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Biomedical subjects

T Winkler

Publications and source records attributed to T Winkler.

At least 73 records · Page 4Linked to original sources
PubMed1994

Naloxone reduces alterations in evoked potentials and edema in trauma to the rat spinal cord.

The influence of naloxone (an opioid receptor antagonist) on spinal cord conduction and edema formation as a result of trauma to the cord was investigated in a rat model. The spinal cord injury (SCI) was inflicted in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of the T10-11 segments, about 2 mm deep and 5 mm long. Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. The edema was measured by determining water content of the cord at s h after injury. In rats not given naloxone SCI resulted in an immediate long-lasting depression of the rostral maximal negative peak (MNP) amplitude (about 60%) and a significant increase in the latency of the rostral maximal positive peak (MPP). Pretreatment with naloxone inhibited the immediate post-injury decrease of the rostral MNP and some of the increase of MPP latency. The water content in the traumatized spinal cord was reduced by 3% in naloxone treated animals compared with untreated injured controls. Our results indicate that endogenous opioid peptides participate in changes of spinal cord conduction after trauma and influence edema formation probably via multiple opioid receptors.

Afferent Pathways↗
PubMed1994

Expansion of a B-lymphocyte clone producing IgM auto-antibodies encoded by a somatically mutated VHI gene in the spleen of an autoimmune patient.

Seventy-six human B-cell hybridomas were obtained by fusing B lymphocytes from the spleen of a patient with chronic idiopathic thrombocytopenia (ITP). Two independent hybridoma clones producing IgM autoantibodies reacting with platelets and other antigens from both the internal and the external environments were established from this fusion experiment. The IgM autoantibodies produced by the two hybridoma clones were found to be encoded by identical VHDJH and VLJL genes. The comparison of the VHI gene expressed in both hybridomas with the germline equivalent cloned from the patient's DNA showed two somatic mutations in the complementarity-determining regions CDR1 and CDR2 resulting in amino acid replacements. These data suggest the selection and expansion of an autoantibody-producing B-cell clone in the spleen of an ITP patient, probably as a result of (auto)antigen-driven stimulation.

Adolescent↗
PubMed1994

Opioid receptors influence spinal cord electrical activity and edema formation following spinal cord injury: experimental observations using naloxone in the rat.

The possibility that opioid peptides participate in alteration of spinal cord conduction following trauma to the cord was investigated in a rat model using a pharmacological approach. Spinal cord injury was produced in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of T10-11 segments (2 mm deep and 5 mm long). Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. SCEP from both rostral and caudal segments consisted of a small positive peak followed by a high negative peak. Infliction of trauma in untreated rats resulted in an immediate depression of the rostral maximal negative peak (MNP) amplitude. This depression was long-lasting. Later, a significant increase in the latency of the rostral MNP amplitude occurred. Naloxone was administered in a high dosage (10 mg/kg, i.p.) to block mu-, delta- and kappa-opioid receptors 30 min before injury. This drug treatment inhibited the immediate post-injury decrease of the rostral MNP amplitude without any significant effect on latency changes. Measurement of water content in the traumatized spinal cord segment showed a significant reduction in the drug treated animals 5 h after trauma (71.46 +/- 0.54) as compared with untreated controls (74.65 +/- 0.76). However, 1 mg or 5 mg/kg dosages of the drug were not effective in reducing the SCEP changes or edema after injury. These results strongly suggest that blockade of kappa-opioid receptors with high doses of naloxone is important in reduction of trauma induced alteration of SCEP and edema formation in spinal cord injury.

Animals↗
PubMed1994

Epitope-specific distribution of IgG subclasses against antigenic domains on glycoproteins of human cytomegalovirus.

The IgG subclass pattern against linear antibody binding sites on glycoproteins of human cytomegalovirus (HCMV) was investigated in HCMV-positive healthy blood donors, human immunodeficiency virus-infected persons, sera from mothers with primary HCMV infection during pregnancy and their children, and sequential sera from transplant recipients. As antigens, three immunodominant domains capable of inducing neutralizing antibodies during natural infection were selected on glycoproteins gp58/116 (gB) and gp86 (gH). Bacterial fusion proteins representing these regions were used as antigens in a subclass-specific ELISA. Reactivity against the antibody binding site on gp86 was detected in both the IgG1 and IgG3 subclasses. In contrast, exclusively IgG1 antibodies were found against both linear domains on glycoprotein complex gp58/116 and also against full-length gp58/116 expressed in insect cells. The data demonstrate a differential regulation of the antibody response to envelope components of HCMV.

AIDS-Related Opportunistic Infections↗
PubMed1994

Roles of IgH and L chains and of surrogate H and L chains in the development of cells of the B lymphocyte lineage.

Proteins expressed from productively rearranged H and L chain gene loci have been implied in the regulation of Ig gene rearrangements during B lymphopoiesis. However, recent findings suggest that early B cell development can occur without expression of surrogate L chain, without deposition of microH chains into membranes, without productive H chain gene rearrangements, and even without any rearrangements of Ig gene loci. In bone marrow, 2-5% of all B220-, sIgM-, c-kit+ cells are pro B cells that undergo differentiation from B220- via B220+, c-kit+, CD43+, clonable long-term proliferating pre B-I cells to B220+, c-kit-, CD43-, IL-2 receptor+ pre B-II cells and immature B cells, only to die by apoptosis in situ within less than 4 days. A membrane-bound complex of surrogate H chain (gp130/gp35-65) and surrogate L chain expressed on pro B and pre B-I cells has apparently no influence on this early development. Pre B-I cells carrying DHJH-rearrangements in reading frame (rf) II are counter-selected, probably because they can express an Ig-like complex of truncated DHJHC mu-protein and surrogate L chain, while pre B-I cells DHJH-rearranged in rf I or III are not suppressed. Immature sIg+ B cells, also from bcl-2 transgenic mice, can continue to rearrange L chain gene loci. Thus, mere membrane deposition of Ig, even with concomitant expression of bcl-2, terminates neither expression of RAG-1 and 2, nor secondary L chain gene rearrangements, nor does it allow the development of mature B cells. Membrane-bound expression of an Ig-like complex of microH chains and surrogate L chains appears to be needed to generate the 50-70 million pre B-II cells in bone marrow. However, the membrane-bound expression of Ig is mandatory for negative and positive selection of immature B cells. Autoantigens delete or anergize self-reactive B cells. We speculate that all mature, resting, primary antigen-reactive B cells in the periphery have been selected from immature sIg+ B cells by unknown antigens and have, thereby, changed their lifestyle from rapid death by apoptosis to longevity.

Animals↗
PubMed1993

Independent expression of the transforming amino-terminal domain of SV40 large I antigen from an alternatively spliced third SV40 early mRNA.

We found that simian virus 40 (SV40), in addition to the SV40 early proteins large T antigen (large T) and small antigen (small t), codes for a third early protein with a molecular weight of 17 kDa. This protein (17kT) is expressed from an alternatively spliced third SV40 early mRNA, using a splice donor site at position 4425 and a splice acceptor site at position 3679 of the SV40 genome. The 17kT protein consists of 135 amino acids. Of these, 131 correspond to the amino-terminus of large T, while the four carboxy-terminal amino acids are unique and encoded by a different reading frame. 17kT mRNA, and the corresponding protein, were found in all SV40 transformed cells analyzed, as well as in SV40 infected cells. Transfection of a cDNA expression vector encoding the 17kT protein into rat F111 fibroblasts induced phenotypic transformation of these cells. The expression of the transforming amino-terminal domain of large T as an independent 17kT protein might provide a means for individually regulating the various functions associated with this domain.

Alternative Splicing↗
PubMed1993

Indomethacin, an inhibitor of prostaglandin synthesis attenuates alteration in spinal cord evoked potentials and edema formation after trauma to the spinal cord: an experimental study in the rat.

The potential efficacy of indomethacin (a potent inhibitor of endogenous prostaglandin synthesis) on spinal cord-evoked potentials and edema formation occurring after a focal trauma to the spinal cord was examined in a rat model. The spinal cord evoked potentials were recorded in urethane-anesthetized male rats using monopolar electrodes placed epidurally over the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral right tibial and sural nerves. Reference electrodes were placed in the corresponding paravertebral muscles. The spinal cord evoked potential consisted of a small positive peak followed by a broad and high negative peak. Amplitudes and latencies of the maximal positive peak and the maximal negative peak were measured. The latencies and amplitudes 30 min before injury were used as references (100%). A complete loss was denoted as 0%. All the potentials were quite stable during 30 min of recording before injury. Infliction of trauma to the T10-T11 segments of the spinal cord with a sterile scalpel blade (about 5 mm longitudinal and 2 mm deep incision into the right dorsal horn extending to Rexed's laminae VII) in untreated animals resulted in an immediate depression of the rostral maximal negative peak amplitude (60-100%) which persisted during 5 h of recording. The latencies of the rostral as well as caudal maximal negative and positive peaks increased successively from 2 h post-trauma. In this group of animals, 5 h after injury the spinal cord water content in the traumatized segments was increased by more than 6% as compared with a group of uninjured animals. Pretreatment with indomethacin (10 mg/kg body weight i.p. 30 min before injury) markedly attenuated the immediate decrease in the maximal negative peak amplitude after injury, but did not influence the successive latency increase. However, the increase in the water content of the traumatized cord after 5 h was less pronounced compared with untreated injured rats. Our results show a beneficial effect of indomethacin on trauma-induced spinal cord evoked potential changes and edema formation. Prostaglandins may thus influence early bioelectrical changes occurring in traumatized spinal cord not reported earlier. The findings support the view that early recording of spinal cord evoked potential may be useful to predict the outcome in some forms of spinal cord injuries.

Analysis of Variance↗
PubMed1992

Cardiopulmonary bypass for resuscitation of patients with accidental hypothermia and cardiac arrest.

Hypothermic patients have been successfully rewarmed by a number of methods. However, when cardiac arrest occurs, as it frequently does at core temperatures of less than 27 degrees C, prolonged cardiopulmonary resuscitation (CPR) is required, because defibrillation can rarely be achieved until the patient has been rewarmed to 30 degrees to 34 degrees C. Five cases of accidental hypothermia with cardiac arrest treated with cardiopulmonary bypass are discussed. The first patient died as a result of inadequate low-flow cardiopulmonary bypass by the femorofemoral route. The second patient had prolonged CPR by closed-chest cardiac massage and warm peritoneal lavage followed by transthoracic cardiopulmonary bypass. This patient regained consciousness but was found to be paraplegic and died from bowel infarction related to peritoneal rewarming without adequate perfusion. In the last three patients, high-flow cardiopulmonary bypass was rapidly achieved using a no. 28 French chest tube for femoral venous cannulation, and they recovered completely. In cases of accidental hypothermia with cardiac arrest, rapid institution of full cardiopulmonary bypass provides excellent circulatory support and rapid rewarming. This avoids the complications of prolonged inadequate circulation that occur when closed-chest cardiac massage and external rewarming are used.

Adult↗
PubMed1991

Uni- and bipolar surface recording of human nerve responses.

Nerve conduction studies are of great clinical value in diagnosing nerve pathology and injury. In most neurophysiological laboratories nerve conduction recordings are routinely made with surface bipolar electrodes. More rarely, needle electrodes are used. A bipolarly recorded nerve action potential (NAP) is the difference between 2 unipolar NAPs recorded from each pole of a bipolar electrode and a remote reference. The delay between the 2 separated unipolar NAPs depends on the distance between the poles and the conduction velocity (CV). When the delay between the unipolar NAPs was increased (partly through simulation), the following changes of the bipolar NAP occurred: (1) total amplitude was maximal at a certain delay but decreased if the delay was shorter or longer, (2) latencies of the first positive and the first negative peaks increased slightly until their amplitudes reached maximal values, (3) a second negative peak of increasing latency appeared with longer delays, (4) latencies of later peaks increased linearly, and (5) total area increased nonlinearly. All parameters of the bipolarly recorded NAP (except the onset of the first positive phase) changed with increasing delay. The significance of this is that if NAPs are recorded with a bipolar electrode, standard values obtained for each nerve cannot be transferred between laboratories if different interelectrode (interpolar) distances are used. Furthermore, the assumption that a fixed interelectrode distance allows comparisons between reference values and patient data is incorrect.

Action Potentials↗
PubMed1991

Evaluation of traumatic spinal cord edema using evoked potentials recorded from the spinal epidural space. An experimental study in the rat.

Spinal cord evoked potentials (SCEP) elicited by simultaneous distal tibial and sural nerve stimulation were continuously recorded from the epidural space at the T9 and T12 levels of urethane anaesthetized rats before and after a unilateral incision (about 3 mm deep and 5 mm long) in the right dorsal horn of the T10-11 segments. The changes in SCEP were correlated with the increase in spinal cord water content measured 5 h after injury. In addition, the influence of serotonin (5-HT) in mediating such changes was explored using a pharmacological approach. The changes in SCEP immediately after injury correlated well with development of spinal cord edema measured 5 h after injury. Thus, the maximal negative peak (MNP) amplitude of SCEP decreased by an average of 64.0% immediately after injury and the water content of the spinal cord was increased from 71.6% (controls) to 77.6% 5 h after injury. Pretreatment with p-CPA (a serotonin synthesis inhibitor) prevented the initial decrease of the MNP amplitude and also the increase of water content (72.5%). On the other hand, pretreatment with cyproheptadine (a 5-HT2 receptor antagonist) enhanced both the initial decrease of the MNP amplitude as well as the increase of water content (81.3%). The results show a good correlation between changes of SCEP immediately after injury and the magnitude of spinal cord edema (r = 0.9) measured 5 h after injury. The findings reveal a major role of serotonin in mediating early changes of SCEP and later development of spinal cord edema and demonstrate a prognostic value of early SCEP recordings in predicting the final outcome of traumatic spinal cord injuries.

Animals↗
PubMed1991

Human anti-mouse antibody response induced by anti-CD4 monoclonal antibody therapy in patients with rheumatoid arthritis.

The development of human anti-mouse monoclonal antibodies (HAMAs) was investigated in 10 patients with rheumatoid arthritis (RA) who had undergone an experimental therapeutic trial with an anti-CD4 monoclonal antibody. In this patient group, the antibody 16H5 of the IgG1 isotype had been administered in a median total dosage of 140 mg per treatment cycle. Four patients took part in a second treatment regimen 6-8 weeks later. After the first treatment cycle, detectable HAMAs developed in 5 out of 10 patients. In 4 individuals undergoing a second course of therapy, increases of HAMAs were evident only in the 3 patients with previous HAMA responses. HAMAs were primarily of the IgG isotype, while the presence of rheumatoid factors usually interfered with the detectability of IgM HAMAs. However, using isolated F(ab)2 fragments of the monoclonal reagent used for therapy, HAMAs of the IgM isotype were also detectable. HAMAs of the IgG isotype did not exceed levels of 2.0 mg/liter after a single treatment cycle and 2.2 mg/liter after a repeated cycle. No IgE responses were detectable. Absorption experiments indicated that approximately 25% of the HAMA activity was directed against specific determinants of the 16H5 monoclonal antibody, presumably including anti-idiotypic reactivities. These data demonstrate that HAMAs developed only in a proportion of RA patients treated with the anti-CD4 monoclonal antibody 16H5. However, the amounts were rather low compared to other monoclonal reagents used in cancer patients and were therefore allowed for repeated applications without an apparent loss of efficacy.

Antibodies, Monoclonal↗
PubMed1990

Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.

Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.

Administration, Oral↗
PubMed1988

Surface anodal stimulation of human peripheral nerves.

Bipolar surface stimulation of human peripheral nerves with short square pulses elicits action potentials in the A-alpha fibers at the beginning of the stimulus pulse both at the cathode (cathodal stimulation) and simultaneously in a hypopolarized region surrounding the anode (anodal stimulation). When recording with a bipolar surface electrode on the "anodal side" of the stimulating electrode a stimulus of medium strength gives a double peak response of submaximal amplitude. The peak with long latency is generated by the cathode and the peak with short latency by the anode. With a strong stimulus and recording on the "anodal side" only the short latency peak (with a maximal amplitude) is recorded. With a weak stimulus only the long latency peak (with a submaximal or maximal amplitude) is seen. These findings have importance in standard neurography investigations since mistakes concerning the polarity of the stimulating electrode affect the calculation of latencies, nerve conduction velocities, F-responses and SEPs. A nerve action potential with dual peaks may also be mistaken as a sign of anomalous innervation or activation of nerve axon subpopulations.

Action Potentials↗
PubMed1988

A new metabolite of diclofenac sodium in human plasma.

1. Among the phenolic metabolites of diclofenac in human plasma, an unknown compound (metabolite VI) was detected by h.p.l.c. and g.c. methods. This was also found in baboon plasma. 2. Metabolite VI was identified as 3'-hydroxy-4'-methoxy diclofenac by mass and n.m.r. spectroscopic analysis. Comparison with synthetic reference compound confirmed its structure. 3. In plasma, metabolite VI persists much longer than do unchanged diclofenac and the other phenolic metabolites. In urine, metabolite VI and its conjugates are excreted in trace amounts only. 4. A synthetic sample of metabolite VI was shown to be virtually inactive in animal models of inflammation and pain.

Adult↗