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Biomedical subjects

P Weiser

Publications and source records attributed to P Weiser.

At least 19 recordsLinked to original sources
PubMed2004

[A gearing mechanism with 4 degrees of freedom for robotic applications in medicine].

Applications in robot-aided surgery are currently based on modifications of manipulators used in industrial manufacturing processes. In this paper we describe novel rotatory kinematics for a manipulator, specially developed for deployment in robot-aided surgery. The construction of the gearing mechanism used for the positioning and orientation of a linkage point is described. Forward and inverse kinematics were calculated, and a constructive solution proposed. The gearing mechanism is based on two disk systems, each of which consists of two opposing rotatable discs. The construction was designed in such a way that the linkage point can be positioned freely anywhere within the mechanism's range of motion. The kinematics thus permits an x-y-positioning via rotating movements only. The spatial arrangement of two of such disc systems permits movements in four degrees of freedom (DOF). The construction is compact, but can be further miniaturized, is flexible and manufacturing costs are low. On the basis of this mechanical concept a new, small automated manipulator for surgical application will be developed.

Computer-Aided Design↗
PubMed2001

BB rat thymocytes cultured in the presence of islets lose their ability to transfer autoimmune diabetes.

Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes would be present in long-term ATOCs but could be rendered nondiabetogenic by co-culture with appropriate antigens. We observed that cells recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14 days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with polyinosinic: polycytidylic acid and a monoclonal antibody to preclude development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the presence of BBDR thyrocytes had no effect on the ability of recovered cells to induce diabetes in 70-80% of adoptive recipients. In contrast, co-culture in the presence of islets prevented transfer of diabetes, on average, in >90% of recipients. Fresh islets, frozen islets, and islets pretreated with streptozotocin to deplete insulin were equally effective in preventing diabetes, but none prevented insulitis in nondiabetic recipients. Co-culture in the presence of islets was not associated with detectable alterations in phenotype or in the secretion of gamma-interferon or interleukin-4, either in cultures or in cells recovered from adoptive recipients. We conclude that islet antigens involved in the initiation of autoimmune diabetes in BB rats may be absent or deficient in BB rat thymi. Exposure of ATOCs to exogenous islets may lead to deletion or anergy of diabetogenic T-cells or to the positive selection of regulatory T-cells.

Adoptive Transfer↗
PubMed1999

Recapitulation of normal and abnormal BioBreeding rat T cell development in adult thymus organ culture.

Congenitally lymphopenic diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous T cell-dependent autoimmunity. Coisogenic diabetes-resistant (DR) BB rats are not lymphopenic and are free of spontaneous autoimmune disease, but become diabetic in response to depletion of RT6+ T cells. The basis for the predisposition to autoimmunity in BB rats is unknown. Abnormal T cell development in DP-BB rats can be detected intrathymically, and thymocytes from DR-BB rats adoptively transfer diabetes. The mechanisms underlying these T cell developmental abnormalities are not known. To study these processes, we established adult thymus organ cultures (ATOC). We report that cultured DR- and DP-BB rat thymi generate mature CD4 and CD8 single-positive cells with up-regulated TCRs. DR-BB rat cultures also generate T cells that express RT6. In contrast, DP-BB rat cultures generate fewer CD4+, CD8+, and RT6+ T cells. Analysis of the cells obtained from ATOC suggested that the failure of cultured DP-BB rat thymi to generate T cells with a mature phenotype is due in part to an increased rate of apoptosis. Consistent with this inference, we observed that addition of the general caspase inhibitor Z-VAD-FMK substantially increases the number of both mature and immature T cells produced by DP-BB rat ATOC. We conclude that cultured DR-BB and DP-BB rat thymi, respectively, recapitulate the normal and abnormal T cell developmental kinetics and phenotypes observed in these animals in vivo. Such cultures should facilitate identification of the underlying pathological processes that lead to immune dysfunction and autoimmunity in BB rats.

ADP Ribose Transferases↗
PubMed1998

Syk tyrosine kinase and B cell antigen receptor (BCR) immunoglobulin-alpha subunit determine BCR-mediated major histocompatibility complex class II-restricted antigen presentation.

Stimulation of CD4(+) helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-alpha/Ig-beta heterodimers which, second, target antigens to MHC class II-containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-alpha-associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-alpha cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide- MHC class II complexes through antigen targeting by BCR subunits.

Animals↗
PubMed1997

Endosomal targeting by the cytoplasmic tail of membrane immunoglobulin.

Membrane-bound immunoglobulin (mIg) of the IgG, IgA, and IgE classes have conserved cytoplasmic tails. To investigate the function of these tails, a B cell line was transfected with truncated or mutated gamma2a heavy chains. Transport to the endosomal compartment of antigen bound by the B cell antigen receptor did not occur in the absence of the cytoplasmic tail; and one or two mutations, respectively, in the Tyr-X-X-Met motif of the tail partially or completely interrupted the process. Experiments with chimeric antigen receptors confirmed these findings. Thus, a role for the cytoplasmic tail of mIg heavy chains in endosomal targeting of antigen is revealed.

Animals↗
PubMed1994

The internalization of the IgG2a antigen receptor does not require the association with Ig-alpha and Ig-beta but the activation of protein tyrosine kinases does.

The B cell antigen receptor of class IgM is a multimeric protein complex containing the membrane-bound immunoglobulin molecule and a heterodimer of the two B cell-specific transmembrane proteins Ig-alpha and Ig-beta. The B cell antigen receptor fulfills a dual role on the surface of B cells. First, it is a signal transduction complex which can activate protein tyrosine kinases and induce the release of Ca2+ ions from intracellular stores. Second, its internalization mediates the specific uptake of bound antigens, which are processed intracellularly and presented as major histocompatibility complex-bound peptides on the cell surface. In case of the IgM antigen receptor, the association with the heterodimer is necessary for expression of large amounts of IgM on the surface. We show here that the IgG2a antigen receptor can be expressed on the surface of myeloma cells in two structurally different forms: either with or without the Ig-alpha/Ig-beta heterodimer. A functional comparison of the two forms of antigen receptors demonstrates that the Ig-alpha and Ig-beta molecules are required for the activation of protein tyrosine kinases after cross-linking of the B cell antigen receptor. In contrast, both forms of IgG2a are equally well internalized. This suggests that Ig-alpha and Ig-beta are essential for signal transduction through the IgG2a antigen receptor, whereas internalization can occur independently of the heterodimer.

Animals↗
PubMed1993

Molecular mimicry of the antigen receptor signalling motif by transmembrane proteins of the Epstein-Barr virus and the bovine leukaemia virus.

BACKGROUND: Many transmembrane proteins of eukaryotic cells have only a short cytoplasmic tail of 10 - 100 amino acids, which has no obvious catalytic function. These tails are thought to be involved either in signal transduction or in the association of transmembrane proteins with the cytoskeleton. We have previously identified, in the cytoplasmic tails of components of B and T lymphocyte antigen receptors, an amino-acid motif that is required for signalling. The same motif is also found in the cytoplasmic tails of two viral proteins: the latent membrane protein, LMP2A, of Epstein Barr virus and the envelope protein, gp30, of bovine leukaemia virus. Interestingly, both viruses can activate infected B lymphocytes to proliferate, as does signalling by the B-cell receptor. RESULTS: In this study, we show that the cytoplasmic tails of the two viral proteins, and the cytoplasmic tail of the B-cell receptor immunoglobulin-alpha chain, when linked to CD8 in chimeric transmembrane proteins, can transduce signals in B cells. Cross-linking of these chimeric receptors activates B-cell protein tyrosine kinases and results in calcium mobilization. Furthermore, these cytoplasmic sequences are also protein tyrosine kinase substrates and may interact with cytosolic proteins carrying SH2 protein-protein interaction domains. CONCLUSION: Our findings suggest that viral transmembrane proteins can mimic the antigen-induced stimulation of the B-cell antigen receptor and thus can influence the activation and/or survival of infected B lymphocytes.

Journal Article↗
PubMed1993

Differential signaling through the Ig-alpha and Ig-beta components of the B cell antigen receptor.

The B cell antigen receptor is a complex containing the antigen-binding immunoglobulin molecules and the Ig-alpha/Ig-beta heterodimer which presumably connects the B cell antigen receptor to intracellular signaling components. To analyze the functional properties of the cytoplasmic parts of the B cell antigen receptor, we used the K46 B lymphoma line (IgG2a, kappa) to express chimeric molecules composed of the extracellular and transmembrane part of the CD8 alpha molecule and the cytoplasmic sequence of either the Ig-alpha (CD8 alpha/Ig-alpha), the Ig-beta (CD8 alpha/Ig-beta) protein or the membrane-bound gamma 2a heavy chain (CD8 alpha/gamma 2a). From these three types of chimeric molecules only (CD8 alpha/Ig-alpha and CD8 alpha/Ig-beta, but not CD8 alpha/gamma 2a, could transduce signals, thus providing the first evidence that the cytoplasmic tail of Ig-alpha and Ig-beta have a signaling capacity. After cross-linking with anti-CD8 alpha antibodies, both molecules induced a similar increase in intracellular free calcium ion and in MAP kinase phosphorylation. Protein tyrosine kinases, however, were strongly activated via the CD8 alpha/Ig-alpha and only marginally via the CD8 alpha/Ig-beta molecule. This suggests that the Ig-alpha and Ig-beta proteins have distinct roles during signal transduction through the B cell antigen receptor.

Amino Acid Sequence↗
PubMed1991

[Pharmacokinetics of articaine in mandibular nerve block].

Up to now, mandibular nerve blocks have been carried out without knowing the exact blood concentrations resulting from the use of the local anesthetics. Due to the high vascularity a rapid increase in serum local anesthetic levels is to be expected. Due to analytical problems, the literature provides controversial statements about the pharmacokinetics of articaine which is generally used for this block. The given half-life periods following intramuscular application range from 39 min [8] to 31 h [6]. For this reason, mandibular nerve blocks with 2 ml 4% articaine with 1:200,000 epinephrine were carried out in 10 awake patients and 10 patients during intubation anesthesia. RESULTS. Blood samples from peripheral veins showed an average maximum concentration of 2.1 +/- 1.3 mg/l after 12.5 +/- 2.5 min. After 8 h the value had fallen below the minimum detection limit of 0.05 mg/l. In the present study, a half-life of approximately 20 min was determined for articaine after conduction anesthesia. This local anesthetic holds an exceptional position because as an amide-type local anesthetic it contains an additional ester group that is hydrolytically metabolized in the blood. The concentration of the resulting metabolite reaches a maximum value of 2.6 +/- 1.6 mg/l after 40 to 50 min. CONCLUSIONS. Compared to other amide-type local anesthetics, whose terminal plasma half-life varies between 1 and 3.6 h [5], the value of 20 min found for articaine is very low. This is in part due to its structure, as the ester group is rapidly metabolized by plasma esterases. Because of its rapid breakdown articaine is very suitable for use in oral surgery. The HPLC method represents an uncomplicated analytical technique for the determination of local anesthetics levels in blood and other body fluids.

Carticaine↗
PubMed1988

Inspiratory pressure generation: comparison of subjects with COPD and age-matched normals.

We continuously monitored esophageal (Pes) and gastric (Pga) pressures and used these measurements in a three-component model to estimate instantaneous diaphragmatic (DIA), inspiratory accessory muscle (IAM), and postexpiratory recoil (PER) pressures at various times during inspiration. We validated our model both by volume-pressure relationships of the respiratory system (Vrc-Pga and Vab-Pga, where Vrc and Vab are the rib cage and abdominal volumes, respectively) as well as electromyography of the respiratory muscles. Measurements were carried out at rest and during graded treadmill exercise in 11 subjects with chronic obstructive pulmonary disease (COPDs) and 8 age-matched normal subjects (AMNs). AMNs were 59 +/- 2 (SE) yr and had a forced expiratory volume at 1 s (FEV1.0) of 3.6 +/- 0.2 liters; COPDs were 66 +/- 2 yr and had a FEV1.0 of 1.0 +/- 0.1 liters. We noted the following. At rest, both AMNs and COPDs exhibited an increasing DIA pressure (PDIA) across inspiratory time (TI) at rest. As expired minute ventilation increased with exercise intensity, AMNs continued to maintain this PDIA ramp across inspiration; in contrast, COPDs exhibited higher values of PDIA during the first half of TI than during the second half. At all intensities of exercise, COPDs exhibited higher IAM and PER pressures than the AMNs.

Age Factors↗
PubMed1986

Description and validation of an ECG removal procedure for EMGdi power spectrum analysis.

We describe a cross-correlation procedure for removing contaminating electrocardiogram (ECG) complexes from the diaphragmatic electromyogram (EMGdi). First, the operator selects ECG templates from the EMGdi signal during expiratory intervals. Second, these templates are used to locate ECG complexes occurring during inspiratory EMGdi activity. Third, at the point of maximum correlation between the template and these ECG complexes, the template is adjusted in size and offset to "match" the ECG complex, and adjustments are determined by the linear regression coefficients. Finally, the modified template is subtracted from the EMGdi signal. To evaluate our method, we compared the power spectral density (PSD) obtained from processing EMGdi signals by our method with those obtained from the EMGdi signal in which ECG complexes had been removed by gating. Our results indicate that PSD obtained by these two different methods shows no statistically significant differences with respect to the following features: centroid frequency, median frequency, total power, standard deviation, skewness, and kurtosis.

Analysis of Variance↗
PubMed1986

Evaluation of a ventilatory muscle endurance training program in the rehabilitation of patients with chronic obstructive pulmonary disease.

To evaluate the role of ventilatory muscle endurance training (VMET) in the rehabilitation of outpatients with chronic obstructive pulmonary disease, we carried out a prospective random allocation trial of VMET versus IPPB. Data were obtained from 15 men allocated to VMET and from 17 men assigned to IPPB. The mean age of our experimental cohort was 61 +/- SEM 1 yr, and the FEV1 was 1.2 +/- 0.1 L. Prior to and after 6 wk of daily therapy, the following data were obtained on each subject: (1) vital statistics, (2) standard pulmonary function tests, (3) activities of daily living (ADL), (4) maximal sustainable ventilatory capacity (MSVC), (5) psychologic status (PS), and (6) exercise tolerance (ET). Prior to therapy, the VMET and IPPB groups showed no significant differences with respect to these parameters. After therapy, VMET subjects exhibited a greater increase (p less than 0.05) in MSVC than did IPPB subjects. However, VMET and IPPB groups did not differ with respect to improvements noted in ADL, PS, and ET. These results from our controlled study raise the possibility that some aspect of the experimental protocol, other than VMET, accounted for the improvements noted in ADL, PS, and ET.

Adult↗
PubMed1979

Health effects of urban air pollution. Special consideration of areas at 1,500 m and above.

Urban air pollution, when sufficiently severe, can cause death in humans; these deaths occur preponderantly among those with increased susceptibility. Pollution--carbon monoxide and oxidants in particular--is capable of aggravating preexisting chronic heart and lung diseases. Pollution and tobacco (especially cigarette) smoke act synergistically in a causative role in chronic bronchitis and in an aggravating role in emphysema. Susceptibility to the effects of urban air pollution varies widely, with the most susceptible being fetuses, the newborn, the elderly, the infirm, those with chronic heart and lung diseases, and those who smoke. The carbon monoxide standards for sea level are probably too lenient for an altitude of 1,500 m and above. Using a broad definition of health, which takes into account concepts such as quality of life and social and mental well-being, few metropolitan residents would deny that their health is compromised by air that is malodorous, that irritates mucous membranes, and that obscures beautiful scenery.

Adult↗
PubMed1975

Metastatic carcinoma simulating inflammatory colitis.

Metastatic carcinoma to the colon may be mistaken for inflammatory colitis, particulary Crohn's disease, both clinically and roentgenologically. Characteristic changes include mucosal thickening, nodular masses, multiple and eccentric strictures, asymmetric involvement, pseudosacculations, and spiculations of contour. This report, based upon experience with 12 cases, establishes the distinctive roentgen features of metastatic disease to the colon from a variety of primary sites. It is shown that these changes are dependent upon pathways of spread, growth characteristics, and local tissue response. The clinical importance of making this differential diagnosis is two-fold. A patient with an occult or a known primary malignancy may present clinically with metastatic disease to the colon masquerading as inflammatory colitis. Recognition of the characteristic roentgenologic changes immediately either leads to a search for the primary neoplasm or establishes the diagnosis of widespread disease.

Adult↗