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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 307 records · Page 17Linked to original sources
PubMed1996

Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein.

Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.

Amino Acid Sequence↗
PubMed1996

Analysis of a 22,956 bp region on the right arm of Saccharomyces cerevisiae chromosome XV.

We present here the sequence analysis of a DNA fragment (cosmid pUOA1258) located on the right arm of chromosome XV. The 22,956 bp sequence reveals 14 open reading frames (ORFs) longer than 300 bp and the 201 bp RPS33 gene. Among the 14 large ORFs, two overlapping frames are likely to be non-expressed and one corresponds to the known GLN4 gene encoding glutaminyl-tRNA synthetase. Two ORFs, O3571 and O3620, encode putative transcriptional regulators with a Zn(2)-Cys(6) DNA binding domain characteristic of members of the GAL4 family. Among the nine remaining ORFs, five (O3568, O3575, O3590, O3615 and O3625) present significant similarity to proteins of unknown function and four (O3580, O3595, O3630 and O3635) lack homology to sequences present in the databases screened.

Amino Acid Sequence↗
PubMed1996

Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99).

We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.

Amino Acid Sequence↗
PubMed1996

Experimental immunotherapies for multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system (CNS) principally in young adults. Although its etiology is as yet unknown current evidence suggests that tissue damage is mediated by autoimmune T cells. The examination of an experimental animal model for MS, experimental allergic encephalomyelitis (EAE), has demonstrated that myelin basic protein (MBP)- or proteolipid protein (PLP)-specific T cells mediate the destruction of CNS myelin. In recent years, elegant studies in EAE have shown that encephalitogenic T cells recognize short peptides of MBP or PLP in the context of MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR) molecules and secrete interferon-gamma and tumor necrosis factor-alpha/beta. Understanding the pathogenetic steps in lesion development at the molecular level led to highly specific immunotherapies for EAE targeting each individual molecule. It has been the hope of many investigators that immunological events resembling those in EAE can be found in patients with MS and that the specific immunotherapies effective in EAE could also be applied to MS. However, to date, the evidence for a unique immunological abnormality in MS is not strong. Although MBP- and PLP-specific T cells with properties similar to those that are encephalitogenic in animals can be isolated from patients, they are not specific for MS and occur with similar frequency in controls. In addition, the variability in specificity and TCR usage has raised questions regarding the relevance of these cells in patients. The importance of the T cell responses to myelin antigens in MS may not be established until the effects of abrogating their activity through specific therapies targeting the trimolecular complex (TMC) have been demonstrated. Consequently, attention has begun to focus on modifying the biology of the MS lesion rather than targeting the initiating event at the level of the TMC, and the success of this approach is reflected by the effect of interferon-beta on lesion development in MS. The recent approval for the use of interferon-beta for the treatment of relapsing-remitting MS has raised great interest in examining novel strategies for immunotherapies in MS. The basic concepts as well as the current candidates for such new immunotherapies will be outlined in this short review.

Humans↗
PubMed1996

Changes in chromosomal ultrastructure during the cell cycle.

The surface structure of mitotic barley and rye chromosomes was studied by high-resolution scanning electron microscopy. Chromosomes with various degrees of chromatin condensation were prepared from untreated meristematic tissue of root tips. At lower magnifications the highly condensed chromosomes in metaphase and anaphase showed a compact structure with a smooth surface. The condensation starts from the centromeric region and the chromatids are often discernible in the still uncondensed telomeric region. Decondensation begins at the telomeric region during telophase. Parallel arrangement of fibres is a characteristic feature predominately seen in prophase and telophase chromosomes. Chromatin structures that resemble tiles on a roof or braided strands were often observed. Prophase and telophase chromosomes are particularly suitable for further studies of chromatin arrangement and organization in plant chromosomes.

Cell Cycle↗
PubMed1996

The structure of the neurofilament cytoskeleton in the squid giant axon and synapse.

Stereo views of thick sections (< 0.5 micron), or freeze etch replicas taken from selected regions of the squid giant axon and giant synapse, using an electron energy loss spectroscopic ultrastructural method, revealed a meshwork of anastomosing neurofilaments intersecting at a wide range of angles. This type of architectural organisation differs significantly from the ladder-like construction of the mammalian neurofilament cytoskeleton, in which longitudinally oriented core filaments are interconnected by lateral crossbridges. The deviant organization of squid neurofilaments is consistent with recent evidence that squid neurofilament proteins more closely resemble nuclear lamin rather than mammalian neurofilament proteins. A proximo-distal gradient of increasing width of the neurofilament meshes along the giant axon correlated well with the previously described gradient of increasing neurofilament phosphorylation. In these thick sections the presynaptic terminal of the giant synapse exhibited a mature neurofilament cytoskeleton that extended to the active zones without detectable signs of degradation. The observations are discussed in the context of current hypotheses concerned with the function of phosphorylation of neurofilaments, and with the steady state maintenance of the cytoskeleton in the squid axon and presynaptic terminal.

Animals↗
PubMed1996

Neuromuscular monitoring: does it make a difference?

PURPOSE: The objective of the present prospective study was to evaluate the influence of neuromuscular monitoring on the level of neuromuscular blockade from induction of anaesthesia until extubation of the trachea. METHODS: Forty-two patients aged between 18 and 73 yr undergoing a range of surgical procedures under general anaesthesia were randomly distributed into two groups of 21 patients each. In both groups a Datex NMT Monitor was used and electromyographic responses of the ulnar muscles to supramaximal stimulation of the ulnar nerve were recorded. In Group 1, the anaesthetist could see the movements of the stimulated hand, but not the monitor. In Group 2, the anaesthetist could see neither the stimulated hand nor the monitor. The same anaesthetist administered the neuromuscular relaxants which were succinylcholine 1.5 mg.kg-1 for tracheal intubation and vecuronium 0.1 mg.kg-1 for neuromuscular relaxation during surgery, followed by 1 to 2 mg maintenance injections. Possible residual curarization was evaluated in the recovery room by head life tests and pulse oximetry. RESULTS: Patients in Group 1 had deeper neuromuscular block throughout surgery, despite the use of a comparable dose of vecuronium (10.1 mg for G1 vs 11.2 mg for G2). The EMG values of T1 and train-of-four values were not different at tracheal intubation or at extubation. No patients presented signs of residual curarization in the recovery room. CONCLUSION: The study demonstrates that with the same amount of vecuronium the neuromuscular relaxation was deeper with the use of a simple neuromuscular monitoring (visual evaluation of the thumb movements). Despite the deeper neuromuscular block in the monitored group, there was no residual curarization in the recovery room.

Adolescent↗
PubMed1996

[Neurologic side-effects of pharmacologic corticoid therapy].

Many side effects of steroid treatment have been reported. Even experienced neurologists may not know all important side effects to the nervous system. Autonomic nervous system dysfunction, psychosis and myopathy are more frequently encountered than dependency, reversible dementia, brain atrophy and benign intracranial hypertension. This review describes symptomatology, pathogenesis and treatment of these steroid-induced side effects.

Adrenal Cortex Hormones↗
PubMed1996

Expression pattern of activation and adhesion molecules on peripheral blood CD4+ T-lymphocytes in relapsing-remitting multiple sclerosis patients: a serial analysis.

We studied the expression of various cell surface molecules (CD25, CD28, CD29, CD45RO, CD56, LFA-1, VLA-4) on peripheral blood CD4+ T-cells in 6 relapsing-remitting multiple sclerosis (RR-MS) patients. Furthermore, changes in the expression pattern of these surface markers during intervals of increased disease activity, which was measured by gadolinium (Gd-DTPA) magnetic resonance imaging (MRI) were examined. Although several patients showed signs of increased disease activity during the observation period, this was not paralleled by a relevant change in the expression of these activation and adhesion molecules.

Adult↗
PubMed1996

The antibody repertoire in experimental allergic neuritis: evidence for PMP-22 as a novel neuritogen.

Experimental allergic neuritis (EAN) is an autoimmune disease that serves as an animal model for the Guillain-Barré syndrome (GBS). In both disorders there is still great uncertainty as to the significance and diversity of autoantibodies involved. We focused on the characterization of serum antibody production in response to various peripheral nervous system (PNS) myelin proteins during the course of actively induced EAN in Lewis rats. These data were compared with EAN induced by adoptive transfer of P2-specific CD4+ T cells (AT-EAN) and with inoculation with complete Freund's adjuvant (CFA) alone. Semiquantitative Western blotting was applied to measure serum IgM and IgG titers against specific myelin proteins, including P2, P0, myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and PMP-22. Considerable differences in the dynamics of antibody titers against individual myelin proteins were observed in active EAN and after inoculation with CFA alone. Our data suggest a pathogenic role of IgM antibodies against HNK adhesion carbohydrate epitope expressing PNS proteins P0, MAG and PMP-22. Among these, PMP-22, a novel candidate neuritogen may be of particular relevance. Thus, we provide evidence for the involvement of antibody-mediated immune response in actively induced EAN and a basis for similar studies on related human disorders such as GBS or other demyelinating neuropathies.

Animals↗
PubMed1996

Blanket use of intranasal mupirocin for outbreak control and long-term prophylaxis of endemic methicillin-resistant Staphylococcus aureus in an open ward.

In December 1992, a thoracic ward in a Melbourne teaching hospital experienced an increase in patients infected with methicillin-resistant Staphylococcus aureus (MRSA). It was decided to attempt to control the outbreak by cohorting positive patients (infected and colonized), as well as nurse cohorting, emphasis on handwashing, and use of intranasal mupirocin initially three times a day for three days, then thrice weekly, for all patients in the ward (with or without MRSA). The campaign comprised for phases of 53, 45, 92 and 365 days, respectively. Patient and nurse cohorting stopped at the end of phase I. In phases I and II, surveillance nose swabs were taken on admission, then twice weekly; in phase III, on admission and weekly and in phase IV, on admission until the end of 1993. In phases I and II (98 days), only one patient acquired MRSA. When the frequency of mupirocin prophylaxis was decreased to once weekly (phase III), two patients acquired MRSA in 92 days (no significant difference): thrice weekly administration resumed (phase IV), during which there were three acquisitions in 365 days. The rates of nose colonization of admissions were 6.4%, 6.3%, 9.7% and 3.1% in phase I-IV, respectively. Only three patients were treated with vancomycin between July 1993 and June 1994 (significantly lower than historical rates, P = 0.0086). No mupirocin resistance was seen in MRSA isolates from this ward during phases I, II and III. In areas of low-level endemic MRSA, the blanket use of thrice-weekly intranasal mupirocin may be effective in decreasing serious infections with MRSA, and does not necessarily elicit mupirocin resistance.

Administration, Intranasal↗
PubMed1996

Effect of integration of injury control information into a high school physics course.

STUDY OBJECTIVE: To investigate the effects on knowledge, attitudes, and self-reported behaviors of a 1-week course of injury control and crash safety information integrated within a high school physics curriculum. METHODS: Students in an intervention high school (n=129) were compared with students in a control high school (n=74) enrolled in a comparable physics curriculum. A standardized survey was administered before instruction (time T1), and at 2 weeks (T2) and 6 months (T3) after instruction was completed. The behaviors measured were self-reported use of seat belts, speeding, drinking and driving, and intention to use seat belts in the future. RESULTS: At T2, students in the intervention group reported attitudes that were less favorable toward risk-taking in regard to speeding and seat belt use than those of the control group. At T3, there was still a difference in attitudes toward speeding but not toward seat belt use. The intervention significantly altered the knowledge level of the course participants, and these changes persisted to T3. The strongest and most persistent change was that students in the intervention group reported increasing their use of seat belts when riding as a passenger. (Seat belt use as a driver was high for both groups.) The intervention group showed a significant increase in their 1-year intentions to use seat belts both as a driver and as a passenger. CONCLUSION: This study demonstrated that driver safety education can be successfully integrated into a mainstream high school science curriculum. Future studies measuring the effects of this curriculum on observed behaviors are needed.

Accidents, Traffic↗
PubMed1996

Structure-based design of a potent transition state analogue for TEM-1 beta-lactamase.

The structure of the plasmid-mediated beta-lactamase TEM-1 has been solved in complex with a designed boronic acid inhibitor (1R)-1-acetamido-2-(3-carboxyphenyl)ethane boronic acid at 1.7 A resolution. The boronate inhibitor was designed based on the crystallographic coordinates of the acyl-enzyme intermediate of TEM-1 bound to the substrate penicillin G. The boronate-TEM-1 complex is highly ordered and defines a novel transition state analogue of the deacylation step in the beta-lactamase reaction pathway. The design principles of this highly effective inhibitor (Ki = 110 nM) and the resulting structural and mechanistic implications are presented.

Acetamides↗
PubMed1996

Light and electron microscopic immunohistochemical localization of protein gene product 9.5 and ubiquitin immunoreactivities in the human epididymis and vas deferens.

The distribution of protein gene product 9.5 (PGP) and ubiquitin immunoreactivities in the ductuli efferentes, ductus epididymidis, and ductus deferens of humans was studied by Western blot analyses and light and electron microscopic immunocytochemistry. PGP immunoreactivity was intense in the ductuli efferentes and weak in the ductus epididymidis and ductus deferens, while ubiquitin immunoreactivity was intense in the ductuli efferentes and ductus epididymidis and very weak in the ductus deferens. In the ductuli efferentes epithelium, PGP immunolabeling was observed in the cytoplasm of principal cells, whereas ubiquitin immunoreactivity was found in the nucleus and cytoplasm of principal cells and ciliated cells. In the ductus epididymidis epithelium, only scattered cells (mitochondria-rich cells) showed PGP immunoreaction in their cytoplasm, whereas ubiquitin immunostaining was detected in the nucleus and cytoplasm of most epithelial cells, except for the cauda, where ubiquitin immunolabeling was observed only in the nuclei. The ductus deferens showed no immunostaining for PGP, and only nuclear immunoreactivity to ubiquitin. The ultrastructural localization of PGP immunoreactivity was in the apical cytosol and microvilli. In addition to these locations, ubiquitin immunoreactivity was also found in the nucleus of all cell types and cilia of ciliated cells. Although the distribution of PGP and ubiquitin immunoreactivities in humans differs from that reported in rats, it seems that PGP and ubiquitinated proteins are secreted into the epididymal lumen in both species.

Adult↗
PubMed1996

Effect of proximal and distal venting during intramedullary nailing.

During intramedullary manipulation, 2 main phenomena occur. A dramatic rise in intramedullary pressure occurs followed by intravasation of damaged marrow tissue. There are concerns about the development of increased interosseous pressure during reaming and the potential for this to contribute to fat embolism syndrome. The intramedullary pressures generated with various intramedullary devices was determined and the effects of a fracture, with and without proximal and distal venting on these pressures were studied. Pressures generated in 78 embalmed anatomic specimen femurs and tibias were studied, leaving all soft tissues intact. Pressures were recorded for awl, guide rod, reamer, and nail insertion. Venting was done by creating a 4.5-mm hole in the cortex directly opposite the transducer. Proximal venting reduced proximal pressures to 80 mm Hg in the tibia (90% reduction) and 460 mm Hg in the femur (70% reduction). Distal venting reduced distal pressures to 65 mm and 30 mm in the tibias and femurs, respectively (90% reduction in pressures). Intramedullary pressures generated during nail or alignment rod insertion in anatomic specimen bone greatly exceeds the critical thresholds (150 mm Hg) thought to be responsible for fat emboli to the lung in the dogs. The introduction of a vent may reduce the chance of fat embolism. Despite the high association of raised intramedullary pressures and fat emboli in animal studies, there is no known critical threshold for humans. Therefore, although venting seems effective in reducing the intramedullary pressure in anatomic specimen bones, its efficacy in the patient with trauma remains to be determined.

Biomechanical Phenomena↗