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Biomedical subjects

R Mayer

Publications and source records attributed to R Mayer.

At least 145 records · Page 8Linked to original sources

Referrals to child psychiatry--a survey of staff attitudes.

A questionnaire study was conducted in a health district to evaluate the attitudes of paediatricians and child psychiatry staff as to which categories of problems should be referred to child psychiatry. In the majority of categories the two groups disagreed as to the frequency with which the problem should be referred. In the categories relating to child sexual abuse responses were often not in accord with Department of Health and Social Security guidelines. Reasons for not referring were also looked at and again it was found that there were a number of significant differences in opinion as to what are reasons for not referring to child psychiatry. Both groups agree that lack of communication is a reason for non-referral. Some suggestions are made as to how this problem could be addressed.

Attitude of Health Personnel↗

Malignant CD5 B cells--biased immunoglobulin variable gene usage and autoantibody production.

Malignant CD5 B cells obtained from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) were analyzed for immunoglobulin variable gene usage, CD5 gene expression and autoantibody production. A statistically significant biased usage of the VH5, VH6 and VKIII immunoglobulin variable gene families was observed. It is important to point out that both VH5 and VH6 are extremely small families which are located at the 3' extremity of the immunoglobulin variable gene locus. We determined that the transcription of the CD5 gene in T cell malignancies, CLL, SLL and a selected group of EBV transformed lines was identical. Autoantibody production was studied in a panel of heterohybridomas obtained by the fusion of CLL cells with mouse myeloma line SP2/0. A large fraction of these heterohybridomas secrete autoantibodies; some were monospecific, some bispecific and some polyspecific.

Antigens, CD↗

Two pathways of signal transduction are activated in the same cell by different cytokines.

NFS60, a murine leukemia cell line, responds to both interleukin 3 and 6 by proliferating, apparently by different signal transduction pathways. Although stimulation by both cytokines increases the uptake of 3H-arachidonic acid, the response to IL-6 was much faster. Furthermore, the effect of various arachidonic acid metabolites on the response to cytokine was different. PGE2 inhibited IL-6-induced proliferation and potentiated the response to IL-3. Additionally the G proteins which coupled the IL-3 and IL-6 receptor to the proliferative response are probably different, based on the ability of cholera toxin to inhibit the IL-3 but not the IL-6 response. These data are evidence of two pathways of signal transduction.

Animals↗

A comparative pathological study of three strains of Trypanosoma cruzi in an experimental model.

Trypanosoma cruzi, the etiological agent of Chagas' disease, shows a wide variation in its biological behaviour depending on the geographical distribution of different strains. Moreover, some strains can show variations with the course of time. We have studied the tissular tropism of three strains of T. cruzi, Cali, Bolivia and Y, from different geographical origins (Colombia, Bolivia and Brasil respectively) on Swiss mice in order to detect any possible modification in their behaviour attributable only to parasite but not to host variations. The anatomopathological study of sections from heart, brain, liver, spleen, lymphatic ganglion, skeletal muscle and colon from Swiss mice infected with these strains has evidenced the presence of some important discrepancies between the tissular tropism expected from their former descriptions, and classical typification and then observed lesions. The greatest variations were found in the Y strain which had been described as eminently reticulotropic but presented lesions in all the organs except the spleen and lymphatic ganglion. We consider that the variations found in our study can only be explained in terms of changes in the properties of the strains considered, and conclude that the classic typification techniques based on the constancy of the characteristics of the parasite are not fully reliable for the description and clinical management of some evolving strains.

Animals↗

[An underestimated forerunner: Marc-Jacob D'Espine (1806-1860) and medical statistics].

This article relates the life and work of Marc-Jacob D'Espine, a disciple of P.C.A. Louis and a somewhat unrecognised predecessor of medical statistics. Many extracts of his unpublished correspondence are given. After a short biography, the scientific work of D'Espine as well as his action to diffuse his ideas--in Switzerland as well as in foreign countries--are discussed.

History, 19th Century↗

[Esthetic adhesive filling in posterior teeth--an illusion?].

This study demonstrates once more the high caries incidence of the proximal surfaces of molar teeth. If the lesions are completely excavated so that the cervical margin is free of any caries, more than 33-57% of all cavities, depending on the type of tooth, are not suited for acid etch procedures, because there is less than 1 mm of sound enamel, or none at all. In these cases the adhesive filling technique is contraindicated.

Acrylic Resins↗

Hemodynamic effects of pressure support ventilation in cardiac surgery patients.

Hemodynamic consequences of pressure support ventilation (PSV) were compared with intermittent mandatory ventilation (IMV) in 20 patients following aortocoronary bypass. On the morning following surgery, all patients were weaned by IMV to a rate of eight breaths per minute, tidal volume of 12 ml/kg and inspired oxygen concentration of 40 per cent. With patients awake and able to breath spontaneously, PSV was begun at 20 cm of water. In patients with static lung compliance, less than 0.06 l/cm H2O, 30 cm H2O of PSV was used. Subsequently, all patients were weaned to PSV 10 cm of water, continuous positive airway pressure (CPAP) at 5 cm water and extubated. Hemodynamic data including oxygen transport were obtained at each level of PSV and at IMV prior to weaning. Analysis using ANOVA showed comparable hemodynamic and oxygen transport parameters for PSV of 30 cm H2O in comparison with IMV. PSV at levels of 20 and 10 cm H2O produced statistically significant increases in heart rate, mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure. Cardiac output was stable, and these increases were not clinically significant. In awake patients following cardiac surgery, PSV up to 30 cm H2O can be safely applied without hemodynamic embarrassment in patients with good left ventricular ejection fractions.

Blood Gas Analysis↗

The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phosphothioate derivatives.

An unusual compound, cyclic-bis(3'----5') diguanylic acid (c-di-GMP or cGpGp), is involved in the regulation of cellulose synthesis in the bacterium Acetobacter xylinum. This cyclic dinucleotide acts as an allosteric, positive effector of cellulose synthase activity in vitro (Ka = 0.31 microM) and is inactivated via degradation by a Ca2(+)-sensitive phosphodiesterase, PDE-A (Km = 0.25 microM). A series of 13 analogs cyclic dimer and trimer nucleotides were synthesized, employing a phosphotriester approach, and tested for the ability to mimick c-di-GMP as activators of cellulose synthase and as substrates for PDE-A. Seven of the synthetic compounds stimulate cellulose synthase activity and all of these activators undergo the Ca2(+)-inhibited degradation reaction. The order of affinities for synthase activators is cGpGp approximately cdGpGp approximately cGp(S)Gp (S-diastereomer) greater than cIpGp greater than cdGpdGp greater than cXpGp greater than cIpIp greater than cGp(S)Gp (R-diastereomer). Three cyclic dinucleotides of negligible affinity for either enzyme are cApAp, cUpUp, and cCpCp. This same order of affinities essentially pertains to the analogs as inhibitors of PDE-A activity, but at least one cyclic dinucleotide, cXpXp, which does not bind to cellulose synthase, is also a substrate for the degradation reaction, demonstrating that although the two enzymes share a similar, high degree of specificity for c-di-GMP, their cyclic dinucleotide binding sites are not identical. Phosphodiester bonds of activators in which an exocyclic oxygen is replaced with an atom of sulfur (cGp(S)Gp isomers) resist the action of PDE-A, and such derivatives may be prototypes for synthetic non-hydrolyzable c-di-GMP analogs.

Allosteric Regulation↗

Germline V genes encode viable motheaten mouse autoantibodies against thymocytes and red blood cells.

Autoantibodies against thymocytes and RBC may contribute to the pathophysiology of homozygous viable motheaten (mev) autoimmune disease. Whether the production of these autoantibodies in mev mouse results from polyclonal nonspecific B cell activation or specific Ag-driven stimulation is not known. To understand the mechanisms involved in the induction of antithymocyte autoantibody response in mev mouse, we have studied the fine antigenic specificity, structure, and origin of three antithymocyte autoantibodies derived from mev splenic B cell hybridomas. Western blot analysis showed that these mAb bind to polypeptides of 33 and 105 kDa present in RBC and thymocytes, respectively. Additional specificities for the epitopes present in other polypeptides distinguished these three autoantibodies. Northern hybridization and flow microfluorimetry analysis indicated that these hybridomas are derived from the Ly1+ B cell subset. These autoreactive Ly-1 B cell hybridomas, chosen on the basis of their specificity, expressed L chain V genes from a single VK family (VK9) and VH genes from J606 and S107 families. Hybridomas UN34.11 and UN42.5 expressed the VK9 gene identical to that used by peritoneal Ly1+ B cells from various mouse strains and malignant B lymphoma cells secreting anti-mouse RBC treated with proteolytic enzyme bromelin and anti-SRBC antibodies. The third hybridoma, S2-14.2, used a VK9 gene identical to that expressed by MOPC41. None of the VK genes encoding these autoantibodies showed any somatic mutations. In the case of VH genes, the two hybridomas UN42.5 and S2-14.2 derived from two separate fusions, used identical VH genes from the J606 family. The third hybridoma UN34.11 used unmutated V11 germline VH gene, a member of the S107 family. Southern hybridizations, using oligonucleotide probes specific for CDR1 and CDR2, showed that the VH genes encoding the J606 autoantibodies were derived from a germline gene found in the 6.7-kb fragment of EcoRI-digested germline DNA. This germline VH gene is distinct from VH22.1 germline gene that codes for antigalactan antibodies. Sequence analysis of this gene showed perfect homology with the rearranged VH genes confirming the lack of somatic mutations. Thus, our data demonstrate that antithymocyte antibody response occurring in mev mouse is polyclonal and it involves Ly-1 B cells expressing unmutated germline VH and VK genes. These results indicate that antigen driven stimulation may not play an important role in the induction of anti-thymocyte antibody response in mev mouse.

Animals↗

Identification of a new V kappa gene family that is highly expressed in hybridomas from an autoimmune mouse strain.

We have identified a new murine V kappa family that contains five to seven members, one member of which encodes the L chain V region of an anti-dsDNA antibody produced by a BALB/c hybridoma, C8.5. The cloned C8.5 V kappa gene exhibits highest homology with a human V kappa gene that was cloned from a nonproductive rearrangement but has never been seen in an expressed repertoire. Because this family was first identified in an autoantibody, we studied its expression in an autoimmune mouse strain. This V kappa family is expressed in 20% of hybridomas from NZB mice.

Amino Acid Sequence↗

CD5 and immunoglobulin V gene expression in B-cell lymphomas and chronic lymphocytic leukemia.

We studied the expression of CD5 and immunoglobulin variable gene families in a panel of monoclonal Epstein-Barr virus (EBV) transformed lines, chronic lymphocytic leukemias (CLLs) and CD5+ and CD5- B-cell lymphomas. The CD5 gene expression was in all cases identical to that of T-cell malignancies. The utilization of the various VH and VK gene families was roughly proportional to the estimated gene family size in EBV lines obtained from adult healthy subjects. In contrast we found a statistically significant biased usage of VH6 in CLL and VH5 in CD5+ lymphomas as compared with EBV lines, and of VKIII in both CLL and CD5+ lymphomas as compared with EBV lines. Some differences in the variable gene usage were also noted when comparing CD5+ and CD5- lymphomas. These findings are analyzed in the context of possible mechanisms involved in the malignant transformation of CD5+ B cells.

Antigens, CD↗

Autoantibodies, LY-1, and immunoglobulin V gene expression in hybridomas obtained from young and from old New Zealand black mice.

We obtained a large number of hybridomas from 1-month-old and 16-month-old New Zealand black mice to study the fine specificities of the autoantibodies produced, the expression of Ly-1, and the expression of the immunoglobulin V gene families in this autoimmune strain. Analysis of the autoantibody specificities yielded 2 major classifications: those specific for a single autoantigen and those that exhibited multispecific binding. Among the multispecific antibodies, 2 categories were found: an antigen-inhibitable group and an antigen-noninhibitable group. A large proportion of VHJ558 and VH7183 gene families was observed in hybridomas obtained from 1-month-old mice, and in hybridomas obtained from 16-month-old mice, there was a large proportion of VHJ558 and VH36-60 gene families. Among the autoantibody kappa chains secreted by the hybridomas, there was a higher frequency of the V kappa 1, V kappa 8, and V kappa 9 gene families. Autoantibodies were produced by both the Ly-1+ and the Ly-1- B cell subsets.

Age Factors↗

Lung damage from exposure to the fields of an electrohydraulic lithotripter.

Threshold pressures for hemorrhage in mouse lung exposed to the fields of an electrohydraulic lithotripter appear to be less than 2 MPa with as few as 10 pulses and with severe damage occurring at levels between 5 and 6 MPa. This is very much smaller than the fields required to fragment kidney and gallstones and smaller than the thresholds for damage to kidney tissues. Fetal lung, in contrast, did not show signs of damage at 20 MPa. The lower sensitivity of fetal lung is consistent with a cavitation-related mechanism for lung damage by shock waves. Since the pressures in these exposures are almost entirely positive, it suggests that the value of negative pressures as predictors of the behavior of gas bodies in tissues should be reconsidered.

Animals↗

Test for kidney hemorrhage following exposure to intense, pulsed ultrasound.

A recent study has found that the threshold for extravasation in mouse kidney tissues by exposure to a spark-generated shock wave is of the order of 3-5 MPa (peak positive pressure). Since the mode pressure used by commercial pulsed Doppler ultrasound units is approximately 5 MPa, it is essential to determine whether these observations are relevant to diagnostic ultrasound. Hence, a comparable study has been completed using the same pathological endpoints but with exposure to pulsed ultrasound (10 microseconds pulse length) at 1.2 MHz and 3.8 MHz in which peak positive pressures exceeded 10 MPa. At these levels the focal waves are in shock because of the nonlinear properties of the propagating medium. The results of the pulsed ultrasound study were negative. Although this finding is encouraging for the use of diagnostic ultrasound, the two studies eventually must be integrated into a single mechanistic picture before the limits of safety will be known.

Animals↗