficit found, i.e. 12 patients had neither a pre- nor a postoperative deficit. 2 patients (with central lesions) of 4 presenting with preoperative deficits showed an impressive recovery, while in the other 2 patients with lesions in the dominant temporal lobe the neurologic deficit remained unchanged. Stereotaxy-guided microsurgery allows safe resection of small or deep-seated cerebral lesions without postoperative morbidity in our series.

Adult↗
PubMed1993

[Efficacy of 2 different leukocyte filters for erythrocyte concentrates].

By leukocyte reduction in red blood cell concentrates to < 5 x 10(6) leukocytes per transfused unit, febrile non-hemolytic transfusion reaction as well as alloimmunization and transmission of certain viral diseases (CMV, HTLV-1) can be prevented. Using a Nageotte hemocytometer with a large-volume chamber, the residual leukocyte number after filtration of 40 buffy-coat free red blood cell units with the filters Pall RC100 and Sepacell R500 B1 was determined in a clinical routine setting. Both tested filters underscored the limit (< 5 x 10(6) leukocytes per unit) set by the American Association of Blood Banks. Hemoglobin loss accounted for 8.9 g (Pall RC100) versus 7.7 g (Sepacell R500 B1), which is about 15-18% of the hemoglobin content of a red blood cell concentrate.

Blood Component Removal↗
PubMed1993

[Unexpectedly prolonged thrombin time].

The thrombin time assay is able to detect abnormalities of the terminal phase of plasmatic coagulation. The differential diagnosis of thrombin time prolongation includes (1) inhibition of the added thrombin by exogenous heparin or endogenous heparin-like anticoagulant, seldom by acquired antibovine thrombin antibodies, (2) qualitative fibrinogen disorders (congenital and acquired dysfibrinogemia, (3) quantitative fibrinogen disorders (hypo- and afibrinogenemia), and (4) delayed fibrin polymerization due to fibrin/fibrinogen degradation products, paraproteins or seldom acquired antibodies against fibrinogen.

Adult↗
PubMed1993

The clinical and topographic spectrum of cerebellar infarcts: a clinical-magnetic resonance imaging correlation study.

We studied 34 consecutive patients with non-mass-producing cerebellar infarcts using a standard protocol of investigations including magnetic resonance imaging (MRI). We analyzed the topography of infarcts to determine the involved arterial territories and we correlated the findings with neurological dysfunction and potential causes of stroke. Sixteen patients had an infarct in the territory of the posterior inferior cerebellar artery (PICA); 2, in the territory of the anterior inferior cerebellar artery (AICA); 13, in the territory of the superior cerebellar artery (SCA); and 8 had junctional infarcts between the territories of the medial and lateral branches of the PICA or PICA/SCA territories. PICA or medial PICA territory infarcts were manifested by acute vertigo and truncal ataxia, while the patients with lateral PICA territory infarcts presented with unsteadiness, limb ataxia and dysmetria without dysarthria. Patients with infarcts in the AICA territory were characterized by limb and trunk ataxia associated with signs of lateropontine involvement. Patients with SCA territory infarcts presented with dysarthria, unsteadiness and/or vertigo, limb ataxia, and dysmetria. Cardiac embolism was the main cause of large infarcts in the territories of the PICA (8/16) or SCA (4/7). Multiple small infarcts were associated with vertebrobasilar atherosclerosis (8/12). These clinical-MRI correlations allow better definition of the topographic and etiological spectrum of cerebellar infarction, which was previously based on pathological studies in subjects with severe infarction.

Aged↗
PubMed1993

Enzymatic activity of CD26 (dipeptidylpeptidase IV) is not required for its signalling function in T cells.

CD26 is a proteolytic enzyme (dipeptidylpeptidase IV) expressed on the T cell surface that defines an alternative activation signal for human T lymphocytes. Crosslinking of CD26 via monoclonal antibodies triggers proliferation and cytotoxicity in preactivated T cells. In this study, we used highly specific competitive and irreversible inhibitors of dipeptidylpeptidase IV to study the role of the enzymatic activity in activation of CD26-transfected T cells as well as of CD26-expressing normal human T cell clones. These inhibitors at concentrations that blocked up to 95% of the enzymatic activity, did not specifically inhibit T cell activation neither via TCR/CD3 nor via CD26 itself. This demonstrates that the enzymatic activity of CD26 is not required for its T cell activating properties.

Animals↗
PubMed1993

Is the analgesic activity of epibatidine caused by a chemical reaction with the morphine opioid receptor?

Using the molecular modeling program SYBYL, a conformational analysis of epibatidine has been performed. Two pairs of stable conformations due to the rotational degree of freedom for the pyridine ring have been found. These conformations were compared with morphine regarding spatial arrangements as well as electronic aspects. A very close agreement between the essential receptor positions occurring in morphine and epibatidine could be demonstrated. The protonable nitrogen atom in epibatidine is in exactly the same spatial position as in morphine, if the pyridine ring and the phenolic ring of morphine were matched to each other. Interestingly, it is also apparent that the pyridine nitrogen atom is in a close position to the bridging oxygen atom of morphine. Furthermore, the chlorine substituent fits very well with the hydroxyl group of morphine. A chemical reaction is postulated to permit epibatidine to function as an analgesic. The carbon-chlorine bond should be activated by the neighbourhood of the nitrogen atom in the pyridine ring and therefore undergo a chemical reaction resulting in formation of a covalent bond, perhaps of an oxygen bridge between the opioid receptor and epibatidine.

Analgesics, Non-Narcotic↗
PubMed1993

Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V.

We report on a 34-year-old woman whose plasma showed a marked prolongation of thrombin time (TT) (> 200 s) using bovine thrombin. The patient had previously been exposed twice to topical bovine thrombin contained in fibrin glue during cardiac surgery. TT was normal when human thrombin was used as reagent. The patient's purified IgG reacted with bovine prothrombin and bovine thrombin in immunoblotting studies but showed virtually no cross-reaction with human thrombin. In addition, following surgery, factor V clotting activity (FV:C) was reduced to 9% of normal. The inhibitor of bovine thrombin persisted over a period of more than a year, while the level of FV:C progressively returned to normal within this time period. Development of thrombin and FV:C inhibitors was also investigated in plasma of 34 consecutive patients who had undergone either cardiac surgery or neurosurgery with use of fibrin glue containing bovine thrombin. Eleven of 24 patients after cardiac surgery and two of 10 patients after neurosurgery presented with TT > or = 25 s (normal plasma 15 s). Two patients had been re-exposed to fibrin glue during cardiac re-operation and showed markedly prolonged TT (> 60 s). All 13 patients who had acquired a thrombin inhibitor also had low FV:C activity (10-60% of normal plasma), whereas FV:C activity remained in the normal range in the 21 patients with normal TT. Our findings indicate that development of inhibitors of bovine thrombin as well as co-immunization to factor V occurs frequently and is associated with the amount of applied fibrin glue and with the type of operation. Re-exposure to fibrin glue seems to enhance formation of inhibitors of bovine thrombin and human factor V.

Adult↗
PubMed1993

Peptidyl ammonium methyl ketones as substrate analog inhibitors of proline-specific peptidases.

Prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DP IV) are serine enzymes cleaving highly specific prolyl peptide bonds. Both enzymes were found to be inhibited by newly designed peptidyl ammonium and pyridinium methyl ketones acting as slow binding inhibitors. The most potent inhibitor of PEP is Z-Pro-Pro-CH2N+C5H5 exhibiting a Ki* value of 1.8 nM with a first-order rate constant of Kon 0.0022 s-1 for the formation of the tight enzyme-inhibitor complex. DP IV and H-Pro-Pro-CH2N+ (CH3)3 form an enzyme-inhibitor-complex with an apparent second order rate constant of 2713 M-1 s-1. In contrast to the very stable N-terminal protected Z-Pro-Pro-CH2N+ (CH3)3, the deblocked derivative decomposes rapidly in aqueous solution.

Dipeptidyl Peptidase 4↗
PubMed1993

A new consistent model explaining structure (conformation)-activity relationships of opiates with mu-selectivity.

Several different classes of opiates such as PET (7-alpha-(1-Hydroxy-1-methyl-3-phenylpropyl)-6,14-endo-ethenotetra - hydronorthebaine), phenazocine, fentanyl, carfentanil, ohmefentanyl, prodine derivatives, methadone and etonitazene have been investigated using the molecular modelling program package SYBYL and the TRIPOS empirical force field. Comparison of the energetically optimized structures and their corresponding molecular electrostatic potentials was used for the development of a new model of conformation-activity relationships of mu-selective opiates. We considered six important spatial positions of these molecules which were assumed to be directly implicated in the interaction with the opiate receptor. We found that these opiates may bind to the receptor with their protonated nitrogen atom assuming one or the other of two different orientations. The obtained results offer new insights into important receptor interactions and the diverse opiate activities of all the compounds examined can be explained in a unified manner. For example, the most active ohmefentanyl stereo-isomer was predicted on the basis of the proposed model.

Analgesics↗