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Biomedical subjects

M Schubert

Publications and source records attributed to M Schubert.

At least 91 records · Page 5Linked to original sources
PubMed1996

Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles.

The use of Moloney murine leukemia virus (Mo-MLV)-based vectors to deliver therapeutic genes into target cells is limited by their inability to transduce nondividing cells. To test the capacity of HIV-based vectors to deliver genes into nondividing cells, we have generated replication-defective HIV type 1 (HIV-1) reporter vectors carrying neomycin phosphotransferase or mouse heat stable antigen, replacing the HIV-1 sequences encoding gp160. These vectors also harbor inactive vpr, vpu, and nef coding regions. Pseudotyped HIV-1 particles carrying either the ecotropic or the amphotropic Mo-MLV envelope proteins or the vesicular stomatitis virus G protein were released after single or double transfections of either human 293T or monkey COS-7 cells with titers of up to 10(7) colony-forming units per milliliter. A simple ultrafiltration procedure resulted in an additional 10- to 20-fold concentration of the pseudotyped particles. These vectors along with Mo-MLV-based vectors were used to transduce primary human skin fibroblasts and human peripheral blood CD34+ cells. The HIV-1 vector system was significantly more efficient than its Mo-MLV-based counterpart in transducing human skin fibroblasts arrested at the G0/G1 stage of the cell cycle by density-dependent inhibition of growth. Human CD34+ cells were transduced efficiently using HIV-1 pseudotype particles without prior stimulation with cytokines.

Animals↗
PubMed1996

Human evoked potentials to long duration vibratory stimuli: role of muscle afferents.

Tonic vibratory stimuli of 1000 ms duration and different frequencies were delivered to muscles of the forearms of young human subjects. Evoked potentials (EPs) were recorded from 29 scalp channels and revealed phasic highly lateralised and focally distributed EPs during the first 100 ms of the recording epoch that could be adequately modelled with a single point dipole source located in the vicinity of the central sulcus contralateral to the stimulated arm. A later negativity with an onset of about 400 ms and a duration of about 800 ms was found to be symmetrically distributed over fronto-central regions. This negativity is interpreted in terms of cortical activation beyond the primary sensory fields and could be related to the kinaesthetic phenomena experienced during muscle vibration.

Adult↗
PubMed1996

Muscle fatigue, lactate, and pyruvate in mitochondrial myopathy with progressive external ophthalmoplegia.

We studied muscle fatigue and serum lactate and pyruvate levels in 20 patients with mitochondrial myopathy with progressive external ophthalmoplegia (PEO). Fatigue was assessed in the adductor pollicis muscle (AP) using a low-intensity exercise protocol (20 min). Forces (TFs) and relaxation times of ulnar nerve evoked twitches, compound muscle action potentials (CMAPs), and maximal voluntary contractions (MVCs) were monitored. Serum lactate and pyruvate levels were independently measured at rest and after exercise on a bicycle (15 min, 30 W). Most patients showed abnormal fatigue of the AP with a reduction of TFs and MVCs and normal CMAPs. The reduced TFs were significantly correlated with lactate levels at rest (r= - 0.60, P<0.05) and less so with those after exercise (r=- 0.47,P<0.05). Pyruvate levels revealed a similar correlation although they were widely scattered. We conclude that abnormal fatigue in PEO is metabolic, is localized beyond the muscle fiber membrane, and involves the electrome-chanical coupling and the contractile apparatus. Serum lactate levels at rest are good predictors of fatigue in PEO.

Action Potentials↗
PubMed1996

Early detection of metastasis by alterations in the cellular immune system in the murine liver and blood.

We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor alpha. The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.

Animals↗
PubMed1996

Functional gliding spaces of the dorsal side of the human finger.

Although the clinical and functional importance of gliding and connective tissue spaces has been repeatedly emphasized (e.g. their role in the spreading of suppurative phlegmonic inflammation) only few literary findings can be presented dealing with the connective tissue spaces in the finger in the metacarpo-phalangeal transition region. Three separate gliding spaces of the finger above the dorsal aponeurosis and their various regional connections can be displayed by means of a plastic injection technique followed by plastination and production of sectional series. These gliding spaces were also examined on fixed and unfixed hands using plastic injection and subsequent dissection. A space was depicted between the proximal interphalangeal joint and the insertion of the dorsal aponeurosis on the distal phalanx of the finger, as well as a further bursa-like space over the proximal interphalangeal joint. A third space was also depicted between the metacarpophalangeal joint and the proximal interphalangeal joint, which displays a variable connection to the gliding canal of the respective extensor tendons. Methodical, functional and clinical aspects will be discussed.

Cadaver↗
PubMed1996

Mononeuropathia multiplex and idiopathic intracranial hypertension.

A young obese woman with menstrual irregularities presented with bilateral papilledema, abducens nerve paresis, visual obscurations and severe headache. Neuroimaging studies were normal but CSF opening pressure was elevated. The diagnosis of idiopathic intracranial hypertension was made. Insertion of a shunt quickly alleviated the symptoms. A few weeks later the patient developed a left femoral nerve paresis and an ulnar nerve paresis on the right. Electrodiagnostic tests confirmed the diagnosis of mononeuropathia multiplex. Bone marrow histology showed a vasculitis. We hypothesize that the vasculitis is underlying both, idiopathic intracranial hypertension and mononeuropathia multiplex.

Adult↗
PubMed1996

[Recruitment detection--a comparison of category loudness scaling and classical supra-threshold audiometry].

BACKGROUND: The assessment and localization of hearing impairments require reliable and valid recruitment indicators. Although many diagnostic tests are available, which of these tests are most important is still the subject of controversy. METHOD: To compare the efficacy of various diagnostic audiometric tests, 51 subjects with monaural sensorineural hearing loss were submitted to the following tests at 500 and 2000 Hz: category loudness scaling of narrowband noise bursts, alternate binaural loudness balance (ABLB), intensity difference limen test, SISI test, fixed frequency Békésy audiometry, and contralateral determination of the acoustic reflex threshold for pure tones. RESULTS: Using the findings of the ABLB test as reference, the results of the present study revealed that category loudness scaling and acoustic reflex audiometry are reliable quantitative recruitment indicators. This holds for the intensity difference limen test to a lesser extend as well. However, the recruitment selectivity of the SISI test and Békésy audiometry turned out to be considerably poorer. CONCLUSIONS: Category loudness scaling has proven to be a valuable element in the conventional recruitment test battery particularly for patients with symmetrical hearing loss. Therefore, category loudness scaling, ABLB test (when feasible), acoustic reflex measurement, and to a lesser extend the intensity difference limen test should be given the highest priority when selecting appropriate diagnostic audiometric tests. The efficacy of the SISI test and Békésy audiometry should be comprehensively reevaluated on the basis of expanded data. Until such material is available and a final judgement of the clinical value is possible, both these tests should be used and interpreted carefully.

Audiometry, Pure-Tone↗
PubMed1996

Adaptive fitting of hearing instruments by category loudness scaling (ScalAdapt).

The introduction of programmable as well as non-linear hearing instruments has shown that audiogram-based fitting procedures are inappropriate for meeting the individual needs of hearing aid users with sensorineural loss. Particularly the present and future development of hearing instruments with advanced analog and digital signal processing requires suitable fitting procedures. In this context, we developed an adaptive fitting strategy (ScalAdapt) using category loudness scaling. In this paper the procedure is described and tested using programmable 3-channel AGC instruments. However, it can be modified for any other hearing aid design. The underlying idea is to normalize the aided loudness perception for two input levels, one around the most comfortable level (MCL) and the other just below the uncomfortable level (UCL), as anchor points in each channel by interactive fine-tuning of the fitting parameters (channel gain, compression onset, compression ratio, etc.). The benefits of ScalAdapt have been evaluated by a field test study in 17 experienced hearing aid users. The results showed that ScalAdapt provides consistently higher objective (speech recognition in noise) and subjective benefits (self-assessment inventory) than for instance NAL-based fittings.

Hearing Aids↗
PubMed1995

Short term synchronization of human motor units and their responses to transcranial magnetic stimulation.

1. The voluntary discharge characteristics, short term synchronization, coherence and responses to transcranial magnetic stimulation of a sample of twenty-two pairs of simultaneously recorded low threshold motor units in the right human first dorsal interosseus muscle have been determined. 2. Peristimulus time histograms and cumulative sums (cusums) of motor unit discharge showed either excitatory or inhibitory responses to cortical stimuli. Over the whole motor unit sample, the primary excitatory response had a mean onset of 24.6 ms and the inhibitory response a mean onset of 31.0 ms. Responses of pairs of motor units to magnetic stimulation could be dissimilar; at some stimulus intensities one of the motor unit pair could be excited by the stimulus whilst the other was inhibited. 3. Most pairs of motor units showed short term synchrony in their voluntary discharge, but the same motor units driven by magnetic cortical stimuli showed little tendency to discharge together more frequently than would be predicted from their independent behaviour. This held true for discharges in both the early primary excitatory peak and in the later secondary peak in peristimulus time histograms. 4. Series of magnetic stimuli, causing either excitation or inhibition of individual tonically active motor units, had no effect on the size of the central peak of the cross-correlogram of the motor unit pair. However, frequency analysis of pairs of motor unit spike trains showed an increase in coherence in the 16-32 Hz band during magnetic stimulation. 5. It is concluded that, whilst many corticospinal fibres branch extensively within motoneurone pools, there are also fast conducting corticomotoneuronal fibres allowing the independent monosynaptic activation of individual motoneurones. 6. It is also suggested that during sustained voluntary tonic activity, magnetic stimuli applied to the brain can increase the synchrony in common input fibres to pairs of motoneurones.

Adult↗
PubMed1995

Morphology of the dorsal phalangeal connective tissue body.

BACKGROUND: The connective tissue body of the dorsal finger is partitioned by multiple horizontal lamellae derived from expansions of intercellular spaces. These connective fibres are involved in providing gliding spaces for the extensor apparatus, and they formed spreading rooms of infection processes. METHODS: In order to describe the topographical histological and histochemical behavior of cellular and intercellular elements of the border lamellae of the dorsal aponeurosis of the fingers, a modified method of Epoxid resin embedding technique without pre-infiltration is used. RESULTS: The bordering elements of the connective tissue lamellae described in this investigation are especially well defined in the region of the dorsal aponeurosis. The morphological examinations show that both the expansions of the intercellular space as well as defined fibrocytic cellular elements function in a manner equivalent to a synovial membrane of tendon sheaths. CONCLUSIONS: Saving or reconstructing these structures appears to be of importance in preventing for adhesive disorders of finger motion following surgical intervention in this region.

Aged↗
PubMed1995

Inducible and conditional inhibition of human immunodeficiency virus proviral expression by vesicular stomatitis virus matrix protein.

Besides its role in viral assembly, the vesicular stomatitis virus (VSV) matrix (M) protein causes cytopathic effects such as cell rounding (D. Blondel, G. G. Harmison, and M. Schubert, J. Virol. 64:1716-1725, 1990). DNA cotransfection assays demonstrated that VSV M protein was able to inhibit the transcription of a reporter gene (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). We have confirmed these observations by using cotransfections with an infectious clone of human immunodeficiency virus type 1 (HIV-1) and found that the amino-terminal 32 amino acids of M protein which are essential for viral assembly were not required for this inhibition. For the study of the potential role of M protein in the shutoff of transcription from chromosomal DNA, we have isolated stable HeLa T4 cell lines which encode either a wild-type or a temperature-sensitive (ts) VSV M gene under control of the HIV-1 long terminal repeat promoter. Transcription of the M mRNA was transactivated after HIV-1 infections. A cell line which encodes the wild-type M protein was nonpermissive for either HIV-1 or HIV-2. A cell line that encodes the ts M gene was transfected with the infectious HIV-1 DNA or was infected with HIV-1 or HIV-2. In all cases, at 32 degrees C, the permissive temperature for M protein, the cells were nonpermissive for HIV replication. At 40 degrees C, the ts M protein was nonfunctional and both HIV-1 and HIV-2 were able to replicate at high levels. A comparison of the amounts of proviral HIV-1 DNAs and HIV-1 mRNAs at 10 and 36 h after HIV-1 infection demonstrated that proviral insertion had not been prevented by M protein and that the block in HIV-1 replication was at the level of proviral expression. The severe reduction of HIV-1 proviral transcripts demonstrates that the VSV M protein alone can inhibit expression from chromosomal DNA. These results strongly support the hypothesis that the VSV M protein is involved in the shutoff of host cell transcription. M protein was able to attenuate HIV-1 infections and protect the cell population from HIV-1 pathogenesis. The temperature-dependent switch from a persistent to a lytic HIV-1 infection in the presence of ts M protein could be useful for studies of HIV-1 replication and pathogenesis.

Base Sequence↗
PubMed1995

Vesicular stomatitis virus infection induces a nuclear DNA-binding factor specific for the interferon-stimulated response element.

Vesicular stomatitis virus (VSV) has a broad host range. It replicates in the cytoplasm and causes rapid cytopathic effects. We show that following VSV infection, a nuclear factor that binds to a select set of interferon-stimulated responsive elements (ISRE) is induced in many cell types. This factor, tentatively called VSV-induced binding protein (VIBP), was estimated to have an approximate molecular mass of 50 kDa and was distinct from known members of the interferon regulatory factor family, that are known to bind to the ISRE. Induction of VIBP required tyrosine kinase activity but did not require cellular transcription. Treatment of cells with cycloheximide, which inhibits translation, only partially inhibited induction of VIBP. However, type I interferons and staurosporine, both of which inhibit VSV transcription, inhibited VIBP induction. Moreover, a double-stranded RNA analog, poly(I)-poly(C) also induced a DNA-binding activity very similar to that of VIBP. These results indicate that a preexisting cellular protein is activated upon VSV infection and that this activation requires primary viral transcripts. The functional activity of VIBP was analyzed in cells stably transfected with a herpesvirus thymidine kinase-luciferase reporter gene that is under control of the ISRE. While activity of the control promoter without ISRE was strongly inhibited following VSV infection (as a result of virus-mediated transcriptional shutdown of the host cell), the inhibition was reversed by the ISRE-containing promoter, albeit partially, which suggests that VSV infection differentially affects transcription of host genes. Although VIBP was induced in all other cells tested, it was not induced in embryonal carcinoma cells after VSV infection, suggesting developmental regulation of VIBP inducibility.

Amino Acid Sequence↗
PubMed1995

[Comparison of the effectiveness of orally administered clorazepate dipotassium and nordiazepam on preoperative anxiety].

Clorazepate dipotassium (Tranxilium) is one of the benzodiazepines which is widely used for oral premedication. After oral administration it is decarboxylated to its active metabolite nordiazepam (desmethyldiazepam). Nordiazepam is also commercially available in the form of drops (Tranxilium N). The aim of the present study was to compare the effect of these drugs on preoperative anxiety. One hundred and eight patients scheduled for orthopaedic surgery (ASA I-II) were studied. Medication was administered at 10 p.m. the evening before surgery (E) and at 7 a.m. on the morning of surgery (M). There were four groups: 1) E no medication; M clorazepate dipotassium; 2) E no medication; M nordiazepam; 3) E clorazepate dipotassium; M clorazepate dipotassium, 4) E clorazepate dipotassium; M nordiazepam. Dosages were: clorazepate dipotassium: body weight < 55 kg: 10 mg; body weight > 55 kg: 20 mg; nordiazepam: 1 gtt/kg; 5 mg = 24 gtt). Anxiety was measured by using the self-evaluating Erlangen anxiety scales, which measure both background and situational anxiety. Background anxiety (EAS-H) was evaluated during the evening before surgery; situational anxiety (EAS-S) was evaluated at the same time and also on the day of surgery before premedication and immediately before surgery. Pulse rate was measured each time the test was administered. There were no differences between the groups in sex, age, weight or the intervals between premedication and anaesthesia induction (p > 0.05). There were no statistically significant differences between the groups with respect to background anxiety. Situational anxiety did not significantly increase or decrease at any of the testing times, nor were there any differences between the groups (p > 0.05). Heart rate did not vary between the groups or with time (p > 0.05). In this group of patients undergoing elective orthopaedic procedures, clorazepate prevented a rise in anxiety in the immediate preoperative period. Since clorazepate is rapidly metabolized to nordiazepam when administered orally it might be predicted that the two drugs have similar properties. This hypothesis is confirmed by the results of the present study. We conclude that orally administered clorazepate dipotassium and nordiazepam have a similar effect on preoperative anxiety.

Administration, Oral↗
PubMed1994

Suppression and long latency excitation of single spinal motoneurons by transcranial magnetic stimulation in health, multiple sclerosis, and stroke.

Whether or not suppression at the level of the spinal motoneuron plays a role in motor deficits such as central paresis is unknown. In this study suppression in the firing of tonically active low threshold single motoneurons following low intensity transcranial magnetic stimulation is described in health and disease. Changes in firing probability in the absence of an early excitatory response were studied in a total of 14 motor units from 4 healthy subjects, 5 patients with multiple sclerosis, and 1 patient with stroke. Firing probability began to fall 18-59 ms after the stimulus and remained low for a period of 27-133 ms. There were no obvious differences between the three subject groups. The change in firing probability was not associated with specific physical signs. Late rises in firing probability were seen in 7 of the 14 motor units at latencies that were similar to the secondary peak which is known to occur with higher stimulus intensities. It is argued that the mechanism of partial suppression is not dependent on the full integrity of the pyramidal tract and is likely to involve a transient withdrawal of descending excitatory drive rather than an inhibitory postsynaptic potential at the spinal motoneuron.

Adult↗